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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. PMID:18179075

  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. Autoantibodies to Insulin Receptor Spontaneously Develop as Anti-Idiotypes in Mice Immunized with Insulin

    NASA Astrophysics Data System (ADS)

    Shechter, Yoram; Maron, Ruth; Elias, Dana; Cohen, Irun R.

    1982-04-01

    Mice immunized with insulin developed antibodies to both insulin and the insulin receptor. The antibodies to insulin receptor displaced labeled insulin from insulin receptors and mimicked the actions of insulin in stimulating the oxidation of glucose and its incorporation into lipids, and in inhibiting lipolysis. The antibodies to insulin receptor could be blocked by or bound to the antibodies to insulin, and therefore were identified as anti-idiotypes. Thus, immunization against a hormone may activate spontaneously an idiotype-anti-idiotype network resulting in antibodies to the hormone receptor.

  5. 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.

  6. 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.

  7. The idiotypic network in the regulation of autoimmunity: Theoretical and experimental studies.

    PubMed

    Menshikov, Igor; Beduleva, Liubov; Frolov, Maksim; Abisheva, Nadezhda; Khramova, Tatyana; Stolyarova, Elena; Fomina, Kseniya

    2015-06-21

    The regulation of autoimmunity is a key issue in fundamental immunology. Despite outstanding achievements on this front, we currently have more questions than answers. The idea of an immune network as a regulatory mechanism is quite attractive, since it enables us to explain the selectivity (specificity), and moreover the clonality, of the regulation. Nevertheless it remains unclear how this mysterious network of immune cells is organized, how it operates, and how it exerts control over autoimmunity. This article presents an attempt to understand how the immune network functions and how it controls autoreactivity. We present a mathematical model of the immune network that is based on principles of immune network organization and function that we arrived at from a survey of the available literature. To test the principles on which the mathematical model is based, we studied the model and compared the different responses to antigen that it generated with the results obtained from experimental studies of immune response. The modeled kinetics of idiotype and anti-idiotype in response to the administration of antigen are in good agreement with the experimental kinetics of idiotypic and anti-idiotypic antibodies. To obtain evidence of the existence of idiotypic mechanisms for regulating autoimmunity, we studied a mathematical model containing autoclones and compared the model results with data from experimental studies in a model of autoimmune hemolytic anemia in mice. Because the results from the theoretical and the experimental studies coincide, there is justification to conclude that autoreactive lymphocytes are normal components of the immune network within which they are regulated. We discuss a possible molecular/cellular mechanism for negative control of autoreactive cells as affected by anti-idiotypic antibodies. PMID:25445185

  8. Analysis and modulation of the immune response of mice to acetylcholine receptor by anti-idiotypes.

    PubMed

    Souroujon, M C; Barchan, D; Fuchs, S

    1985-01-01

    Anti-idiotypes were raised in mice against three well-characterized anti-acetylcholine receptor (AChR) monoclonal antibodies (mcAbs), as well as against polyclonal mouse anti-AChR antibodies. In binding experiments, the anti-idiotypic antibodies inhibited the binding of AChR only to the immunizing idiotype. However, a less restricted specificity was found in in vivo experiments. Mice producing anti-idiotypes were challenged with AChR and the idiotypic composition of their anti-AChR response was analysed using specific rabbit anti-idiotypic antibodies. It was found that preimmunization with a certain idiotype leads to the preferential suppression of this particular idiotype in the polyclonal response to AChR. However, preimmunization with either polyclonal or monoclonal anti-AChR antibodies resulted in a reduction of the overall anti-Torpedo AChR and anti-muscle AChR titers. This reduction was greater than would be expected from the representation of each of the respective idiotypes in the polyclonal anti-AChR serum, and may imply that in addition to the immunizing idiotype other anti-AChR idiotypes are also suppressed. Our results suggest that anti-idiotypes may have a potential for the modulation of the autoimmune response directed against AChR in myasthenia. PMID:3874156

  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. Randomly evolving idiotypic networks: Structural properties and architecture

    NASA Astrophysics Data System (ADS)

    Schmidtchen, Holger; Thüne, Mario; Behn, Ulrich

    2012-07-01

    We consider a minimalistic dynamic model of the idiotypic network of B lymphocytes. A network node represents a population of B lymphocytes of the same specificity (idiotype), which is encoded by a bit string. The links of the network connect nodes with complementary and nearly complementary bit strings, allowing for a few mismatches. A node is occupied if a lymphocyte clone of the corresponding idiotype exists; otherwise it is empty. There is a continuous influx of new B lymphocytes of random idiotype from the bone marrow. B lymphocytes are stimulated by cross-linking their receptors with complementary structures. If there are too many complementary structures, steric hindrance prevents cross-linking. Stimulated cells proliferate and secrete antibodies of the same idiotype as their receptors; unstimulated lymphocytes die. Depending on few parameters, the autonomous system evolves randomly towards patterns of highly organized architecture, where the nodes can be classified into groups according to their statistical properties. We observe and describe analytically the building principles of these patterns, which make it possible to calculate number and size of the node groups and the number of links between them. The architecture of all patterns observed so far in simulations can be explained this way. A tool for real-time pattern identification is proposed.

  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. PMID:23207664

  12. 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.

  13. Idiotype vaccines for lymphoma: Potential factors predicting the induction of immune responses.

    PubMed

    Inoges, Susana; de Cerio, Ascension Lopez-Diaz; Villanueva, Helena; Pastor, Fernando; Soria, Elena; Bendandi, Maurizio

    2011-06-10

    Over the last two decades, lymphoma idiotype vaccines have been the first human cancer vaccines to show striking evidence of biological and clinical efficacy on the one hand, as well as clinical benefit on the other. More recently, however, three large-scale, independent, randomized clinical trials on idiotypic vaccination have failed to achieve their main clinical endpoints for reasons likely to depend more on flaws in each clinical trial's study design than on each vaccination strategy per se. Independently of these considerations, a major hurdle for the development of this substantially innocuous and yet potentially very effective type of treatment has been the fact that, even to date, no factors ascertainable before vaccination have been prospectively singled out as predictors of subsequently vaccine-induced, idiotype-specific immune as well as clinical responses. The aim of this review article is precisely to analyze what has been and what could be done in this respect in order to give a greater chance of success to future trials aimed at regulatory approval of idiotype vaccines. PMID:21773074

  14. IgM anti-idiotypes that block anti-HLA antibodies: naturally occurring or immune antibodies?

    PubMed Central

    Urlacher, A; Tongio, M M; Pasquali, J L

    1991-01-01

    Using dithiothreitol (DTT) technique, IgM anti-HLA anti-idiotypic antibodies were detected in a multiparous multitransfused woman. These antibodies were able to inhibit the binding of specific IgG anti-HLA antibodies on their corresponding antigen. The recognized determinants were cross-reactive determinants since they were partially found on anti-HLA antibodies from unrelated individuals. By studying the patient's sera over a period of 2 years, no IgM-IgG switch was observed but the presence of these antibodies was stable in time, despite the disappearance of the idiotypes (anti-HLA antibodies). However, when looking at the patient's earlier serum, it was shown that these IgM anti-idiotypic antibodies were absent from the first available serum. Thus, these anti-idiotypic antibodies seem to behave both like natural and immune antibodies. The incidence of such antibodies in pretransplant patients is discussed. PMID:1703054

  15. Human EBV-transformed lymphocytes of patients with Schistosoma japonicum infection secrete idiotypically related immunoregulatory antibodies.

    PubMed

    Kresina, T F; Cheever, L W; Chireau, M; Johnson, J; Ramirez, B; Peters, P; Olds, G R

    1992-12-01

    Lymphocytes derived from the peripheral blood of individuals infected with Schistosoma japonica were transformed in vitro with Ebstein-Barr virus (EBV). Serological characterization of antibody molecules revealed both antigen reactive (idiotypic) and anti-idiotypic transformants. One idiotypic EBV transformant, LO2C2, describes a major cross-reactive idiotype associated with anti-antigen binding molecules. Other antibody populations expressing idiotypic cross-reactivity were derived from separate individuals showing shared idiotypy in S. japonicum field study populations in the Republic of Philippines. Both idiotypic and anti-idiotypic molecules suppressed parasite antigen-driven blastogenesis of heterologous human peripheral blood lymphocytes. The data show a serologically related immunoregulatory immune network in patients in the Republic of the Philippines which is serologically distinct from idiotypy expressed in other selected S. japonicum endemic areas in the Far East. PMID:1333380

  16. 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.

  17. 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

  18. 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

  19. 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.

  20. Evidence from the anti-idiotypic network that the acetylcholine receptor is a rabies virus receptor.

    PubMed Central

    Hanham, C A; Zhao, F; Tignor, G H

    1993-01-01

    We have developed idiotype-anti-idiotype monoclonal antibodies that provide evidence for rabies virus binding to the acetylcholine receptor (AChR). Hybridoma cell lines 7.12 and 7.25 resulted after fusion of NS-1 myeloma cells with spleen cells from a BALB/c mouse immunized with rabies virus strain CVS. Antibody 7.12 reacted with viral glycoprotein and neutralized virus infectivity in vivo. It also neutralized infectivity in vitro when PC12 cells, which express neuronal AChR, but not CER cells or neuroblastoma cells (clone N18), which have no AChR, were used. Antibody 7.25 reacted with nucleocapsid protein. Anti-idiotypic monoclonal antibody B9 was produced from fusion of NS-1 cells with spleen cells from a mouse immunized with 7.12 Fab. In an enzyme-linked immunosorbent assay and immunoprecipitation, B9 reacted with 7.12, polyclonal rabies virus immune dog serum, and purified AChR. The binding of B9 to 7.12 and immune dog serum was inhibited by AChR. B9 also inhibited the binding of 7.12 to rabies virus both in vitro and in vivo. Indirect immunofluorescence revealed that B9 reacted at neuromuscular junctions of mouse tissue. B9 also reacted in indirect immunofluorescence with distinct neurons in mouse and monkey brain tissue as well as with PC12 cells. B9 staining of neuronal elements in brain tissue of rabies virus-infected mice was greatly reduced. Rabies virus inhibited the binding of B9 to PC12 cells. Mice immunized with B9 developed low-titer rabies virus-neutralizing antibody. These mice were protected from lethal intramuscular rabies virus challenge. In contrast, anti-idiotypic antibody raised against nucleocapsid antibody 7.25 did not react with AChR. Images PMID:7677960

  1. Anti-idiotypic immunization provides protection against lethal endotoxaemia in BALB/c mice.

    PubMed Central

    Cornelissen, J J; Maassen, K; van Emst, L; Weers, P M; Harmsen, M; Benaissa-Trouw, B J; Oosterlaken, T A; Kraaijeveld, C A; Verhoef, J

    1993-01-01

    Against lipid A (the conserved moiety of lipopolysaccharides from Gram-negative bacteria) neutralizing IgM monoclonal antibodies (mAb) 8-2 and 26-20 anti-idiotypic (Ab2) mAb were produced: Ab2 mAb KM-04 (IgG1) against mAb 8-2, and Ab2 mAb PW-1 (IgG2a) and PW-2 (IgG1) against mAb 26-20. The binding of Ab2 mAb KM-04 to 8-2 (Ab1) was strongly inhibited by a lipopolysaccharide (LPS) extract from either Salmonella minnesota R595 (Re LPS) or Escherichia coli J5 (Rc LPS), whereas the binding of Ab2 mAb PW-1 and PW-2 to 26-20 (Ab1) was only marginally inhibited by both Re LPS and Rc LPS. The results indicated that Ab2 mAb KM-04 recognizes a lipid A-binding site related idiotope on mAb 8-2 and therefore KM-04 might bear the internal image of a neutralization determining epitope of lipid A. Consequently Ab2 KM-04 might induce antibodies to lipid A. Indeed anti-idiotypic immunization of syngeneic BALB/c mice with Ab2 mAb KM-04 resulted in development of lipid A-binding anti-anti-idiotypic (Ab3) antibodies in serum. Similar immunizations with Ab2 mAb PW-1 and PW-2 were unsuccessful. However, induction of lipid A-binding Ab3 by mAb KM-04 proved to be genetically restricted to BALB/c mice. DBA/2 mice, Swiss mice and rabbits did not develop lipid A-binding antibodies upon immunization with mAb KM-04. In protection experiments, it was shown that BALB/c mice vaccinated with mAb KM-04 showed significantly enhanced survival from challenge with either rough (Re) LPS from Salmonella minnesota or smooth LPS from E. coli 0111:B4 when compared to BALB/c mice immunized with a non-relevant Ab2 mAb. The results suggest that mAb KM-04 constitutes a non-internal image vaccine to the lethal effect of lipid A in BALB/c mice. Furthermore an Ab3 mAb was prepared against Ab2 mAb KM-04 that showed reactivity with Re LPS. This Ab3 mAb, designated LE-21 (IgG2a) protected mice against an otherwise lethal challenge of Re LPS. PMID:8406595

  2. Idiotype-anti-idiotype regulation. I. Immunization with a levan-binding myeloma protein leads to the appearance of auto-anti-(anti-idiotype) antibodies and to the activation of silent clones

    PubMed Central

    1981-01-01

    BALB/c mice immunized multiple times with ABPC48 (A48 or Ab1), a BALB/c bacterial levan (BL)-binding myeloma proteins, produce anti-Ab1 antibodies (Ab2). Immunization with only tow doses of AB1 often leads to the production of anti (antiA48) (Ab3) as does immunization with hemocyanin conjugates of Ab2. Finally, immunization with hemocyanin conjugates of Abf3 leads to the production of anti- (anti-[anti-A48]) (Ab4). Normal BALB/c mice immunized with BL produce an anti BL antibody response containing no detectable Ab1 idiotype (Id)-bearing molecules. Mice producing Ab3 express substantial amounts of Ab1 Id in their anti- BL response whereas mice producing Ab2 and Ab4 show a generalized inhibition in their anti BL response. These results indicate that states of immunity within an idiotypic chain may have marked effect on antibody responses to the antigen (i.e., BL) which is the putative initiator of the chain. Strikingly, the chain itself has an interesting feature. That is, Ab3 and Ab1 share a cross-reactive Id in that both are bound by Ab4 and Ab2. We propose a model of Id-anti-Id systems to explain this unexpected result. This is based on the concept of regulatory idiotopes on Ab1 molecules which initiate Ab2 (anti- idiotope) responses. In contrast, Ab2 molecules generally fail to initiate anti-Ab2 Id responses eigher because any individual idiotope is present at very low concentration or because Ab2 molecules tend to lack regulatory idiotopes. Thus, Ab2 molecules immunize syngeneic animals because they interact with cells bearing Ab1 like regulatory idiotopes. Thus, Ab3 will share regulatory idiotopes with Ab1. Ab4 and Ab2 will share the ability to bind the Ab1-like regulatory idiotope. PMID:7252415

  3. 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

  4. The promise of the anti-idiotype concept

    PubMed Central

    Kieber-Emmons, Thomas; Monzavi-Karbassi, Bejatohlah; Pashov, Anastas; Saha, Somdutta; Murali, Ramachandran; Kohler, Heinz

    2012-01-01

    A basic tenet of antibody-based immunity is their specificity to antigenic determinates from foreign pathogen products to abnormal cellular components such as in cancer. However, an antibody has the potential to bind to more than one determinate, be it an antigen or another antibody. These observations led to the idiotype network theory (INT) to explain immune regulation, which has wax and waned in enthusiasm over the years. A truer measure of the impact of the INT is in terms of the ideas that now form the mainstay of immunological research and whose roots are spawned from the promise of the anti-idiotype concept. Among the applications of the INT is understanding the structural implications of the antibody-mediated network that has the potential for innovation in terms of rational design of reagents with biological, chemical, and pharmaceutical applications that underlies concepts of reverse immunology which is highlighted herein. PMID:23267437

  5. 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.

  6. Immunization of complex networks

    NASA Astrophysics Data System (ADS)

    Pastor-Satorras, Romualdo; Vespignani, Alessandro

    2002-03-01

    Complex networks such as the sexual partnership web or the Internet often show a high degree of redundancy and heterogeneity in their connectivity properties. This peculiar connectivity provides an ideal environment for the spreading of infective agents. Here we show that the random uniform immunization of individuals does not lead to the eradication of infections in all complex networks. Namely, networks with scale-free properties do not acquire global immunity from major epidemic outbreaks even in the presence of unrealistically high densities of randomly immunized individuals. The absence of any critical immunization threshold is due to the unbounded connectivity fluctuations of scale-free networks. Successful immunization strategies can be developed only by taking into account the inhomogeneous connectivity properties of scale-free networks. In particular, targeted immunization schemes, based on the nodes' connectivity hierarchy, sharply lower the network's vulnerability to epidemic attacks.

  7. Suppression of collagen induced arthritis by idiotype coupled lymphoid cells

    SciTech Connect

    Nagler-Anderson, C.; Gurish, M.F.; Robinson, M.E.; Thorbecke, G.J.

    1986-03-01

    Studies were initiated to evaluate the regulatory influence of idiotype (Id) networks in an experimental auto-immune disease. Collagen induced arthritis is an animal model of polyarthritis induced in susceptible mice by immunization with collagen II (CII). A humoral immune response to CII appears to be critical for the development of diseases. If subpopulations of the anti-CII abs, important for the induction of arthritis, could be identified and manipulated through the presence of a major Id, it should be possible to decrease arthritis incidence by suppressing the production of these Ids. Specifically purified anti-CII abs from arthritic DBA/1 mice were coupled to syngeneic spleen cells and administered IV prior to intradermal immunization with CII. By day 34 after 1/sup 0/ immunization, 100% of control mice and 50% of treated mice had developed arthritis. Suppression of the Id population administered to the treated group was confirmed by RIA. Sera from individual mice were tested as inhibitors of binding of /sup 125/I-labelled polyclonal DBA/1 anti-CII to a rabbit anti-Id directed against polyclonal anti-CII isolated from the sera of arthritic mice. Mean percentage of inhibition of binding of /sup 125/I-Id to rabbit anti-Id by sera from non-arthritic treated mice was found to be significantly lower than that observed in the arthritic control group (p = .045), but did not correlate with total anti-CII ab titers.

  8. 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.

  9. 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.

  10. 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

  11. Monoclonal approach to investigate whether the idiotypic network plays a role in the formation of Graves' autoantibodies

    SciTech Connect

    Hill, B.L.

    1987-01-01

    A monoclonal antibody (LE4) specific for a thyrotropin (TSH) epitope shared by beta subunits of bovine (b), ovine (o), and human (h) TSH was obtained by immunization of mice with mixtures of purified bTSH and hTSH. LE4 also bound the beta subunits of bovine, ovine, and human lutropin (LH), and human chorionic gonadotropin (hCG) but not the beta subunits of porcine LH and TSH. Preliminary studies with deglycosylated (dg) bTSH and dg-hCG indicated that part of the epitope may be carbohydrate. Preincubation of LE4 with (/sup 125/I)bTSH inhibited the binding of the hormone to TSH receptor of bovine thyroid membranes in a dose-dependent manner. LE4 also inhibited TSH-induced mitogenesis of FRTL-5 cells. We conclude that LE4 binds to a site on the bTSH molecule that participates in high affinity binding of hormone to TSH receptor.

  12. Model IgG Monoclonal Autoantibody–Anti-Idiotype Pair for Dissecting the Humoral Immune Response to Oxidized Low Density Lipoprotein

    PubMed Central

    Chang, Shang-Hung; Johns, Michael; Boyle, Joseph J.; McConnell, Ellen; Kirkham, Paul A.; Bicknell, Colin; Zahoor-ul-Hassan Dogar, M.; Edwards, Robert J.; Gale-Grant, Oliver; Khamis, Ramzi; Ramkhelawon, Kurrun V.V.

    2012-01-01

    Increasing evidence implicates IgG autoantibodies against oxidized forms of low density lipoprotein (oxLDL) in the pathophysiology of atherosclerotic arterial disease. However, insufficient knowledge of their structure and function is a key gap. Using an elderly LDL receptor-deficient atherosclerotic mouse, we isolated a novel IgG3k against oxLDL (designated MAb LO1). LO1 reacts with copper-oxidized LDL, but minimally with native LDL. Further analysis showed that MAb LO1 also reacts in vitro with malondialdehyde-conjugated LDL (MDA-LDL), a known key epitope in copper-oxidized LDL preparations. By screening a phage library expressing single chain variable region antibodies (scFv), we selected an anti-idiotype scFv (designated H3) that neutralizes MAb LO1 binding to MDA-LDL. Amino acid substitutions between H3 and an irrelevant control scFv C12 showed that residues in the H3 CDRH2, CDRH3, and CDRL2 are all critical for MAb LO1 binding, consistent with a conformational epitope on H3 involving both heavy and light chains. Comparison of amino acids in H3 CDRH2 and CDRL2 with apoB, the major LDL protein, showed homologous sequences, suggesting H3 has structural similarities to the MAb LO1 binding site on MDA-LDL. Immunocytochemical staining showed that MAb LO1 binds epitopes in mouse and human atherosclerotic lesions. The MAb LO1-H3 combination therefore provides a very promising model for analyzing the structure and function of an individual IgG autoantibody in relation to atherosclerosis. PMID:22509912

  13. 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.

  14. 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

  15. Idiotypes of monoclonal anti-DNA antibodies produced in autoimmune B/W mice are expressed in normal mice.

    PubMed Central

    Jacob, L; Tron, F; Lety, M A; Bach, J F

    1986-01-01

    An anti-idiotypic antiserum was prepared in a rabbit immunized against a pool of six monoclonal anti-DNA antibodies generated in B/W mice. This antiserum detected idiotypic determinants in four of the six monoclonal anti-DNA antibodies but also in the serum of several non autoimmune strains (BALB/c, NZB X BALB/c) F1 hybrids & CBA/LH). The antiserum also reacted, but only to a weak degree, with B/W mouse sera. These results indicate that some idiotypes of anti-DNA antibodies produced by autoimmune B/W mice are present in normal mouse sera. PMID:3486065

  16. 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

  17. US Veterinary Immune Reagent Network: Prioritization & Progress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US Veterinary Immune Reagent Network represents a broad community plan to begin to systematically address the immunological reagent gap for the US veterinary immunology research community including for the following groups: ruminants (concentrating on cattle), swine, poultry (primarily chickens)...

  18. 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

  19. Preparation of humanized ovarian carcinoma anti-idiotypic minibody.

    PubMed

    Chang, Xiaohong; Cui, Heng; Feng, Jie; Li, Yi; Liu, Bei; Cao, Shanjin; Cheng, Yexia; Qian, Henian

    2003-04-01

    Murine anti-idiotypic monoclonal antibody (MAb) 6B11 mimicking the tumor-associated antigen OC166-9 is used as a vaccine for the induction of an anti-tumoral immunity in experiments of in vitro and in vivo animal model with ovarian carcinoma. In this article, we have humanized 6B11 anti-idiotypic minibody using overlap polymerase chain reaction (PCR) and DNA recombinant technique, prokaryotic expression vector was produced by genetic fusion of 6B11V(L)-V(H) to human IgG1 hinge and CH3 region. Transformed E. coli BL21(DE3) were propagated and induced by isopropyl-beta D-thiogalactopyranoside (IPTG). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that a protein band with molecular weight of 50kD appeared as the expected size after transformation. Molecular weight of 100 kDa may be examined by electrophoresis in nondenaturing systems. The fusion protein was analyzed with enzyme-linked immunosorbant assay (ELISA), inhibition ELISA tests and Western blot, respectively. The humanized anti-idiotype minibody showed capacity of bivalent binding to ovarian cancer MAb COC166-9 and goat anti-human immunoglobulin IgG1. It is useful reagents for clinical use. PMID:12831536

  20. 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

  1. 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

  2. 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

  3. Genetics of the. cap alpha. 1,6-dextran response: expression of the QUPC52 idiotype in different inbred and congenic strains of mice

    SciTech Connect

    D'Hoostelaere, L.; Potter, M.

    1982-01-01

    Antibodies to dextran B512 were raised in various strains of mice and were assayed by a radioimunoassay procedure. Idiotypic antibodies to the IgA(k) dextran B512 binding myeloma proteins QUOC52 and W3129 of BALB/c origin were prepred in rabbits. After adsorption, each antiserum was specific for the immunizing myeloma protein and did not react with hundreds of other myeloma proteins; nonetheless, antibodies to dextran B512 from various strains of mice cross-reacted in these test systems. Of the 2 idiotypes tested, the W3129 idiotype was more universally expressed in different strains of mice. The QUPC52 idiotype was the predominant idiotype in BALB/c anti-dextran B512 antibodies and was found in only a few other inbred strains. Using a battery of congenic and inbred strains, it was shown that the QUPC52 idiotype was controlled by genes linked to the Igh complex locus (chromosome 12) and to the Ig k complex locus (chromosome 6). The W3129 idiotype was found in a number of stocks of mice in the genus Mus recently isolated from the wild. The QUPC52 idiotype thus far was found only in inbred mice.

  4. Individual and meta-immune networks

    NASA Astrophysics Data System (ADS)

    Bransburg-Zabary, Sharron; Kenett, Dror Y.; Dar, Gittit; Madi, Asaf; Merbl, Yifat; Quintana, Francisco J.; Tauber, Alfred I.; Cohen, Irun R.; Ben-Jacob, Eshel

    2013-04-01

    Networks can be found everywhere—in technology, in nature and in our bodies. In this paper we present how antigen networks can be used as a model to study network interaction and architecture. Utilizing antigen microarray data of the reactivity of hundreds of antibodies of sera of ten mothers and their newborns, we reconstruct networks, either isotype specific (IgM or IgG) or person specific—mothers or newborns—and investigate the network properties. Such an approach makes it possible to decipher fundamental information regarding the personal immune network state and its unique characteristics. In the current paper we demonstrate how we are successful in studying the interaction between two dependent networks, the maternal IgG repertoire and the one of the offspring, using the concept of meta-network provides essential information regarding the biological phenomenon of cross placental transfer. Such an approach is useful in the study of coupled networks in variety of scientific fields.

  5. Anti-idiotypic antibody to an anti-alprenolol monoclonal antibody: promotion of ligand binding to the idiotype

    SciTech Connect

    Sawutz, G.; Homcy, C.J.

    1986-03-01

    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/k), was used to generate polyclonal anti-idiotypic antisera in rabbits. In contrast to the predicted results, the anti-idiotypic antisera (R-9) promoted (/sup 125/I)-CYP binding to the monoclonal antibody 5B7. In the presence of R-9 antisera (1:300 dilution), the binding affinity improved with the dissociation constant decreasing 100-fold from 10nM to 0.1nM. This effect could not be reproduced with pre-immune, rabbit anti-mouse, or antiidiotypic antisera generated to monoclonal antibodies of different specificity. Furthermore, R-9 alone did not bind ligand. The R-9 IgG fraction was isolated by DEAE-cellulose chromatography then adsorbed to a 5B7-immunoaffinity resin and eluted with 0.5 M NaCl. This yielded a fraction with enhanced binding activity. F(ab) fragments of 5B7 and R-9 produced the same effect indicating that polyvalency was not necessary for the enhanced ligand binding. Finally, the ligand alprenolol promoted the binding of (/sup 125/I)-5B7 to %-9 as assessed by fractionating the resulting soluble complex by size exclusion chromatography on a TSK-3000 HPLC column. These results demonstrate that anti-idiotypic antibodies can be generated which will promote the binding of antigen to the original idiotype.

  6. 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.

  7. Production, isolation, and characterization of rabbit anti-idiotypic antibodies directed against human antithyrotrophin receptor antibodies.

    PubMed Central

    Baker, J R; Lukes, Y G; Burman, K D

    1984-01-01

    Previous studies have shown that anti-idiotypic antibodies can be developed in vivo through animal immunization with idiotype, and that these antibodies can be isolated from other anti-immunoglobulin antibodies by affinity purification. These techniques have relied on large amounts of idiotype, which were produced either by hyperimmunization or by monoclonal antibodies, to serve as the affinity adsorbent. In the present study, we produced anti-idiotypic antibodies to human anti-thyroid-stimulating hormone (TSH) receptor antibodies by first injecting rabbits with (TSH receptor purified) IgG from Graves' patients. The resulting antiserum was then adsorbed with Sepharose-coupled TSH in an attempt to specifically bind and isolate the anti-idiotype. The antibody obtained from this process was shown to bind specifically to TSH receptor-binding antibodies from Graves' patients, and this binding could be inhibited by 56% with the addition of 10(-4) M TSH but not by HCG (10(-2) M). The anti-idiotype also bound to TSH, and this binding could be specifically inhibited by receptor-purified Graves' IgG (60% inhibition at 10 micrograms/ml IgG), but not by IgG from normal subjects (no inhibition at 50 micrograms/ml IgG). In a TSH receptor binding assay, the anti-idiotype could inhibit TSH receptor binding in Graves' sera at a 1,000-fold lower concentration than could anti-kappa/lambda antiserum; the anti-idiotypic antiserum also inhibited in vitro TSH-mediated adenylate cyclase stimulation at an IgG concentration of 5 micrograms/ml, while heterologous anti-TSH antisera and normal IgG at similar concentrations had no effect. Finally, despite being generated against a single patient's TSH receptor binding antibody, the anti-idiotype was able to block TSH receptor binding in the serum of six other Graves' patients, thus suggesting that there may be conformational conservation in the antigen that is recognized by different individuals' TSH receptor-binding immunoglobulins. PMID

  8. On the maternal transmission of immunity: a 'molecular attention' hypothesis.

    PubMed

    Anderson, R W

    1995-01-01

    Maternally-derived antibodies can provide passive protection to their offspring. More subtle phenomena associated with maternal antibodies concern their influence in shaping the immune repertoire and priming the neonatal immune response. These phenomena suggest that maternal antibodies play a role in the education of the neonatal immune system. The educational effects are thought to be mediated by idiotypic interactions among antibodies and B cells in the context of an idiotypic network. This paper proposes that maternal antibodies trigger localized idiotypic network activity that serves to amplify and translate information concerning the molecular shapes of potential antigens. The triggering molecular signals are contained in the binding regions of the antibody molecules. These antibodies form complexes and are taken up by antigen presenting cells or retained by follicular dendritic cells and thereby incorporated into more traditional cellular immune memory mechanisms. This mechanism for maternal transmission of immunity is termed the molecular attention hypothesis and is contrasted to the dynamic memory hypothesis. Experiments are proposed that may help indicate which models are more appropriate and will further our understanding of these intriguing natural phenomena. Finally, analogies are drawn to attention in neural systems. PMID:7727708

  9. Production of mouse monoclonal antibodies for the analysis of idiotypes in serum of patients with chronic lymphatic leukaemia.

