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Sample records for adverse immune response

  1. Evidence Report: Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Sams, Clarence F.

    2013-01-01

    The Risk of Crew Adverse Health Event Due to Altered Immune Response is identified by the National Aeronautics and Space Administration (NASA) Human Research Program (HRP) as a recognized risk to human health and performance in space. The HRP Program Requirements Document (PRD) defines these risks. This Evidence Report provides a summary of the evidence that has been used to identify and characterize this risk. It is known that human immune function is altered in- and post-flight, but it is unclear at present if such alterations lead to increased susceptibility to disease. Reactivation of latent viruses has been documented in crewmembers, although this reactivation has not been directly correlated with immune changes or with observed diseases. As described in this report, further research is required to better characterize the relationships between altered immune response and susceptibility to disease during and after spaceflight. This is particularly important for future deep-space exploration missions.

  2. Management of immune-related adverse events and kinetics of response with ipilimumab.

    PubMed

    Weber, Jeffrey S; Kähler, Katharina C; Hauschild, Axel

    2012-07-20

    Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy. PMID:22614989

  3. 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 ...

  4. Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects

    PubMed Central

    Long, Michelle; Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.

    2013-01-01

    In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years. PMID:22190130

  5. 2013 Immune Risk Standing Review Panel Evidence Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on February 3-4, 2014. The SRP reviewed the new Evidence Report for the Risk of Crew Adverse Health Event Due to Altered Immune Response (from here on referred to as the 2013 Immune Evidence Report), as well as the Research Plan for this Risk that is in the current version of the Human Research Program’s (HRP) Integrated Research Plan (IRP).

  6. Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Kunz, Hawley; Sams, Clarence F.

    2015-01-01

    Determining the effect of space travel on the human immune system has proven to be extremely challenging. Limited opportunities for in-flight studies, varying mission durations, technical and logistical obstacles, small subject numbers, and a broad range of potential assays have contributed to this problem. Additionally, the inherent complexity of the immune system, with its vast array of cell populations, sub-populations, diverse regulatory molecules, and broad interactions with other physiological systems, makes determining precise variables to measure very difficult. There is also the challenge of determining the clinical significance of any observed immune alterations. Will such a change lead to disease, or is it a transient subclinical observation related to short-term stress? The effect of this problem may be observed by scanning publications associated with immunity and spaceflight, which began to appear during the 1970s. Although individually they are each valid studies, the comprehensive literature to date suffers from widely varying sampling methods and assay techniques, low subject counts, and sometimes a disparate focus on narrow aspects of immunity. The most clinically relevant data are derived from in-flight human studies, which have demonstrated altered cell-mediated immunity and reactivation of latent herpes viruses. Much more data are available from post-flight testing of humans, with clear evidence of altered cytokine production patterns, altered leukocyte distribution, continued latent viral reactivation, and evidence of dramatically altered virus-specific immunity. It is unknown if post-flight assessments relate to the in-flight condition or are a response to landing stress and readaptation. In-flight culture of cells has clearly demonstrated that immune cells are gravity-sensitive and display altered functional characteristics. It is unknown if these data are related to in vivo immune cell function or are an artifact of microgravity culture

  7. 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 ...

  8. 2013 Immune Risk Standing Review Panel Research Plan Review for: The Risk of Crew Adverse Health Event Due to Altered Immune Response

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    The 2013 Immune Risk Standing Review Panel (from here on referred to as the SRP) participated in a meeting with representatives from the Human Research Program (HRP) Human Health Countermeasures (HHC) Element and HRP management on February 3-4, 2014 in Houston, TX to review the updated Research Plan for the Risk of Crew Adverse Health Event Due to Altered Immune Response in the HRP Integrated Research Plan. The SRP is impressed with the work the immune discipline has done since the 2012 SRP review and agrees with the new wording of the Gaps, no longer questions, now statements. The SRP also likes the addition of adding targets for closing the Gaps, but it is not clear how they got to some of the interim stages (interval percentages). A major concern that the SRP has mentioned since the initial 2009 SRP meeting is that there is still not enough emphasis on the interdisciplinary aspect of the immune risk associated with other risks (i.e., nutrition, radiation, etc.). The SRP recommends that a "translational SRP" or advisory group be developed that is composed of members from all of the HRP SRPs. The SRP also thinks that the immune discipline should consider a more systems biology approach. Lastly, the SRP is concerned that the risks observed in research from low Earth orbit (LEO) missions may not accurately reflect all the risks of longer duration flight beyond LEO. Also, there does not seem to be a concern for immune responses that may occur when someone is in space longer than six months, for example, a Mars mission would take three years. The absence of disease in past and current flight scenarios does not mean the risk may not be there in future flight settings.

  9. The agr Inhibitors Solonamide B and Analogues Alter Immune Responses to Staphylococccus aureus but Do Not Exhibit Adverse Effects on Immune Cell Functions.

    PubMed

    Baldry, Mara; Kitir, Betül; Frøkiær, Hanne; Christensen, Simon B; Taverne, Nico; Meijerink, Marjolein; Franzyk, Henrik; Olsen, Christian A; Wells, Jerry M; Ingmer, Hanne

    2016-01-01

    Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure-function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization. PMID:26731096

  10. The agr Inhibitors Solonamide B and Analogues Alter Immune Responses to Staphylococccus aureus but Do Not Exhibit Adverse Effects on Immune Cell Functions

    PubMed Central

    Baldry, Mara; Kitir, Betül; Frøkiær, Hanne; Christensen, Simon B.; Taverne, Nico; Meijerink, Marjolein; Franzyk, Henrik; Olsen, Christian A.; Wells, Jerry M.; Ingmer, Hanne

    2016-01-01

    Staphylococcus aureus infections are becoming increasingly difficult to treat due to antibiotic resistance with the community-associated methicillin-resistant S. aureus (CA-MRSA) strains such as USA300 being of particular concern. The inhibition of bacterial virulence has been proposed as an alternative approach to treat multi-drug resistant pathogens. One interesting anti-virulence target is the agr quorum-sensing system, which regulates virulence of CA-MRSA in response to agr-encoded autoinducing peptides. Agr regulation confines exotoxin production to the stationary growth phase with concomitant repression of surface-expressed adhesins. Solonamide B, a non-ribosomal depsipeptide of marine bacterial origin, was recently identified as a putative anti-virulence compound that markedly reduced expression of α-hemolysin and phenol-soluble modulins. To further strengthen solonamide anti-virulence candidacy, we report the chemical synthesis of solonamide analogues, investigation of structure–function relationships, and assessment of their potential to modulate immune cell functions. We found that structural differences between solonamide analogues confer significant differences in interference with agr, while immune cell activity and integrity is generally not affected. Furthermore, treatment of S. aureus with selected solonamides was found to only marginally influence the interaction with fibronectin and biofilm formation, thus addressing the concern that application of compounds inducing an agr-negative state may have adverse interactions with host factors in favor of host colonization. PMID:26731096