    PubMed

    de Rie, M A; van Heemstra, D J; Huijgens, P C; Zeijlemaker, W P; Out, T A; Melief, C J; von dem Borne, A E

    1988-01-01

    In this report a simple procedure for the production of murine monoclonal antibodies (MoAb) against the idiotype of malignant B cells is described. Mice were immunized with lymphoid cells from patients with B-cell chronic lymphocytic leukaemia (B-CLL). After fusion of the spleen cells, hybridoma supernatants were screened for anti-idiotypic MoAb in ELISA with immunoglobulins obtained from tumour-cell lysates, xenohybridomas and patients' sera. The anti-idiotypic MoAb were used to study tumour cells and serum immunoglobulins (Ig) from four different patients with B-CLL. It was found that the serum IgM and IgD in one patient shared the same idiotype. Evidence is presented that IgG-secreting cell populations are not restricted to lambda-Ig-light chain-expressing B-CLL cells. With the help of anti-idiotype MoAb accurate measurements of total and idiotype-positive serum immunoglobulin levels during chemotherapy were possible. PMID:3257881

  10. 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

  11. 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. PMID:24526340

  12. Immune System Network and Cancer Vaccine

    NASA Astrophysics Data System (ADS)

    Bianca, Carlo; Pennisi, Marzio; Motta, Santo; Ragusa, Maria Alessandra

    2011-09-01

    This paper deals with the mathematical modelling of the immune system response to cancer disease, and specifically with the treatment of the mammary carcinoma in presence of an immunoprevenction vaccine. The innate action of the immune system network, the external stimulus represented by repeated vaccine administrations and the competition with cancer are described by an ordinary differential equations-based model. The mathematical model is able to depict preclinical experiments on transgenic mice. The results are of great interest both in the applied and theoretical sciences.

  13. 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

  14. 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.

  15. 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

  16. Immune networks: multitasking capabilities near saturation

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    Pattern-diluted associative networks were recently introduced as models for the immune system, with nodes representing T-lymphocytes and stored patterns representing signalling protocols between T- and B-lymphocytes. It was shown earlier that in the regime of extreme pattern dilution, a system with NT T-lymphocytes can manage a number N_B={ {O}}(N_T^\\delta ) of B-lymphocytes simultaneously, with δ < 1. Here we study this model in the extensive load regime NB = αNT, with a high degree of pattern dilution, in agreement with immunological findings. We use graph theory and statistical mechanical analysis based on replica methods to show that in the finite-connectivity regime, where each T-lymphocyte interacts with a finite number of B-lymphocytes as NT → ∞, the T-lymphocytes can coordinate effective immune responses to an extensive number of distinct antigen invasions in parallel. As α increases, the system eventually undergoes a second order transition to a phase with clonal cross-talk interference, where the system’s performance degrades gracefully. Mathematically, the model is equivalent to a spin system on a finitely connected graph with many short loops, so one would expect the available analytical methods, which all assume locally tree-like graphs, to fail. Yet it turns out to be solvable. Our results are supported by numerical simulations.

  17. Decline in Titers of Anti-Idiotypic Antibodies Specific to Autoantibodies to GAD65 (GAD65Ab) Precedes Development of GAD65Ab and Type 1 Diabetes

    PubMed Central

    Larsson, Helena Elding; Jönsson, Ida; Lernmark, Åke; Ivarsson, Sten; Radtke, Jared R.; Hampe, Christiane S.

    2013-01-01

    The humoral Idiotypic Network consisting of antibodies and their anti-idiotypic antibodies (anti-Id) can be temporarily upset by antigen exposure. In the healthy immune response the original equilibrium is eventually restored through counter-regulatory mechanisms. In certain autoimmune diseases however, autoantibody levels exceed those of their respective anti-Id, indicating a permanent disturbance in the respective humoral Idiotypic Network. We investigated anti-Id directed to a major Type 1 diabetes (T1D)-associated autoantibody (GAD65Ab) in two independent cohorts during progression to disease. Samples taken from participants of the Natural History Study showed significantly lower anti-Id levels in individuals that later progressed to T1D compared to non-progressors (anti-Id antibody index of 0.06 vs. 0.08, respectively, p = 0.02). We also observed a significant inverse correlation between anti-Id levels and age at sampling, but only in progressors (p = 0.014). Finally, anti-Id levels in progressors showed a significant decline during progression as compared to longitudinal anti-Id levels in non-progressors (median rate of change: −0.0004 vs. +0.0004, respectively, p = 0.003), suggesting a loss of anti-Id during progression. Our analysis of the Diabetes Prediction in Skåne cohort showed that early in life (age 2) individuals at risk have anti-Id levels indistinguishable from those in healthy controls, indicating that low anti-Id levels are not an innate characteristic of the immune response in individuals at risk. Notably, anti-Id levels declined significantly in individuals that later developed GAD65Ab suggesting that the decline in anti-Id levels precedes the emergence of GAD65Ab (median rate of change: −0.005) compared to matched controls (median rate of change: +0.001) (p = 0.0016). We conclude that while anti-Id are present early in life, their levels decrease prior to the appearance of GAD65Ab and to the development of T1D. PMID

  18. 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

  19. 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

  20. Swine Toolkit Progress for US Veterinary Immune Reagent Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US Veterinary Immune Reagent Network (http://www.umass.edu/vetimm/) was established to address the lack of immunological reagents for veterinary species. Within this context, plans are underway to produce sets of reagents needed to evaluate immune changes during disease and following vaccination...

  1. U. S. Veterinary Immune Reagents Network: Progress with poultry immune reagents development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major obstacle to advances in veterinary immunology and disease research is the lack of sufficient immunological reagents specific for veterinary animal species. In 2006, U. S. Veterinary Immune Reagent Network (VIRN) Consortium (www.vetimm.org) was developed to develop immune reagents against ma...

  2. 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.

  3. 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

  4. 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

  5. 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

  6. Physicochemical and biological characterization of 1E10 Anti-Idiotype vaccine

    PubMed Central

    2011-01-01

    Background 1E10 monoclonal antibody is a murine anti-idiotypic antibody that mimics N-glycolyl-GM3 gangliosides. This antibody has been tested as an anti-idiotypic cancer vaccine, adjuvated in Al(OH)3, in several clinical trials for melanoma, breast, and lung cancer. During early clinical development this mAb was obtained in vivo from mice ascites fluid. Currently, the production process of 1E10 is being transferred from the in vivo to a bioreactor-based method. Results Here, we present a comprehensive molecular and immunological characterization of 1E10 produced by the two different production processes in order to determine the impact of the manufacturing process in vaccine performance. We observed differences in glycosylation pattern, charge heterogeneity and structural stability between in vivo-produced 1E10 and bioreactor-obtained 1E10. Interestingly, these modifications had no significant impact on the immune responses elicited in two different animal models. Conclusions Changes in 1E10 primary structure like glycosylation; asparagine deamidation and oxidation affected 1E10 structural stability but did not affect the immune response elicited in mice and chickens when compared to 1E10 produced in mice. PMID:22108317

  7. Immunization strategy for epidemic spreading on multilayer networks

    NASA Astrophysics Data System (ADS)

    Buono, C.; Braunstein, L. A.

    2015-01-01

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

  8. A Danger-Theory-Based Immune Network Optimization Algorithm

    PubMed Central

    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. PMID:23483853

  9. 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. PMID:26092524

  10. Anti-idiotypic antibodies as cancer vaccines: achievements and future improvements

    PubMed Central

    Ladjemi, Maha Z.

    2012-01-01

    Since the discovery of tumor-associated antigens (TAAs), researchers have tried to develop immune-based anti-cancer therapies. Thanks to their specificity, monoclonal antibodies (mAbs) offer the major advantage to induce fewer side effects than those caused by non-specific conventional treatments (e.g., chemotherapy, radiotherapy). Passive immunotherapy by means of mAbs or cytokines has proved efficacy in oncology and validated the use of immune-based agents as part of anti-cancer treatment options. The next step was to try to induce an active immune protection aiming to boost own’s host immune defense against TAAs. Cancer vaccines are thus developed to specifically induce active immune protection targeting only tumor cells while preserving normal tissues from a non-specific toxicity. But, as most of TAAs are self antigens, an immune tolerance against them exists representing a barrier to effective vaccination against these oncoproteins. One promising approach to break this immune tolerance consists in the use of anti-idiotypic (anti-Id) mAbs, so called Ab2, as antigen surrogates. This vaccination strategy allows also immunization against non-proteic antigens (such as carbohydrates). In some clinical studies, anti-Id cancer vaccines indeed induced efficient humoral and/or cellular immune responses associated with clinical benefit. This review article will focus on recent achievements of anti-Id mAbs use as cancer vaccines in solid tumors. PMID:23133825

  11. 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.

  12. Targeting lymphoma with precision using semisynthetic anti-idiotype peptibodies.

    PubMed

    Torchia, James; Weiskopf, Kipp; Levy, Ronald

    2016-05-10

    B-cell lymphomas express a functionally active and truly tumor-specific cell-surface product, the variable region of the B-cell receptor (BCR), otherwise known as idiotype. The tumor idiotype differs, however, from patient to patient, making it a technical challenge to exploit for therapy. We have developed a method of targeting idiotype by using a semisynthetic personalized therapeutic that is more practical to produce on a patient-by-patient basis than monoclonal antibodies. In this method, a small peptide with affinity for a tumor idiotype is identified by screening a library, chemically synthesized, and then affixed to the amino terminus of a premade IgG Fc protein. We demonstrate that the resultant semisynthetic anti-idiotype peptibodies kill tumor cells in vitro with specificity, trigger tumor cell phagocytosis by macrophages, and efficiently clear human lymphoma in a murine xenograft model. This method could be used to target tumor with true precision on a personalized basis. PMID:27114517

  13. Isolation of alpaca anti-idiotypic heavy-chain single-domain antibody for the aflatoxin immunoassay.

    PubMed

    Wang, Yanru; Li, Peiwu; Majkova, Zuzana; Bever, Candace R S; Kim, Hee Joo; Zhang, Qi; Dechant, Julie E; Gee, Shirley J; Hammock, Bruce D

    2013-09-01

    Anti-idiotypic antibodies recognize the antigenic determinants of an antibody, thus they can be used as surrogate antigens. Single-domain antibodies from camlid heavy-chain antibodies with the benefit features of small size, thermostability, and ease in expression, are leading candidates to produce anti-idiotypic antibodies. In this work, we constructed an antibody phage library from the mRNA of an alpaca immunized with an antiaflatoxin monoclonal antibody (mAb) 1C11. Three anti-idiotypic VHH antibodies were isolated and applied to immunoassay toward aflatoxin as a coating antigen. The best immunoassay developed with one of these VHH antibodies shows an IC50 of 0.16 ng/mL toward aflatoxin B1 and cross-reactivity toward aflatoxin B2, G1, and G2 of 90.4%, 54.4%, and 37.7%, respectively. The VHH-based immunoassay was successfully applied to the analysis of peanuts, corn, and rice, which are the predominant commodities regularly contaminated by aflatoxins. A good correlation (r(2) = 0.89) was found between the data obtained from the conventional ELISA and the ELISA based on a VHH coating antigen for the analysis of aflatoxins in peanuts and feedstuff. The use of biotechnology in developing the surrogate, the absence of standard aflatoxin and organic solvents in the synthesis procedures, and the reproducibility of the VHH antibody makes it an ideal strategy for replacing conventional synthesized antigens. PMID:23965250

  14. Single-chain anti-idiotypic antibody retains its specificity to porcine reproductive and respiratory syndrome virus GP5.

    PubMed

    Yu, Ying; Wang, Gang; Li, Qiongyi; Du, Yongkun; Du, Taofeng; Mu, Yang; Xiao, Shuqi; Zhao, Qin; Wang, Chengbao; Sun, Yani; Xu, Xingang; Zhang, Gaiping; Hsu, Walter H; Cai, Xuehui; Zhou, En-Min

    2015-01-01

    Monoclonal anti-idiotypic antibody (Mab2-5G2) raised against idiotypic antibodies to membrane glycoprotein GP5 of porcine reproductive and respiratory syndrome virus (PRRSV). The variable regions of the heavy chain (VH) and light chain (VL) of Mab2-5G2 were cloned and connected with a (Gly4Ser)3 linker. The recombinant scFv gene was cloned into the pEasy-E1 vector and expressed in E. coli as inclusion bodies. The expressed scFv-His proteins renatured in a pH and urea gradient buffer retained the same immunological properties as that of Mab2-5G2. Renatured scFv-His protein retained the same characteristics as that of Mab2-5G2 by recognizing and binding to Marc-145 cells. Furthermore, renatured scFv-His along with Mab2-5G2 were used to immunize rabbits to produce anti-anti-idiotypic antibodies (Ab3) that neutralized PRRSV infection of Marc-145 cells. These results demonstrated that the expressed scFv-His protein possessed the same characteristics of Mab2-5G2 and will be suitable for future investigations of Mab2-5G2 antibody structure and its ability to interact with potential PRRSV cellular receptor as well as immunological properties against PRRSV infection. PMID:25448704

  15. Immunization against the Spread of Rumors in Homogenous Networks

    PubMed Central

    Zhao, Laijun; Wang, Jiajia; Huang, Rongbing

    2015-01-01

    Since most rumors are harmful, how to control the spread of such rumors is important. In this paper, we studied the process of "immunization" against rumors by modeling the process of rumor spreading and changing the termination mechanism for the spread of rumors to make the model more realistic. We derived mean-field equations to describe the dynamics of the rumor spread. By carrying out steady-state analysis, we derived the spreading threshold value that must be exceeded for the rumor to spread. We further discuss a possible strategy for immunization against rumors and obtain an immunization threshold value that represents the minimum level required to stop the rumor from spreading. Numerical simulations revealed that the average degree of the network and parameters of transformation probability significantly influence the spread of rumors. More importantly, the simulations revealed that immunizing a higher proportion of individuals is not necessarily better because of the waste of resources and the generation of unnecessary information. So the optimal immunization rate should be the immunization threshold. PMID:25933430

  16. Immunization against the Spread of Rumors in Homogenous Networks.

    PubMed

    Zhao, Laijun; Wang, Jiajia; Huang, Rongbing

    2015-01-01

    Since most rumors are harmful, how to control the spread of such rumors is important. In this paper, we studied the process of "immunization" against rumors by modeling the process of rumor spreading and changing the termination mechanism for the spread of rumors to make the model more realistic. We derived mean-field equations to describe the dynamics of the rumor spread. By carrying out steady-state analysis, we derived the spreading threshold value that must be exceeded for the rumor to spread. We further discuss a possible strategy for immunization against rumors and obtain an immunization threshold value that represents the minimum level required to stop the rumor from spreading. Numerical simulations revealed that the average degree of the network and parameters of transformation probability significantly influence the spread of rumors. More importantly, the simulations revealed that immunizing a higher proportion of individuals is not necessarily better because of the waste of resources and the generation of unnecessary information. So the optimal immunization rate should be the immunization threshold. PMID:25933430

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. Monoclonal anti-idiotypes induce neutralizing antibodies to enterovirus 70 conformational epitopes.

    PubMed Central

    Wiley, J A; Hamel, J; Brodeur, B R

    1992-01-01

    Monoclonal antibodies (MAbs) directed against the prototype enterovirus 70 (EV-70) strain J670/71 were generated and characterized in order to produce anti-idiotypic MAbs (MAb2s) for use as surrogate immunogens. Western immunoblot and radioimmunoprecipitation assays suggested that all the MAbs recognize conformational epitopes on the virion surface. An EV-70-neutralizing antibody, MAb/ev-12 (MAb1), was selected for the production of MAb2s. Five MAb2s were selected for their capacities to inhibit the interaction of MAb/ev-12 with EV-70 in dot immunobinding inhibition and immunofluorescence assays. In addition, these five MAb2s inhibited virus neutralization mediated by MAb/ev-12, suggesting that they recognize paratope-associated idiotopes. In competition enzyme immunosorbent assays, none of the five MAb2s recognized other neutralizing and nonneutralizing EV-70-specific MAbs, demonstrating that the MAb2s were specific for private idiotopes. Immunization with each of the MAb2s was carried out for the production of anti-anti-idiotypic antibodies (Ab3). All five MAb2s induced an immune response. Moreover, results suggested that they share idiotopes, since MAb2-MAb/ev-12 binding could be inhibited by homologous as well as heterologous Ab3s. Ab3 sera were shown to possess antibodies capable of immunoprecipitating 35S-labeled viral proteins in the same manner as MAb/ev-12. Nine of 15 mice immunized with MAb2s demonstrated Ab3 neutralizing activity specific for the prototype EV-70 strain, J670/71. The potential application of MAb2s to serve as surrogate immunogens for conformational epitopes is substantiated by the results presented in this report. Images PMID:1382141

  2. Dissemination strategy for immunizing scale-free networks

    NASA Astrophysics Data System (ADS)

    Stauffer, Alexandre O.; Barbosa, Valmir C.

    2006-11-01

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

  3. 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.

  4. 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.

  5. Abagovomab: an anti-idiotypic CA-125 targeted immunotherapeutic agent for ovarian cancer

    PubMed Central

    Grisham, Rachel N; Berek, Jonathan; Pfisterer, Jacobus; Sabbatini, Paul

    2011-01-01

    Ovarian cancer remains the leading cause of death due to gynecologic malignancies. Most patients present with advanced disease at the time of diagnosis. Although many have a good initial response to surgical debulking and platinum-based chemotherapy, relapse is common, with the eventual development of chemotherapy resistance. Innovative treatments are needed in the remission setting to prolong the disease-free interval or prevent recurrence. Abagovomab is a murine monoclonal anti-idiotypic antibody (molecular wieght: 165–175 kDa) that functionally imitates the tumor-associated antigen, CA-125. It has been shown to be well tolerated and to induce a sustained immune response in initial Phase I and II clinical trials. An ongoing, double-blind, placebo-controlled, multicenter, Phase III trial (MIMOSA) completed its double-blind period in December 2010 and will compare abagovomab maintenance therapy to placebo, which will definitively determine the efficacy of this immunotherapeutic approach in patients with ovarian cancer. PMID:21322756

  6. Towards an integrated network of coral immune mechanisms

    PubMed Central

    Palmer, C. V.; Traylor-Knowles, N.

    2012-01-01

    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

  7. 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

  8. Effects of immunity on global oscillations in epidemic spreading in small-world networks

    NASA Astrophysics Data System (ADS)

    Gao, Ke; Hua, Da-yin

    2010-08-01

    Considering a decay of an individual immunity, we investigated a susceptible-infectedrefractory-susceptible (SIRS) model in Watts-Strogatz (WS) small-word networks. It is found that when an individual immunity does not change or decays slowly in an immune period, the system can exhibit a transition from a stationary state to a large amplitude sustained oscillation. When the immunity decays rapidly in the immune period, the transition disappears and there is no oscillation. Furthermore, based on the spatio-temporal evolution patterns, it is disclosed that a long immunity period takes an important role in the emergence of the global oscillation in small world networks.

  9. 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.

  10. 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.

  11. 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

  12. Immunological signaling networks: Integrating the body's immune response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune system’s role is to eliminate disease from the host. Immune cells are primarily responsible for eliminating pathogens or cancerous cells. In addition, immune cells regulate the immune response affecting the types of cells that are activated or suppressed. The following discussion is an...

  13. 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.

  14. Aβ anti-idiotypic antibodies are present in intravenous immunoglobulin and are produced in mice following its administration.

    PubMed

    Loeffler, David A; Klaver, Andrea C; Coffey, Mary P

    2015-06-01

    The effects of intravenous immunoglobulin (IVIG) products were recently examined in patients with Alzheimer's disease (AD). Although encouraging results were obtained in pilot studies, later trials produced negative results. The rationale for these studies was that IVIG contains antibodies to amyloid-beta (Aβ). However, if Aβ anti-idiotypic antibodies (antibodies which bind to anti-Aβ antibodies) are present in IVIG or induced by its administration, these antibodies could potentially reduce its neuroprotective effects in AD. The objective of this study was to determine if IVIG contained such antibodies. Enzyme-linked immunosorbent assays (ELISAs) measured specific binding of IVIG Gamunex to purified human anti-Aβ IgG. The mean concentration of its Aβ anti-idiotypic antibodies in four experiments was 1.85 μg/mL (18.5 μg/g IgG; range = 1.82-1.89 μg/mL [18.2-18.9 μg/g IgG]), and their mean percentage of specific binding was 72.2% (range = 68.3-75.3%). We then performed ELISAs to determine if antibodies to purified human anti-Aβ were produced in C57BL/6 mice injected with the IVIG product Gammagard in an earlier study. After subtracting the expected immune response to normal human immunoglobulins, the median concentrations of these antibodies were 15.6 ng/mL (range = 1.2-108.2 ng/mL) in pre-treatment sera and 2419.4 ng/mL (range = 327.4-8478.4 ng/mL) in post-treatment sera. These results indicate that specific Aβ anti-idiotypic antibodies are detectable in IVIG and may be induced in mice by its administration. The presence of Aβ anti-idiotypic antibodies in IVIG products might decrease neuroprotective effects of their anti-Aβ antibodies in AD. PMID:25392130

  15. 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.

  16. From network-to-antibody robustness in a bio-inspired immune system.

    PubMed

    Fernandez-Leon, Jose A; Acosta, Gerardo G; Mayosky, Miguel A

    2011-01-01

    Behavioural robustness at antibody and immune network level is discussed. The robustness of the immune response that drives an autonomous mobile robot is examined with two computational experiments in the autonomous mobile robots trajectory generation context in unknown environments. The immune response is met based on the immune network metaphor for different low-level behaviours coordination. These behaviours are activated when a robot sense the appropriate conditions in the environment in relation to the network current state. Results are obtained over a case study in computer simulation as well as in laboratory experiments with a Khepera II microrobot. In this work, we develop a set of tests where such an immune response is externally perturbed at network or low-level behavioural modules to analyse the robust capacity of the system to unexpected perturbations. Emergence of robust behaviour and high-level immune response relates to the coupling between behavioural modules that are selectively engaged with the environment based on immune response. Experimental evidence leads discussions on a dynamical systems perspective of behavioural robustness in artificial immune systems that goes beyond the isolated immune network response. PMID:21315135

  17. Epidemic outbreak for an SIS model in multiplex networks with immunization.

    PubMed

    Wu, Qingchu; Lou, Yijun; Zhu, Wenfang

    2016-07-01

    With the aim of understanding epidemic spreading in a general multiplex network and designing optimal immunization strategies, a mathematical model based on multiple degree is built to analyze the threshold condition for epidemic outbreak. Two kinds of strategies, the multiplex node-based immunization and the layer node-based immunization, are examined. Theoretical results show that the general framework proposed here can illustrate the effect of diverse correlations and immunizations on the outbreak condition in multiplex networks. Under a set of conditions on uncorrelated coefficients, the specific epidemic thresholds are shown to be only dependent on the respective degree distribution in each layer. PMID:27105863

  18. 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.

  19. 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

  20. 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

  1. 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

  2. Internal-image anti-idiotype HIV-1gp120 antibody in human immunodeficiency virus 1 (HIV-1)-seropositive individuals with thrombocytopenia.

    PubMed Central

    Karpatkin, S; Nardi, M A; Kouri, Y H

    1992-01-01

    Anti-CD4 antibody was found in 30% of human immunodeficiency virus (HIV-1)-seropositive thrombocytopenic patients compared with 5% of nonthrombocytopenic seropositive patients (chi 2 = 21.7, P less than 0.001) and was shown by the following observations to contain internal-image anti-idiotype antibody (Ab2) directed against the antibody (Ab1) to gp120, the HIV-1 envelope glycoprotein that binds to CD4: (i) affinity-purified anti-CD4 (Ab2) bound to affinity-purified anti-HIV-1gp120 (Ab1) on solid-phase radioimmunoassay, and binding could be blocked by recombinant CD4 (rCD4) as well as recombinant gp120 (rgp120); (ii) F(ab')2 fragments of Ab1 inhibited the binding of Ab2 to rCD4; (iii) Ab2 inhibited the binding of Ab1 to HIV-1 beads; (iv) Ab2 inhibited the binding of Ab1 to gp120 on immunoblot; (v) Ab2 bound to the CD4 receptor on a CD4-bearing T-cell line, H9; (vi) Ab3 (anti-rgp120) could be produced in vivo by immunizing mice with Ab2, and binding of Ab3 to rgp120 could be blocked with rCD4; and (vii) three different Ab2 preparations bound to two different homologous Ab1 preparations. Ab1 or Ab2 alone did not bind to platelets, whereas the idiotype-anti-idiotype complex did bind to platelets in a concentration-dependent manner. Binding of the internal-image complex was 10-fold greater than that of a non-internal-image Ab1-Ab2 complex composed of anti-HIV-1gp120 and anti-anti-HIV-1gp120. Thus, patients with HIV-1 thrombocytopenia contain internal-image idiotype-anti-idiotype complexes that could be affecting CD4 cell number or function, inhibiting HIV-1 binding to CD4 cells or contributing to HIV-1 thrombocytopenia. Images PMID:1741404

  3. Revealing shared and distinct gene network organization in Arabidopsis immune responses by integrative analysis.

    PubMed

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

    2015-03-01

    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. 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

  5. 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. PMID:25910884

  6. 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.

  7. Alterations of idiotypic profiles: The cellular basis of T15 dominance in BALB/c mice

    SciTech Connect

    Wemhoff, G.A.; Quintans, J. )

    1987-01-01

    Phosphorylcholine (PC) is a component of cell walls and membranes from a variety of widely distributed microorganisms. It is highly immunogenic in mice and most murine strains have circulating anti-PC antibodies which are known to confer protection against certain bacterial infections. BALB/c mice offer a striking example of a high responsiveness to PC, a propensity to generate PC-binding myelomas, and a great restriction of idiotype expression in anti-PC antibodies; in fact, most BALB/c anti-PC IgM antibodies express the T15 idiotype marker. Although it has been suspected that T15 dominance is somewhat related to the continuous antigenic load presented by microorganismal flora found in conventional mice, a complete experimental account of how antigenic selection brings about such extreme idiotypic dominance is not yet available. In the studies presented below, we investigated the role played by the host environment, T cells, and antigen in affecting the generation of the anti-PC T15 idiotype profile in lethally irradiated adoptive hosts reconstituted with syngeneic neonatal liver cells. The results presented herein indicate that the transfer of mature carrier-primed T cells with neonatal liver cells does not influence the generation of the T15 idiotype profile. We also demonstrated that anti-T15 idiotype suppressed mice, used as lethally irradiated hosts of immature immunocompetent cells, allow an increased rate of reconstitution of the anti-PC response when compared to nonsuppressed hosts. Since the administration of a T15+ anti-PC antibody inhibits both reconstitution and idiotype expansion, we conclude that T15+ B cells do not self-promote themselves. In contrast, we observed that exposure of adoptive hosts to PC antigens can enhance the anti-PC response and alter the idiotypic profile in favor of T15-bearing clones.

  8. 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

  9. 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

  10. 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. ...

  11. 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 ...

  12. Immunization

    MedlinePlus

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

  13. Cellular networks controlling Th2 polarization in allergy and immunity.

    PubMed

    Kool, Mirjam; Hammad, Hamida; Lambrecht, Bart N

    2012-01-01

    In contrast to the development of Th1 (type 1 T helper cells), Th17 and Treg (regulatory T cells), little is known of the mechanisms governing Th2 development, which is important for immunity to helminths and for us to understand the pathogenesis of allergy. A picture is emerging in which mucosal epithelial cells instruct dendritic cells to promote Th2 responses in the absence of IL-12 (interleukin 12) production and provide instruction through thymic stromal lymphopoieitin (TSLP) or granulocyte-macrophage colony stimulating factor (GM-CSF). At the same time, allergens, helminths and chemical adjuvants elicit the response of innate immune cells like basophils, which provide more polarizing cytokines and IL-4 and reinforce Th2 immunity. This unique communication between cells will only be fully appreciated if we study Th2 immunity in vivo and in a tissue-specific context, and can only be fully understood if we compare several models of Th2 immune response induction. PMID:22403589

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

    PubMed

    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 [Met(5)]-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 [Met(5)]-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

  15. 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

  16. 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.

  17. 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.

  18. Inflammatory networks and immune surveillance of pancreatic carcinoma

    PubMed Central

    Vonderheide, Robert H.; Bayne, Lauren J.

    2013-01-01

    Cancer-associated inflammation plays an important role in restraining anti-tumor immunity, particularly in pancreatic ductal adenocarcinoma (PDA) for which a massive infiltration of immunosuppressive leukocytes into the tumor stroma is an early and consistent event in oncogenesis. This pathophysiology is in contrast to many other solid tumors for which infiltration of effector T cells is often prominent, associated with improved clinical outcomes, and mechanistically contributes to tumor immunoediting that ultimately can mediate immune escape. In PDA, increasing evidence suggests that the ras oncogene drives an inflammatory program that establishes immune privilege in the tumor microenvironment. Indeed, PDA cells might remain intrinsically sensitive to T cell killing because they have never been exposed to T cell selective pressure in vivo. In support of this hypothesis, recent studies demonstrate that derailing immune suppressive pathways in the PDA microenvironment, such as tumor derived GM-CSF, facilitates T-cell mediated tumor rejection. These findings carry major implications for the development of novel, combination immunotherapies for pancreatic cancer. PMID:23422836

  19. 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.

  20. 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

  1. 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.

  2. [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

  3. Automata network theories in immunology: their utility and their underdetermination.

    PubMed

    Atlan, H

    1989-01-01

    Small networks of threshold automata are used to model complex interactions between populations of regulatory cells (helpers and suppressors, antigen specific and anti-idiotypic) which participate in the immune response. The models, being discrete and semiquantitative, are well adapted to the situation of incomplete information often encountered in vivo. However, the dynamics of many different network structures usually end up in the same attractor set. Thus, many different theories are equivalent in their explicative power for the same facts. This property, known as underdetermination of the theories by the facts, is given a quantitative estimate. It appears that such an underdetermination, as a kind of irreducible complexity, can be expected in many in vivo biological processes, even when the number of interacting and functionally coupled elements is relatively small. PMID:2924021

  4. 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

  5. IMMUNOCHEMICAL ANALYSIS OF THE IDIOTYPES OF MOUSE MYELOMA PROTEINS WITH SPECIFICITY FOR LEVAN OR DEXTRAN

    PubMed Central

    Weigert, Martin; Raschke, William C.; Carson, Dennis; Cohn, Melvin

    1974-01-01

    This paper deals solely with idiotypic determinants, the configurations of which are modified when the antibody bearing them interacts with its ligand. This phenomenon is measured as an inhibition of the reaction between anti-idiotype and idiotype. Two points are made: (a) The assay for ligand-modifiable determinants can be used to determine the "size" of the combining site. This is illustrated here with the anti-α(1 → 6) dextran mouse myeloma immunoglobulin W3129. Whether the interaction between a homologous series of α(1 → 6) oligosaccharide ligands and the combining site of W3129 is measured by inhibition of precipitation with α(1 → 6) dextran (4) or of binding of W3129 to anti-W3129 idiotype, the finding is the same. The order of inhibition is isomaltohexaose = isomaltopentaose >> isomaltotetraose > isomaltotriose >>> isomaltose. The combining site is optimally complementary to isomaltopentaose. (b) Cross-idiotypic specificity is closely correlated with cross-combining specificity; the converse is not true. This is illustrated here with three groups of mouse myeloma immunoglobulin, each specific for α(1 → 3) dextran, α(1 →6) dextran, β(2 → 1) or β(2 → 6) levan. If a given anti-idiotypic serum cross-reacted with several myeloma proteins, they always had similar combining specificity. Thus the three proteins, J558, MOPC 104E, and UPC 102, which cross-react with anti-J558 have combining specificity for α(1 → 3) dextran; cross-reacting W3082, UPC 61, and Y5476 have specificity for levan; and cross-reacting W3129 and W3434 have specificity for α(1 → 6) dextran. This extends previous studies with proteins specific for phosphorylcholine (7) or γ-globulin (8). As expected, the converse is not true, for proteins may have combining specificity for α(1 → 6) dextran e.g. QUPC 52, or levan e.g. J606, UPC 10 and yet not carry the above-mentioned reference idiotypes. The correlation between cross-idiotypic and combining specificity breaks down

  6. Immune Cells and Molecular Networks in Experimentally Induced Pulpitis.

    PubMed

    Renard, E; Gaudin, A; Bienvenu, G; Amiaud, J; Farges, J C; Cuturi, M C; Moreau, A; Alliot-Licht, B

    2016-02-01

    Dental pulp is a dynamic tissue able to resist external irritation during tooth decay by using immunocompetent cells involved in innate and adaptive responses. To better understand the immune response of pulp toward gram-negative bacteria, we analyzed biological mediators and immunocompetent cells in rat incisor pulp experimentally inflamed by either lipopolysaccharide (LPS) or saline solution (phosphate-buffered saline [PBS]). Untreated teeth were used as control. Expression of pro- and anti-inflammatory cytokines, chemokine ligands, growth factors, and enzymes were evaluated at the transcript level, and the recruitment of the different leukocytes in pulp was measured by fluorescence-activated cell-sorting analysis after 3 h, 9 h, and 3 d post-PBS or post-LPS treatment. After 3 d, injured rat incisors showed pulp wound healing and production of reparative dentin in both LPS and PBS conditions, testifying to the reversible pulpitis status of this model. IL6, IL1-β, TNF-α, CCL2, CXCL1, CXCL2, MMP9, and iNOS gene expression were significantly upregulated after 3 h of LPS stimulation as compared with PBS. The immunoregulatory cytokine IL10 was also upregulated after 3 h, suggesting that LPS stimulates not only inflammation but also immunoregulation. Fluorescence-activated cell-sorting analysis revealed a significant, rapid, and transient increase in leukocyte levels 9 h after PBS and LPS stimulation. The quantity of dendritic cells was significantly upregulated with LPS versus PBS. Interestingly, we identified a myeloid-derived suppressor cell-enriched cell population in noninjured rodent incisor dental pulp. The percentage of this population, known to regulate immune response, was higher 9 h after inflammation triggered with PBS and LPS as compared with the control. Taken together, these data offer a better understanding of the mechanisms involved in the regulation of dental pulp immunity that may be elicited by gram-negative bacteria. PMID:26472753

  7. Mechanisms of tumour cell escape encountered in treating lymphocytic leukaemia with anti-idiotypic antibody.

    PubMed Central

    Gordon, J.; Abdul-Ahad, A. K.; Hamblin, T. J.; Stevenson, F. K.; Stevenson, G. T.

    1984-01-01

    Four patients with chronic lymphocytic leukaemia were treated by one or more infusions of polyclonal antibody specific for the immunoglobulin idiotype expressed on their leukaemic cells. The antibody was in the form of IgG from sheep antiserum. Three of the 4 cases showed a significant fall in blood lymphocyte count. On one occasion most of the residual circulating lymphocytes were apparently dead. However on all occasions the cell counts rebounded to near pre-infusion levels within one week. Viable lymphocytes recovered from the blood after infusion always showed evidence of antigenic modulation: a diminished level of surface idiotype in a patched distribution, with an accompanying refractoriness to lysis by anti-idiotype plus complement. When cultured in vitro blood lymphocytes from three of the four patients revealed an appreciable export of idiotypic Ig. These 3 patients showed plasma levels of idiotypic Ig up to 400 micrograms ml-1, reduced by plasma exchange prior to infusion. The fourth patient had a level of less than 4 micrograms ml-1, and was the only one in whom free antibody could be found in the plasma after infusion. These cases demonstrate two major factors which thwart antibody attack on leukaemic cells--extracellular antigen and antigenic modulation--as well as problems relating to sparseness of surface antigen, recruitment of effectors, and exhaustion of effectors. PMID:6722005

  8. Neutrophil Priming by Cigarette Smoke Condensate and a Tobacco Anti-Idiotypic Antibody

    PubMed Central

    Koethe, Susan M.; Kuhnmuench, John R.; Becker, Carl G.

    2000-01-01

    A polyphenol-rich reagent, referred to as CSC, was isolated from cigarette smoke condensate and shown to prime purified human neutrophils. A mouse monoclonal anti-idiotypic antibody directed against the polyphenol-reactive determinants on a rabbit polyclonal anti-tobacco glycoprotein antibody was generated and shown to also prime neutrophils. After priming by CSC or tobacco anti-idiotypic antibody, there was a 2.5-fold to threefold increase in CD11b/18 expression and doubling of the number of formyl-methionyl-leucyl-phenylalanine receptors on the cells. The primed cells showed a twofold increase, compared with unprimed cells, in production of superoxide and release of neutrophil elastase after stimulation with formyl-methionyl-leucyl-phenylalanine. Neutrophils in peripheral blood of cigarette smokers have been shown to be primed and more responsive to activating agents. The priming effects attributed to whole cigarette smoke have been demonstrated in these studies using purified neutrophils and CSC or tobacco anti-idiotypic antibody. These studies are a first step in testing the hypothesis that the inflammatory process contributing to progression of chronic obstructive pulmonary disease in ex-smokers may be driven, in part, by tobacco anti-idiotypic antibodies. This hypothesis is novel and carries with it the implication of a heretofore unrecognized autoimmune component in the disease process manifested through production of anti-idiotypic antibodies with tobacco-like activity. PMID:11073832

  9. 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.

  10. Swine Toolkit Plans and Progress for the US Veterinary Immune Reagent Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The US Veterinary Immune Reagent Network (http://www.umass.edu/vetimm/) was established to address the lack of immunological reagents specific for ruminant, porcine, poultry, equine and aquaculture species and accordingly has set a minimum goal of 20 reagents per species group. Current plans are to...

  11. 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.

  12. Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines

    PubMed Central

    Kafi, Kamran; Betting, David J.; Yamada, Reiko E.; Bacica, Michael; Steward, Kristopher K.; Timmerman, John M.

    2009-01-01

    The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically-conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8+ T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

  13. Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines.

    PubMed

    Kafi, Kamran; Betting, David J; Yamada, Reiko E; Bacica, Michael; Steward, Kristopher K; Timmerman, John M

    2009-01-01

    The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8(+) T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

  14. 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.

  15. Characterization of the human immune cell network at the gingival barrier

    PubMed Central

    Greenwell-Wild, Teresa; Moutsopoulos, Niki M.

    2015-01-01

    The oral mucosa is a barrier site constantly exposed to rich and diverse commensal microbial communities, yet little is known of the immune cell network maintaining immune homeostasis at this interface. We have performed a detailed characterization of the immune cell subsets of the oral cavity in a large cohort of healthy subjects. We focused our characterization on the gingival interface, a particularly vulnerable mucosal site, with thin epithelial lining and constant exposure to the tooth adherent biofilm. In health, we find a predominance of T cells, minimal B cells, a large presence of granulocytes/neutrophils, a sophisticated network of professional antigen presenting cells (APC) and a small population of innate lymphoid cells (ILC) policing the gingival barrier. We further characterize cellular subtypes in health and interrogate shifts in immune cell populations in the common oral inflammatory disease periodontitis. In disease we document an increase in neutrophils and an up regulation of IL-17 responses. We identify the main source of IL-17 in health and periodontitis within the CD4+ T cell compartment. Collectively our studies provide a first view of the landscape of physiologic oral immunity and serve as a baseline for the characterization of local immunopathology. PMID:26732676

  16. Viral immune modulators perturb the human molecular network by common and unique strategies.

    PubMed

    Pichlmair, Andreas; Kandasamy, Kumaran; Alvisi, Gualtiero; Mulhern, Orla; Sacco, Roberto; Habjan, Matthias; Binder, Marco; Stefanovic, Adrijana; Eberle, Carol-Ann; Goncalves, Adriana; Bürckstümmer, Tilmann; Müller, André C; Fauster, Astrid; Holze, Cathleen; Lindsten, Kristina; Goodbourn, Stephen; Kochs, Georg; Weber, Friedemann; Bartenschlager, Ralf; Bowie, Andrew G; Bennett, Keiryn L; Colinge, Jacques; Superti-Furga, Giulio

    2012-07-26

    Viruses must enter host cells to replicate, assemble and propagate. Because of the restricted size of their genomes, viruses have had to evolve efficient ways of exploiting host cell processes to promote their own life cycles and also to escape host immune defence mechanisms. Many viral open reading frames (viORFs) with immune-modulating functions essential for productive viral growth have been identified across a range of viral classes. However, there has been no comprehensive study to identify the host factors with which these viORFs interact for a global perspective of viral perturbation strategies. Here we show that different viral perturbation patterns of the host molecular defence network can be deduced from a mass-spectrometry-based host-factor survey in a defined human cellular system by using 70 innate immune-modulating viORFs from 30 viral species. The 579 host proteins targeted by the viORFs mapped to an unexpectedly large number of signalling pathways and cellular processes, suggesting yet unknown mechanisms of antiviral immunity. We further experimentally verified the targets heterogeneous nuclear ribonucleoprotein U, phosphatidylinositol-3-OH kinase, the WNK (with-no-lysine) kinase family and USP19 (ubiquitin-specific peptidase 19) as vulnerable nodes in the host cellular defence system. Evaluation of the impact of viral immune modulators on the host molecular network revealed perturbation strategies used by individual viruses and by viral classes. Our data are also valuable for the design of broad and specific antiviral therapies. PMID:22810585

  17. Characterization of the human immune cell network at the gingival barrier.

    PubMed

    Dutzan, N; Konkel, J E; Greenwell-Wild, T; Moutsopoulos, N M

    2016-09-01

    The oral mucosa is a barrier site constantly exposed to rich and diverse commensal microbial communities, yet little is known of the immune cell network maintaining immune homeostasis at this interface. We have performed a detailed characterization of the immune cell subsets of the oral cavity in a large cohort of healthy subjects. We focused our characterization on the gingival interface, a particularly vulnerable mucosal site, with thin epithelial lining and constant exposure to the tooth adherent biofilm. In health, we find a predominance of T cells, minimal B cells, a large presence of granulocytes/neutrophils, a sophisticated network of professional antigen-presenting cells (APCs), and a small population of innate lymphoid cells (ILCs) policing the gingival barrier. We further characterize cellular subtypes in health and interrogate shifts in immune cell populations in the common oral inflammatory disease periodontitis. In disease, we document an increase in neutrophils and an upregulation of interleukin-17 (IL-17) responses. We identify the main source of IL-17 in health and Periodontitis within the CD4(+) T-cell compartment. Collectively, our studies provide a first view of the landscape of physiologic oral immunity and serve as a baseline for the characterization of local immunopathology. PMID:26732676

  18. 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.

  19. Spatial and functional heterogeneities shape collective behavior of tumor-immune networks.

    PubMed

    Wells, Daniel K; Chuang, Yishan; Knapp, Louis M; Brockmann, Dirk; Kath, William L; Leonard, Joshua N

    2015-04-01

    Tumor growth involves a dynamic interplay between cancer cells and host cells, which collectively form a tumor microenvironmental network that either suppresses or promotes tumor growth under different conditions. The transition from tumor suppression to tumor promotion is mediated by a tumor-induced shift in the local immune state, and despite the clinical challenge this shift poses, little is known about how such dysfunctional immune states are initiated. Clinical and experimental observations have indicated that differences in both the composition and spatial distribution of different cell types and/or signaling molecules within the tumor microenvironment can strongly impact tumor pathogenesis and ultimately patient prognosis. How such "functional" and "spatial" heterogeneities confer such effects, however, is not known. To investigate these phenomena at a level currently inaccessible by direct observation, we developed a computational model of a nascent metastatic tumor capturing salient features of known tumor-immune interactions that faithfully recapitulates key features of existing experimental observations. Surprisingly, over a wide range of model formulations, we observed that heterogeneity in both spatial organization and cell phenotype drove the emergence of immunosuppressive network states. We determined that this observation is general and robust to parameter choice by developing a systems-level sensitivity analysis technique, and we extended this analysis to generate other parameter-independent, experimentally testable hypotheses. Lastly, we leveraged this model as an in silico test bed to evaluate potential strategies for engineering cell-based therapies to overcome tumor associated immune dysfunction and thereby identified modes of immune modulation predicted to be most effective. Collectively, this work establishes a new integrated framework for investigating and modulating tumor-immune networks and provides insights into how such interactions may

  20. Immunizations.

    PubMed

    Sanford, Christopher A; Jong, Elaine C

    2016-03-01

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

  1. 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…

  2. 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.

  3. 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

  4. Potentially pathogenic immune cells and networks in apparently healthy lacrimal glands.

    PubMed

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

    2015-01-01

    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

  5. 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. PMID:16252818

  6. 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

  7. 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

  8. Idiotypic sensitization in utero of children born to mothers with schistosomiasis or Chagas' disease.

    PubMed Central

    Eloi-Santos, S M; Novato-Silva, E; Maselli, V M; Gazzinelli, G; Colley, D G; Correa-Oliveira, R

    1989-01-01

    Cord blood mononuclear cells (CBMC) of neonates born of mothers with Chagas' disease or schistosomiasis exhibited strong proliferative responses against idiotypes expressed on antibodies with specificity for Trypanosoma cruzi or Schistosoma mansoni antigens, respectively. These immunoaffinity-purified preparations were stimulatory if they were prepared from pools of patients' sera or from the mother's own serum, taken early during her pregnancy. These CBMC did not respond to normal immunoglobulin, and CBMC of neonates born of uninfected mothers did not respond to antibodies against either T. cruzi or S. mansoni, or normal immunoglobulin preparations. We propose that in utero exposure of a fetus to some idiotypes expressed on placentally transferred antibodies induces anti-Id T lymphocyte sensitization, which we detect as a proliferative response by CBMC exposed to immunoaffinity-purified antibodies expressing the relevant idiotypes. This is the first experimental evidence that children born of mothers with chronic infections undergo natural in utero idiotypic manipulations and are born possessing cellular anti-Id reactivity. PMID:2503542

  9. 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

  10. Cellular Neural Network Models of Growth and Immune of Effector Cells Response to Cancer

    NASA Astrophysics Data System (ADS)

    Su, Yongmei; Min, Lequan

    Four reaction-diffusion cellular neural network (R-D CNN) models are set up based on the differential equation models for the growths of effector cells and cancer cells, and the model of the immune response to cancer proposed by Allison et al. The CNN models have different reaction-diffusion coefficients and coupling parameters. The R-D CNN models may provide possible quantitative interpretations, and are good in agreement with the in vitro experiment data reported by Allison et al.

  11. Mapping a Dynamic Innate Immunity Protein Interaction Network Regulating Type I Interferon Production

    PubMed Central

    Li, Shitao; Wang, Lingyan; Berman, Michael; Kong, Young-Yun; Dorf, Martin E.

    2011-01-01

    SUMMARY To systematically investigate innate immune signaling networks regulating production of type I interferon, we analyzed protein complexes formed after microbial recognition. Fifty-eight baits were associated with 260 interacting proteins forming a human innate immunity interactome for type I interferon (HI5) of 401 unique interactions; 21% of interactions were modulated by RNA, DNA, or LPS. Overexpression and depletion analyses identified 22 unique genes that regulated NF-κB and ISRE reporter activity, viral replication, or virus-induced interferon production. Detailed mechanistic analysis defined a role for mind bomb (MIB) E3 ligases in K63-linked ubiquitination of TBK1, a kinase that phosphorylates IRF transcription factors controlling interferon production. Mib genes selectively controlled responses to cytosolic RNA. MIB deficiency reduced antiviral activity, establishing the role of MIB proteins as positive regulators of antiviral responses. The HI5 provides a dynamic physical and regulatory network that serves as a resource for mechanistic analysis of innate immune signaling. PMID:21903422

  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. 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

  14. 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

  15. 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

  16. The immune tolerance network: a new paradigm for developing tolerance-inducing therapies.

    PubMed

    Rotrosen, Daniel; Matthews, Jeff B; Bluestone, Jeffrey A

    2002-07-01

    Immune tolerance therapies are designed to reprogram immune cells in a highly specific fashion to eliminate pathogenic responses while preserving protective immunity. A concept that has tantalized immunologists for decades, the development of tolerance-inducing therapies, would revolutionize the management of a wide range of chronic and often debilitating diseases by obviating the need for lifelong immunosuppressive regimens. The advances of the past decade have provided a more detailed understanding of the molecular events associated with T-cell recognition and activation. Building on these advances, immunologists have demonstrated the feasibility of various tolerance-inducing approaches in small- and large-animal models of autoimmunity, allergy, and transplant graft rejection. Unprecedented opportunities to test these approaches in a variety of human diseases have now emerged. To capitalize on these advances, the National Institutes of Health recently established the Immune Tolerance Network (ITN), an international consortium of more than 70 basic and clinical immunologists dedicated to the evaluation of novel tolerance-inducing therapies and associated studies of immunologic mechanisms. By using a unique interactive approach to accelerate the development of clinical tolerance therapies, the ITN is partnering with the biotechnology and pharmaceutical industries to examine innovative tolerogenic approaches in a range of allergic and autoimmune diseases and to prevent graft rejection after transplantation. Two years since its inception, the ITN now has approximately 2 dozen clinical trials or tolerance assays studies ongoing or in later stages of protocol development. This report summarizes the rationale for emphasizing clinical research on immune tolerance and highlights the progress of the ITN. PMID:12110811

  17. Anti-ganglioside anti-idiotypic monoclonal antibody-based cancer vaccine induces apoptosis and antiangiogenic effect in a metastatic lung carcinoma.

    PubMed

    Diaz, Y; Gonzalez, A; Lopez, A; Perez, R; Vazquez, A M; Montero, E

    2009-07-01

    Anti-idiotype monoclonal antibody (mAb) 1E10 was generated by immunizing BALB/c mice with an Ab1 mAb which recognizes NeuGc-containing gangliosides, sulfatides and some tumor antigens. 1E10 mAb induces therapeutic effects in a primary breast carcinoma and a melanoma model. However, the tumor immunity mechanisms have not been elucidated. Here we show that aluminum hydroxide-precipitated 1E10 mAb immunization induced anti-metastatic effect in the 3LL-D122 Lewis Lung carcinoma, a poorly immunogenic and highly metastatic model in C57BL/6 mice. The therapeutic effect was associated to the increment of T cells infiltrating metastases, the reduction of new blood vessels formation and the increase of apoptotic tumor cells in lung nodules. Interestingly, active immunization does not induce measurable antibodies to the 1E10 mAb, the NeuGc-GM3 or tumor cells, which may suggest a different mechanism which has to be elucidated. These findings may support the relevance of this target for cancer biotherapy. PMID:19066887

  18. Adaptive dynamic networks as models for the immune system and autocatalytic sets

    SciTech Connect

    Farmer, J.D.; Kauffman, S.A.; Packard, N.H.; Perelson, A.S.

    1986-04-01

    A general class of network models is described that can be used to present complex adaptive systems. These models have two purposes: On a practical level they are closely based on real biological phenomena, and are intended to model detailed aspects of them. On a more general level, however, they provide a framework to address broader questions concerning evolution, pattern recognition, and other properties of living systems. This paper concentrates on the more general level, illustrating the basic concepts with two examples, a model of the immune system and a model for the spontaneous emergence of autocatalytic sets in a chemically reactive polymer soup. 10 refs., 3 figs.

  19. 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

  20. CDR molecular localization of possible anti-idiotypic anti-DNA antibodies in normal subjects, patients with SLE, and SLE first-degree relatives.

    PubMed

    Williams, R W; Malone, C C; Silvestris, F

    1995-07-01

    Patients with active systemic lupus erythematosus (SLE) with disease worsening or severe flares frequently show very low levels of serum immunoglobulin G (IgG) anti-F(ab')2 antibody. Anti-F(ab')2 antibody probably represents a polyclonal collection of generic anti-idiotypic antibodies involved in immune homeostasis. We synthesized the entire variable regions of the heavy and light chains (VH and VL) of two monoclonal anti-DNA antibodies, V88 and 2A4, as overlapping 7-mers on small polypropylene pins and tested these linear segments of anti-DNA V-regions for reactivity against serum samples from 10 normal subjects with high serum IgG anti-F(ab')2, 11 normal subjects with low anti-F(ab')2, 5 patients with SLE with active uncontrolled disease, 3 patients with SLE in remission, and 8 unaffected normal first-degree SLE relatives. VH and VL regions of a human monoclonal IgG anti-rabies antibody were also tested as a control. Concordant IgG antibody reacting with the same complementarity-determining regions (CDRs) was arbitrarily scored as indicative of the presence of anti-idiotypic antibody in test serum samples. Among normal subjects with either high or low serum anti-F(ab')2 levels, 10% to 21% showed strong concordant anti-CDR reactions with either the monoclonal anti-DNA or the control monoclonal anti-rabies V-region sequences. However, all patients with active SLE showed no detectable anti-CDR-reactive antibody. Patients with SLE in remission often showed return of strong concordant anti-CDR antibody. Normal unaffected SLE relatives also showed high levels of anti-CDR reactivity for both monoclonal anti-DNA and anti-rabies antibody sequences. PMID:7602233

  1. Prevalence of 13 autoantibodies and of the 16/6 and related pathogenic idiotypes in 465 patients with systemic lupus erythematosus and their relationship with disease activity.

    PubMed

    Villarreal, G M; Drenkard, C; Villa, A R; Slor, H; Shafrir, S; Bakimer, R; Shoenfeld, Y; Alarcón-Segovia, D

    1997-01-01

    With a cross sectional study of 465 consecutive systemic lupus erythematosus (SLE) patients tested for 13 autoantibodies (Aab) and two idiotypes we determined the prevalence of Aab according to disease activity, both general and at particular organ systems. Seventy seven percent of SLE sera had at least one Aab and 56% had it at high titres. Pathogenic idiotypes had a prevalence of less than 10% and 166 sera had Aab to 5 or more antigens and 9 sera had Aab against all 13 antigens tested. Patients with active disease had increased prevalence of Aab to DNP, ssDNA, ENA, mitochondria and histones when considered at 5 s.d. above the mean of normal controls. The higher positivity of Aab in patients with active disease was confirmed in logistic regression analysis adjusted by age, disease duration, and intensity of treatment. A trend was observed of increased prevalence and titres of Aab from inactive disease without treatment, to inactive disease but still being treated, to active disease. Only 22% of patients with active disease had no Aab and the higher the number of Aab the higher the frequency of active disease. Patients with active arthritis, and to a lesser degree those with active mucocutaneous involvement, had higher prevalence and titres of most autoantibodies than patients with disease activity at other organ systems. Active renal disease associated only with anti-dsDNA, whereas active CNS disease associated with anti-mitochondrial Aab. Our findings support the vision of SLE as an immune dysregulation leading to polyclonal B cell activation with resulting production of multiple Aab. Their profiles seem influenced by genetical, hormonal and environmental factors and, in turn, they contribute to the clinical picture in each patient. Disease activity influences the presence of some, but not all, Aab and some of them may remain present in some patients, even in remission. PMID:9229360

  2. 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

  3. Citrinin detection using phage-displayed anti-idiotypic single-domain antibody for antigen mimicry.

    PubMed

    Xu, Yang; Xiong, Liang; Li, Yanping; Xiong, Yonghua; Tu, Zhui; Fu, Jinheng; Tang, Xiao

    2015-06-15

    Anti-idiotypic antibodies (AIds) can mimic antigen molecules and can thus offer an alternative to conventional antigens in immunoassays. In this study, citrinin (CIT) was chosen as a target analyte, and an anti-idiotypic single-domain antibody (VHH) was selected from a naïve alpaca VHHs library to serve as a surrogate for CIT hapten. The phage-displayed VHH was used as a signal-amplification carrier to develop an indirect competitive phage enzyme-linked immunosorbent assay (P-ELISA) for the sensitive detection of CIT. The half-inhibition concentration (IC50) of P-ELISA was 10.9 μg/kg, which was 9-fold better than that of conventional ELISA (IC50=102.1 μg/kg). Results on P-ELISA analysis of naturally contaminated samples were also consistent with those obtained by conventional ELISA. In conclusion, the proposed P-ELISA demonstrates the potential use of phage-displayed anti-idiotypic VHH as surrogate for small molecules and signal-amplification carrier to improve assay performance for more sensitive analyte detection in food safety monitoring. PMID:25660863

  4. 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

  5. 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

  6. The Signaling Networks of the Herpesvirus Entry Mediator (TNFRSF14) in Immune Regulation

    PubMed Central

    Steinberg, Marcos; Cheung, Timothy C.; Ware, Carl F.

    2012-01-01

    Summary The tumor necrosis factor (TNF) receptor superfamily member herpesvirus entry mediator (HVEM) (TNFRSF14) regulates T-cell immune responses by activating both inflammatory and inhibitory signaling pathways. HVEM acts as both a receptor for the canonical TNF-related ligands, LIGHT [lymphotoxin-like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed on T lymphocytes] and lymphotoxin-α, and as a ligand for the immunoglobulin superfamily proteins BTLA (B and T lymphocyte attenuator) and CD160, a feature distinguishing HVEM from other immune regulatory molecules. The ability of HVEM to interact with multiple ligands in distinct configurations creates a functionally diverse set of intrinsic and bidirectional signaling pathways that control both inflammatory and inhibitory responses. The HVEM system is integrated into the larger LTβR and TNFR network through extensive shared ligand and receptor usage. Experimental mouse models and human diseases indicate that dysregulation of HVEM network may contribute to autoimmune pathogenesis, making it an attractive target for drug intervention. PMID:22017438

  7. 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

  8. 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

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

    PubMed Central

    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. PMID:23267436

  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. 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

  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. 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.