  11. Immune-Related Adverse Events From Immune Checkpoint Inhibitors.

    PubMed

    Marrone, K A; Ying, W; Naidoo, J

    2016-09-01

    Immunotherapy for cancer treatment has come of age, specifically with the use of immune checkpoint antibodies directed against molecules such as CTLA-4, PD-1, and PD-L1. Single-agent and combinatorial approaches utilizing these agents and other immunotherapies that may enhance antitumor effects are under investigation. With increasing clinical use of these agents, an appreciation for their toxicities comes to the fore. Adverse events that occur as a result of the immunologic effects of these therapies are termed "immune-related adverse events" (irAEs), and range in both frequency and severity in reported single-agent and combination studies. Improvements in our understanding of how and why irAEs develop and how to effectively manage them are needed. Herein we provide a state-of-the-art synopsis of the incidence, clinical features, mechanisms, and management of selected irAEs with immune checkpoint inhibitors currently in use. PMID:27170616

  12. Managing Adverse Events With Immune Checkpoint Agents.

    PubMed

    Dadu, Ramona; Zobniw, Chrystia; Diab, Adi

    2016-01-01

    Immune checkpoint inhibitors (anti-cytotoxic T-lymphocyte antigen 4 and anti programmed cell death 1/programmed cell death 1 ligand antibodies) have shown impressive clinical activity in multiple cancer types. Despite achieving great clinical success, challenges and limitations of these drugs as monotherapy or various combinational strategies include the development of a unique set of immune-related adverse events (irAEs) that can be severe and even fatal. Therefore, identification of patients at risk, prevention, consistent communication between patients and medical team, rapid recognition, and treatment of irAEs are critical in optimizing treatment outcomes. This review focuses on the description of more common irAEs and provides a suggested approach for management of specific irAEs. PMID:27111908

  13. 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: ...

  14. 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 ...

  15. 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

  16. Consumer reporting of adverse events following immunization

    PubMed Central

    Clothier, Hazel J; Selvaraj, Gowri; Easton, Mee Lee; Lewis, Georgina; Crawford, Nigel W; Buttery, Jim P

    2014-01-01

    Surveillance of adverse events following immunisation (AEFI) is an essential component of vaccine safety monitoring. The most commonly utilized passive surveillance systems rely predominantly on reporting by health care providers (HCP). We reviewed adverse event reports received in Victoria, Australia since surveillance commencement in July 2007, to June 2013 (6 years) to ascertain the contribution of consumer (vaccinee or their parent/guardian) reporting to vaccine safety monitoring and to inform future surveillance system development directions. Categorical data included were: reporter type; serious and non-serious AEFI category; and, vaccinee age group. Chi-square test and 2-sample test of proportions were used to compare categories; trend changes were assessed using linear regression. Consumer reporting increased over the 6 years, reaching 21% of reports received in 2013 (P <0.001), most commonly for children aged less than 7 years. Consumer reports were 5% more likely to describe serious AEFI than HCP (P = 0.018) and 10% more likely to result in specialist clinic attendance (P <0.001). Although online reporting increased to 32% of all report since its introduction in 2010, 85% of consumers continued to report by phone. Consumer reporting of AEFI is a valuable component of vaccine safety surveillance in addition to HCP reporting. Changes are required to AEFI reporting systems to implement efficient consumer AEFI reporting, but may be justified for their potential impact on signal detection sensitivity. PMID:25483686

  17. Exposure to residual concentrations of elements from a remediated coal fly ash spill does not adversely influence stress and immune responses of nestling tree swallows

    PubMed Central

    Beck, Michelle L.; Hopkins, William A.; Hallagan, John J.; Jackson, Brian P.; Hawley, Dana M.

    2014-01-01

    Anthropogenic activities often produce pollutants that can affect the physiology, growth and reproductive success of wildlife. Many metals and trace elements play important roles in physiological processes, and exposure to even moderately elevated concentrations of essential and non-essential elements could have subtle effects on physiology, particularly during development. We examined the effects of exposure to a number of elements from a coal fly ash spill that occurred in December 2008 and has since been remediated on the stress and immune responses of nestling tree swallows. We found that nestlings at the site of the spill had significantly greater blood concentrations of Cu, Hg, Se and Zn in 2011, but greater concentrations only of Se in 2012, in comparison to reference colonies. The concentrations of elements were below levels of significant toxicological concern in both years. In 2011, we found no relationship between exposure to elements associated with the spill and basal or stress-induced corticosterone concentrations in nestlings. In 2012, we found that Se exposure was not associated with cell-mediated immunity based on the response to phytohaemagglutinin injection. However, the bactericidal capacity of nestling plasma had a positive but weak association with blood Se concentrations, and this association was stronger at the spill site. Our results indicate that exposure to these low concentrations of elements had few effects on nestling endocrine and immune physiology. The long-term health consequences of low-level exposure to elements and of exposure to greater element concentrations in avian species require additional study. PMID:27293639

  18. A review of adverse events caused by immune checkpoint inhibitors.

    PubMed

    Fukushima, Satoshi

    2016-01-01

      There has been no effective therapy in the unresectable melanoma for more than 40 years. Anti-PD-1 antibody and anti-CTLA-4 antibody have totally changed the situation. They have clearly shown the survival benefits of the patients with metastatic melanoma. However, immune checkpoint inhibitors sometimes induce various kinds of immune-related adverse events (irAEs). It is very important for the clinicians to know the reported cases of irAEs and to keep in mind the symptoms of irAEs for the early detection. This review describes the previously reported irAEs and adequate managements for irAEs induced by immune checkpoint inhibitors. PMID:27181232

  19. An approach to death as an adverse event following immunization.

    PubMed

    Gold, Michael S; Balakrishnan, Madhava Ram; Amarasinghe, Ananda; MacDonald, Noni E

    2016-01-01

    Co-incidental death occurring proximate to vaccination may be reported as an adverse event following immunization. Such events are particularly concerning because they may raise community and health provider concerns about the safety of the specific vaccine and often the immunization programme in general. Coincidental events need to be differentiated from vaccine reactions, such as anaphylaxis, which may very rarely result in death. In 2013, the World Health Organization (WHO) released an updated manual for the Causality Assessment of an AEFI. The purpose of this review is to apply the WHO causality methodology to death when this is reported as an AEFI. The causality assessment scheme recommends a four step process to enable classification of the AEFI and to differentiate events which are causally consistent from those that are inconsistent with immunization. However, for some events causality maybe indeterminate. Consistent causal reactions that may result in death are very rare and maybe related to the vaccine product (e.g. anaphylaxis, viscerotrophic disease), vaccine quality defect (e.g. an incompletely attenuated live vaccine agent) or an immunization error (e.g. vaccine vial contamination). Events that are inconsistent with immunizations are due to co-incidental conditions that may account for infant and childhood mortality. In countries with a high infant mortality rate the coincidental occurrence of death and immunization may occur not infrequently and a robust mechanism to obtain information from autopsy and perform an AEFI investigation and causality assessment is essential. Communication with the community and all stakeholders to maintain confidence in the immunization programme is critical. PMID:26608326

  20. 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

  1. Diversity Against Adversity: How Adaptive Immune System Evolves Potent Antibodies

    NASA Astrophysics Data System (ADS)

    Heo, Muyoung; Zeldovich, Konstantin B.; Shakhnovich, Eugene I.