  14. Genetic associations with micronutrient levels identified in immune and gastrointestinal networks.

    PubMed

    Morine, Melissa J; Monteiro, Jacqueline Pontes; Wise, Carolyn; Teitel, Candee; Pence, Lisa; Williams, Anna; Ning, Baitang; McCabe-Sellers, Beverly; Champagne, Catherine; Turner, Jerome; Shelby, Beatrice; Bogle, Margaret; Beger, Richard D; Priami, Corrado; Kaput, Jim

    2014-07-01

    The discovery of vitamins and clarification of their role in preventing frank essential nutrient deficiencies occurred in the early 1900s. Much vitamin research has understandably focused on public health and the effects of single nutrients to alleviate acute conditions. The physiological processes for maintaining health, however, are complex systems that depend upon interactions between multiple nutrients, environmental factors, and genetic makeup. To analyze the relationship between these factors and nutritional health, data were obtained from an observational, community-based participatory research program of children and teens (age 6-14) enrolled in a summer day camp in the Delta region of Arkansas. Assessments of erythrocyte S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), plasma homocysteine (Hcy) and 6 organic micronutrients (retinol, 25-hydroxy vitamin D3, pyridoxal, thiamin, riboflavin, and vitamin E), and 1,129 plasma proteins were performed at 3 time points in each of 2 years. Genetic makeup was analyzed with 1 M SNP genotyping arrays, and nutrient status was assessed with 24-h dietary intake questionnaires. A pattern of metabolites (met_PC1) that included the ratio of erythrocyte SAM/SAH, Hcy, and 5 vitamins were identified by principal component analysis. Met_PC1 levels were significantly associated with (1) single-nucleotide polymorphisms, (2) levels of plasma proteins, and (3) multilocus genotypes coding for gastrointestinal and immune functions, as identified in a global network of metabolic/protein-protein interactions. Subsequent mining of data from curated pathway, network, and genome-wide association studies identified genetic and functional relationships that may be explained by gene-nutrient interactions. The systems nutrition strategy described here has thus associated a multivariate metabolite pattern in blood with genes involved in immune and gastrointestinal functions. PMID:24879315

  15. Positive Network Assortativity of Influenza Vaccination at a High School: Implications for Outbreak Risk and Herd Immunity

    PubMed Central

    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. PMID:24505274

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

    PubMed

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

    2007-11-01

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

  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. 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

  19. Gene Networks Specific for Innate Immunity Define Post-Traumatic Stress Disorder

    PubMed Central

    Breen, Michael S.; Maihofer, Adam X.; Glatt, Stephen J.; Tylee, Daniel S.; Chandler, Sharon D.; Tsuang, Ming T.; Risbrough, Victoria B.; Baker, Dewleen G.; O’Connor, Daniel T.; Nievergelt, Caroline M.; Woelk, Christopher H.

    2015-01-01

    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. PMID:25754082

  20. Analysis of schizophrenia and hepatocellular carcinoma genetic network with corresponding modularity and pathways: novel insights to the immune system

    PubMed Central

    2013-01-01

    Background Schizophrenic patients show lower incidences of cancer, implicating schizophrenia may be a protective factor against cancer. To study the genetic correlation between the two diseases, a specific PPI network was constructed with candidate genes of both schizophrenia and hepatocellular carcinoma. The network, designated schizophrenia-hepatocellular carcinoma network (SHCN), was analysed and cliques were identified as potential functional modules or complexes. The findings were compared with information from pathway databases such as KEGG, Reactome, PID and ConsensusPathDB. Results The functions of mediator genes from SHCN show immune system and cell cycle regulation have important roles in the eitology mechanism of schizophrenia. For example, the over-expressing schizophrenia candidate genes, SIRPB1, SYK and LCK, are responsible for signal transduction in cytokine production; immune responses involving IL-2 and TREM-1/DAP12 pathways are relevant for the etiology mechanism of schizophrenia. Novel treatments were proposed by searching the target genes of FDA approved drugs with genes in potential protein complexes and pathways. It was found that Vitamin A, retinoid acid and a few other immune response agents modulated by RARA and LCK genes may be potential treatments for both schizophrenia and hepatocellular carcinoma. Conclusions This is the first study showing specific mediator genes in the SHCN which may suppress tumors. We also show that the schizophrenic protein interactions and modulation with cancer implicates the importance of immune system for etiology of schizophrenia. PMID:24564241

  1. Alteration of transcriptional networks in the entorhinal cortex after maternal immune activation and adolescent cannabinoid exposure.

    PubMed

    Hollins, Sharon L; Zavitsanou, Katerina; Walker, Frederick Rohan; Cairns, Murray J

    2016-08-01

    Maternal immune activation (MIA) and adolescent cannabinoid exposure (ACE) have both been identified as major environmental risk factors for schizophrenia. We examined the effects of these two risk factors alone, and in combination, on gene expression during late adolescence. Pregnant rats were exposed to the viral infection mimic polyriboinosinic-polyribocytidylic acid (poly I:C) on gestational day (GD) 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14days starting on postnatal day (PND) 35. Gene expression was examined in the left entorhinal cortex (EC) using mRNA microarrays. We found prenatal treatment with poly I:C alone, or HU210 alone, produced relatively minor changes in gene expression. However, following combined treatments, offspring displayed significant changes in transcription. This dramatic and persistent alteration of transcriptional networks enriched with genes involved in neurotransmission, cellular signalling and schizophrenia, was associated with a corresponding perturbation in the expression of small non-coding microRNA (miRNA). These results suggest that a combination of environmental exposures during development leads to significant genomic remodeling that disrupts maturation of the EC and its associated circuitry with important implications as the potential antecedents of memory and learning deficits in schizophrenia and other neuropsychiatric disorders. PMID:26923065

  2. Regulation of Immune Response by Autogenous Antibody against Receptor

    PubMed Central

    Kluskens, L.; Köhler, H.

    1974-01-01

    BALB/c mice repeatedly immunized with Pneumococcus R36A vaccine produce antibodies to phosphorylcholine having the TEPC-15 myeloma idiotype (murine IgA myeloma protein that binds phosphorylcholine). The plaque-forming cell response to phosphorylcholine shows a decrease with repeated immunizations. In contrast, spleen cells from multiply immunized mice responded better in vitro than spleen cells from nonimmunized mice. The serum of animals immunized four or five times agglutinates TEPC-15-coated sheep erythrocytes. Inhibition of hemagglutination shows that the agglutinating activity is directed against the TEPC-15 idiotype. Sera from these mice, when added to cultures of normal spleen cells, specifically suppress the response to phosphorylcholine. The suppressive activity in the serum can be removed by solid absorption with TEPC-15. Evidently, repeated immunization with antigen induces two kinds of antibody responses: one directed against antigen and the other directed against the antibody to the antigen. It is proposed that this “auto” antibody against receptor is involved in the regulation of the immune response. PMID:4140517

  3. 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.

  4. Immunity factor contributes to altered brain functional networks in individuals at risk for Alzheimer's disease: Neuroimaging-genetic evidence.

    PubMed

    Bai, Feng; Shi, Yongmei; Yuan, Yonggui; Xie, Chunming; Zhang, Zhijun

    2016-08-01

    Clusterin (CLU) is recognized as a secreted protein that is related to the processes of inflammation and immunity in the pathogenesis of Alzheimer's disease (AD). The effects of the risk variant of the C allele at the rs11136000 locus of the CLU gene are associated with variations in the brain structure and function. However, the relationship of the CLU-C allele to architectural disruptions in resting-state networks in amnestic mild cognitive impairment (aMCI) subjects (i.e., individuals with elevated risk of AD) remains relatively unknown. Using resting-state functional magnetic resonance imaging and an imaging genetic approach, this study investigated whether individual brain functional networks, i.e., the default mode network (DMN) and the task-positive network, were modulated by the CLU-C allele (rs11136000) in 50 elderly participants, including 26 aMCI subjects and 24 healthy controls. CLU-by-aMCI interactions were associated with the information-bridging regions between resting-state networks rather than with the DMN itself, especially in cortical midline regions. Interestingly, the complex communications between resting-state networks were enhanced in aMCI subjects with the CLU rs11136000 CC genotype and were modulated by the degree of memory impairment, suggesting a reconstructed balance of the resting-state networks in these individuals with an elevated risk of AD. The neuroimaging-genetic evidence indicates that immunity factors may contribute to alterations in brain functional networks in aMCI. These findings add to the evidence that the CLU gene may represent a potential therapeutic target for slowing disease progression in AD. PMID:26899953

  5. Transcription-inhibition and RNA-binding domains of influenza A virus matrix protein mapped with anti-idiotypic antibodies and synthetic peptides.

    PubMed Central

    Ye, Z P; Baylor, N W; Wagner, R R

    1989-01-01

    We have undertaken by biochemical and immunological experiments to locate the region of the matrix (M1) protein responsible for down-regulating endogenous transcription of A/WSN/33 influenza virus. A more refined map of the antigenic determinants of the M1 protein was obtained by binding of epitope-specific monoclonal antibodies (MAbs) to chemically cleaved fragments. Epitope 2-specific MAb 289/4 and MAb 7E5 reverse transcription inhibition by M1 protein and react with a 4-kilodalton cyanogen bromide fragment extending from amino acid Gly-129 to Gln-164. Anti-idiotype serum immunoglobulin G prepared in rabbits immunized with MAb 289/4 or MAb 7E5 mimicked the action of M1 protein by inhibiting transcription in vitro of influenza virus ribonucleoprotein cores. This transcription-inhibition activity of anti-MAb 7E5 immunoglobulin G and anti-MAb 289/4 immunoglobulin G could be reversed by MAb 7E5 and MAb 289/4 or could be removed by MAb 7E5-Sepharose affinity chromatography. Transcription of influenza virus ribonucleoprotein was inhibited by one of three synthetic oligopeptides, a nonodecapeptide SP3 with an amino acid sequence corresponding to Pro-90 through Thr-108 of the M1 protein. Of all the structural proteins of influenza virus, only NP and M1 showed strong affinity for binding viral RNA or other extraneous RNAs. The 4-kilodalton cyanogen bromide peptide (Gly-129 to Gln-164), exhibited marked affinity for viral RNA, the binding of which was blocked by epitope 2-specific MAb 7E5 but not by MAbs directed to three other epitopes. Viral RNA also bound strongly to the nonodecapeptide SP3 and rather less well to anti-idiotype anti-MAb 7E5; these latter viral RNA-binding reactions were only slightly blocked by preincubation of anti-MAb 7E5 or SP3 with MAb 7E5. These experiments suggest the presence of at least two RNA-binding sites, which also serve as transcription-inhibition sites, centered around amino acid sequences 80 through 109 (epitope 4?) and 129 through 164

  6. Presence of a 16/6 related human anti-DNA common idiotype (SA1) in the anticardiolipin antibodies of patients with primary antiphospholipid syndrome.

    PubMed

    Villarreal, G M; Alarcón-Segovia, D; Villa, A R; Cabral, A R; Shoenfeld, Y

    1991-10-01

    Patients with primary antiphospholipid syndrome (PAPS) have few or no autoantibodies, other than the antiphospholipid antibodies (aPL) that could be natural autoantibodies encoded by germline genes. Some of the autoantibodies marked by the human anti-DNA common idiotype 16/6 have been found to be encoded by unmutated germline genes. Hence, we tested the sera of 19 patients with PAPS for the presence of the 16/6 idiotype which has also been found to be expressed on antibodies that bind cardiolipin. For this we used an ELISA method with antiserum against the SA1 idiotype which recognizes the 16/6. Five of our patients had the idiotype in at least one serum. Among the patients there was one with a variant of PAPS with hemolytic anemia and an IgM antibody to phosphatidylcholine that is akin to the natural autoantibody of normal mice encoded by germline genes VH11 and VH12. Inhibition studies with ssDNA, dsDNA and cardiolipin revealed that all 3 antigens decreased the serum levels of the SA1 idiotype despite absence of detectable anti-DNA antibodies by other methods. Our findings suggest that within the B cell clones that produce aPL in patients with PAPS there are some that produce immunoglobulins bearing 16/6 related idiotypes. This could indicate that some of the aPL present in patients with PAPS derive from natural autoantibody producing cell clones. PMID:1765979

  7. Anti-idiotypic nanobody: A strategy for development of sensitive and green immunoassay for Fumonisin B₁.

    PubMed

    Shu, Mei; Xu, Yang; Wang, Dan; Liu, Xing; Li, Yanping; He, Qinghua; Tu, Zhui; Qiu, Yulou; Ji, Yanwei; Wang, Xianxian

    2015-10-01

    Nanobodies that are small and thermally stable, as well as have high expression level, are leading alternative to produce anti-idiotypic antibodies. These antibodies have the advantage of replacing mycotoxins and their conjugates for immunoassays. In this work, anti-fumonisin B1 (FB1) monoclonal antibody (mAb) was used as the target for biopanning from a naïve alpaca nanobody (Nb) phage display library. After three cycles of panning, one anti-idiotypic nanobody (Ab2β Nb) was isolated and subjected to a Nb-ELISA for the detection of FB1. Surface plasmon resonance was used to analyze the reaction kinetics between the Ab2β Nb and anti-FB1 mAb. The developed assay showed a half inhibitory concentration (IC50) of 0.95±0.12 ng/mL, a limit of detection of 0.15 ng/mL, a linear range of 0.27-5.92 ng/mL, and a low cross-reactivity toward FB2 of 4.93%. The sensitivity was enhanced approximately 20-fold compared with that of the chemosynthetic FB1-BSA conjugates. The equilibrium dissociation constant (KD) measured for Ab2β Nb: anti-FB1 mAb was 164.6 nM. The assay was compared with conventional ELISA (the commercial ELISA kit), and the results indicated the reliability of Ab2β Nb replacing the antigen-carrier protein conjugates. The use of biotechnology in developing the surrogate is an ideal strategy for replacing conventional synthesized antigens. PMID:26078175

  8. Anti-Idiotypic Antibodies in Patients with Different Clinical Forms of Paracoccidioidomycosis

    PubMed Central

    Souza, A. R.; Gesztesi, J.-L.; del Negro, G. M. B.; Benard, G.; Sato, J.; Santos, M. V. B.; Abrahão, T. B.; Lopes, J. D.

    2000-01-01

    Paracoccidioidomycosis (PCM) is the most prevalent systemic mycosis in Latin America. Patients with PCM show a wide spectrum of clinical and pathological manifestations depending on both host and pathogen factors. Two clinical forms of the disease are recognized: the acute or juvenile form and the chronic or adult form. The major antigenic component of the parasite is a glycoprotein of 43 kDa (gp43). All patient sera present antibodies against gp43 (anti-gp43) and, as demonstrated before by our group, spontaneous anti-idiotypic (anti-Id) antibodies (Ab2) can be detected in patient sera with high titers of anti-gp43. Since it has been postulated that anti-Id antibodies may have a modulating function, we decided to purify and characterize anti-Id antibodies in this system. The possible correlation of Ab2 titers with different clinical forms of disease was also verified. Results showed that purified human anti-Id antibodies (human Ab2) recognized specifically the idiotype of some murine monoclonal anti-gp43 (17c and 3e) but not others (40.d7, 27a, and 8a). Spontaneous anti-Id antibodies were found in all clinical forms of disease. The majority of patients (88%, n = 8) with the acute form of PCM had high titers of Ab2. However, among patients with the multifocal chronic form of the disease, only 29% (n = 14) had high titers of Ab2; 70% (n = 10) of patients with the unifocal chronic form had low titers of Ab2. A correlation between Ab2 titers and anti-gp43 titers was observed before and during antimycotic treatment. Our results suggest that titers of anti-Id antibodies correlate with the severity of PCM in humans. PMID:10702489

  9. 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

  10. 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

  11. 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

  12. 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

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

    NASA Astrophysics Data System (ADS)

    Nian, Fuzhong; Wang, Ke

    2015-04-01

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

  14. 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

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

    PubMed

    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

  16. 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

  17. Mathematical modeling of the circadian dynamics of the neuroendocrine-immune network in experimentally induced arthritis.

    PubMed

    Rao, R; DuBois, D; Almon, R; Jusko, W J; Androulakis, I P

    2016-08-01

    The circadian dynamics of important neuroendocrine-immune mediators have been implicated in progression of rheumatoid arthritis pathophysiology, both clinically as well as in animal models. We present a mathematical model that describes the circadian interactions between mediators of the hypothalamic-pituitary-adrenal (HPA) axis and the proinflammatory cytokines. Model predictions demonstrate that chronically elevated cytokine expression results in the development of adrenal insufficiency and circadian variability in paw edema. Notably, our model also predicts that an increase in mean secretion of corticosterone (CST) after the induction of the disease is accompanied by a decrease in the amplitude of the CST oscillation. Furthermore, alterations in the phase of circadian oscillation of both cytokines and HPA axis mediators are observed. Therefore, by incorporating the circadian interactions between the neuroendocrine-immune mediators, our model is able to simulate important features of rheumatoid arthritis pathophysiology. PMID:27221115

  18. 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 ...

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. An immune orthogonal learning particle swarm optimisation algorithm for routing recovery of wireless sensor networks with mobile sink

    NASA Astrophysics Data System (ADS)

    Hu, Yifan; Ding, Yongsheng; Hao, Kuangrong; Ren, Lihong; Han, Hua

    2014-03-01

    The growth of mobile handheld devices promotes sink mobility in an increasing number of wireless sensor networks (WSNs) applications. The movement of the sink may lead to the breakage of existing routes of WSNs, thus the routing recovery problem is a critical challenge. In order to maintain the available route from each source node to the sink, we propose an immune orthogonal learning particle swarm optimisation algorithm (IOLPSOA) to provide fast routing recovery from path failure due to the sink movement, and construct the efficient alternative path to repair the route. Due to its efficient bio-heuristic routing recovery mechanism in the algorithm, the orthogonal learning strategy can guide particles to fly on better directions by constructing a much promising and efficient exemplar, and the immune mechanism can maintain the diversity of the particles. We discuss the implementation of the IOLPSOA-based routing protocol and present the performance evaluation through several simulation experiments. The results demonstrate that the IOLPSOA-based protocol outperforms the other three protocols, which can efficiently repair the routing topology changed by the sink movement, reduce the communication overhead and prolong the lifetime of WSNs with mobile sink.

  5. CD45, CD148, and Lyp/Pep: Critical Phosphatases Regulating Src Family Kinase Signaling Networks in Immune Cells

    PubMed Central

    Hermiston, Michelle L.; Zikherman, Julie; Zhu, Jing W.

    2009-01-01

    Summary Reciprocal regulation of tyrosine phosphorylation by protein tyrosine kinases and phosphatases is central to normal immune cell function. Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity can result in immunodeficiency, autoimmunity, or malignancy. Src family kinases play a central role in both immune cell function and disease due to their proximal position in numerous signal transduction cascades including those emanating from integrin, T and B cell antigen receptors, Fc, growth factor, and cytokine receptors. Given that tight regulation of Src family kinase activity is critical for appropriate responses to stimulation of these various signaling pathways, it is perhaps not surprising that multiple protein tyrosine phosphatases are involved in their regulation. Here, we focus on the role of three phosphatases, CD45, CD148, and LYP/PEP, which are critical regulators of src family kinase activity in hematopoietic cells. We review our current understanding of their structures, expression, functions in different hematopoietic cell subsets, regulation, and putative roles in disease. Finally, we discuss remaining questions that must be addressed if we are to have a clearer understanding of the coordinated regulation of tyrosine phosphorylation and signaling networks in hematopoietic cells and how they could potentially be manipulated therapeutically in disease. PMID:19290935

  6. 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

  7. 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

  8. 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

  9. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

    PubMed Central

    Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

    2012-01-01

    Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id+ tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id+ single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id+ fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id+ tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id+ scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients. PMID:23115759

  10. Clonal frequency analysis of B cells producing pathogenic anti-DNA antibody-associated idiotypes in systemic lupus erythematosus.

    PubMed

    Shibata, S; Sasaki, T; Hatakeyama, A; Munakata, Y; Hirabayashi, Y; Yoshinaga, K

    1992-06-01

    In order to identify the mechanism responsible for autoantibody production in systemic lupus erythematosus (SLE), B cell repertoires associated with anti-DNA idiotypes were explored by a limiting dilution analysis using Epstein-Barr virus (EBV) transformation methods and ELISA spot assays. The frequencies of B cell clones producing antibodies to DNA and to conventional antigens, tetanus toxoid, dinitrophenyl, or keyhole limpet hemocyanin were higher in active SLE compared to those in inactive SLE and in normal subjects. In addition, there was a disproportionate increase in anti-DNA antibody- and anti-DNA idiotype (Id)-producing clones at the precursor cell levels as well as at the mature cell level. On the other hand, numbers of anti-Id clones against anti-DNA-Id, termed 0-81 Id, were markedly increased at inactive stages of the disease but not at active stages. These were confirmed by serial studies in some patients with SLE. These results support a two-step mechanism for autoantibody production, in which initial polyclonal activation is followed by an antigen-driven process, and indicate an alteration of the precursor B cell repertoire in SLE, which may also associate with a preferential expansion of anti-DNA clones. PMID:1320474

  11. A Small-molecule Screen Yields Idiotype-specific Blockers of Neuromyelitis Optica Immunoglobulin G Binding to Aquaporin-4*

    PubMed Central

    Phuan, Puay-Wah; Anderson, Marc O.; Tradtrantip, Lukmanee; Zhang, Hua; Tan, Joseph; Lam, Chiwah; Bennett, Jeffrey L.; Verkman, A. S.

    2012-01-01

    Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system caused by binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) to AQP4 on astrocytes. A screen was developed to identify inhibitors of NMO-IgG-dependent, complement-dependent cytotoxicity. Screening of 50,000 synthetic small molecules was done using CHO cells expressing human AQP4 and a human NMO recombinant monoclonal antibody (rAb-53). The screen yielded pyrano[2,3-c]pyrazoles that blocked rAb-53 binding to AQP4 and prevented cytotoxicity in cell culture and spinal cord slice models of NMO. Structure-activity analysis of 82 analogs yielded a blocker with IC50 ∼ 6 μm. Analysis of the blocker mechanism indicated idiotype specificity, as (i) pyrano[2,3-c]pyrazoles did not prevent AQP4 binding or cytotoxicity of other NMO-IgGs, and (ii) surface plasmon resonance showed specific rAb-53 binding. Antibody structure modeling and docking suggested a putative binding site near the complementarity-determining regions. Small molecules with idiotype-specific antibody targeting may be useful as research tools and therapeutics. PMID:22989877

  12. 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 ...

  13. The Lymphotoxin Network: Orchestrating a Type I Interferon Response to Optimize Adaptive Immunity

    PubMed Central

    Gommerman, Jennifer L.; Browning, Jeffrey L.; Ware, Carl F.

    2014-01-01

    The Lymphotoxin (LT) pathway is best known for its role in orchestrating the development and homeostasis lymph nodes and Peyer's patch through the regulation of homeostatic chemokines. More recently an appreciation of the LT! R pathway in the production of Type I interferons (IFN-I) during homeostasis and infection has emerged. LT! R signaling is essential in differentiating stromal cells and macrophages in lymphoid organs to rapidly produce IFN-I in response to virus infections independently of the conventional TLR signaling systems. In addition, LT! R signaling is required to produce homeostatic levels of IFN-I from dendritic cells in order to effectively cross-prime a CD8+ T cell response to protein antigen. Importantly, pharmacological inhibition of LT! R signaling in mice has a profound positive impact on a number of autoimmune disease models, although it remains unclear if this efficacy is linked to IFN-I production during chronic inflammation. In this review, we will provide a brief overview of how the “Lymphotoxin Network” is linked to the IFN-I response and its impact on the immune system. PMID:24698108

  14. Cremophor EL as an adjuvant affecting immunoglobulin class switch in the immune response to the thymus-independent antigen alpha(1- greater than 3) dextran B 1355 S.

    PubMed

    Austrup, F; Kucharzik, T; Kölsch, E

    1991-08-01

    The humoral immune response to the so-called thymus independent antigen dextran B 1355 S in conventionally raised BALB/c mice consists solely of IgM antibodies. Expression of IgG anti-Dex antibodies in these mice is prevented by pre- or perinatally activated idiotype-specific T-suppressor lymphocytes. IgG B-memory cells nevertheless develop during the course of immunization, but are arrested in an anergic state. In the presence of Cremophor EL the induction of this anergic state is inhibited and the immune response shifts fully to an IgG anti-Dex response. PMID:1717371

  15. 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

  16. 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

  17. 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

  18. 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 ...

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. Immuno-Navigator, a batch-corrected coexpression database, reveals cell type-specific gene networks in the immune system

    PubMed Central

    Vandenbon, Alexis; Dinh, Viet H.; Mikami, Norihisa; Kitagawa, Yohko; Teraguchi, Shunsuke; Ohkura, Naganari; Sakaguchi, Shimon

    2016-01-01

    High-throughput gene expression data are one of the primary resources for exploring complex intracellular dynamics in modern biology. The integration of large amounts of public data may allow us to examine general dynamical relationships between regulators and target genes. However, obstacles for such analyses are study-specific biases or batch effects in the original data. Here we present Immuno-Navigator, a batch-corrected gene expression and coexpression database for 24 cell types of the mouse immune system. We systematically removed batch effects from the underlying gene expression data and showed that this removal considerably improved the consistency between inferred correlations and prior knowledge. The data revealed widespread cell type-specific correlation of expression. Integrated analysis tools allow users to use this correlation of expression for the generation of hypotheses about biological networks and candidate regulators in specific cell types. We show several applications of Immuno-Navigator as examples. In one application we successfully predicted known regulators of importance in naturally occurring Treg cells from their expression correlation with a set of Treg-specific genes. For one high-scoring gene, integrin β8 (Itgb8), we confirmed an association between Itgb8 expression in forkhead box P3 (Foxp3)-positive T cells and Treg-specific epigenetic remodeling. Our results also suggest that the regulation of Treg-specific genes within Treg cells is relatively independent of Foxp3 expression, supporting recent results pointing to a Foxp3-independent component in the development of Treg cells. PMID:27078110

  5. 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

  6. Staphylococcus aureus infection induces protein A-mediated immune evasion in humans.

    PubMed

    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; Wilson, Patrick C

    2014-11-17

    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

  7. Phage displayed peptides and anti-idiotype antibodies recognised by a monoclonal antibody directed against a diagnostic antigen of Mycoplasma capricolum subsp. capripneumoniae.

    PubMed

    Bengurić, D R; Dungu, B; Thiaucourt, F; du Plessis, D H

    2001-07-26

    A monoclonal antibody (Mab 4.52) raised against Mycoplasma capricolum subsp. capripneumoniae (Mccp) cell lysate was used as a template to obtain substitute antigens recognised by its paratope. Two approaches were investigated: a 17-mer random peptide library displayed on the surface of a filamentous phage was screened by panning on the immobilised Mab 4.52 and anti-idiotype antibodies were generated by immunising a chicken with the F(ab')(2) fragments of the antibody. Analysis of the peptide sequences displayed by the isolated phages identified two peptides. Both contained two cysteine residues and had identical or similar amino acids in positions 5 (P), 8 (I/L) and 13 (L). The fusion phages were also recognised by Mab 4.52 in enzyme-linked immunosorbent assay (ELISA) and binding was shown by surface plasmon resonance. One of the peptides was a markedly better inhibitor (67%) of the binding of Mab 4.52 to its original antigen than the other (20%) at 1mg/ml. After absorption, to remove isotypic and allotypic reactivities, the anti-idiotype IgY was specifically recognised by Mab 4.52 in ELISA and was able to inhibit its binding to the original antigen, whereas anti-idiotype antibodies raised against a bluetongue virus-specific antibody had no effect. In spite of unequivocal binding of the anti-idiotype antibodies and the fusion phages to the paratope of Mab 4.52, goat antisera appeared not to react with either of the surrogate antigens. In contrast, the test sera bound to the original antigen suggesting that Mab 4.52 does not recognise exactly the same antigenic site as antibodies in the goat antisera. PMID:11376960

  8. Acquisition of an anti-idiotypic cytotoxic T lymphocyte repertoire in B cell-transferred or tetraparental bone marrow chimeric mice

    SciTech Connect

    Yamamoto, H.; Bitoh, S.; Fujimoto, S.

    1987-10-01

    In previous studies we showed that major histocompatibility complex-restricted cytotoxic T lymphocytes (CTL) specific for the cross-reactive idiotype (CRI) of MOPC-104E myeloma protein could only be induced in BALB/c or BAB-14 mice which have the ability to produce the CRI, but not in C.AL-20 or C.B-20 mice which have no ability to produce the CRI. The strong correlation between CRI-specific CTL responder strains and CRI producers supports the idea that the VH gene products are intrinsic primary antigenic stimuli for the generation of the anti-idiotypic CTL. To investigate the role of B lymphocytes in the selection of T lymphocyte repertoire, the purified B cells of CRI producer strains were repeatedly injected into anti-CRI CTL nonresponder neonatal mice. CRI-specific CTL activity was successfully induced in the CRI nonproducer mice only when they were exposed to CRI producer strain B lymphocytes from neonatal life. When the CTL nonresponder adult mice received CRI producer B lymphocytes, the nonresponder phenotype was not changed into the responder phenotype. Inducibility of CRI-specific CTL was also analyzed in tetraparental bone marrow chimeras. When CRI nonproducer bone marrow cells repopulated along with CRI producer bone marrow cells, the anti-CRI CTL of CRI nonproducer origin were generated. Adaptive differentiation of haplotype preference was also observed. When these observations are taken collectively, we see that the anti-idiotypic T lymphocyte repertoire is not a genetically determined one, but rather that the repertoire of T lymphocytes strongly depends on the postnatal selection process through the intrinsic idiotypic repertoire of B lymphocytes, i.e., internal images.

  9. 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

  10. 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

  11. 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

  12. 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 ...

  13. 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

  14. 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

  15. 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

  16. Relationship of the CD5 B cell to human tonsillar lymphocytes that express autoantibody-associated cross-reactive idiotypes.

    PubMed Central

    Kipps, T J; Duffy, S F

    1991-01-01

    We examined human tonsillar B cells for expression of autoantibody heavy-chain or kappa light-chain cross-reactive idiotypes (CRIs), respectively defined by murine MAbs G6 or 17.109. We find 17.109 or G6 each specifically binds a subpopulation of B cells, respectively reacting with 3.8 +/- 3% (mean +/- SD) or 2.0 +/- 1.2% of all tonsillar lymphocytes. Cells reactive with both 17.109 and G6 comprise only 0.4 +/- 0.3% of tonsillar lymphocytes. Although each tested specimen had 17.109-positive cells, 2 of 19 tonsils (11%) did not have any G6-reactive cells. We find that CRI-positive cells and CD5 B cells both co-express slgD but fail to bind peanut agglutinin or MAbs specific for CD10, indicating that both cell types reside in the mantle zones of secondary B cell follicles. However, less than half of the B cells bearing one or both of these CRIs express detectable levels of CD5. Nevertheless, we find that G6-reactive lymphocytes constitute a multiclonal population of cells that express homologous heavy chain variable region genes, each rearranged to one of several distinct and apparently nonmutated D and JH gene segments. Collectively, these studies indicate that expression of nondiversified autoantibody-encoding variable region genes may not be an exclusive property of B cells that bear detectable levels of the CD5 surface antigen. PMID:1710233

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

    PubMed

    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

  18. 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

  19. 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

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

    PubMed

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

    2015-10-20

    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 CD4(+) T cell-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 lipopolysaccharide to stimulate innate immune cells) enabled integrative analysis of secreted profiles. Two major effects in HIV(+) PBMCs were not reproduced upon depletion of CD4(+) T cells in healthy PBMCs: (i) HIV(+) PBMCs maintained T cell-associated secreted profiles after T cell stimulation; (ii) HIV(+) PBMCs showed impaired interferon-γ (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 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

  1. 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

  2. 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 ...

  3. Immune response

    MedlinePlus Videos and Cool Tools

    ... 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 ...

  4. 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

  5. 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

  6. 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

  7. Endocannabinoids and immune regulation☆

    PubMed Central

    Pandey, Rupal; Mousawy, Khalida; Nagarkatti, Mitzi; Nagarkatti, Prakash

    2010-01-01

    Cannabinoid pharmacology has made important advances in recent years after the discovery of the cannabinoid receptors. These discoveries have added to our understanding of exogenous and endogenous cannabinoid signaling along with exploring the various pathways of their biosynthesis, molecular structure, inactivation, and anatomical distribution of their receptors throughout the body. The endocannabinoid system is involved in immunoregulation and neuroprotection. In this article, we have reviewed the possible mechanisms of the regulation of the immune response by endocannabinoids which include modulation of immune response in different cell types, effect on cytokine network, induction of apoptosis in immune cells and downregulation of innate and adaptive immune response. Studies from our laboratory have suggested that administration of endocannabinoids or use of inhibitors of enzymes that breakdown the endocannabinoids, leads to immunosuppression and recovery from immune-mediated injury to organs such as the liver. Thus, manipulation of endocannabinoids in vivo may constitute a novel treatment modality against inflammatory disorders. PMID:19428268

  8. 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.

  9. Diversity in Compartmental Dynamics of Gene Regulatory Networks: The Immune Response in Primary Influenza A Infection in Mice

    PubMed Central

    Hilchey, Shannon P.; Thakar, Juilee; Liu, Zhi-Ping; Welle, Stephen L.; Henn, Alicia D.; Wu, Hulin; Zand, Martin S.

    2015-01-01

    Current approaches to study transcriptional profiles post influenza infection typically rely on tissue sampling from one or two sites at a few time points, such as spleen and lung in murine models. In this study, we infected female C57/BL6 mice intranasally with mouse-adapted H3N2/Hong Kong/X31 avian influenza A virus, and then analyzed the gene expression profiles in four different compartments (blood, lung, mediastinal lymph nodes, and spleen) over 11 consecutive days post infection. These data were analyzed by an advanced statistical procedure based on ordinary differential equation (ODE) modeling. Vastly different lists of significant genes were identified by the same statistical procedure in each compartment. Only 11 of them are significant in all four compartments. We classified significant genes in each compartment into co-expressed modules based on temporal expression patterns. We then performed functional enrichment analysis on these co-expression modules and identified significant pathway and functional motifs. Finally, we used an ODE based model to reconstruct gene regulatory network (GRN) for each compartment and studied their network properties. PMID:26413862

  10. Networks.

    ERIC Educational Resources Information Center

    Maughan, George R.; Petitto, Karen R.; McLaughlin, Don

    2001-01-01

    Describes the connectivity features and options of modern campus communication and information system networks, including signal transmission (wire-based and wireless), signal switching, convergence of networks, and network assessment variables, to enable campus leaders to make sound future-oriented decisions. (EV)

  11. Variable region expression in the antibody responses of infants vaccinated with Haemophilus influenzae type b polysaccharide-protein conjugates. Description of a new lambda light chain-associated idiotype and the relation between idiotype expression, avidity, and vaccine formulation. The Collaborative Vaccine Study Group.

    PubMed Central

    Granoff, D M; Shackelford, P G; Holmes, S J; Lucas, A H

    1993-01-01

    Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappa II-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambda VII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines. PMID:8450060

  12. Chilling acclimation provides immunity to stress by altering regulatory networks and inducing genes with protective functions in Cassava

    PubMed Central

    2014-01-01

    Background Stress acclimation is an effective mechanism that plants acquired for adaption to dynamic environment. Even though generally considered to be sensitive to low temperature, Cassava, a major tropical crop, can be tolerant to much lower temperature after chilling acclimation. Improvement to chilling resistance could be beneficial to breeding. However, the underlying mechanism and the effects of chilling acclimation on chilling tolerance remain largely unexplored. Results In order to understand the mechanism of chilling acclimation, we profiled and analyzed the transcriptome and microRNAome of Cassava, using high-throughput deep sequencing, across the normal condition, a moderate chilling stress (14°C), a harsh stress (4°C) after chilling acclimation (14°C), and a chilling shock from 24°C to 4°C. The results revealed that moderate stress and chilling shock triggered comparable degrees of transcriptional perturbation, and more importantly, about two thirds of differentially expressed genes reversed their expression from up-regulation to down-regulation or vice versa in response to hash stress after experiencing moderate stress. In addition, microRNAs played important roles in the process of this massive genetic circuitry rewiring. Furthermore, function analysis revealed that chilling acclimation helped the plant develop immunity to further harsh stress by exclusively inducing genes with function for nutrient reservation therefore providing protection, whereas chilling shock induced genes with function for viral reproduction therefore causing damage. Conclusions Our study revealed, for the first time, the molecular basis of chilling acclimation, and showed potential regulation role of microRNA in chilling response and acclimation in Euphorbia. PMID:25090992

  13. 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

  14. 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 ...

  15. 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. PMID:27131327

  16. Humanized mouse G6 anti-idiotypic monoclonal antibody has therapeutic potential against IGHV1-69 germline gene-based B-CLL.

    PubMed

    Chang, De-Kuan; Kurella, Vinodh B; Biswas, Subhabrata; Avnir, Yuval; Sui, Jianhua; Wang, Xueqian; Sun, Jiusong; Wang, Yanyan; Panditrao, Madhura; Peterson, Eric; Tallarico, Aimee; Fernandes, Stacey; Goodall, Margaret; Zhu, Quan; Brown, Jennifer R; Jefferis, Roy; Marasco, Wayne A

    2016-01-01

    In 10-20% of the cases of chronic lymphocytic leukemia of B-cell phenotype (B-CLL), the IGHV1-69 germline is utilized as VH gene of the B cell receptor (BCR). Mouse G6 (MuG6) is an anti-idiotypic monoclonal antibody discovered in a screen against rheumatoid factors (RFs) that binds with high affinity to an idiotope expressed on the 51p1 alleles of IGHV1-69 germline gene encoded antibodies (G6-id(+)). The finding that unmutated IGHV1-69 encoded BCRs are frequently expressed on B-CLL cells provides an opportunity for anti-idiotype monoclonal antibody immunotherapy. In this study, we first showed that MuG6 can deplete B cells encoding IGHV1-69 BCRs using a novel humanized GTL mouse model. Next, we humanized MuG6 and demonstrated that the humanized antibodies (HuG6s), especially HuG6.3, displayed ∼2-fold higher binding affinity for G6-id(+) antibody compared to the parental MuG6. Additional studies showed that HuG6.3 was able to kill G6-id(+) BCR expressing cells and patient B-CLL cells through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Finally, both MuG6 and HuG6.3 mediate in vivo depletion of B-CLL cells in NSG mice. These data suggest that HuG6.3 may provide a new precision medicine to selectively kill IGHV1-69-encoding G6-id(+) B-CLL cells. PMID:26963739

  17. Networking.

    ERIC Educational Resources Information Center

    Duvall, Betty

    Networking is an information giving and receiving system, a support system, and a means whereby women can get ahead in careers--either in new jobs or in current positions. Networking information can create many opportunities: women can talk about how other women handle situations and tasks, and previously established contacts can be used in…

  18. 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

  19. 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.

  20. DNA Immunization

    PubMed Central

    Wang, Shixia; Lu, Shan

    2013-01-01

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

  1. 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

  2. US Veterinary Immune Reagents Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major obstacle to advances in veterinary immunology and disease control is the lack of sufficient immunological reagents specific for ruminants, swine, poultry, equine and aquaculture species". Sets of reagents, i.e., monoclonal (mAb) and polyclonal antibodies, that can identify the major leukocy...

  3. US Veterinary Immune Reagents Network

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A major obstacle to advances in veterinary immunology and disease control is the lack of sufficient immunological reagents specific for ruminants, swine, poultry, equine, and aquaculture species. Sets of reagents, i.e. monoclonal (mAb) and polyclonal antibodies (Ab), that can identify the major leu...

  4. 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...

  5. 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

  6. Maternal Immunization

    PubMed Central

    Chu, Helen Y.; Englund, Janet A.

    2014-01-01

    Maternal immunization has the potential to protect the pregnant woman, fetus, and infant from vaccine-preventable diseases. Maternal immunoglobulin G is actively transported across the placenta, providing passive immunity to the neonate and infant prior to the infant's ability to respond to vaccines. Currently inactivated influenza, tetanus toxoid, and acellular pertussis vaccines are recommended during pregnancy. Several other vaccines have been studied in pregnancy and found to be safe and immunogenic and to provide antibody to infants. These include pneumococcus, group B Streptococcus, Haemophilus influenzae type b, and meningococcus vaccines. Other vaccines in development for potential maternal immunization include respiratory syncytial virus, herpes simplex virus, and cytomegalovirus vaccines. PMID:24799324

  7. Immunity challenge.

    PubMed

    Davenport, R John

    2003-06-11

    As people get older, their immune systems falter. The elderly are more susceptible to infections than youngsters are, and hyperactive inflammatory responses appear to contribute to some age-associated illnesses, including Alzheimer's disease and atherosclerosis. Investigating the effect of aging on the immune system was once a scientific stepchild, but card-carrying immunologists are now tackling the problem head-on. Despite the immune system's complexity, researchers have started to make sense of how its components change with age. As the research progresses, scientists hope to bolster elderly people's response to infectious diseases and quiet the inflammation that can make aging a painful experience. PMID:12844525

  8. 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 ...

  9. Immune response

    MedlinePlus

    ... inflammation and tissue repair. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ... and adaptive immune systems. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, PA: ...

  10. Childhood Immunization

    MedlinePlus

    Today, children in the United States routinely get vaccines that protect them from more than a dozen ... lowest levels in history, thanks to years of immunization. Children must get at least some vaccines before ...

  11. Immune response

    MedlinePlus Videos and Cool Tools

    The immune system includes specialized white blood cells, called lymphocytes that adapt themselves to fight specific foreign invaders. These cells develop into two groups in the bone marrow. From the bone ...

  12. 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. PMID:26656674

  13. 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.

  14. 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. PMID:27181644

  15. Anti-idiotypic nanobody-phage based real-time immuno-PCR for detection of hepatocarcinogen aflatoxin in grains and feedstuffs.

    PubMed

    Lei, Jiawen; Li, Peiwu; Zhang, Qi; Wang, Yanru; Zhang, Zhaowei; Ding, Xiaoxia; Zang, Wen

    2014-11-01

    Aflatoxins are a group of extremely toxic small molecules that have been involved in human hepatic and extrahepatic carcinogenesis as causative agents. Herein, we developed a real-time immuno polymerase chain reaction (IPCR) assay for the accurately quantitative detection of aflatoxins in agri-products base on a M13 phage containing aflatoxin anti-idiotypic nanobody and its encoding DNA which was used to design the specific primers. The limit of detection (LOD) of the assay is 0.02 ng/mL, which exhibits a 4-fold improvement over traditional phage ELISA. The developed method was successfully validated with the samples of corn, rice, peanut, and feedstuff, which are major aflatoxin-contaminated agri-products. And the recoveries were from 77.05 to 122.16%. For further validation, the developed assay was also compared with a reference HPLC method for the analysis of aflatoxins in corn and peanuts, and concordant results (R(2) = 0.991) were obtained. In this context, this study provides a novel opportunity to analyze aflatoxins in agri-products. PMID:25273352

  16. 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

  17. Skin Immunization Obviates Alcohol-Related Immune Dysfunction

    PubMed Central

    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

  18. Immune thrombocytopenia.

    PubMed

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age-specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

  19. 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.

  20. 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...

  1. Down modulation of MHC surface molecules on B cells by suppressive immune complexes obtained from chronic intestinal schistosomiasis patients.

    PubMed

    Rezende, S A; Gollob, K J; Correa-Oliveira, R; Goes, A M

    1998-06-01

    Granulomatous inflammation around parasite eggs is the prominent lesion in human schistosomiasis. Studies have suggested the involvement of a series of suppressive mechanisms in the control of this reaction, such as macrophages, cytokines, idiotypic interactions and immune complexes (IC). The studies examine the role of IC obtained from chronic intestinal schistosomiasis patients (ISP) in the reactivity of peripheral blood mononuclear cells (PBMC). The results have shown that these immune complexes are able to suppress cell reactivity by inducing an increase in the production of soluble mediators such as prostaglandins and IL-10. To gain a better understanding of how this suppression occurs the present study examines the phenotypic pattern of PBMC after immune complex treatment in cell proliferation assays. These data show that cultures including immune complex present a higher percentage of B lymphocytes in which a lower expression of a MHC-class II gene product, HLA-DR was detected. This altered expression of the HLA-DR molecule on B lymphocytes after IC treatment suggests a novel mechanism for the suppression observed, that is, IC might decrease the antigen-presenting function of B lymphocytes. PMID:9698100

  2. A human and a mouse anti-idiotypic antibody specific for human T14(+) anti-DNA antibodies reconstructed by phage display.

    PubMed

    Leung, D T; Yam, N W; Chui, Y L; Wong, K C; Lim, P L

    2000-09-19

    Little is known about human anti-idiotypic antibodies. Phage display methodology was used to reconstruct these antibodies from lupus patients, which recognize a subset (T14(+)) of anti-DNA antibodies. Antigen-specific B cells were isolated from the blood using a peptide based on a complementarity determining region (V(H)CDR3) of the prototypic T14(+) antibody. cDNA fragments of the V(H) and V(L) genes prepared from the cells were expressed as phage displayed single chain Fv (scFv) fragments using the pCANTAB-5E phagemid vector. From a reactive clone obtained, the Ig genes used were identified to be V(H)3, D5-D3, J(H)4b, V(kappa)I and J(kappa)2. The heavy chain was highly mutated, especially in CDR3, which bears mutations mostly of the replacement type; this region is also unusual in being extremely long due to a D-D fusion. In contrast, a mouse hybridoma antibody, made to the same T14(+) peptide and transformed as a scFv fragment, uses a short V(H)CDR3 comprising five amino acids, three of which are tyrosines. Tyrosines may be important for antigen binding because two of these also exist in the human V(H)CDR3. The light chains of both antibodies may also contribute to the specificity of the protein, because their V(L) segments, including the CDRs, are highly homologous to each other. PMID:11024298

  3. 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

  4. Immune Thrombocytopenia

    PubMed Central

    Kistanguri, Gaurav; McCrae, Keith R.

    2013-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP, with the risk of bleeding and related morbidity increased in elderly patients. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Thrombocytopenia is caused by antibodies that react with glycoproteins expressed on platelets and megakaryocytes (glycoprotein IIb/IIIa, Ib/IX and others), causing shortened survival of circulating platelets and impairing platelet production. Diminished numbers and function of regulatory T cells, as well as the effects of cytotoxic T cells also contribute to the pathogenesis of ITP. Corticosteroids remain the most common first line therapy for ITP, occasionally in conjunction with intravenous immunoglobulin (IVIg) and anti-Rh(D). However, these agents do not lead to durable remissions in the majority of adults with ITP, and considerable heterogeneity exists in the use of second line approaches, which may include splenectomy, Rituximab, or thrombopoietin receptor agonists (TRAs). This review summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. Remarkable advances in the understanding and management of ITP have been achieved over the last decade, though many questions remain. PMID:23714309

  5. 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 ...

  6. 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

  7. Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo

    PubMed Central

    Franki, Suzanne N.; Steward, Kristopher K.; Betting, David J.; Kafi, Kamran; Yamada, Reiko E.

    2008-01-01

    The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of antitumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit antitumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were cocultured with bone marrow–derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs cocultured with mAb-coated tumor cells were protected from tumor challenge (60% long-term survival), whereas DCs loaded with tumor cells alone were much less effective. The opsonized whole tumor cell–DC vaccine elicited significantly better tumor protection than a traditional lymphoma idiotype (Id) protein vaccine, and in combination with chemotherapy could eradicate preexisting tumor. Moreover, the DC vaccine protected animals from both wild-type and Id-negative variant tumor cells, indicating that Id is not a major target of the induced tumor immunity. Protection was critically dependent upon CD8+ T cells, with lesser contribution by CD4+ T cells. Importantly, opsonized whole tumor cell–DC vaccination did not result in tissue-specific autoimmunity. Since opsonized whole tumor cell–DC and Id vaccines appear to target distinct tumor antigens, optimal antilymphoma immunity might be achieved by combining these approaches. PMID:17993615

  8. Dendritic cells loaded with apoptotic antibody-coated tumor cells provide protective immunity against B-cell lymphoma in vivo.

    PubMed

    Franki, Suzanne N; Steward, Kristopher K; Betting, David J; Kafi, Kamran; Yamada, Reiko E; Timmerman, John M

    2008-02-01

    The in vitro priming of tumor-specific T cells by dendritic cells (DCs) phagocytosing killed tumor cells can be augmented in the presence of antitumor monoclonal antibody (mAb). We investigated whether DCs phagocytosing killed lymphoma cells coated with tumor-specific antibody could elicit antitumor immunity in vivo. Irradiated murine 38C13 lymphoma cells were cocultured with bone marrow-derived DCs in the presence or absence of tumor-specific mAb. Mice vaccinated with DCs cocultured with mAb-coated tumor cells were protected from tumor challenge (60% long-term survival), whereas DCs loaded with tumor cells alone were much less effective. The opsonized whole tumor cell-DC vaccine elicited significantly better tumor protection than a traditional lymphoma idiotype (Id) protein vaccine, and in combination with chemotherapy could eradicate preexisting tumor. Moreover, the DC vaccine protected animals from both wild-type and Id-negative variant tumor cells, indicating that Id is not a major target of the induced tumor immunity. Protection was critically dependent upon CD8(+) T cells, with lesser contribution by CD4(+) T cells. Importantly, opsonized whole tumor cell-DC vaccination did not result in tissue-specific autoimmunity. Since opsonized whole tumor cell-DC and Id vaccines appear to target distinct tumor antigens, optimal antilymphoma immunity might be achieved by combining these approaches. PMID:17993615

  9. 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

  10. 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.

  11. Docking studies and network analyses reveal capacity of compounds from Kandelia rheedii to strengthen cellular immunity by interacting with host proteins during tuberculosis infection

    PubMed Central

    Zaman, Aubhishek

    2012-01-01

    Kandelia rheedii (locally known as Guria or Rasunia), widely found and used in Indian subcontinent, is a well-known herbal cure to tuberculosis. However, neither the mechanism nor the active components of the plant extract responsible for mediating this action has yet been confirmed. Here in this study, molecular interactions of three compounds (emodin, fusaric acid and skyrin) from the plant extract with the host protein targets (casein kinase (CSNK), estrogen receptor (ERBB), dopamine β-hydroxylase (DBH) and glucagon receptor (Gcgr)) has been found. These protein targets are known to be responsible for strengthening cellular immunity against Mycobacteria tuberculosis. The specific interactions of these three compounds with the respective protein targets have been discussed here. The insights from study should further help us designing molecular medicines against tuberculosis. PMID:23275699

  12. Immune thrombocytopenia.

    PubMed

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  13. 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

  14. 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

  15. 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/ ...

  16. 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 ...

  17. 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 ...

  18. Immune System and Disorders

    MedlinePlus

    ... substances that are usually not harmful Immune deficiency diseases - disorders in which the immune system is missing one or more of its parts Autoimmune diseases - diseases causing your immune system to attack your ...

  19. [Signal systems of plant immunity].

    PubMed

    Dmitriev, A P

    2002-01-01

    Plants can recognise the penetrating pathogen and respond to the attack with an array of defense reactions. Signal transduction from receptor in plasma membrane to genome is necessary to activate these reactions. Plant cell signaling systems which take part in signal transduction were discovered and identified recently. The obtained results suggest that plant cells have complex and well coordinated signal network which regulates their immune potential. PMID:12187855

  20. Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N-glycolyl-containing gangliosides, with or without chemotherapy in a mouse model of non-small cell lung cancer.

    PubMed

    Segatori, Valeria I; Vazquez, Ana M; Gomez, Daniel E; Gabri, Mariano R; Alonso, Daniel F

    2012-01-01

    N-glycolylneuraminic acid (NeuGc) is a sialic acid molecule usually found in mammalian cells as terminal constituents of different membrane glycoconjugates such as gangliosides. The NeuGcGM3 ganglioside has been described as a tumor antigen for non-small cell lung cancer (NSCLC) in humans. Racotumomab is an anti-NeuGc-containing gangliosides anti-idiotype monoclonal antibody (mAb) (formerly known as 1E10) that has received attention as a potential active immunotherapy for advanced lung cancer in clinical trials. In this work, we have examined the antitumor activity of racotumomab in combination or not with chemotherapy, using the 3LL Lewis lung carcinoma as a preclinical model of NSCLC in C57BL/6 mice. Vaccination with biweekly doses of racotumomab at 50-200 μg/dose formulated in aluminum hydroxide (racotumomab-alum vaccine) demonstrated a significant antitumor effect against the progression of lung tumor nodules. Racotumomab-alum vaccination exerted a comparable effect on lung disease to that of pemetrexed-based chemotherapy (100 mg/kg weekly). Interestingly, chemo-immunotherapy was highly effective against lung nodules and well-tolerated, although no significant synergistic effect was observed as compared to each treatment alone in the present model. We also obtained evidence on the role of the exogenous incorporation of NeuGc in the metastatic potential of 3LL cells. Our preclinical data provide support for the combination of chemotherapy with the anti-idiotype mAb racotumomab, and also reinforce the biological significance of NeuGc in lung cancer. PMID:23162791

  1. Preclinical evaluation of racotumomab, an anti-idiotype monoclonal antibody to N-glycolyl-containing gangliosides, with or without chemotherapy in a mouse model of non-small cell lung cancer

    PubMed Central

    Segatori, Valeria I.; Vazquez, Ana M.; Gomez, Daniel E.; Gabri, Mariano R.; Alonso, Daniel F.

    2012-01-01

    N-glycolylneuraminic acid (NeuGc) is a sialic acid molecule usually found in mammalian cells as terminal constituents of different membrane glycoconjugates such as gangliosides. The NeuGcGM3 ganglioside has been described as a tumor antigen for non-small cell lung cancer (NSCLC) in humans. Racotumomab is an anti-NeuGc-containing gangliosides anti-idiotype monoclonal antibody (mAb) (formerly known as 1E10) that has received attention as a potential active immunotherapy for advanced lung cancer in clinical trials. In this work, we have examined the antitumor activity of racotumomab in combination or not with chemotherapy, using the 3LL Lewis lung carcinoma as a preclinical model of NSCLC in C57BL/6 mice. Vaccination with biweekly doses of racotumomab at 50–200 μg/dose formulated in aluminum hydroxide (racotumomab-alum vaccine) demonstrated a significant antitumor effect against the progression of lung tumor nodules. Racotumomab-alum vaccination exerted a comparable effect on lung disease to that of pemetrexed-based chemotherapy (100 mg/kg weekly). Interestingly, chemo-immunotherapy was highly effective against lung nodules and well-tolerated, although no significant synergistic effect was observed as compared to each treatment alone in the present model. We also obtained evidence on the role of the exogenous incorporation of NeuGc in the metastatic potential of 3LL cells. Our preclinical data provide support for the combination of chemotherapy with the anti-idiotype mAb racotumomab, and also reinforce the biological significance of NeuGc in lung cancer. PMID:23162791

  2. The skin as an immune organ.

    PubMed Central

    Salmon, J K; Armstrong, C A; Ansel, J C

    1994-01-01

    As a protective interface between internal organs and the environment, the skin encounters a host of toxins, pathogenic organisms, and physical stresses. To combat these attacks on the cutaneous microenvironment, the skin functions as more than a physical barrier: it is an active immune organ. Immune responses in the skin involve an armamentarium of immune-competent cells and soluble biologic response modifiers including cytokines. Traversed by a network of lymphatic and blood vessels, the dermis contains most of the lymphocytes in the skin, other migrant leukocytes, mast cells, and tissue macrophages. Although the epidermis has no direct access to the blood or lymphatic circulation, it is equipped with immune-competent cells: Langerhans cells, the macrophage-like antigen-presenting cells of the epidermis; keratinocytes, epithelial cells with immune properties; dendritic epidermal T lymphocytes, resident cells that may serve as a primitive T-cell immune surveillance system; epidermotropic lymphocytes, migrants from vessels in the dermis; and melanocytes, epidermal pigment cells with immune properties. Although the components of the epidermis and dermis work in concert to execute immune responses in the skin, for purposes of this review, we focus on the cells and cytokines of the epidermal immunologic unit, the frontline of immune protection against environmental toxins and microbes. PMID:8160465

  3. 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.

  4. 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, ” ...

  5. 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 ...

  6. 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 ...

  7. The modulation of immunity

    SciTech Connect

    Mitchell, M.S.

    1985-01-01

    This book contains 13 chapters. Some of the chapter titles are: Modulation of Immunity by Thymus-Derived Lymphocytes; Modulation of Immunity by Macrophages; Modulation of Immunity by Soluble Mediators; Viruses and the Immune Response; and Methanol Extraction Residue: Effects and Mechanisms of Action.

  8. Epigenetic Control of Immunity

    PubMed Central

    Busslinger, Meinrad; Tarakhovsky, Alexander

    2014-01-01

    Immunity relies on the heterogeneity of immune cells and their ability to respond to pathogen challenges. In the adaptive immune system, lymphocytes display a highly diverse antigen receptor repertoire that matches the vast diversity of pathogens. In the innate immune system, the cell's heterogeneity and phenotypic plasticity enable flexible responses to changes in tissue homeostasis caused by infection or damage. The immune responses are calibrated by the graded activity of immune cells that can vary from yeast-like proliferation to lifetime dormancy. This article describes key epigenetic processes that contribute to the function of immune cells during health and disease. PMID:24890513

  9. 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.

  10. 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

  11. 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

  12. Systems biology of circadian-immune interactions

    PubMed Central

    Mavroudis, P.D.; Scheff, J.D.; Calvano, S.E.; Androulakis, I.P.

    2013-01-01

    There is increasing evidence that immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators such as cytokines, undergo daily fluctuations. Current experimental data indicates that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune system. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies requires not only an accurate identification of the signaling pathways that mediate host’s response, but also a systems-level description and evaluation. PMID:23006670

  13. 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. PMID:26794634

  14. Systems biology of circadian-immune interactions.

    PubMed

    Mavroudis, P D; Scheff, J D; Calvano, S E; Androulakis, I P

    2013-01-01

    There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental data indicate that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune systems. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies require not only an accurate identification of the signaling pathways that mediate host responses, but also a system-level description and evaluation. PMID:23006670

  15. Intersection of mTOR and STAT signaling in immunity

    PubMed Central

    Saleiro, Diana; Platanias, Leonidas C.

    2014-01-01

    Optimal regulation of immune networks is essential for generation of effective immune responses, and defects in such networks can lead to immunodeficiency, while uncontrolled responses can result in autoimmune disorders. mTOR and STAT signaling cascades are key regulators of differentiation and function of cells of the immune system. Both pathways act as sensors and transducers of environmental stimuli, and recent evidence has revealed points of crosstalk between these pathways, highlighting synergistic regulation of immune cell differentiation and function. Here we review the current understanding of mTOR and STAT interactions in T cells and innate immune cells, and discuss potential mechanisms underlying these events. We further outline models for the intersection of these pathways in the regulation of immunity, and highlight important areas for future research. PMID:25592035

  16. 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

  17. 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

  18. Immune regulation of epithelial cell function: Implications for GI pathologies

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammalian immune system is a complex and dynamic network that recognizes, responds, and adapts to numerous foreign and self molecules. CD4+ T cells orchestrate adaptive immune responses, and upon stimulation by antigen, naive CD4+ T cells proliferate and differentiate into various T cell subsets...

  19. Immunizations: Active vs. Passive

    MedlinePlus

    ... they’ve been exposed. For example, the passive rabies immunization (rabies immune globulin) is commonly used after a certain ... of your pediatrician. There may be variations in treatment that your pediatrician may recommend based on individual ...

  20. 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

  1. Immune system structures (image)

    MedlinePlus

    The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat or any other cause.

  2. Immune system structures (image)

    MedlinePlus

    The immune system protects the body from potentially harmful substances. The inflammatory response (inflammation) is part of innate immunity. It occurs when tissues are injured by bacteria, trauma, toxins, heat, or any other cause.

  3. Aging changes in immunity

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/004008.htm Aging changes in immunity To use the sharing features ... cells and antibodies that destroy these harmful substances. Aging Changes and Their Effects on the Immune System ...