    2011-07-01

    Adaptive immunity is an amazing mechanism, whereby new protein functions—affinity of antibodies (Immunoglobulins) to new antigens—evolve through mutation and selection in a matter of a few days. Despite numerous experimental studies, the fundamental physical principles underlying immune response are still poorly understood. In considerable departure from past approaches, here, we propose a microscopic multiscale model of adaptive immune response, which consists of three essential players: The host cells, viruses, and B-cells in Germinal Centers (GC). Each moiety carries a genome, which encodes proteins whose stability and interactions are determined from their sequences using laws of Statistical Mechanics, providing an exact relationship between genomic sequences and strength of interactions between pathogens and antibodies and antibodies and host proteins (autoimmunity). We find that evolution of potent antibodies (the process known as Affinity Maturation (AM)) is a delicate balancing act, which has to reconcile the conflicting requirements of protein stability, lack of autoimmunity, and high affinity of antibodies to incoming antigens. This becomes possible only when antibody producing B cells elevate their mutation rates (process known as Somatic Hypermutation (SHM)) to fall into a certain range—not too low to find potency increasing mutations but not too high to destroy stable Immunoglobulins and/or already achieved affinity. Potent antibodies develop through clonal expansion of initial B cells expressing marginally potent antibodies followed by their subsequent affinity maturation through mutation and selection. As a result, in each GC the population of mature potent Immunoglobulins is monoclonal being ancestors of a single cell from initial (germline) pool. We developed a simple analytical theory, which provides further rationale to our findings. The model and theory reveal the molecular factors that determine the efficiency of affinity maturation

  2. Adverse neuro-immune-endocrine interactions in patients with active tuberculosis.

    PubMed

    Bottasso, Oscar; Bay, María Luisa; Besedovsky, Hugo; Del Rey, Adriana

    2013-03-01

    The nervous, endocrine and immune systems play a crucial role in maintaining homeostasis and interact with each other for a successful defensive strategy against injurious agents. However, the situation is different in long-term diseases with marked inflammation, in which defensive mechanisms become altered. In the case of tuberculosis (TB), this is highlighted by several facts: an imbalance of plasma immune and endocrine mediators, that results in an adverse environment for mounting an adequate response against mycobacteria and controlling inflammation; the demonstration that dehidroepiandrosterone (DHEA) secretion by a human adrenal cell line can be inhibited by culture supernatants from Mycobacterium tuberculosis-stimulated peripheral blood mononuclear cells - PBMC - of TB patients, with this effect being partly reverted when neutralizing transforming growth factor-β in such supernantants; the in vitro effects of adrenal steroids on the specific immune response of PBMC from TB patients, that is a cortisol inhibition of mycobacterial antigen-driven lymphoproliferation and interferon-γ production as well as a suppression of TGF-β production in DHEA-treated PBMC; and lastly the demonstration that immune and endocrine compounds participating in the regulation of energy sources and immune activity correlated with the consumption state of TB patients. Collectively, immune-endocrine disturbances of TB patients are involved in critical components of disease pathology with implications in the impaired clinical status and unfavorable disease outcome. This article is part of a Special Issue entitled 'Neuroinflammation in neurodegeneration and neurodysfunction'. PMID:23147110

  3. 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

  4. Algorithm to assess causality after individual adverse events following immunizations.

    PubMed

    Halsey, Neal A; Edwards, Kathryn M; Dekker, Cornelia L; Klein, Nicola P; Baxter, Roger; Larussa, Philip; Marchant, Colin; Slade, Barbara; Vellozzi, Claudia

    2012-08-24

    Assessing individual reports of adverse events following immunizations (AEFI) can be challenging. Most published reviews are based on expert opinions, but the methods and logic used to arrive at these opinions are neither well described nor understood by many health care providers and scientists. We developed a standardized algorithm to assist in collecting and interpreting data, and to help assess causality after individual AEFI. Key questions that should be asked during the assessment of AEFI include: Is the diagnosis of the AEFI correct? Does clinical or laboratory evidence exist that supports possible causes for the AEFI other than the vaccine in the affected individual? Is there a known causal association between the AEFI and the vaccine? Is there strong evidence against a causal association? Is there a specific laboratory test implicating the vaccine in the pathogenesis? An algorithm can assist with addressing these questions in a standardized, transparent manner which can be tracked and reassessed if additional information becomes available. Examples in this document illustrate the process of using the algorithm to determine causality. As new epidemiologic and clinical data become available, the algorithm and guidelines will need to be modified. Feedback from users of the algorithm will be invaluable in this process. We hope that this algorithm approach can assist with educational efforts to improve the collection of key information on AEFI and provide a platform for teaching about causality assessment. PMID:22507656

  5. 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.

  6. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  7. Childhood adversity increases vulnerability for behavioral symptoms and immune dysregulation in women with breast cancer

    PubMed Central

    Witek Janusek, Linda; Tell, Dina; Albuquerque, Kevin; Mathews, Herbert L.

    2012-01-01

    Women respond differentially to the stress-associated with breast cancer diagnosis and treatment, with some women experiencing more intense and/or sustained behavioral symptoms and immune dysregulation than others. Childhood adversity has been identified to produce long-term dysregulation of stress response systems, increasing reactivity to stressors encountered during adulthood. This study determined whether childhood adversity increased vulnerability for more intense and sustained behavioral symptoms (fatigue, perceived stress, and depressive symptoms), poorer quality of life, and greater immune dysregulation in women (N=40) with breast cancer. Evaluation was after breast surgery and through early survivorship. Hierarchical linear modeling was used to examine intra-individual and inter-individual differences with respect to initial status and to the pattern of change (i.e. trajectory) of outcomes. At initial assessment, women exposed to childhood emotional neglect/abuse had greater perceived stress, fatigue, depressive symptoms and poorer quality of life, as well as lower natural killer cell activity (NKCA). Although these outcomes improved over time, women with greater childhood emotional neglect/abuse exhibited worse outcomes through early survivorship. No effect was observed on the trajectory for these outcomes. In contrast, childhood physical neglect predicted sustained trajectories of greater perceived stress, worse quality of life, and elevated plasma IL-6; with no effect observed at initial assessment. Thus, childhood adversity leaves an enduring imprint, increasing vulnerability for behavioral symptoms, poor quality of life, and elevations in IL-6 in women with breast cancer. Further, childhood adversity predisposes to lower NKCA at a critical time when this immune-effector mechanism is most effective at halting nascent tumor seeding. PMID:22659062