  4. Pneumonia - weakened immune system

    MedlinePlus

    ... medlineplus.gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... fighting off infection because of problems with the immune system. This type of disease is called "pneumonia in ...

  5. 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.

  6. NATIONAL IMMUNIZATION SURVEY (NIS)

    EPA Science Inventory

    The National Immunization Survey (NIS) is sponsored by the National Immunization Program (NIP) and conducted by the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention.

  7. Exercise and immunity

    MedlinePlus

    ... know exactly if or how exercise increases your immunity to certain illnesses, but there are several theories ( ... not exercise more intensely just to increase their immunity. Heavy, long-term exercise (such as marathon running ...

  8. 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 ...

  9. 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

  10. 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…

  11. 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

  12. 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

  13. Non-covalent association of protein and capsular polysaccharide on bacteria-sized latex beads as a model for polysaccharide-specific humoral immunity to intact Gram-positive extracellular bacteria1

    PubMed Central

    Colino, Jesus; Duke, Leah; Snapper, Clifford M.

    2013-01-01

    Intact Streptococcus pneumoniae, expressing type 14 capsular polysaccharide (PPS14) and type III Streptococcus agalactiae containing a PPS14 core capsule identical to PPS14, exhibit non-covalent associations of PPS14 and bacterial protein, in contrast to soluble covalent conjugates of these respective antigens. 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, utilize 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. PPS14+[PspA] beads, 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 PPS14+[PspA] beads peaked rapidly, with the secondary response highly enriched for the 44.1-idiotype and lacking affinity maturation. These results demonstrate that non-covalent 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 antigens. PMID:23926322

  14. Chapter 2: Innate Immunity

    PubMed Central

    Turvey, Stuart E.; Broide, David H.

    2009-01-01

    Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

  15. 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.

  16. 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

  17. A dynamical model of the adaptive immune system: effects of cells promiscuity, antigens and B-B interactions

    NASA Astrophysics Data System (ADS)

    Bartolucci, Silvia; Annibale, Alessia

    2015-08-01

    We analyse a minimal model for the primary response in the adaptive immune system comprising three different players: antigens, T and B cells. We assume B-T interactions to be diluted and sampled locally from heterogeneous degree distributions, which mimic B cells receptors' promiscuity. We derive dynamical equations for the order parameters quantifying the B cells activation and study the nature and stability of the stationary solutions using linear stability analysis and Monte Carlo simulations.The system's behaviour is studied in different scaling regimes of the number of B cells, dilution in the interactions and number of antigens. Our analysis shows that: (i) B cells activation depends on the number of receptors in such a way that cells with an insufficient number of triggered receptors cannot be activated; (ii) idiotypic (i.e. B-B) interactions enhance parallel activation of multiple clones, improving the system's ability to fight different pathogens in parallel; (iii) the higher the fraction of antigens within the host the harder is for the system to sustain parallel signalling to B cells, crucial for the homeostatic control of cell numbers.

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  19. Assessing barriers to immunization.

    PubMed

    Niederhauser, Victoria; Ferris, Catherine

    2016-05-01

    Parental barriers to childhood immunizations vary among countries, states and communities. There is a plethora of studies that exist to examine barriers to immunizations including many intervention studies designed to improve immunization rates in children. Often, intervention studies designed to minimize barriers and increase immunization uptake among children lack the inclusion of a standardized instrument to measure accurately parental barriers to childhood immunizations before and after interventions. The Searching for Hardships and Obstacles To Shots (SHOTS) survey is a standardized survey instrument to measure parental barriers to childhood immunizations. In several studies, the SHOTS survey has demonstrated consistent reliability and has been validated in diverse populations. The inclusion of the SHOTS survey instrument in studies to examine barriers to childhood immunization will provide researchers and clinicians with a better understanding of parents' individualized barriers to immunizations. Furthermore, use of the SHOTS survey instrument to collect information about parental barriers to immunizations can lead to targeted interventions to minimize these obstacles at the individual and community level and to help us to achieve our national, state and community childhood immunization goals. PMID:26810618

  20. Dynamic Nature of Noncoding RNA Regulation of Adaptive Immune Response

    PubMed Central

    Curtale, Graziella; Citarella, Franca

    2013-01-01

    Immune response plays a fundamental role in protecting the organism from infections; however, dysregulation often occurs and can be detrimental for the organism, leading to a variety of immune-mediated diseases. Recently our understanding of the molecular and cellular networks regulating the immune response, and, in particular, adaptive immunity, has improved dramatically. For many years, much of the focus has been on the study of protein regulators; nevertheless, recent evidence points to a fundamental role for specific classes of noncoding RNAs (ncRNAs) in regulating development, activation and homeostasis of the immune system. Although microRNAs (miRNAs) are the most comprehensive and well-studied, a number of reports suggest the exciting possibility that long ncRNAs (lncRNAs) could mediate host response and immune function. Finally, evidence is also accumulating that suggests a role for miRNAs and other small ncRNAs in autocrine, paracrine and exocrine signaling events, thus highlighting an elaborate network of regulatory interactions mediated by different classes of ncRNAs during immune response. This review will explore the multifaceted roles of ncRNAs in the adaptive immune response. In particular, we will focus on the well-established role of miRNAs and on the emerging role of lncRNAs and circulating ncRNAs, which all make indispensable contributions to the understanding of the multilayered modulation of the adaptive immune response. PMID:23975170

  1. Systems-Level Analysis of Innate Immunity

    PubMed Central

    Zak, Daniel E.; Tam, Vincent C.; Aderem, Alan

    2014-01-01

    Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology. PMID:24655298

  2. 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

  3. 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. PMID:26512000

  4. Endocrine factors modulating immune responses in pregnancy.

    PubMed

    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

  5. Lipid antigens in immunity

    PubMed Central

    Dowds, C. Marie; Kornell, Sabin-Christin

    2014-01-01

    Lipids are not only a central part of human metabolism but also play diverse and critical roles in the immune system. As such, they can act as ligands of lipid-activated nuclear receptors, control inflammatory signaling through bioactive lipids such as prostaglandins, leukotrienes, lipoxins, resolvins, and protectins, and modulate immunity as intracellular phospholipid- or sphingolipid-derived signaling mediators. In addition, lipids can serve as antigens and regulate immunity through the activation of lipid-reactive T cells, which is the topic of this review. We will provide an overview of the mechanisms of lipid antigen presentation, the biology of lipid-reactive T cells, and their contribution to immunity. PMID:23999493

  6. Immune interventions in stroke

    PubMed Central

    Fu, Ying; Liu, Qiang; Anrather, Josef

    2016-01-01

    Inflammatory and immune responses in the brain can shape the clinical presentation and outcome of stroke. Approaches for effective management of acute stroke are sparse and many measures for brain protection fail, but our ability to modulate the immune system and modify the disease progression of multiple sclerosis is increasing. As a result, immune interventions are currently being explored as therapeutic interventions in acute stroke. In this Review, we compare the immunological features of acute stroke with those of multiple sclerosis, identify unique immunological features of stroke, and consider the evidence for immune interventions. In acute stroke, microglia activation and cell death products trigger an inflammatory cascade that damages vessels and the parenchyma within minutes to hours of the ischaemia or haemorrhage. Immune interventions that restrict brain inflammation, vascular permeability and tissue oedema must be administered rapidly to reduce acute immune-mediated destruction and to avoid subsequent immunosuppression. Preliminary results suggest that the use of drugs that modify disease in multiple sclerosis might accomplish these goals in ischaemic and haemorrhagic stroke. Further elucidation of the immune mechanisms involved in stroke is likely to lead to successful immune interventions. PMID:26303850

  7. 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…

  8. Chemoimmunotherapy: reengineering tumor immunity

    PubMed Central

    Chen, Gang

    2013-01-01

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

  9. Innate immunity and adjuvants.

    PubMed

    Akira, Shizuo

    2011-10-12

    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

  10. 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

  11. 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...

  12. 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

  13. 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

  14. 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…

  15. 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.

  16. Resident commensals shaping immunity

    PubMed Central

    Erturk-Hasdemir, Deniz; Kasper, Dennis L.

    2013-01-01

    All animals coexist with myriad commensal microorganisms in a symbiotic relationship that plays a key role in health and disease. Continuous commensal–host interactions profoundly affect the development and regulation of the host’s immune system. The complex interaction of the commensal microbiota with the immune system is a topic of substantial interest. An understanding of these interactions and the mechanisms through which commensal microbes actively shape host immunity may yield new insights into the pathogenesis of many immune-mediated diseases and lead to new prophylactic and therapeutic interventions. This review examines recent advances in this field and their potential implications not just for the colonized tissues but also for the entire immune system. PMID:23830047

  17. 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

  18. 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

  19. Siglecs and Immune Regulation

    PubMed Central

    Pillai, Shiv; Netravali, Ilka Arun; Cariappa, Annaiah; Mattoo, Hamid

    2013-01-01

    Sialic acid binding Ig-like lectins or Siglecs vary in their specificity for sialic acid containing ligands and are mainly expressed by cells of the immune system. Many siglecs are inhibitory receptors expressed in innate immune cells that regulate inflammation mediated by DAMPs and PAMPs. This family also includes molecules involved in adhesion and phagocytosis and receptors that can associate with the ITAM containing DAP12 adaptor. Siglecs contribute to the inhibition of immune cells both by binding to cis-ligands (expressed in the same cells) as well as by responding to pathogen derived sialoglycoconjugates. They can help maintain tolerance in B lymphocytes, modulate the activation of conventional and plasmacytoid dendritic cells, and contribute to the regulation of T cell function both directly and indirectly. Siglecs modulate immune responses influencing almost every cell in the immune system, and are of relevance both in health and disease. PMID:22224769

  20. 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

  1. 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. PMID:26808310

  2. Neuroimmunoregulation and natural immunity.

    PubMed

    Berczi, I; Chow, D A; Sabbadini, E R

    1998-09-01

    The development and function of the immune system is regulated by neuroendocrine factors. Immune function may be divided into adaptive and natural immunity. Adaptive immune responses are driven by specific determinants of the antigen (epitopes), require 5-10 d to fully develop, and show an accelerated or memory response after repeated exposure to the same antigen. Natural immunity may be divided into host defense mediated by non-immune factors (e.g., antimicrobial proteins, enzymes, mucus etc.) and polyspecific responses of the immune system. This polyspecific response relies on natural antibodies and on some other serum proteins (e.g., lipopolysaccharide-binding protein-LBP, C-reactive protein-CRP), and on surface receptors of macrophages, natural killer cells and B and T lymphocytes for activation. Highly conserved homologous (crossreactive) epitopes, or homotopes for short, are recognized by the natural immune system. Natural antibodies, LBP, and CRP are capable of activating the entire immune system after combination with the appropriate homotope. During febrile illness natural immune host defense is promptly elevated because of the rapid rise of natural antibodies, LBP, and CRP in the serum. This is known as the acute phase response (APR), which is initiated by a sudden rise of cytokines in the circulation, such as IL-1, IL-6, and TNF-alpha. The cytokines act on the brain, the neuroendocrine system, and on other tissues and organs, which leads to fever and profound hormonal and metabolic changes. The hypothalamus-pituitary adrenal axis is activated and serves as the primary regulator of immune and inflammatory reactions. Insulin, glucagon, and catecholeamine levels are also raised. Bone marrow activity and leukocyte function are high and the liver is converted to the rapid production of acute-phase proteins (APP). APP include LBP, CRP, fibrinogen, some complement components, enzyme inhibitors, and anti-inflammatory proteins, which may rise in the serum from

  3. Exercise, immunity and aging.

    PubMed

    Venjatraman, J T; Fernandes, G

    1997-01-01

    In general population, many protective immune responses are impaired in old age, leading to an increased risk of infection. However, recent studies in SENIEUR subjects (healthy centenarians who are examples of successful aging) suggest that complex remodeling and reshaping of the immune system occurs with aging. An appropriate regular regimen of endurance exercise might help elderly to lead a quality of life by preserving immune function. However, very little is known regarding the interaction between exercise, aging and the immune system. Given that a number of age-related changes occur in many physiological systems which are known to alter the immune function both at rest and during exercise, it would be of value to learn the extent to which both acute and chronic exercise influence immune function in the elderly. The immune system response to exercise is multifaceted, depending on the nature of exercise. Significant interaction between the neuroendocrine and immune systems, and the role of lifestyle factors in immune function are known to occur. In theory, moderate exercise should help to reverse the adverse effects of aging upon the immune system by increasing the production of endocrine hormones which may contribute to less accumulation of autoreactive immune cells by enhancing the programmed cell death. Active elderly subjects demonstrated a significantly greater proliferative response to phytohemagglutinins (PHA) and to pokeweed mitogen (PWM), and higher rates of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) production. A moderate training program can enhance the resting natural killer (NK) cell function of healthy elderly people, potentially increasing resistance to both viral infections and preventing the formation of malignant cells. Recent studies have suggested that endurance training in later life is associated with a lesser age-related decline in certain aspects of circulating T cell function and related cytokine

  4. 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, ...

  5. Interacting epidemics on overlay networks

    NASA Astrophysics Data System (ADS)

    Funk, Sebastian; Jansen, Vincent A. A.

    2010-03-01

    The interaction between multiple pathogens spreading on networks connecting a given set of nodes presents an ongoing theoretical challenge. Here, we aim to understand such interactions by studying bond percolation of two different processes on overlay networks of arbitrary joint degree distribution. We find that an outbreak of a first pathogen providing immunity to another one spreading subsequently on a second network connecting the same set of nodes does so most effectively if the degrees on the two networks are positively correlated. In that case, the protection is stronger the more heterogeneous the degree distributions of the two networks are. If, on the other hand, the degrees are uncorrelated or negatively correlated, increasing heterogeneity reduces the potential of the first process to prevent the second one from reaching epidemic proportions. We generalize these results to cases where the edges of the two networks overlap to arbitrary amount, or where the immunity granted is only partial. If both processes grant immunity to each other, we find a wide range of possible situations of coexistence or mutual exclusion, depending on the joint degree distribution of the underlying networks and the amount of immunity granted mutually. These results generalize the concept of a coexistence threshold and illustrate the impact of large-scale network structure on the interaction between multiple spreading agents.

  6. Rebuilding immunity with Remune.

    PubMed

    Whitfield, L

    1998-01-01

    Remune, an immune response therapy composed of inactivated HIV, is designed to enhance the immune system's ability to recognize and kill HIV proteins. Developed by Dr. Jonas Salk, researchers hope Remune's actions can alter the course of HIV infection and slow disease progression. Remune has gained Food and Drug Administration (FDA) approval to enter the critical Phase III trial stage. Two clinical trials are tracking Remune's immunogenicity (ability to provoke an immune response), its immunogenicity relative to dose level, and its effect on viral load. An ongoing trial, approved in February of 1996, enrolled 2,500 patients at 74 sites. The manufacturer, Immune Response Corporation (IRC), announced earlier this year that treatment with Remune induces an immune response to HIV that cross-reacts with different strains of the virus. This immune response is crucial for developing an effective worldwide treatment. Remune decreases levels of tumor necrosis factor alpha (TNF-a). IRC recently began a Phase I clinical trial in Great Britain that combines Remune with a protease inhibitor, two antiviral nucleoside analogues, and Interleukin-2. The trial is designed to determine the role that the drug may play in restoring immune response. PMID:11365486

  7. Immunizations for foreign travel.

    PubMed Central

    Hill, D. R.

    1992-01-01

    One of the most important aspects of preparing travelers for destinations throughout the world is providing them with immunizations. Before administering any vaccines, however, a careful health and immunization history and travel itinerary should be obtained in order to determine vaccine indications and contraindications. There are three categories of immunizations for foreign travel. The first category includes immunizations which are routinely recommended whether or not the individual is traveling. Many travelers are due for primary vaccination or boosting against tetanus-diphtheria, measles-mumps-rubella, pneumococcal pneumonia, and influenza, for example, and the pre-travel visit is an ideal time to administer these. The second category are immunizations which might be required by a country as a condition for entry; these are yellow fever and cholera. The final category contains immunizations which are recommended because there is a risk of acquiring a particular disease during travel. Typhoid fever, meningococcal disease, rabies, and hepatitis are some examples. Travelers who are pregnant or who are infected with the human immunodeficiency virus require special consideration. Provision of appropriate immunizations for foreign travel is an important aspect of preventing illness in travelers. PMID:1337807

  8. Immunity to Francisella

    PubMed Central

    Cowley, Siobhán C.; Elkins, Karen L.

    2011-01-01

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

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

    PubMed

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

    2014-09-01

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

  10. 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

  11. 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

  12. 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.

  13. Immune mechanisms in cerebral ischemic tolerance

    PubMed Central

    Garcia-Bonilla, Lidia; Benakis, Corinne; Moore, Jamie; Iadecola, Costantino; Anrather, Josef

    2014-01-01

    Stressor-induced tolerance is a central mechanism in the response of bacteria, plants, and animals to potentially harmful environmental challenges. This response is characterized by immediate changes in cellular metabolism and by the delayed transcriptional activation or inhibition of genetic programs that are not generally stressor specific (cross-tolerance). These programs are aimed at countering the deleterious effects of the stressor. While induction of this response (preconditioning) can be established at the cellular level, activation of systemic networks is essential for the protection to occur throughout the organs of the body. This is best signified by the phenomenon of remote ischemic preconditioning, whereby application of ischemic stress to one tissue or organ induces ischemic tolerance (IT) in remote organs through humoral, cellular and neural signaling. The immune system is an essential component in cerebral IT acting simultaneously both as mediator and target. This dichotomy is based on the fact that activation of inflammatory pathways is necessary to establish IT and that IT can be, in part, attributed to a subdued immune activation after index ischemia. Here we describe the components of the immune system required for induction of IT and review the mechanisms by which a reprogrammed immune response contributes to the neuroprotection observed after preconditioning. Learning how local and systemic immune factors participate in endogenous neuroprotection could lead to the development of new stroke therapies. PMID:24624056

  14. Innate Immune Sensing and Response to Influenza

    PubMed Central

    Pulendran, Bali; Maddur, Mohan S.

    2015-01-01

    Influenza viruses pose a substantial threat to human and animal health worldwide. Recent studies in mouse models have revealed an indispensable role for the innate immune system in defense against influenza virus. Recognition of the virus by innate immune receptors in a multitude of cell types activates intricate signaling networks, functioning to restrict viral replication. Downstream effector mechanisms include activation of innate immune cells and, induction and regulation of adaptive immunity. However, uncontrolled innate responses are associated with exaggerated disease, especially in pandemic influenza virus infection. Despite advances in the understanding of innate response to influenza in the mouse model, there is a large knowledge gap in humans, particularly in immunocom-promised groups such as infants and the elderly. We propose here, the need for further studies in humans to decipher the role of innate immunity to influenza virus, particularly at the site of infection. These studies will complement the existing work in mice and facilitate the quest to design improved vaccines and therapeutic strategies against influenza. PMID:25078919

  15. Sulfhydryl-based tumor antigen-carrier protein conjugates stimulate superior antitumor immunity against B cell lymphomas.

    PubMed

    Betting, David J; Kafi, Kamran; Abdollahi-Fard, Alireza; Hurvitz, Sara A; Timmerman, John M

    2008-09-15

    Therapeutic vaccination of B cell lymphoma patients with tumor-specific Ig (idiotype, or Id) chemically coupled to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde has shown promising results in early clinical trials, and phase III trials are underway. However, glutaraldehyde Id-KLH vaccines fail to elicit anti-Id immune and clinical responses in many patients, possibly because glutaraldehyde reacts with lysine, cysteine, tyrosine, and histidine residues, damaging critical immunogenic epitopes. A sulfhydryl-based tumor Ag-carrier protein conjugation system using maleimide chemistry was used to enhance the efficacy of Id-KLH vaccines. Maleimide Id-KLH conjugates eradicated A20 lymphoma from most tumor-bearing mice, whereas glutaraldehyde Id-KLH had little efficacy. Maleimide Id-KLH elicited tumor-specific IgG Abs and T cells, with CD8(+) T cells being the major effectors of antilymphoma immunity. Maleimide Id-KLH vaccines also demonstrated superior efficacy in 38C13 and BCL-1 lymphoma models, where Abs were shown to be critical for protection. Importantly, standard glutaraldehyde Id-KLH conjugation procedures could result in "overconjugation" of the tumor Ag, leading to decreased efficacy, whereas the heterobifunctional maleimide-based conjugation yielded potent vaccine product regardless of conjugation duration. Under lysosomal processing conditions, the Id-carrier protein linkage was cleavable only after maleimide conjugation. Maleimide KLH conjugation was easily performed with human Igs analogous to those used in Id-KLH clinical trials. These data support the evaluation of sulfhydryl-based Id-KLH vaccines in lymphoma clinical trials and possibly the use of tumor Ag-carrier protein vaccines for other cancers. PMID:18768870

  16. Local immunization strategy based on the scores of nodes

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Deng, Yong; Wei, Bo

    2016-01-01

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

  17. 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

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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, ...

  2. 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 . ...

  3. 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)

  4. Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity.

    PubMed

    Yang, Luanna; Wu, Eveline Y; Tarrant, Teresa K

    2016-07-01

    Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness. PMID:27401913

  5. Is there a psychoneuroimmunological pathway between alexithymia and immunity? Immune and physiological correlates of alexithymia.

    PubMed

    Guilbaud, Olivier; Corcos, Maurice; Hjalmarsson, Linnea; Loas, Gwenolé; Jeammet, Philippe

    2003-09-01

    The term "alexithymia" was coined by Sifneos. It is characterised by a lack of words to express emotion (a: absence of; lexi: words; thymia: emotions, affects). Its characteristics were suggested to occur more frequently in individuals with so-called "psychosomatic disorders", but this is still a matter of controversy. Here we review the psychosomatic network of alexithymia, i.e. the immune and physiological correlates of alexithymia. Some studies suggest that inaccuracy in recognising emotional states, or the way of coping with negative emotions, may influence immune function. Alexithymia is associated with higher tonic baseline levels of sympathetic activity and lower sympathetic reactivity during acute stress. Few studies have reported a diminished immune-mediated cellular response in alexithymics with oversecretion of glucocorticoids. We hypothesise that alexithymic subjects may suffer from unnoticed chronic stress with physiological and endocrine and immune consequences. Alexithymia may skew the Th-1/Th-2 balance toward Th-2 dominant immunity and lower cell-mediated (Th-1) immune response and may increase an individual's risk for stress-related disorder. PMID:14499176

  6. Immune Deficiency Foundation

    MedlinePlus

    ... expert immunologists and healthcare professionals Connect IDF Social Networks IDF Friends Our social network created exclusively for ... place. Conveniently access your health records from your computer, tablet or smartphone to track your medical activities. ...

  7. Innate Immunity and Neuroinflammation

    PubMed Central

    Bonifati, Domenico Marco

    2013-01-01

    Inflammation of central nervous system (CNS) is usually associated with trauma and infection. Neuroinflammation occurs in close relation to trauma, infection, and neurodegenerative diseases. Low-level neuroinflammation is considered to have beneficial effects whereas chronic neuroinflammation can be harmful. Innate immune system consisting of pattern-recognition receptors, macrophages, and complement system plays a key role in CNS homeostasis following injury and infection. Here, we discuss how innate immune components can also contribute to neuroinflammation and neurodegeneration. PMID:23843682

  8. Reproduction-Immunity Trade-Offs in Insects.

    PubMed

    Schwenke, Robin A; Lazzaro, Brian P; Wolfner, Mariana F

    2016-01-01

    Immune defense and reproduction are physiologically and energetically demanding processes and have been observed to trade off in a diversity of female insects. Increased reproductive effort results in reduced immunity, and reciprocally, infection and activation of the immune system reduce reproductive output. This trade-off can manifest at the physiological level (within an individual) and at the evolutionary level (genetic distinction among individuals in a population). The resource allocation model posits that the trade-off arises because of competition for one or more limiting resources, and we hypothesize that pleiotropic signaling mechanisms regulate allocation of that resource between reproductive and immune processes. We examine the role of juvenile hormone, 20-hydroxyecdysone, and insulin/insulin-like growth factor-like signaling in regulating both oogenesis and immune system activity, and propose a signaling network that may mechanistically regulate the trade-off. Finally, we discuss implications of the trade-off in an ecological and evolutionary context. PMID:26667271

  9. Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium

    PubMed Central

    Pukkila-Worley, Read; Ausubel, Frederick M

    2013-01-01

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

  10. 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. An immunity-based model for dynamic distributed intrusion detection

    NASA Astrophysics Data System (ADS)

    Qiao, Peili; Wang, Tong; Su, Jie

    2008-03-01

    The traditional intrusion detection systems mostly adopt the analysis engine of the concentrating type, so the misinformation rate is higher and lack of self-adaptability, which is already difficult to meet increasing extensive security demand of the distributed network environment. An immunity-based model combining immune theory, data mining and data fusion technique for dynamic distributed intrusion detection is proposed in this paper. This system presents the method of establishing and evolving the set of early gene, and defines the sets of Self, Nonself and Immunity cells. Moreover, a detailed description is given to the architecture and work mechanism of the model, and the characters of the model are analyzed.

  12. [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

  13. Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells.

    PubMed

    Betting, David J; Mu, Xi Y; Kafi, Kamran; McDonnel, Desmond; Rosas, Francisco; Gold, Daniel P; Timmerman, John M

    2009-01-01

    Therapeutic vaccination of lymphoma patients with tumor-specific immunoglobulin (idiotype, Id) coupled to the carrier protein keyhole limpet hemocyanin (Id-KLH) is undergoing clinical investigation, and methods to improve the immunogenicity of these and other protein tumor antigen vaccines are being sought. Id proteins can be produced via tumor-myeloma hybridomas or recombinant methods in mammalian, bacteria, or insect cells. We now demonstrate that terminal mannose residues, characteristic of recombinant proteins produced in insect cells, yield Id proteins with significantly enhanced immunostimulatory properties compared to Id proteins derived from mammalian cells. Recombinant baculovirus-infected insect cell-derived Id showed higher binding to and activation of human dendritic cells mediated by mannose receptors. In vivo, insect cell-derived Id elicited higher levels of tumor-specific CD8+ cytotoxic T lymphocyte (CTL) and improved eradication of pre-established murine lymphoma. Insect cell and mammalian Id generated similar levels of tumor-specific antibodies, showing no impairment in antibody responses to native tumor antigen despite the glycoslylation differences in the immunogen. Combining insect cell production and maleimide-based KLH conjugation offered the highest levels of anti-tumor immunity. Our data comparing sources of recombinant Id protein tumor antigens used in therapeutic cancer vaccines demonstrate that insect cell-derived antigens can offer several immunologic advantages over proteins derived from mammalian sources. PMID:19000731

  14. Enhanced immune stimulation by a therapeutic lymphoma tumor antigen vaccine produced in insect cells involves mannose receptor targeting to antigen presenting cells

    PubMed Central

    Betting, David J.; Mu, Xi Y.; Kafi, Kamran; McDonnel, Desmond; Rosas, Francisco; Gold, Daniel P.; Timmerman, John M.

    2009-01-01

    Therapeutic vaccination of lymphoma patients with tumor-specific immunoglobulin (idiotype, Id) coupled to the carrier protein keyhole limpet hemocyanin (Id-KLH) is undergoing clinical investigation, and methods to improve the immunogenicity of these and other protein tumor antigen vaccines are being sought. Id proteins can be produced via tumor-myeloma hybridomas or recombinant methods in mammalian, bacteria, or insect cells. We now demonstrate that terminal mannose residues, characteristic of recombinant proteins produced in insect cells, yield Id proteins with significantly enhanced immunostimulatory properties compared to Id proteins derived from mammalian cells. Recombinant baculovirus-infected insect cell-derived Id showed higher binding to and activation of human dendritic cells mediated by mannose receptors. In vivo, insect cell-derived Id elicited higher levels of tumor-specific CD8+ CTL and improved eradication of pre-established murine lymphoma. Insect cell and mammalian Id generated similar levels of tumor-specific antibodies, showing no impairment in antibody responses to native tumor antigen despite the glycoslylation differences in the immunogen. Combining insect cell production and maleimide-based KLH conjugation offered the highest levels of anti-tumor immunity. Our data comparing sources of recombinant Id protein tumor antigens used in therapeutic cancer vaccines demonstrate that insect cell-derived antigens can offer several immunologic advantages over proteins derived from mammalian sources. PMID:19000731

  15. Adaptive immunity in the liver.

    PubMed

    Shuai, Zongwen; Leung, Miranda Wy; He, Xiaosong; Zhang, Weici; Yang, Guoxiang; Leung, Patrick Sc; Eric Gershwin, M

    2016-05-01

    The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver. PMID:26996069

  16. Adaptive immunity in the liver

    PubMed Central

    Shuai, Zongwen; Leung, Miranda WY; He, Xiaosong; Zhang, Weici; Yang, Guoxiang; Leung, Patrick SC; Eric Gershwin, M

    2016-01-01

    The anatomical architecture of the human liver and the diversity of its immune components endow the liver with its physiological function of immune competence. Adaptive immunity is a major arm of the immune system that is organized in a highly specialized and systematic manner, thus providing long-lasting protection with immunological memory. Adaptive immunity consists of humoral immunity and cellular immunity. Cellular immunity is known to have a crucial role in controlling infection, cancer and autoimmune disorders in the liver. In this article, we will focus on hepatic virus infections, hepatocellular carcinoma and autoimmune disorders as examples to illustrate the current understanding of the contribution of T cells to cellular immunity in these maladies. Cellular immune suppression is primarily responsible for chronic viral infections and cancer. However, an uncontrolled auto-reactive immune response accounts for autoimmunity. Consequently, these immune abnormalities are ascribed to the quantitative and functional changes in adaptive immune cells and their subsets, innate immunocytes, chemokines, cytokines and various surface receptors on immune cells. A greater understanding of the complex orchestration of the hepatic adaptive immune regulators during homeostasis and immune competence are much needed to identify relevant targets for clinical intervention to treat immunological disorders in the liver. PMID:26996069

  17. 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.