  8. 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

  9. Immune responses to improving welfare.

    PubMed

    Berghman, L R

    2016-09-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that "increased vigilance of the immune system is by definition better" because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as "sickness behavior," includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  10. Immune response to H pylori

    PubMed Central

    Suarez, Giovanni; Reyes, Victor E; Beswick, Ellen J

    2006-01-01

    The gastric mucosa separates the underlying tissue from the vast array of antigens that traffic through the stomach lumen. While the extreme pH of this environment is essential in aiding the activation of enzymes and food digestion, it also renders the gastric epithelium free from bacterial colonization, with the exception of one important human pathogen, H pylori. This bacterium has developed mechanisms to survive the harsh environment of the stomach, actively move through the mucosal layer, attach to the epithelium, evade immune responses, and achieve persistent colonization. While a hallmark of this infection is a marked inflammatory response with the infiltration of various immune cells into the infected gastric mucosa, the host immune response is unable to clear the infection and may actually contribute to the associated pathogenesis. Here, we review the host responses involved during infection with H pylori and how they are influenced by this bacterium. PMID:17007009

  11. Physiology of the Immune Response

    PubMed Central

    Denburg, J. A.; Bienenstock, J.

    1979-01-01

    The established mechanisms of immune responsiveness to foreign or self components are reviewed, with particular reference to relevant clinical problems and current research. A multitiered immunological system of cellular and subcellular elements are involved when the body deals with perturbations from without or within. The concept exists that a delicate balance between positive ('helper') and negative ('suppressor') forces is essential to maintaining health. Brief discussion is given to diagnosis of immune abnormalities in the light of these facts. PMID:21297689

  12. Immune responses in space flight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.

    1998-01-01

    Space flight has been shown to have profound effects on immunological parameters of humans, monkeys and rodents. These studies have been carried out by a number of different laboratories. Among the parameters affected are leukocyte blastogenesis, natural killer cell activity, leukocyte subset distribution, cytokine production - including interferons and interleukins, and macrophage maturation and activity. These changes start to occur only after a few days space flight, and some changes continue throughout long-term space flight. Antibody responses have received only very limited study, and total antibody levels have been shown to be increased after long-term space flight. Several factors could be involved in inducing these changes. These factors could include microgravity, lack of load-bearing, stress, acceleration forces, and radiation. The mechanism(s) for space flight-induced changes in immune responses remain(s) to be established. Certainly, there can be direct effects of microgravity, or other factors, on cells that play a fundamental role in immune responses. However, it is now clear that there are interactions between the immune system and other physiological systems that could play a major role. For example, changes occurring in calcium use in the musculoskeletal system induced by microgravity or lack of use could have great impact on the immune system. Most of the changes in immune responses have been observed using samples taken immediately after return from space flight. However, there have been two recent studies that have used in-flight testing. Delayed-type hypersensitivity responses to common recall antigens of astronauts and cosmonauts have been shown to be decreased when tested during space flights. Additionally, natural killer cell and blastogenic activities are inhibited in samples taken from rats during space flight. Therefore, it is now clear that events occurring during space flight itself can affect immune responses. The biological

  13. A global survey of adverse event following immunization surveillance systems for pregnant women and their infants

    PubMed Central

    Cassidy, Christine; MacDonald, Noni E.; Steenbeek, Audrey; Ortiz, Justin R.; Zuber, Patrick L. F.; Top, Karina A.

    2016-01-01

    ABSTRACT Strengthening antenatal care as a platform for maternal immunization is a priority of the World Health Organization (WHO). Systematic surveillance for adverse events following immunization (AEFI) in pregnancy is needed to identify vaccine safety events. We sought to identify active and passive AEFI surveillance systems for pregnant women and infants. Representatives from all National Pharmacovigilance Centers and a convenience sample of vaccine safety experts were invited to complete a 14-item online survey in English, French or Spanish. The survey captured maternal immunization policies, and active and passive AEFI surveillance systems for pregnant women and infants in respondents' countries. The analysis was descriptive. We received responses from 51/185 (28%) invited persons from 47/148 (32%) countries representing all WHO regions, and low, middle and high-income countries. Thirty countries had national immunization policies targeting pregnant women. Eleven countries had active surveillance systems to detect serious AEFI in pregnant women and/or their infants, including six low and middle-income countries (LMIC). Thirty-nine countries had passive surveillance systems, including 23 LMIC. These active and passive surveillance programs cover approximately 8% and 56% of the worldwide annual birth cohort, respectively. Data from one active and four passive systems have been published. We identified 50 active and passive AEFI surveillance systems for pregnant women and infants, but few have published their findings. AEFI surveillance appears to be feasible in low and high resource settings. Further expansion of AEFI surveillance for pregnant women and sharing of vaccine safety information will provide additional evidence in support of maternal immunization policies. PMID:27159639

  14. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  15. Immune responses to improving welfare

    PubMed Central

    Berghman, L. R.

    2016-01-01

    The relationship between animal welfare and the immune status of an animal has a complex nature. Indeed, the intuitive notion that “increased vigilance of the immune system is by definition better” because it is expected to better keep the animal healthy, does not hold up under scrutiny. This is mostly due to the fact that the immune system consists of 2 distinct branches, the innate and the adaptive immune system. While they are intimately intertwined and synergistic in the living organism, they are profoundly different in their costs, both in terms of performance and wellbeing. In contrast to the adaptive immune system, the action of the innate immune system has a high metabolic cost as well as undesirable behavioral consequences. When a pathogen breaches the first line of defense (often a mucosal barrier), that organism's molecular signature is recognized by resident macrophages. The macrophages respond by releasing a cocktail of pro-inflammatory cytokines (including interleukin-1 and -6) that signal the brain via multiple pathways (humoral as well as neural) of the ongoing peripheral innate immune response. The behavioral response to the release of proinflammatory cytokines, known as “sickness behavior,” includes nearly all the behavioral aspects that are symptomatic for clinical depression in humans. Hence, undesired innate immune activity, such as chronic inflammation, needs to be avoided by the industry. From an immunological standpoint, one of the most pressing poultry industry needs is the refinement of our current veterinary vaccine arsenal. The response to a vaccine, especially to a live attenuated vaccine, is often a combination of innate and adaptive immune activities, and the desired immunogenicity comes at the price of high reactogenicity. The morbidity, albeit limited and transient, caused by live vaccines against respiratory diseases and coccidiosis are good examples. Thankfully, the advent of various post-genomics technologies, such as DNA