  18. Associations between transcriptional changes and protein phenotypes provide insights into immune regulation in corals.

    PubMed

    Fuess, Lauren E; Pinzόn C, Jorge H; Weil, Ernesto; Mydlarz, Laura D

    2016-09-01

    Disease outbreaks in marine ecosystems have driven worldwide declines of numerous taxa, including corals. Some corals, such as Orbicella faveolata, are particularly susceptible to disease. To explore the mechanisms contributing to susceptibility, colonies of O. faveolata were exposed to immune challenge with lipopolysaccharides. RNA sequencing and protein activity assays were used to characterize the response of corals to immune challenge. Differential expression analyses identified 17 immune-related transcripts that varied in expression post-immune challenge. Network analyses revealed several groups of transcripts correlated to immune protein activity. Several transcripts, which were annotated as positive regulators of immunity were included in these groups, and some were downregulated following immune challenge. Correlations between expression of these transcripts and protein activity results further supported the role of these transcripts in positive regulation of immunity. The observed pattern of gene expression and protein activity may elucidate the processes contributing to the disease susceptibility of species like O. faveolata. PMID:27109903

  19. 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

  20. The mucosal immune system for vaccine development.

    PubMed

    Lamichhane, Aayam; Azegamia, Tatsuhiko; Kiyonoa, Hiroshi

    2014-11-20

    Mucosal surfaces are continuously exposed to the external environment and therefore represent the largest lymphoid organ of the body. In the mucosal immune system, gut-associated lymphoid tissues (GALTs), including Peyer's patches and isolated lymphoid follicles, play an important role in the induction of antigen-specific immune responses in the gut. GALTs have unique organogenesis characteristics and interact with the network of dendritic cells and T cells for the simultaneous induction and regulation of IgA responses and oral tolerance. In these lymphoid tissues, antigens are up taken by M cells in the epithelial layer, and antigen-specific immune responses are subsequently initiated by GALT cells. Nasopharynx- and tear-duct-associated lymphoid tissues (NALTs and TALTs) are key organized lymphoid structures in the respiratory tract and ocular cavities, respectively, and have been shown to interact with each other. Mucosal surfaces are also characterized by host-microbe interactions that affect the genesis and maturation of mucosa-associated lymphoid tissues and the induction and regulation of innate and acquired mucosal immune responses. Because most harmful pathogens enter the body through mucosal surfaces by ingestion, inhalation, or sexual contact, the mucosa is a candidate site for vaccination. Mucosal vaccination has some physiological and practical advantages, such as decreased costs and reduced risk of needle-stick injuries and transmission of bloodborne diseases, and it is painless. Recently, the application of modern bioengineering and biochemical engineering technologies, including gene transformation and manipulation systems, resulted in the development of systems to express vaccine antigens in transgenic plants and nanogels, which will usher in a new era of delivery systems for mucosal vaccine antigens. In this review, based on some of our research group's thirty seven years of progress and effort, we highlight the unique features of mucosal immune

  1. Organising for immunization.

    PubMed

    Michie, S

    1993-06-01

    In the late 1960s, health workers from a mission hospital in rural Zambia began registering children under 14 years old within 30 miles of the hospital (about 3000 children) by incorporating the cooperation of community leaders. They wanted to give every 0-4 year old child a Road to Health card and every 5-14 year old a vaccine record card and to promote the significance of immunization to parents and community leaders. The mission hospital established mobile health units to conduct regular visits in the center of villages. Staff hugh scales from a tree and borrowed a table to conduct the clinic. They kept a good relationship and communication with the community, leading successful education and communication activities. By 1988, many younger mothers were unfamiliar with a measles or whooping cough epidemic so they tended to not have their infants immunized. Epidemics began killing children nationwide, frightening these mothers so they brought their children for immunizations. The medical mission achieved an 85-90% vaccination coverage rate with immunization clinic attendance climbing quickly. 1 mother even walked 30 miles to have her infant injected with the DPT vaccine, but 10 years earlier, she did not bring her children. Further, measles had not reached her area because the immunization level was so high that it stopped the epidemic. PMID:12318293

  2. 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

  3. 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.

  4. 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

  5. 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

  6. Meeting the challenges of measuring human immune regulation.

    PubMed

    Martino, David; Allen, Katrina

    2015-09-01

    Data is now emerging that many human diseases not previously considered immune diseases have an immunological basis. As such human immunology is in need of more standardized systems-wide methods for monitoring immune regulation. Despite significant advances in basic immunology research, thousands of patients visiting health practitioners daily still have no reliable immunological metrics by which to assess the status of their immune health beyond the standard blood count. Further investigations are costly, time consuming and often don't offer significant insights into the mechanics of immune deviation or regulation. The immune system meets many criteria of complex biological networks and therefore systems-wide approaches are highly suitable to determining the emergent properties of immune responses. Standardization of immune monitoring, the development of new technology and integrated informatics approaches are needed in order to identify useful hematological and serological markers that are informative for immune health. This brief review outlines some of the more promising developments in systems immunology. PMID:25956036

  7. Mucosal Immune Development in Early Life: Setting the Stage.

    PubMed

    Brugman, Sylvia; Perdijk, Olaf; van Neerven, R J Joost; Savelkoul, Huub F J

    2015-08-01

    Our environment poses a constant threat to our health. To survive, all organisms must be able to discriminate between good (food ingredients and microbes that help digest our food) and bad (pathogenic microbes, viruses and toxins). In vertebrates, discrimination between beneficial and harmful antigens mainly occurs at the mucosal surfaces of the respiratory, digestive, urinary and genital tract. Here, an extensive network of cells and organs form the basis of what we have come to know as the mucosal immune system. The mucosal immune system is composed of a single epithelial cell layer protected by a mucus layer. Different immune cells monitor the baso-lateral side of the epithelial cells and dispersed secondary lymphoid organs, such as Peyer's patches and isolated lymphoid follicles are equipped with immune cells able to mount appropriate and specific responses. This review will focus on the current knowledge on host, dietary and bacterial-derived factors that shape the mucosal immune system before and after birth. We will discuss current knowledge on fetal immunity (both responsiveness and lymphoid organ development) as well as the impact of diet and microbial colonization on neonatal immunity and disease susceptibility. Lastly, inflammatory bowel disease will be discussed as an example of how the composition of the microbiota might predispose to disease later in life. A fundamental understanding of the mechanisms involved in mucosal immune development and tolerance will aid nutritional intervention strategies to improve health in neonatal and adult life. PMID:25666708

  8. 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

  9. [Immune-mediated neuropathies].

    PubMed

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits. PMID:27474733

  10. 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

  11. [Immune mechanisms in uremia].

    PubMed

    Dobbelstein, H

    1975-05-15

    There is both clinical and experimental evidence that cellular and humoral immunity are suppressed in patients with renal insufficiency: observations in organ transplantation and in vitro stimulation of lymphocytes from uraemic patients, investigations of acute and late hypersensitivity reactions, the immune response after active immunization as well as changes of immunoglobulins and lymphatic organs in uraemia are discussed in the paper. The underlying mechanisms are complex and not yet fully understood. Lymphopenia, atrophy of the thymus gland, toxic serum factors, induction of enhancing mechanisms by certain serum fractions and metabolic defects of lymphocytes--all were shown to be involved or at least considered to be. At present, however, it is impossible to define their rank of importance and the exact place they may occupy in the genesis of this type of "natural immunosuppression". PMID:540

  12. Mechanisms of immune resolution

    PubMed Central

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

    2008-01-01

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

  13. Immune System and Schizophrenia

    PubMed Central

    Müller, Norbert; Schwarz, Markus J.

    2010-01-01

    Although an immune dysfunction and the involvement of infectious agents in the pathophysiology of schizophrenia are discussed since decades, the field never came into the mainstream of research. In schizophrenia a blunted type-1 immune response seems to be associated with a dysbalance in the activation of the enzyme indoleamine 2,3-dioxygenase (IDO) and in the tryptophan - kynurenine metabolism resulting in increased production of kynurenic acid in schizophrenia. This is associated with an imbalance in the glutamatergic neurotransmission, leading to an NMDA antagonism in schizophrenia. The immunological effects of antipsychotics rebalance partly the immune imbalance and the overweight of the production of the kynurenic acid. This immunological imbalance results in an inflammatory state combined with increased prostaglandin E2 (PGE2) production and increased cyclo-oxygenase-2 (COX-2) expression. COX-2 inhibitors have been tested in clinical trials, pointing to favourable effects in schizophrenia. PMID:21057585

  14. 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

  15. 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

  16. Burkitt Lymphoma: Pathogenesis and Immune Evasion

    PubMed Central

    God, Jason M.; Haque, Azizul

    2010-01-01

    B-cell lymphomas arise at distinct stages of cellular development and maturation, potentially influencing antigen (Ag) presentation and T-cell recognition. Burkitt lymphoma (BL) is a highly malignant B-cell tumor associated with Epstein-Barr Virus (EBV) infection. Although BL can be effectively treated in adults and children, leading to high survival rates, its ability to mask itself from the immune system makes BL an intriguing disease to study. In this paper, we will provide an overview of BL and its association with EBV and the c-myc oncogene. The contributions of EBV and c-myc to B-cell transformation, proliferation, or attenuation of cellular network and immune recognition or evasion will be summarized. We will also discuss the various pathways by which BL escapes immune detection by inhibiting both HLA class I- and II-mediated Ag presentation to T cells. Finally, we will provide an overview of recent developments suggesting the existence of BL-associated inhibitory molecules that may block HLA class II-mediated Ag presentation to CD4+ T cells, facilitating immune escape of BL. PMID:20953370

  17. Autophagy in immunity

    PubMed Central

    Zhou, Xu-Jie; Zang, Hong

    2012-01-01

    Autophagy is now emerging as a spotlight in trafficking events that activate innate and adaptive immunity. It facilitates innate pathogen detection and antigen presentation, as well as pathogen clearance and lymphocyte homeostasis. In this review, we first summarize new insights into its functions in immunity, which underlie its associations with autoimmunity. As some lines of evidence are emerging to support its role in autoimmune and autoinflammatory diseases, we further discuss whether and how it affects autoimmune diseases including systemic lupus erythematosus, rheumatoid arthritis, diabetes mellitus and multiple sclerosis, as well as autoinflammatory diseases, such as Crohn disease and vitiligo. PMID:22878595

  18. 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

  19. 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

  20. 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

  1. Spatiotemporal dynamics of intratumoral immune cells reveal the immune landscape in human cancer.

    PubMed

    Bindea, Gabriela; Mlecnik, Bernhard; Tosolini, Marie; Kirilovsky, Amos; Waldner, Maximilian; Obenauf, Anna C; Angell, Helen; Fredriksen, Tessa; Lafontaine, Lucie; Berger, Anne; Bruneval, Patrick; Fridman, Wolf Herman; Becker, Christoph; Pagès, Franck; Speicher, Michael R; Trajanoski, Zlatko; Galon, Jérôme

    2013-10-17

    The complex interactions between tumors and their microenvironment remain to be elucidated. Combining large-scale approaches, we examined the spatio-temporal dynamics of 28 different immune cell types (immunome) infiltrating tumors. We found that the immune infiltrate composition changed at each tumor stage and that particular cells had a major impact on survival. Densities of T follicular helper (Tfh) cells and innate cells increased, whereas most T cell densities decreased along with tumor progression. The number of B cells, which are key players in the core immune network and are associated with prolonged survival, increased at a late stage and showed a dual effect on recurrence and tumor progression. The immune control relevance was demonstrated in three endoscopic orthotopic colon-cancer mouse models. Genomic instability of the chemokine CXCL13 was a mechanism associated with Tfh and B cell infiltration. CXCL13 and IL21 were pivotal factors for the Tfh/B cell axis correlating with survival. This integrative study reveals the immune landscape in human colorectal cancer and the major hallmarks of the microenvironment associated with tumor progression and recurrence. PMID:24138885

  2. 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

  3. 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

  4. Cytokines and antitumor immunity.

    PubMed

    Müller, Ludmila; Pawelec, Graham

    2003-06-01

    Currently, the notion of immunosurveillance against tumors is enjoying something of a renaissance. Even if we still refuse to accept that tumors arising in the normal host are unable to trigger an immune response because of the lack of initiation ("danger") signals, there is no doubt that the immune system can be manipulated experimentally and by implication therapeutically to exert anti-tumor effects. For this activity to be successful, the appropriate cytokine milieu has to be provided, making cytokine manipulation central to immunotherapy. On the other hand, the major hurdle currently preventing successful immunotherapy is the ability of tumors to evolve resistant variants under the pressure of immune selection. Here, too, the cytokine milieu plays an essential role. The purpose of this brief review is to consider the current status of the application of cytokines in facilitating antitumor immunity, as well their role in inhibiting responses to tumors. Clearly, encouraging the former but preventing the latter will be the key to the effective clinical application of cancer immunotherapy. PMID:12779349

  5. Immunizations - general overview

    MedlinePlus

    ... to a very small, very safe amount of viruses or bacteria that have been weakened or killed. Your immune system then learns to recognize and attack the infection if you are exposed to it later in life. As a result, you will not become ill, ...

  6. 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.

  7. 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…

  8. Dioxin and immune regulation

    PubMed Central

    Marshall, Nikki B.; Kerkvliet, Nancy I.

    2014-01-01

    The immune toxicity of the ubiquitous environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to as dioxin, has been studied for over 35 years but only recently has the profound immune suppression induced by TCDD exposure been linked to induction of regulatory T cells (Tregs). The effects of TCDD are mediated through its binding to the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor. The subsequent AHR-dependent effects on immune responses are determined by the cell types involved, their activation status, and the type of antigenic stimulus. Collectively, studies indicate that TCDD inhibits CD4+ T cell differentiation into T helper (Th)1, Th2, and Th17 effector cells, while inducing Foxp3-negative and/or preserving Foxp3+ Tregs. Although it is not yet clear how activation of AHR by TCDD induces Tregs, there is a potential therapeutic role for alternative AHR ligands in the treatment of immune-mediated disorders. PMID:20146706

  9. 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.

  10. Epidemic processes with immunization

    NASA Astrophysics Data System (ADS)

    Jiménez-Dalmaroni, Andrea; Hinrichsen, Haye

    2003-09-01

    We study a model of directed percolation (DP) with immunization, i.e., with different probabilities for the first infection and subsequent infections. The immunization effect leads to an additional non-Markovian term in the corresponding field theoretical action. We consider immunization as a small perturbation around the DP fixed point in d<6, where the non-Markovian term is relevant. The immunization causes the system to be driven away from the neighborhood of the DP critical point. In order to investigate the dynamical critical behavior of the model, we consider the limits of low and high first-infection rate, while the second-infection rate remains constant at the DP critical value. Scaling arguments are applied to obtain an expression for the survival probability in both limits. The corresponding exponents are written in terms of the critical exponents for ordinary DP and DP with a wall. We find that the survival probability does not obey a power-law behavior, decaying instead as a stretched exponential in the low first-infection probability limit and to a constant in the high first-infection probability limit. The theoretical predictions are confirmed by optimized numerical simulations in 1+1 dimensions.

  11. Increasing immunization coverage.

    PubMed

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

    2010-06-01

    In 1977, the American Academy of Pediatrics issued a statement calling for universal immunization of all children for whom vaccines are not contraindicated. In 1995, the policy statement "Implementation of the Immunization Policy" was published by the American Academy of Pediatrics, followed in 2003 with publication of the first version of this statement, "Increasing Immunization Coverage." Since 2003, there have continued to be improvements in immunization coverage, with progress toward meeting the goals set forth in Healthy People 2010. Data from the 2007 National Immunization Survey showed that 90% of children 19 to 35 months of age have received recommended doses of each of the following vaccines: inactivated poliovirus (IPV), measles-mumps-rubella (MMR), varicella-zoster virus (VZB), hepatitis B virus (HBV), and Haemophilus influenzae type b (Hib). For diphtheria and tetanus and acellular pertussis (DTaP) vaccine, 84.5% have received the recommended 4 doses by 35 months of age. Nevertheless, the Healthy People 2010 goal of at least 80% coverage for the full series (at least 4 doses of DTaP, 3 doses of IPV, 1 dose of MMR, 3 doses of Hib, 3 doses of HBV, and 1 dose of varicella-zoster virus vaccine) has not yet been met, and immunization coverage of adolescents continues to lag behind the goals set forth in Healthy People 2010. Despite these encouraging data, a vast number of new challenges that threaten continued success toward the goal of universal immunization coverage have emerged. These challenges include an increase in new vaccines and new vaccine combinations as well as a significant number of vaccines currently under development; a dramatic increase in the acquisition cost of vaccines, coupled with a lack of adequate payment to practitioners to buy and administer vaccines; unanticipated manufacturing and delivery problems that have caused significant shortages of various vaccine products; and the rise of a public antivaccination movement that uses the

  12. 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...

  13. Innate immune memory in plants.

    PubMed

    Reimer-Michalski, Eva-Maria; Conrath, Uwe

    2016-08-01

    The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. PMID:27264335

  14. 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 ...

  15. 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

  16. 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

  17. The role of immune mechanisms in Tourette syndrome.

    PubMed

    Martino, Davide; Zis, Panagiotis; Buttiglione, Maura

    2015-08-18

    Tourette syndrome (TS) is a childhood-onset tic disorder associated with abnormal development of brain networks involved in the sensory and motor processing. An involvement of immune mechanisms in its pathophysiology has been proposed. Animal models based on active immunization with bacterial or viral mimics, direct injection of cytokines or patients' serum anti-neuronal antibodies, and transgenic approaches replicated stereotyped behaviors observed in human TS. A crucial role of microglia in the neural-immune crosstalk within TS and related disorders has been proposed by animal models and confirmed by recent post mortem studies. With analogy to autism, genetic and early life environmental factors could foster the involvement of immune mechanisms to the abnormal developmental trajectories postulated in TS, as well as lead to systemic immune dysregulation in this condition. Clinical studies demonstrate an association between TS and immune responses to pathogens like group A Streptococcus (GAS), although their role as risk-modifiers is still undefined. Overactivity of immune responses at a systemic level is suggested by clinical studies exploring cytokine and immunoglobulin levels, immune cell subpopulations, and gene expression profiling of peripheral lymphocytes. The involvement of autoantibodies, on the other hand, remains uncertain and warrants more work using live cell-based approaches. Overall, a body of evidence supports the hypothesis that disease mechanisms in TS, like other neurodevelopmental illnesses (e.g. autism), may involve dysfunctional neural-immune cross-talk, ultimately leading to altered maturation of brain pathways controlling different behavioral domains and, possibly, differences in organising immune and stress responses. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:24845720

  18. 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. PMID:27146556

  19. 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

  20. 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.

  1. Innate and adaptive immunity at Mucosal Surfaces of the Female Reproductive Tract: Stratification and Integration of Immune Protection against the Transmission of Sexually Transmitted Infections

    PubMed Central

    Hickey, DK; Patel, MV; Fahey, JV; Wira, CR

    2011-01-01

    This review examines the multiple levels of pre-existing immunity in the upper and lower female reproductive tract. In addition, we highlight the need for further research of innate and adaptive immune protection of mucosal surfaces in the female reproductive tract. Innate mechanisms include the mucus lining, a tight epithelial barrier and the secretion of antimicrobial peptides and cytokines by epithelial and innate immune cells. Stimulation of the innate immune system also serves to bridge the adaptive arm resulting in the generation of pathogen-specific humoral and cell-mediated immunity. Less understood are the multiple components that act in a coordinated way to provide a network of ongoing protection. Innate and adaptive immunity in the human female reproductive tract are influenced by the stage of menstrual cycle and are directly regulated by the sex steroid hormones, progesterone and estradiol. Furthermore, the effect of hormones on immunity is mediated both directly on immune and epithelial cells and indirectly by stimulating growth factor secretion from stromal cells. The goal of this review is to focus on the diverse aspects of the innate and adaptive immune systems that contribute to a unique network of protection throughout the female reproductive tract. PMID:21353708

  2. The danger is growing! A new paradigm for immune system activation and peripheral tolerance.

    PubMed

    Bewick, Sharon; Yang, Ruoting; Zhang, Mingjun

    2009-01-01

    Successful immune defense is a complex balancing act. In order to protect a host against invasion by harmful pathogens, an immune response must be rapid and vigorous, and must eliminate foreign invaders before their populations grow beyond control. That same immune response, however, must be selective enough to recognize and ignore commensal bacteria, environmental antigens and host tissue itself. How the immune system makes the crucial decision whether or not to attack a particular antigen has been a long-standing question central to the study of immunology. Here we show that the structure of the signaling network between regulatory T-cells and type 17 helper T-cells allows the immune system to selectively attack pathogens based on whether or not the pathogens represent a growing, and thus dangerous population. We term this mechanism for immune system activation the 'Growth Detection Paradigm', because it offers an entirely new explanation for immune system regulation and peripheral tolerance. PMID:19956616

  3. Adaptive immune resistance: How cancer protects from immune attack

    PubMed Central

    Ribas, Antoni

    2015-01-01

    Adaptive immune resistance is a process where the cancer changes its phenotype in response to a cytotoxic or pro-inflammatory immune response, thereby evading it. This adaptive process is triggered by the specific recognition of cancer cells by T cells, which leads to the production of immune-activating cytokines. Cancers then hijack mechanisms developed to limit inflammatory and immune responses and protect themselves from the T cell attack. Inhibiting adaptive immune resistance is the mechanistic basis of responses to PD-1 or PD-L1 blocking antibodies, and may be of relevance for the development of other cancer immunotherapy strategies. PMID:26272491

  4. 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.

  5. Synthetic RORγt Agonists Enhance Protective Immunity.

    PubMed

    Chang, Mi Ra; Dharmarajan, Venkatasubramanian; Doebelin, Christelle; Garcia-Ordonez, Ruben D; Novick, Scott J; Kuruvilla, Dana S; Kamenecka, Theodore M; Griffin, Patrick R

    2016-04-15

    The T cell specific RORγ isoform RORγt has been shown to be the key lineage-defining transcription factor to initiate the differentiation program of TH17 and TC17 cells, cells that have demonstrated antitumor efficacy. RORγt controls gene networks that enhance immunity including increased IL17 production and decreased immune suppression. Both synthetic and putative endogenous agonists of RORγt have been shown to increase the basal activity of RORγt enhancing TH17 cell proliferation. Here, we show that activation of RORγt using synthetic agonists drives proliferation of TH17 cells while decreasing levels of the immune checkpoint protein PD-1, a mechanism that should enhance antitumor immunity while blunting tumor associated adaptive immune resistance. Interestingly, putative endogenous agonists drive proliferation of TH17 cells but do not repress PD-1. These findings suggest that synthetic agonists of RORγt should activate TC17/TH17 cells (with concomitant reduction in the Tregs population), repress PD-1, and produce IL17 in situ (a factor associated with good prognosis in cancer). Enhanced immunity and blockage of immune checkpoints has transformed cancer treatment; thus such a molecule would provide a unique approach for the treatment of cancer. PMID:26785144

  6. 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

  7. 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

  8. 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.

  9. Humoral immunity in bronchiectasis.

    PubMed

    Barker, A F; Craig, S; Bardana, E J

    1987-09-01

    Bronchiectasis occurs in patients with immunodeficiency and fungal hypersensitivity disorders. To assess the prevalence of abnormal humoral immune parameters in bronchiectasis, a retrospective study was carried out on sera from 30 patients. Studies included immunoglobulin quantitation and specific antibody to fungal species. Eleven patients were found to have immunodeficiency (nine with panhypoglobulinemia and two with selective IgM deficiency). Six patients had elevations of serum IgA and four patients had elevations of serum IgE. Six patients had elevated total antibody to Aspergillus or Candida species and six had precipitin bands to one or more fungal antigens. This study indicates that immunodeficiency is prevalent and plays a causative role in some patients with bronchiectasis. Hypersensitivity reactions to Aspergillus, Candida, and other ubiquitous environmental fungi may also play an etiopathogenic role in this disease (bronchiectasis, humoral immunity, immunodeficiency). PMID:3631652

  10. Effector triggered immunity

    PubMed Central

    Rajamuthiah, Rajmohan; Mylonakis, Eleftherios

    2014-01-01

    Pathogenic bacteria produce virulence factors called effectors, which are important components of the infection process. Effectors aid in pathogenesis by facilitating bacterial attachment, pathogen entry into or exit from the host cell, immunoevasion, and immunosuppression. Effectors also have the ability to subvert host cellular processes, such as hijacking cytoskeletal machinery or blocking protein translation. However, host cells possess an evolutionarily conserved innate immune response that can sense the pathogen through the activity of its effectors and mount a robust immune response. This “effector triggered immunity” (ETI) was first discovered in plants but recent evidence suggest that the process is also well conserved in metazoans. We will discuss salient points of the mechanism of ETI in metazoans from recent studies done in mammalian cells and invertebrate model hosts. PMID:25513770

  11. Immunization Strategies Against Henipaviruses

    PubMed Central

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

    2015-01-01

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

  12. 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

  13. 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

  14. Update on global immunization.

    PubMed

    Weber, Carol J

    2007-10-01

    The international community recognizes that investing in the health development of poor and disadvantaged countries is central to reducing poverty. Immunization is one strategy in the global effort to reduce infant mortality, improve maternal health, and combat infectious disease. In this day of global interdependence, all countries are vulnerable to uncontrolled spread of disease through epidemics. Achieving the Millennium Development Goals will not only help developing countries, but it will also contribute to improving health and security for all. PMID:17990623

  15. 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.

  16. Brucella evasion of adaptive immunity.

    PubMed

    Martirosyan, Anna; Gorvel, Jean-Pierre

    2013-02-01

    The complex immune system of mammals is the result of evolutionary forces that include battles against pathogens, as sensing and defeating intruders is a prerequisite to host survival. On the other hand, microorganisms have evolved multiple mechanisms to evade both arms of immunity: the innate and the adaptive immune systems. The successful pathogenic intracellular bacterium Brucella is not an exception to the rule: Brucella displays mechanisms that allow evasion of immune surveillance in order to establish persistent infections in mammals. In this review, we highlight some key mechanisms that pathogenic Brucella use to evade the adaptive immune system. PMID:23374122

  17. Pentraxins in humoral innate immunity.

    PubMed

    Inforzato, Antonio; Bottazzi, Barbara; Garlanda, Cecilia; Valentino, Sonia; Mantovani, Alberto

    2012-01-01

    Innate immunity represents the first line of defence against pathogens and plays key roles in activation and orientation of the adaptive immune response. The innate immune system comprises both a cellular and a humoral arm. Components of the humoral arm include soluble pattern recognition molecules (PRMs) that recognise pathogens associated molecular patterns (PAMPs) and initiate the immune response in coordination with the cellular arm, therefore acting as functional ancestors of antibodies. The long pentraxin PTX3 is a prototypic soluble PRM that is produced at sites of infection and inflammation by both somatic and immune cells. Gene targeting of this evolutionarily conserved protein has revealed a non-redundant role in resistance to selected pathogens. Moreover, PTX3 exerts important functions at the crossroad between innate immunity, inflammation and female fertility. Here we review the studies on PTX3, with emphasis on pathogen recognition and crosstalk with other components of the innate immune system. PMID:21948359

  18. Ocular Immune Privilege and Transplantation

    PubMed Central

    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. PMID:26904026

  19. 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. PMID:25384142

  20. A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.

    PubMed

    Kumar, Sanjeev; Molina-Cruz, Alvaro; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina

    2010-03-26

    Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses. PMID:20223948

  1. Addressing Immunization Registry Population Inflation in Adolescent Immunization Rates

    PubMed Central

    2015-01-01

    Objective While U.S. adolescent immunization rates are available annually at national and state levels, finding pockets of need may require county or sub-county information. Immunization information systems (IISs) are one tool for assessing local immunization rates. However, the presence of IIS records dating back to early childhood and challenges in capturing mobility out of IIS areas typically leads to denominator inflation. We examined the feasibility of weighting adolescent immunization records by length of time since last report to produce more accurate county adolescent counts and immunization rates. Methods We compared weighted and unweighted adolescent denominators from the Oregon ALERT IIS, along with county-level Census Bureau estimates, with school enrollment counts from Oregon's annual review of seventh-grade school immunization compliance for public and private schools. Adolescent immunization rates calculated using weighted data, for the state as a whole, were also checked against comparable National Immunization Survey (NIS) rates. Results Weighting individual records by the length of time since last activity substantially improved the fit of IIS data to county populations for adolescents. A nonlinear logarithmic (ogive) weight produced the best fit to the school count data of all examined estimates. Overall, the ogive weighted results matched NIS adolescent rates for Oregon. Conclusion The problem of mobility-inflated counts of teenagers can be addressed by weighting individual records based on time since last immunization. Well-populated IISs can rely on their own data to produce adolescent immunization rates and find pockets of need. PMID:25729105

  2. Exercise, nutrition and immune function.

    PubMed

    Gleeson, Michael; Nieman, David C; Pedersen, Bente K

    2004-01-01

    Strenuous bouts of prolonged exercise and heavy training are associated with depressed immune cell function. Furthermore, inadequate or inappropriate nutrition can compound the negative influence of heavy exertion on immunocompetence. Dietary deficiencies of protein and specific micronutrients have long been associated with immune dysfunction. An adequate intake of iron, zinc and vitamins A, E, B6 and B12 is particularly important for the maintenance of immune function, but excess intakes of some micronutrients can also impair immune function and have other adverse effects on health. Immune system depression has also been associated with an excess intake of fat. To maintain immune function, athletes should eat a well-balanced diet sufficient to meet their energy requirements. An athlete exercising in a carbohydrate-depleted state experiences larger increases in circulating stress hormones and a greater perturbation of several immune function indices. Conversely, consuming 30-60 g carbohydrate x h(-1) during sustained intensive exercise attenuates rises in stress hormones such as cortisol and appears to limit the degree of exercise-induced immune depression. Convincing evidence that so-called 'immune-boosting' supplements, including high doses of antioxidant vitamins, glutamine, zinc, probiotics and Echinacea, prevent exercise-induced immune impairment is currently lacking. PMID:14971437

  3. Passive Immunization Against Poliomyelitis

    PubMed Central

    Rinaldo, Charles R.