  16. Immune Responses in Hookworm Infections

    PubMed Central

    Loukas, Alex; Prociv, Paul

    2001-01-01

    Hookworms infect perhaps one-fifth of the entire human population, yet little is known about their interaction with our immune system. The two major species are Necator americanus, which is adapted to tropical conditions, and Ancylostoma duodenale, which predominates in more temperate zones. While having many common features, they also differ in several key aspects of their biology. Host immune responses are triggered by larval invasion of the skin, larval migration through the circulation and lungs, and worm establishment in the intestine, where adult worms feed on blood and mucosa while injecting various molecules that facilitate feeding and modulate host protective responses. Despite repeated exposure, protective immunity does not seem to develop in humans, so that infections occur in all age groups (depending on exposure patterns) and tend to be prolonged. Responses to both larval and adult worms have a characteristic T-helper type 2 profile, with activated mast cells in the gut mucosa, elevated levels of circulating immunoglobulin E, and eosinoophilia in the peripheral blood and local tissues, features also characteristic of type I hypersensitivity reactions. The longevity of adult hookworms is determined probably more by parasite genetics than by host immunity. However, many of the proteins released by the parasites seem to have immunomodulatory activity, presumably for self-protection. Advances in molecular biotechnology enable the identification and characterization of increasing numbers of these parasite molecules and should enhance our detailed understanding of the protective and pathogenetic mechanisms in hookworm infections. PMID:11585781

  17. Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

    PubMed

    Federico, Alessandro; Aitella, Ernesto; Sgambato, Dolores; Savoia, Alfonso; De Bartolomeis, Fabio; Dallio, Marcello; Ruocco, Eleonora; Pezone, Luciano; Abbondanza, Ciro; Loguercio, Carmela; Astarita, Corrado

    2015-01-01

    The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism. PMID:25864225

  18. Surviving Sepsis: Taming a Deadly Immune Response

    MedlinePlus

    ... disclaimer . Subscribe Surviving Sepsis Taming a Deadly Immune Response Many people have never heard of sepsis, or ... tract infection) and then a powerful and harmful response by your body’s own immune system . “With sepsis, ...

  19. Eosinophils in mucosal immune responses

    PubMed Central

    Travers, J; Rothenberg, M E

    2015-01-01

    Eosinophils, multifunctional cells that contribute to both innate and adaptive immunity, are involved in the initiation, propagation and resolution of immune responses, including tissue repair. They achieve this multifunctionality by expression of a diverse set of activation receptors, including those that directly recognize pathogens and opsonized targets, and by their ability to store and release preformed cytotoxic mediators that participate in host defense, to produce a variety of de novo pleotropic mediators and cytokines and to interact directly and indirectly with diverse cell types, including adaptive and innate immunocytes and structural cells. Herein, we review the basic biology of eosinophils and then focus on new emerging concepts about their role in mucosal immune homeostasis, particularly maintenance of intestinal IgA. We review emerging data about their development and regulation and describe new concepts concerning mucosal eosinophilic diseases. We describe recently developed therapeutic strategies to modify eosinophil levels and function and provide collective insight about the beneficial and detrimental functions of these enigmatic cells. PMID:25807184

  20. A genetic inference on cancer immune responsiveness

    PubMed Central

    Wang, Ena; Uccellini, Lorenzo; Marincola, Francesco M.

    2012-01-01

    A cancer immune signature implicating good prognosis and responsiveness to immunotherapy was described that is observed also in other aspects of immune-mediated, tissue-specific destruction (TSD). Its determinism remains, however, elusive. Based on limited but unique clinical observations, we propose a multifactorial genetic model of human cancer immune responsiveness. PMID:22754772

  1. Tilapia show immunization response against Ich

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study compares the immune response of Nile tilapia and red tilapia against parasite Ichthyophthirius multifiliis (Ich) using a cohabitation challenge model. Both Nile and red tilapia showed strong immune response post immunization with live Ich theronts by IP injection or immersion. Blood serum...

  2. Impact of Adverse Events Following Immunization in Viet Nam in 2013 on chronic hepatitis B infection.

    PubMed

    Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien

    2016-02-01

    Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine. PMID:26055296

  3. Immune response during space flight.

    PubMed

    Criswell-Hudak, B S

    1991-01-01

    The health status of an astronaut prior to and following space flight has been a prime concern of NASA throughout the Apollo series of lunar landings, Skylab, Apollo-Soyuz Test Projects (ASTP), and the new Spacelab-Shuttle missions. Both humoral and cellular immunity has been studied using classical clinical procedures. Serum proteins show fluctuations that can be explained with adaptation to flight. Conversely, cellular immune responses of lymphocytes appear to be depressed in both in vivo as well as in vitro. If this depression in vivo and in vitro is a result of the same cause, then man's adaptation to outer space living will present interesting challenges in the future. Since the cause may be due to reduced gravity, perhaps the designs of the experiments for space flight will offer insights at the cellular levels that will facilitate development of mechanisms for adaptation. Further, if the aging process is viewed as an adaptational concept or model and not as a disease process then perhaps space flight could very easily interact to supply some information on our biological time clocks. PMID:1915698

  4. NUTRITION AND THE AGING IMMUNE RESPONSE

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The incidence of neoplastic and infectious diseases is increased in the elderly, as is the resulting morbidity and mortality. The age-related changes of the immune response have mainly been reported for cell-mediated immune functions such as DTH skin response, antibody response to T cell-dependent a...

  5. Baby on board: do responses to stress in the maternal brain mediate adverse pregnancy outcome?

    PubMed

    Douglas, Alison J

    2010-07-01

    Stress and adverse environmental surroundings result in suboptimal conditions in a pregnant mother such that she may experience poor pregnancy outcome including complete pregnancy failure and preterm labor. Furthermore her developing baby is at risk of adverse programming, which confers susceptibility to long term ill health. While some mechanisms at the feto-maternal interface underlying these conditions are understood, the underlying cause for their adverse adaptation is often not clear. Progesterone plays a key role at many levels, including control of neuroendocrine responses to stress, procuring the required immune balance and controlling placental and decidual function, and lack of progesterone can explain many of the unwanted consequences of stress. How stress that is perceived by the mother inhibits progesterone secretion and action is beginning to be investigated. This overview of maternal neuroendocrine responses to stress throughout pregnancy analyses how they interact to compromise progesterone secretion and precipitate undesirable effects in mother and offspring. PMID:20546772

  6. Spaceflight and immune responses of Rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies indicates that alterations in immunological parameters occur after space flight. The objective of this project is to determine the effects of space flight on immune responses of Rhesus monkeys. The expected significance of the work is a determination of the range of immunological functions of the Rhesus monkey, a primate similar in many ways to man, affected by space flight. Changes in immune responses that could yield alterations in resistance to infection may be determined as well as the duration of alterations in immune responses. Additional information on the nature of cellular interactions for the generation of immune responses may also be obtained.

  7. Immune responses to infectious laryngotracheitis virus.

    PubMed

    Coppo, Mauricio J C; Hartley, Carol A; Devlin, Joanne M

    2013-11-01

    Infectious laryngotracheitis (ILT) is an upper respiratory tract disease in chickens caused by infectious laryngotracheitis virus (ILTV), an alphaherpesvirus. Despite the extensive use of attenuated, and more recently recombinant, vaccines for the control of this disease, ILT continues to affect the intensive poultry industries worldwide. Innate and cell-mediated, rather than humoral immune responses, have been identified as responsible for protection against disease. This review examines the current understandings in innate and adaptive immune responses towards ILTV, as well as the role of ILTV glycoprotein G in modulating the host immune response towards infection. Protective immunity induced by ILT vaccines is also examined. The increasing availability of tools and reagents for the characterisation of avian innate and cell-mediated immune responses are expected to further our understanding of immunity against ILTV and drive the development of new generation vaccines towards enhanced control of this disease. PMID:23567343

  8. Noninvasive imaging of immune responses

    PubMed Central

    Rashidian, Mohammad; Keliher, Edmund J.; Bilate, Angelina M.; Duarte, Joao N.; Wojtkiewicz, Gregory R.; Jacobsen, Johanne Tracey; Cragnolini, Juanjo; Swee, Lee Kim; Victora, Gabriel D.; Weissleder, Ralph; Ploegh, Hidde L.

    2015-01-01

    At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (VH) of a camelid heavy-chain only antibody] with 18F or 64Cu. Radiolabeled VHHs rapidly cleared the circulation (t1/2 ≈ 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund’s adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked. PMID:25902531

  9. Noninvasive imaging of immune responses.

    PubMed

    Rashidian, Mohammad; Keliher, Edmund J; Bilate, Angelina M; Duarte, Joao N; Wojtkiewicz, Gregory R; Jacobsen, Johanne Tracey; Cragnolini, Juanjo; Swee, Lee Kim; Victora, Gabriel D; Weissleder, Ralph; Ploegh, Hidde L

    2015-05-12

    At their margins, tumors often contain neutrophils, dendritic cells, and activated macrophages, which express class II MHC and CD11b products. The interplay between stromal cells, tumor cells, and migratory cells such as lymphocytes creates opportunities for noninvasive imaging of immune responses. We developed alpaca-derived antibody fragments specific for mouse class II MHC and CD11b products, expressed on the surface of a variety of myeloid cells. We validated these reagents by flow cytometry and two-photon microscopy to obtain images at cellular resolution. To enable noninvasive imaging of the targeted cell populations, we developed a method to site-specifically label VHHs [the variable domain (VH) of a camelid heavy-chain only antibody] with (18)F or (64)Cu. Radiolabeled VHHs rapidly cleared the circulation (t1/2 ≈ 20 min) and clearly visualized lymphoid organs. We used VHHs to explore the possibility of imaging inflammation in both xenogeneic and syngeneic tumor models, which resulted in detection of tumors with remarkable specificity. We also imaged the infiltration of myeloid cells upon injection of complete Freund's adjuvant. Both anti-class II MHC and anti-CD11b VHHs detected inflammation with excellent specificity. Given the ease of manufacture and labeling of VHHs, we believe that this method could transform the manner in which antitumor responses and/or infectious events may be tracked. PMID:25902531

  10. Pembrolizumab in a BRAF-mutant metastatic melanoma patient following a severe immune-related adverse event with ipilimumab.

    PubMed

    Aya, Francisco; Fernández-Martínez, Aranzazu; Gaba, Lydia; Victoria, Iván; Tosca, Mónica; Carrera, Cristina; Prat, Aleix; Arance, Ana

    2016-06-01

    Currently, limited data exist on the safety of pembrolizumab in patients with metastatic melanoma who have developed severe immune-related adverse events following treatment with ipilimumab. We report a 45-year-old male patient with BRAF-mutant metastatic melanoma who discontinued treatment with ipilimumab due to treatment-related grade 3 colitis and was subsequently treated with the anti-programmed cell death 1 protein (PD-1) antibody pembrolizumab. He has been on treatment with pembrolizumab for more than 20 months with no major toxicities and has achieved an objective partial response, which is ongoing. PMID:27115320

  11. 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

  12. Monitoring immune responses in the tumor microenvironment.

    PubMed

    Wargo, Jennifer A; Reddy, Sangeetha M; Reuben, Alexandre; Sharma, Padmanee

    2016-08-01

    Immune monitoring in the tumor microenvironment allows for important insights into immune mechanisms of response and resistance to various cancer treatments; however clinical challenges exist using current strategies. Significant questions remain regarding monitoring of archival versus fresh tissue, assessment of static versus dynamic markers, evaluation of limited tissue samples, and the translation of insights gained from immunologically 'hot' tumors such as melanoma to other 'cold' tumor microenvironments prevalent in other cancer types. Current and emerging immune monitoring strategies will be examined herein, and genomic-based assays complementing these techniques will also be discussed. Finally, host genomic and external environmental factors influencing anti-tumor immune responses will be considered, including the role of the gut microbiome. Though optimal immune monitoring techniques are in evolution, great promise exists in recent advances that will help guide patient selection as far as type, sequence, and combination of therapeutic regimens to enhance anti-tumor immunity and clinical responses. PMID:27240055

  13. An upside to adversity?: moderate cumulative lifetime adversity is associated with resilient responses in the face of controlled stressors.

    PubMed

    Seery, Mark D; Leo, Raphael J; Lupien, Shannon P; Kondrak, Cheryl L; Almonte, Jessica L

    2013-07-01

    Despite common findings suggesting that lack of negative life events should be optimal, recent work has revealed a curvilinear pattern, such that some cumulative lifetime adversity is instead associated with optimal well-being. This work, however, is limited in that responses to specific stressors as they occurred were not assessed, thereby precluding investigation of resilience. The current research addressed this critical gap by directly testing the relationship between adversity history and resilience to stressors. Specifically, we used a multimethod approach across two studies to assess responses to controlled laboratory stressors (respectively requiring passive endurance and active instrumental performance). Results revealed hypothesized U-shaped relationships: Relative to a history of either no adversity or nonextreme high adversity, a moderate number of adverse life events was associated with less negative responses to pain and more positive psychophysiological responses while taking a test. These results provide novel evidence in support of adversity-derived propensity for resilience that generalizes across stressors. PMID:23673992

  14. Protective host immune responses to Salmonella infection

    PubMed Central

    Pham, Oanh H; McSorley, Stephen J.