    2005-01-01

    Poliomyelitis has gone from being one of the worst scourges of the 20th century to nearing eradication in the 21st. This success is well known to be attributable to the Salk inactivated and Sabin attenuated poliovirus vaccines. However, before introduction of these vaccines, William McDowall Hammon of the University of Pittsburgh Graduate School of Public Health led the first major breakthrough in prevention of the disease by using passive immunization in one of the earliest double-blind, placebo-controlled clinical trials. This study provided the first evidence that antibodies to poliovirus could prevent the disease in humans. PMID:15855454

  4. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    PubMed

    Su, Fei; Patel, Girishchandra B; Hu, Songhua; Chen, Wangxue

    2016-04-01

    Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity. PMID:26752023

  5. Identification and Validation of Ifit1 as an Important Innate Immune Bottleneck

    SciTech Connect

    McDermott, Jason E.; Vartanian, Keri B.; Mitchell, Hugh D.; Stevens, S.L.; Sanfilippo, Antonio P.; Stenzel-Poore, Mary

    2012-06-20

    The innate immune system plays important roles in a number of disparate processes. Foremost, innate immunity is a first responder to invasion by pathogens and triggers early defensive responses and recruits the adaptive immune system. The innate immune system also responds to endogenous damage signals that arise from tissue injury. Recently it has been found that innate immunity plays an important role in neuroprotection against ischemic stroke through the activation of the primary innate immune receptors, Toll-like receptors (TLRs). Using several large-scale transcriptomic data sets from mouse and mouse macrophage studies we identified targets predicted to be important in controlling innate immune processes initiated by TLR activation. Targets were identified as genes with high betweenness centrality, so-called bottlenecks, in networks inferred from statistical associations between gene expression patterns. A small set of putative bottlenecks were identified in each of the data sets investigated including interferon-stimulated genes (Ifit1, Ifi47, Tgtp and Oasl2) as well as genes uncharacterized in immune responses (Axud1 and Ppp1r15a). We further validated one of these targets, Ifit1, in mouse macrophages by showing that silencing it suppresses induction of predicted downstream genes by lipopolysaccharide (LPS)-mediated TLR4 activation through an unknown direct or indirect mechanism. Our study demonstrates the utility of network analysis for identification of interesting targets related to innate immune function, and highlights that Ifit1 can exert a positive regulatory effect on downstream genes.

  6. Immune Privilege of Corneal Allografts

    PubMed Central

    Niederkorn, Jerry Y.; Larkin, D. Frank P.

    2013-01-01

    Corneal transplantation has been performed successfully for over 100 years. Normally, HLA typing and systemic immunosuppressive drugs are not utilized, yet 90% of corneal allografts survive. In rodents, corneal allografts representing maximal histoincompatibility enjoy >50% survival even without immunosuppressive drugs. By contrast, other categories of transplants are invariably rejected in such donor/host combinations. The acceptance of corneal allografts compared to other categories of allografts is called immune privilege. The cornea expresses factors that contribute to immune privilege by preventing the induction and expression of immune responses to histocompatibility antigens on the corneal allograft. Among these are soluble and cell membrane molecules that block immune effector elements and also apoptosis of T lymphocytes. However, some conditions rob the corneal allograft of its immune privilege and promote rejection, which remains the leading cause of corneal allograft failure. Recent studies have examined new strategies for restoring immune privilege to such high-risk hosts. PMID:20482389

  7. Immune Aspects of Female Infertility

    PubMed Central

    Brazdova, Andrea; Senechal, Helene; Peltre, Gabriel; Poncet, Pascal

    2016-01-01

    Immune infertility, in terms of reproductive failure, has become a serious health issue involving approximately 1 out of 5 couples at reproductive age. Semen that is defined as a complex fluid containing sperm, cellular vesicles and other cells and components, could sensitize the female genital tract. The immune rejection of male semen in the female reproductive tract is explained as the failure of natural tolerance leading to local and/or systemic immune response. Present active immune mechanism may induce high levels of anti-seminal/sperm antibodies. It has already been proven that iso-immunization is associated with infertility. Comprehensive studies with regards to the identification of antibody-targets and the determination of specific antibody class contribute to the development of effective immuno-therapy and, on the other hand, potential immuno-contraception, and then of course to complex patient diagnosis. This review summarizes the aspects of female immune infertility. PMID:27123194

  8. Hyperthyroidism and immune thrombocytopenia.

    PubMed Central

    Jacobs, P.; Majoos, F.; Perrotta, A.

    1984-01-01

    Hyperthyroidism and immune thrombocytopenia occurred concurrently in five patients; in a sixth, thyrotoxicosis developed after successful treatment of the thrombocytopenia. Correction of the hyperthyroidism was followed by a variable pattern of clinical response. In one case with mild asymptomatic thrombocytopenia spontaneous complete remission occurred. Two patients required adrenocorticosteroids to control severe thrombocytopenic purpura during the period of hyperthyroidism, after which complete remission occurred. Another patient with severe symptomatic thrombocytopenia remains with a partially compensated thrombocytolytic state but is without purpura and off all therapy. A fifth patient required splenectomy for drug-resistant thrombocytopenia and remains critically dependent on immunosuppressive therapy. The sixth patient had a relapse of immune thrombocytopenia with subsequent development of thyrotoxicosis but platelet count spontaneously returned to normal after correction of the hyperthyroidism. Pregnancy in two of these six patients was not associated with recurrence of either hyperthyroidism or thrombocytopenia. Management of symptomatic purpura in adults with co-existent hyperthyroidism may differ from that customarily employed since adrenocorticosteroid therapy may need to be extended until euthyroidism has been established before proceeding to splenectomy. When surgery is necessary, the risk of thyrotoxic storm should be anticipated, and the patient appropriately premedicated. PMID:6494085

  9. Immune interactions in endometriosis

    PubMed Central

    Herington, Jennifer L; Bruner-Tran, Kaylon L; Lucas, John A; Osteen, Kevin G

    2011-01-01

    Endometriosis is a common, complex gynecologic disorder characterized by the presence of endometrial glands and stroma at extrauterine (ectopic) sites. In women who develop this disease, alterations in specific biological processes involving both the endocrine and immune systems have been observed, which may explain the survival and growth of displaced endometrial tissue in affected women. In the past decade, a considerable amount of research has implicated a role for alterations in progesterone action at both eutopic and ectopic sites of endometrial growth which may contribute to the excessive inflammation associated with progression of endometriosis; however, it remains unclear whether these anomalies induce the condition or are simply a consequence of the disease process. In this article, we summarize current knowledge of alterations within the immune system of endometriosis patients and discuss how endometrial cells from women with this disease not only have the capacity to escape immunosurveillance, but also use inflammatory mechanisms to promote their growth within the peritoneal cavity. Finally, we discuss evidence that exposure to an environmental endocrine disruptor, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin, can mediate the development of an endometrial phenotype that exhibits both reduced progesterone responsiveness and hypersensitivity to proinflammatory stimuli mimicking the endometriosis phenotype. Future studies in women with endometriosis should consider whether a heightened inflammatory response within the peritoneal microenvironment contributes to the development and persistence of this disease. PMID:21895474

  10. Protective immunity against plague.

    PubMed

    Cornelius, Claire; Quenee, Lauriane; Anderson, Deborah; Schneewind, Olaf

    2007-01-01

    Plague, an infectious disease that reached catastrophic proportions during three pandemics, continues to be a legitimate public health concern worldwide. Although antibiotic therapy for the causative agent Yersinia pestis is available, pharmaceutical supply limitations, multi-drug resistance from natural selection as well as malicious bioengineering are a reality. Consequently, plague vaccinology is a priority for biodefense research. Development of a multi-subunit vaccine with Fraction 1 and LcrV as protective antigens seems to be receiving the most attention. However, LcrV has been shown to cause immune suppression and Y. pestis mutants lacking F1 expression are thought to be fully virulent in nature and in animal experiments. The LcrV variant, rV10, retains the well documented protective antigenic properties of LcrV but with diminished inhibitory effects on the immune system. More research is required to examine the molecular mechanisms of vaccine protection afforded by surface protein antigens and to decipher the host mechanisms responsible for vaccine success. PMID:17966437

  11. Immune thrombocytopenia and pregnancy

    PubMed Central

    Sankaran, Srividhya; Robinson, Susan E

    2011-01-01

    Immune thrombocytopenia (ITP) is not infrequently encountered during reproductive years with an estimated incidence of 0.1–1 per 1000 pregnancies. An international consensus group recently re-defined ITP and outlined standardized response criteria and up-to-date investigation and management. The pathogenesis encompasses autoantibody platelet destruction and immune-mediated decreased platelet production. Maternal antibodies may cross the placenta and have the potential to cause fetal and/or neonatal thrombocytopenia. The diagnosis and subsequent management of ITP in pregnancy requires a multidisciplinary approach involving the midwife, obstetrician, haematologist and anaesthetist. Women with ITP diagnosed prior to pregnancy should receive preconception counselling to outline potential treatments and provide information regarding expected maternal and neonatal outcome. Management prior to 36 weeks aims to avoid treatment in the absence of bleeding and ensure an acceptable platelet count for planned procedures. At 34–36 weeks, women are generally reviewed to consider whether a tailored course of treatment is required in preparation for delivery. Further research is required to determine a suitable platelet count for neuraxial anaesthesia. The mode of delivery should be guided by obstetric indication. It is pertinent to consider both the risk of maternal bleeding and thrombosis in maternal ITP. The risk of neonatal intracranial haemorrhage in association with ITP is less than 1%. Postpartum a cord blood platelet count should be checked. Additional management is dependent upon the neonatal platelet count. Data collection using the new standardized terminology should provide robust comparable epidemiological data regarding ITP in pregnancy.

  12. Chemokines and immunity

    PubMed Central

    Palomino, Diana Carolina Torres; Marti, Luciana Cavalheiro

    2015-01-01

    Chemokines are a large family of small cytokines and generally have low molecular weight ranging from 7 to 15kDa. Chemokines and their receptors are able to control the migration and residence of all immune cells. Some chemokines are considered pro-inflammatory, and their release can be induced during an immune response at a site of infection, while others are considered homeostatic and are involved in controlling of cells migration during tissue development or maintenance. The physiologic importance of this family of mediators is resulting from their specificity − members of the chemokine family induce recruitment of well-defined leukocyte subsets. There are two major chemokine sub-families based upon cysteine residues position: CXC and CC. As a general rule, members of the CXC chemokines are chemotactic for neutrophils, and CC chemokines are chemotactic for monocytes and sub-set of lymphocytes, although there are some exceptions. This review discusses the potential role of chemokines in inflammation focusing on the two best-characterized chemokines: monocyte chemoattractant protein-1, a CC chemokine, and interleukin-8, a member of the CXC chemokine sub-family. PMID:26466066

  13. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  14. Marathon training and immune function.

    PubMed

    Nieman, David C

    2007-01-01

    Many components of the immune system exhibit adverse change after marathon-type exertion. These immune changes occur in several compartments of the immune system and body (e.g. the skin, upper respiratory tract mucosal tissue, lung, peritoneal cavity, blood and muscle). Of all immune cells, natural killer (NK) cells, neutrophils and macrophages (of the innate immune system) exhibit the greatest changes in response to marathon competition, both in terms of numbers and function. Many mechanisms appear to be involved, including exercise-induced changes in stress hormone and cytokine concentrations, body temperature changes, increases in blood flow and dehydration. During this 'open window' of immune dysfunction (which may last between 3 and 72 hours, depending on the immune measure), viruses and bacteria may gain a foothold, increasing the risk of subclinical and clinical infection. Of the various nutritional and pharmacological countermeasures to marathon-induced immune perturbations that have been evaluated thus far, ingestion of carbohydrate beverages during intense and prolonged exercise has emerged as the most effective. However, carbohydrate ingestion during a marathon attenuates increases in plasma cytokines and stress hormones, but is largely ineffective against changes in other immune components including suppression of NK and T-cell function, and salivary IgA output. Other countermeasures, such as glutamine, antioxidant supplements and ibuprofen, have had disappointing results and thus the search for companion agents to carbohydrate continues. PMID:17465622

  15. Ubiquitin signaling in immune responses

    PubMed Central

    Hu, Hongbo; Sun, Shao-Cong

    2016-01-01

    Ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological processes, including different aspects of immune functions. Ubiquitination regulates pattern-recognition receptor signaling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Ubiquitination also regulates the development, activation, and differentiation of T cells, thereby maintaining efficient adaptive immune responses to pathogens and immunological tolerance to self-tissues. Like phosphorylation, ubiquitination is a reversible reaction tightly controlled by the opposing actions of ubiquitin ligases and deubiquitinases. Deregulated ubiquitination events are associated with immunological disorders, including autoimmune and inflammatory diseases. PMID:27012466

  16. Ensuring excellence in immunization services.

    PubMed

    MacDonald, Pauline

    2016-01-01

    In order to increase uptake of measles, mumps and rubella (MMR) vaccine, a domiciliary immunization service was established in Dudley primary care trust in England in 2010. Parents of unimmunized children were offered vaccines at home. Uptake of MMR vaccine among 2 year olds rose from 89% in 2007/08 to 96.9% in 2015. Children were also given any other outstanding immunizations. The domiciliary immunization service reached vulnerable unimmunized children who may otherwise have remained unprotected against life threatening childhood illnesses. Domiciliary immunization service was set up in 2010 to reduce inequalities in uptake of MMR vaccine among children aged between 2 and 5 years. PMID:26618244

  17. Host Resistance and Immune Aging.

    PubMed

    Bandaranayake, Thilinie; Shaw, Albert C

    2016-08-01

    Human immune system aging results in impaired responses to pathogens or vaccines. In the innate immune system, which mediates the earliest pro-inflammatory responses to immunologic challenge, processes ranging from Toll-like Receptor function to Neutrophil Extracellular Trap formation are generally diminished in older adults. Dysregulated, enhanced basal inflammation with age reflecting activation by endogenous damage-associated ligands contributes to impaired innate immune responses. In the adaptive immune system, T and B cell subsets and function alter with age. The control of cytomegalovirus infection, particularly in the T lineage, plays a dominant role in the differentiation and diversity of the T cell compartment. PMID:27394014

  18. Innate Immune Recognition of EBV.

    PubMed

    Lünemann, Anna; Rowe, Martin; Nadal, David

    2015-01-01

    The ability of Epstein-Barr virus (EBV) to establish latency despite specific immune responses and to successfully persist lifelong in the human host shows that EBV has developed powerful strategies and mechanisms to exploit, evade, abolish, or downsize otherwise effective immune responses to ensure its own survival. This chapter focuses on current knowledge on innate immune responses against EBV and its evasion strategies for own benefit and summarizes the questions that remain to be tackled. Innate immune reactions against EBV originate both from the main target cells of EBV and from nontarget cells, which are elements of the innate immune system. Thus, we structured our review accordingly but with a particular focus on the innate recognition of EBV in its two stages in its life cycle, latent state and lytic replication. Specifically, we discuss (I) innate sensing and resulting innate immune responses against EBV by its main target cells, focusing on (i) EBV transmission between epithelial cells and B cells and their life cycle stages; and (ii) elements of innate immunity in EBV's target cells. Further, we debate (II) the innate recognition and resulting innate immune responses against EBV by cells other than the main target cells, focusing on (iii) myeloid cells: dendritic cells, monocytes, macrophages, and neutrophil granulocytes; and (iv) natural killer cells. Finally, we address (III) how EBV counteracts or exploits innate immunity in its latent and lytic life cycle stages, concentrating on (v) TLRs; (vi) EBERs; and (vii) microRNAs. PMID:26428378

  19. The microbiome and innate immunity.

    PubMed

    Thaiss, Christoph A; Zmora, Niv; Levy, Maayan; Elinav, Eran

    2016-07-01

    The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host-microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases. PMID:27383981

  20. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease

    PubMed Central

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD. PMID:26900473

  1. SUMO-Enriched Proteome for Drosophila Innate Immune Response

    PubMed Central

    Handu, Mithila; Kaduskar, Bhagyashree; Ravindranathan, Ramya; Soory, Amarendranath; Giri, Ritika; Elango, Vijay Barathi; Gowda, Harsha; Ratnaparkhi, Girish S.

    2015-01-01

    Small ubiquitin-like modifier (SUMO) modification modulates the expression of defense genes in Drosophila, activated by the Toll/nuclear factor-κB and immune-deficient/nuclear factor-κB signaling networks. We have, however, limited understanding of the SUMO-modulated regulation of the immune response and lack information on SUMO targets in the immune system. In this study, we measured the changes to the SUMO proteome in S2 cells in response to a lipopolysaccharide challenge and identified 1619 unique proteins in SUMO-enriched lysates. A confident set of 710 proteins represents the immune-induced SUMO proteome and analysis suggests that specific protein domains, cellular pathways, and protein complexes respond to immune stress. A small subset of the confident set was validated by in-bacto SUMOylation and shown to be bona-fide SUMO targets. These include components of immune signaling pathways such as Caspar, Jra, Kay, cdc42, p38b, 14-3-3ε, as well as cellular proteins with diverse functions, many being components of protein complexes, such as prosß4, Rps10b, SmD3, Tango7, and Aats-arg. Caspar, a human FAF1 ortholog that negatively regulates immune-deficient signaling, is SUMOylated at K551 and responds to treatment with lipopolysaccharide in cultured cells. Our study is one of the first to describe SUMO proteome for the Drosophila immune response. Our data and analysis provide a global framework for the understanding of SUMO modification in the host response to pathogens. PMID:26290570

  2. Centrality measures for networks with community structure

    NASA Astrophysics Data System (ADS)

    Gupta, Naveen; Singh, Anurag; Cherifi, Hocine

    2016-06-01

    Understanding the network structure, and finding out the influential nodes is a challenging issue in large networks. Identifying the most influential nodes in a network can be useful in many applications like immunization of nodes in case of epidemic spreading, during intentional attacks on complex networks. A lot of research is being done to devise centrality measures which could efficiently identify the most influential nodes in a network. There are two major approaches to this problem: On one hand, deterministic strategies that exploit knowledge about the overall network topology, while on the other end, random strategies are completely agnostic about the network structure. Centrality measures that can deal with a limited knowledge of the network structure are of prime importance. Indeed, in practice, information about the global structure of the overall network is rarely available or hard to acquire. Even if available, the structure of the network might be too large that it is too much computationally expensive to calculate global centrality measures. To that end, a centrality measure is proposed here that requires information only at the community level. Indeed, most of the real-world networks exhibit a community structure that can be exploited efficiently to discover the influential nodes. We performed a comparative evaluation of prominent global deterministic strategies together with stochastic strategies, an available and the proposed deterministic community-based strategy. Effectiveness of the proposed method is evaluated by performing experiments on synthetic and real-world networks with community structure in the case of immunization of nodes for epidemic control.

  3. Mosquito Immunity against Arboviruses

    PubMed Central

    Sim, Shuzhen; Jupatanakul, Natapong; Dimopoulos, George

    2014-01-01

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

  4. An Immunization Education Program for Childcare Providers

    ERIC Educational Resources Information Center

    Hayney, Mary S.; Bartell, Julie C.

    2005-01-01

    The childhood immunization schedule includes at least 17 scheduled immunizations prior to the age of 24 months. Immunization laws require childcare centers to maintain immunization records and enforce immunization standards for children who attend these centers. Childcare providers generally receive little formal education about infectious…

  5. Nutrition and immunity in ruminant animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The immune system can be generally separated into three broad components; natural immunity, innate immunity, and acquired immunity, all of which must be fully developed and functioning properly to provide adequate immunological protection. Natural and innate immunity are typically grouped together u...

  6. Plain Talk about Childhood Immunizations.

    ERIC Educational Resources Information Center

    Alaska State Dept. of Health and Social Services, Juneau. Div. of Family and Youth Services.

    This booklet provides parents with information about immunizations and vaccine-preventable diseases, balances the benefits and risk of vaccination, and responds to inaccuracies or misinformation about immunizations and vaccine-preventable diseases. Section 1 presents a message to parents about vaccination. Section 2 offers facts about…

  7. Recommendations for Institutional Prematriculation Immunizations

    ERIC Educational Resources Information Center

    Journal of American College Health, 2006

    2006-01-01

    The "Recommendations for Institutional Prematriculation Immunizations" described in this article are provided to colleges and universities to facilitate the implementation of a comprehensive institutional prematriculation immunization policy. In response to changing epidemiology and the introduction of new vaccines, the American College Health…

  8. Questions of Mind Over Immunity.

    ERIC Educational Resources Information Center

    Bower, Bruce

    1991-01-01

    Discussed is the possibility of disturbed immunity among people experiencing either clinical depression or some type of severe stress. Psychoneuroimmunology, the study of psychological treatment and its ability to shore up a person's immunity and slow the spread of infectious disease, is reviewed. (KR)

  9. Regulation of innate immune cell function by mTOR.

    PubMed

    Weichhart, Thomas; Hengstschläger, Markus; Linke, Monika

    2015-10-01

    The innate immune system is central for the maintenance of tissue homeostasis and quickly responds to local or systemic perturbations by pathogenic or sterile insults. This rapid response must be metabolically supported to allow cell migration and proliferation and to enable efficient production of cytokines and lipid mediators. This Review focuses on the role of mammalian target of rapamycin (mTOR) in controlling and shaping the effector responses of innate immune cells. mTOR reconfigures cellular metabolism and regulates translation, cytokine responses, antigen presentation, macrophage polarization and cell migration. The mTOR network emerges as an integrative rheostat that couples cellular activation to the environmental and intracellular nutritional status to dictate and optimize the inflammatory response. A detailed understanding of how mTOR metabolically coordinates effector responses by myeloid cells will provide important insights into immunity in health and disease. PMID:26403194

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

    PubMed

    Mocchegiani, Eugenio; Malavolta, Marco

    2008-01-01

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

  11. Complement - a key system for immune surveillance and homeostasis

    PubMed Central

    Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D.

    2010-01-01

    Nearly a century after the significance of the human complement system was recognized we have come to realize that its versatile functions extend far beyond the elimination of microbes. Indeed, complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses, and sending `danger' signals, complement contributes substantially to homeostasis, but it may also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure, and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its dual role in homeostasis and disease. PMID:20720586

  12. Plant Innate Immunity Multicomponent Model.

    PubMed

    Andolfo, Giuseppe; Ercolano, Maria R

    2015-01-01

    Our understanding of plant-pathogen interactions is making rapid advances in order to address issues of global importance such as improving agricultural productivity and sustainable food security. Innate immunity has evolved in plants, resulting in a wide diversity of defense mechanisms adapted to specific threats. The postulated PTI/ETI model describes two perception layers of plant innate immune system, which belong to a first immunity component of defense response activation. To better describe the sophisticated defense system of plants, we propose a new model of plant immunity. This model considers the plant's ability to distinguish the feeding behavior of their many foes, such as a second component that modulates innate immunity. This hypothesis provides a new viewpoint highlighting the relevance of hormone crosstalk and primary metabolism in regulating plant defense against the different behaviors of pathogens with the intention to stimulate further interest in this research area. PMID:26617626

  13. Immune Mechanisms in Myelodysplastic Syndrome.

    PubMed

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner; Hadrup, Sine Reker; O'Connell, Casey; Grønbæk, Kirsten

    2016-01-01

    Myelodysplastic syndrome (MDS) is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients-especially younger low-risk patients with HLA-DR15 tissue type-demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS. PMID:27314337

  14. Melatonin: Buffering the Immune System

    PubMed Central

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  15. Immune Mechanisms in Myelodysplastic Syndrome

    PubMed Central

    Glenthøj, Andreas; Ørskov, Andreas Due; Hansen, Jakob Werner; Hadrup, Sine Reker; O’Connell, Casey; Grønbæk, Kirsten

    2016-01-01

    Myelodysplastic syndrome (MDS) is a spectrum of diseases, characterized by debilitating cytopenias and a propensity of developing acute myeloid leukemia. Comprehensive sequencing efforts have revealed a range of mutations characteristic, but not specific, of MDS. Epidemiologically, autoimmune diseases are common in patients with MDS, fueling hypotheses of common etiological mechanisms. Both innate and adaptive immune pathways are overly active in the hematopoietic niche of MDS. Although supportive care, growth factors, and hypomethylating agents are the mainstay of MDS treatment, some patients—especially younger low-risk patients with HLA-DR15 tissue type—demonstrate impressive response rates after immunosuppressive therapy. This is in contrast to higher-risk MDS patients, where several immune activating treatments, such as immune checkpoint inhibitors, are in the pipeline. Thus, the dual role of immune mechanisms in MDS is challenging, and rigorous translational studies are needed to establish the value of immune manipulation as a treatment of MDS. PMID:27314337

  16. Plant Innate Immunity Multicomponent Model

    PubMed Central

    Andolfo, Giuseppe; Ercolano, Maria R.

    2015-01-01

    Our understanding of plant–pathogen interactions is making rapid advances in order to address issues of global importance such as improving agricultural productivity and sustainable food security. Innate immunity has evolved in plants, resulting in a wide diversity of defense mechanisms adapted to specific threats. The postulated PTI/ETI model describes two perception layers of plant innate immune system, which belong to a first immunity component of defense response activation. To better describe the sophisticated defense system of plants, we propose a new model of plant immunity. This model considers the plant’s ability to distinguish the feeding behavior of their many foes, such as a second component that modulates innate immunity. This hypothesis provides a new viewpoint highlighting the relevance of hormone crosstalk and primary metabolism in regulating plant defense against the different behaviors of pathogens with the intention to stimulate further interest in this research area. PMID:26617626

  17. Overview of the Immune Response

    PubMed Central

    Chaplin, David D.

    2010-01-01

    The immune system has evolved to protect the host from a universe of pathogenic microbes that are themselves constantly evolving. The immune system also helps the host eliminate toxic or allergenic substances that enter through mucosal surfaces. Central to the immune system’s ability to mobilize a response to an invading pathogen, toxin or allergen is its ability to distinguish self from non-self. The host uses both innate and adaptive mechanisms to detect and eliminate pathogenic microbes. Both of these mechanisms include self-nonself discrimination. This overview identifies key mechanisms used by the immune system to respond to invading microbes and other exogenous threats and identifies settings in which disturbed immune function exacerbates tissue injury. PMID:20176265

  18. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica

    PubMed Central

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782

  19. Trained immunity: A smart way to enhance innate immune defence.

    PubMed

    van der Meer, Jos W M; Joosten, Leo A B; Riksen, Niels; Netea, Mihai G

    2015-11-01

    The innate arm of the immune system is generally viewed as primitive and non-specific and - in contrast to the adaptive immune arm - not to possess memory. However in plants and invertebrate animals that lack adaptive immunity, innate immunity will exhibit a prolonged enhanced functional state after adequate priming. A similar enhancement of function of the innate immunity has occasionally been described in vertebrates, including humans. Over the past few years we have studied this phenomenon in greater detail and we have coined the term 'Trained (innate) immunity' (TI). TI can be induced by a variety of stimuli, of which we have studied BCG and β-glucan in greater detail. The non-specific protective effects of BCG that have been observed in vaccination studies in the literature are probably due to TI. Monocytes and macrophages are among the main cells of the innate immune arm that can be trained. We have discovered that both BCG (via NOD2 signalling) and β-glucan (via dectin-1) induce epigenetic reprogramming, in particular stable changes in histone trimethylation at H3K4. These epigenetic changes lead to cellular activation, enhanced cytokine production and a change in the metabolic state of the cell with a shift from oxidative phosphorylation to aerobic glycolysis. TI is not only important for host defence and vaccine responses, but most probably also for diseases like atherosclerosis. Modulation of TI is a promising area for new treatments. PMID:26597205

  20. Immune Response of Amebiasis and Immune Evasion by Entamoeba histolytica.

    PubMed

    Nakada-Tsukui, Kumiko; Nozaki, Tomoyoshi

    2016-01-01

    Entamoeba histolytica is a protozoan parasite and the causative agent of amebiasis. It is estimated approximately 1% of humans are infected with E. histolytica, resulting in an estimate of 100,000 deaths annually. Clinical manifestations of amebic infection range widely from asymptomatic to severe symptoms, including dysentery and extra-intestinal abscesses. Like other infectious diseases, it is assumed that only ~20% of infected individuals develop symptoms, and genetic factors of both the parasite and humans as well as the environmental factors, e.g., microbiota, determine outcome of infection. There are multiple essential steps in amebic infection: degradation of and invasion into the mucosal layer, adherence to the intestinal epithelium, invasion into the tissues, and dissemination to other organs. While the mechanisms of invasion and destruction of the host tissues by the amebae during infection have been elucidated at the molecular levels, it remains largely uncharacterized how the parasite survive in the host by evading and attacking host immune system. Recently, the strategies for immune evasion by the parasite have been unraveled, including immunomodulation to suppress IFN-γ production, elimination of immune cells and soluble immune mediators, and metabolic alterations against reactive oxygen and nitrogen species to fend off the attack from immune system. In this review, we summarized the latest knowledge on immune reaction and immune evasion during amebiasis. PMID:27242782