    2015-01-01

    Salmonella enterica serovars Typhi and Paratyphi are the causative agents of human typhoid fever. Current typhoid vaccines are ineffective and are not widely used in endemic areas. Greater understanding of host–pathogen interactions during Salmonella infection should facilitate the development of improved vaccines to combat typhoid and nontyphoidal Salmonellosis. This review will focus on our current understanding of Salmonella pathogenesis and the major host immune components that participate in immunity to Salmonella infection. In addition, recent findings regarding host immune mechanisms in response to Salmonella infection will be also discussed, providing a new perspective on the utility of improved tools to study the immune response to Salmonella infections. PMID:25598340

  15. Immune-Mediated Adverse Events Associated with Ipilimumab CTLA-4 Blockade Therapy: The Underlying Mechanisms and Clinical Management

    PubMed Central

    Tarhini, Ahmad

    2013-01-01

    Immunomodulation with the anti-CTLA-4 monoclonal antibody ipilimumab has been shown to extend overall survival (OS) in previously treated and treatment-naive patients with unresectable stage III or IV melanoma. Blockade of CTLA-4 signaling with ipilimumab prolongs T-cell activation and restores T-cell proliferation, thus amplifying T-cell-mediated immunity and the patient's capacity to mount an effective antitumor immune response. While this immunostimulation has unprecedented OS benefits in the melanoma setting, it can also result in immune-mediated effects on various organ systems, leading to immune-related adverse events (irAEs). Ipilimumab-associated irAEs are common and typically low grade and manageable, but can also be serious and life threatening. The skin and gastrointestinal tract are most frequently affected, while hepatic, endocrine, and neurologic events are less common. With proper management, most irAEs resolve within a relatively short time, with a predictable resolution pattern. Prompt and appropriate management of these irAEs is essential and treatment guidelines have been developed to assist oncologists and their teams. Implementation of these irAE management algorithms will help ensure that patients are able to benefit from ipilimumab therapy with adequate control of toxicities. PMID:24278787

  16. Correction of Adverse Response to Suxamethonium of Susceptible Pigs

    PubMed Central

    Lister, David

    1973-01-01

    The adverse response to suxamethonium in susceptible pigs has been shown to be associated with changes in serum free thyroxine index. Pyrexia and acidosis can be controlled by the cautious administration of L-triiodo-thyronine (T-3). Successful correction has been achieved in eight episodes, and in six of these, where it was intended, rapid, uneventful, and complete recovery occurred. ImagesFIG. 1FIG. 2 PMID:4686556

  17. Routine surveillance of adverse events following immunization as an important tool to monitor vaccine safety.

    PubMed

    Alicino, Cristiano; Merlano, Caterina; Zappettini, Simona; Schiaffino, Sergio; Della Luna, Giovanni; Accardo, Cristina; Gasparini, Roberto; Durando, Paolo; Icardi, Giancarlo

    2015-01-01

    Post licensure surveillance of adverse events following immunization (AEFI) is a fundamental activity to improve safety and maintain public confidence in vaccines.   Since 2011, the Liguria Region has been involved in the inter-regional project of post-marketing surveillance of AEFI, coordinated by the Italian Medicine Agency and the Veneto region. The main objectives of the project are: (1) to coordinate the surveillance activities in the 8 Italian Regions included in the project; (2) to encourage the signal of AEFI by healthcare workers and patients; (3) to organize education activities addressed to health care workers, and, finally; (4) to establish vaccination counseling services in each Region. In particular, the Ligurian multidisciplinary team, composed by physicians expert in the field of vaccination and pharmacists, is involved in the causality assessment between vaccines and all adverse events signaled within the Liguria Region and in the analysis of all adverse events signaled in Italy as possibly related to influenza vaccines. During 2013, the team has organized 4 courses, addressed to healthcare personnel of vaccination outpatient clinics, focused on European and Italian legislation on pharmaco-vigilance and vaccine-vigilance and aimed at promoting signal of AEFI. Since October 2013, the Liguria Region has been participating to the inter-regional project of active surveillance of adverse events aimed at promoting the signal of AEFI by parents of vaccinated infants. After two years of implementation of the project both the number of reported AEFI and the reporting rate per 100 000 administered doses of vaccine increased. The activities need to be consolidated in the next years in order to guarantee high standard of vaccine safety, maintain the confidence in current immunization programs and reach optimal vaccination coverage rate. PMID:25483520

  18. Cellular immune response in intraventricular experimental neurocysticercosis.

    PubMed

    Moura, Vania B L; Lima, Sarah B; Matos-Silva, Hidelberto; Vinaud, Marina C; Loyola, Patricia R A N; Lino, Ruy S

    2016-03-01

    Neurocysticercosis (NCC) is considered a neglected parasitic infection of the human central nervous system. Its pathogenesis is due to the host immune response, stage of evolution and location of the parasite. The aim of this study was to evaluate the in situ and systemic immune response through cytokines dosage (IL-4, IL-10, IL-17 and IFN-γ) as well as the local inflammatory response of the experimental NCC with Taenia crassiceps. The in situ and systemic cellular and inflammatory immune response were evaluated through the cytokines quantification at 7, 30, 60 and 90 days after inoculation and histopathological analysis. All cysticerci were found within the cerebral ventricles. There was a discrete intensity of inflammatory cells of mixed immune profile, polymorphonuclear and mononuclear cells, at the beginning of the infection and predominance of mononuclear cells at the end. The systemic immune response showed a significant increase in all the analysed cytokines and predominance of the Th2 immune profile cytokines at the end of the infection. These results indicate that the location of the cysticerci may lead to ventriculomegaly. The acute phase of the infection showed a mixed Th1/Th17 profile accompanied by high levels of IL-10 while the late phase showed a Th2 immune profile. PMID:26626017

  19. Characterization of the immune response of domestic fowl following immunization with proteins extracted from Dermanyssus gallinae.

    PubMed

    Harrington, David; Din, Hatem Mohi El; Guy, Jonathan; Robinson, Karen; Sparagano, Olivier

    2009-03-23

    Dermanyssus gallinae is the most significant ectoparasite of European poultry egg laying production systems due to high costs of control and associated production losses as well as adverse effects on bird welfare. In this study, soluble proteins were extracted from unfed D. gallinae (DGE) using a urea-based detergent and ultra-filtration, passed through a 0.22 microm filter and blended aseptically with adjuvant. One group of laying hens was immunized with DGE and adjuvant (Montanide ISA 50 V) whilst another group (Control) received physiological saline and adjuvant. All birds were immunized on two occasions, 21 days apart. Antibody response to immunization was determined by ELISA and western blotting using immunoglobulins (Igs) extracted from egg yolk. DGE immunization of hens resulted in a significant (P<0.05) IgY response compared to controls, although there was no significant difference in IgM response between treatments. A number of proteins were identified by western blotting using IgY antibodies from DGE immunized birds, most prominently at 40 and 230kDa. Analysis of proteins from approximately corresponding bands on SDS-PAGE confirmed the identity of tropomyosin, whilst other proteins showed high sequence homology with myosin and actin from other arachnid and insect species. Immunization of hens with DGE resulted in a 50.6% increase in mite mortality (P<0.001) 17h after feeding when tested by an in vitro mite feeding model. Data in this study demonstrate that somatic antigens from D. gallinae can be used to stimulate a protective immune response in laying hens. Further work is needed to identify other proteins of interest that could confer higher protection against D. gallinae, as well as optimization of the vaccination and in vitro testing protocol. PMID:19091480

  20. Human papillomavirus vaccines--immune responses.

    PubMed

    Stanley, Margaret; Pinto, Ligia A; Trimble, Connie

    2012-11-20

    Prophylactic human papillomavirus (HPV) virus-like particle (VLP) vaccines are highly effective. The available evidence suggests that neutralising antibody is the mechanism of protection. However, despite the robust humoral response elicited by VLP vaccines, there is no immune correlate, no minimum level of antibody, or any other immune parameter, that predicts protection against infection or disease. The durability of the antibody response and the importance of antibody isotype, affinity and avidity for vaccine effectiveness are discussed. Once infection and disease are established, then cellular immune responses are essential to kill infected cells. These are complex processes and understanding the local mucosal immune response is a prerequisite for the rational design of therapeutic HPV vaccines. This article forms part of a special supplement entitled "Comprehensive Control of HPV Infections and Related Diseases" Vaccine Volume 30, Supplement 5, 2012. PMID:23199968

  1. EFFECTS OF PESTICIDES ON THE IMMUNE RESPONSE

    EPA Science Inventory

    The influence of various pesticides on the humoral and cellular immune response to fluorescein labeled ovalbumin has been analyzed. Pesticides (Aroclor 1260, Dinoseb, Parathion, pentachloronitrobenzene, piperonyl butoxide, mixed pyrethrins and Resmethrin) were administered intrag...

  2. The immune response to resistance exercise.

    PubMed

    Simonson, S R

    2001-08-01

    The immune response to exercise has received increased attention in the last decade. Most of this attention has focused on aerobic exercise (AEX), whereas the effect of resistance exercise (REX) has received comparatively little notice. Resistance exercise and AEX have different physiologic impacts; perhaps this also applies to the immune system. The purpose of this review was to determine a consensus from the REX immune studies that have been completed. This is complicated by the multitude of immune parameters, the varying methods used to assess them, and the paucity of studies performed. Thus, it is difficult to make a blanket statement. There is a REX-induced leukocytosis. Resistance conditioning (RCO) does not alter this response or affect the resting immune system. From these data, it appears that neither REX nor RCO demonstrates a significant impact on peripheral immunosurveillance. PMID:11710669

  3. The innate immune response in human tuberculosis

    PubMed Central

    Lerner, Thomas R.; Borel, Sophie

    2015-01-01

    Summary M ycobacterium tuberculosis (Mtb) infection can be cleared by the innate immune system before the initiation of an adaptive immune response. This innate protection requires a variety of robust cell autonomous responses from many different host immune cell types. However, Mtb has evolved strategies to circumvent some of these defences. In this mini‐review, we discuss these host–pathogen interactions with a focus on studies performed in human cells and/or supported by human genetics studies (such as genome‐wide association studies). PMID:26135005

  4. Cellular immune response experiment MA-031

    NASA Technical Reports Server (NTRS)

    Criswell, B. S.

    1976-01-01

    Significant changes in phytohemagglutinin (PHA) lymphocytic responsiveness occurred in the cellular immune response of three astronauts during the 9 day flight of the Apollo Soyuz Test Project. Parameters studied were white blood cell concentrations, lymphocyte numbers, B- and T-lymphocyte distributions in peripheral blood, and lymphocyte responsiveness to PHA, pokeweed mitogen, Concanavalin A, and influenza virus antigen.

  5. Mechanistic and dose considerations for supporting adverse pulmonary physiology in response to formaldehyde

    SciTech Connect

    Thompson, Chad M. Subramaniam, Ravi P.; Grafstroem, Roland C.

    2008-12-15

    Induction of airway hyperresponsiveness and asthma from formaldehyde inhalation exposure remains a debated and controversial issue. Yet, recent evidences on pulmonary biology and the pharmacokinetics and toxicity of formaldehyde lend support for such adverse effects. Specifically, altered thiol biology from accelerated enzymatic reduction of the endogenous bronchodilator S-nitrosoglutathione and pulmonary inflammation from involvement of Th2-mediated immune responses might serve as key events and cooperate in airway pathophysiology. Understanding what role these mechanisms play in various species and lifestages (e.g., child vs. adult) could be crucial for making more meaningful inter- and intra-species dosimetric extrapolations in human health risk assessment.

  6. Intravenous immune globulin and thromboembolic adverse events: A systematic review and meta-analysis of RCTs.

    PubMed

    Ammann, Eric M; Haskins, Cole B; Fillman, Kelsey M; Ritter, Rebecca L; Gu, Xiaomei; Winiecki, Scott K; Carnahan, Ryan M; Torner, James C; Fireman, Bruce H; Jones, Michael P; Chrischilles, Elizabeth A

    2016-06-01

    Prior case reports and observational studies indicate that intravenous immune globulin (IVIg) products may cause thromboembolic events (TEEs), leading the FDA to require a boxed warning in 2013. The effect of IVIg treatment on the risk of serious TEEs (acute myocardial infarction, ischemic stroke, or venous thromboembolism) was assessed using adverse event data reported in randomized controlled trials (RCTs) of IVIg. RCTs of IVIg in adult patients from 1995 to 2015 were identified from Pubmed, Embase, ClinicalTrials.Gov, and two large prior reviews of IVIg's therapeutic applications. Trials at high risk of detection or reporting bias for serious adverse events were excluded. 31 RCTs with a total of 4,129 participants (2,318 IVIg-treated, 1,811 control) were eligible for quantitative synthesis. No evidence was found of increased TEE risk among IVIg-treated patients compared with control patients (odds ratio = 1.10, 95% CI: 0.44, 2.88; risk difference = 0.0%, 95% CI: -0.7%, 0.7%, I(2)  = 0%). No significant increase in risk was found when arterial and venous TEEs were analyzed as separate endpoints. Trial publications provided little specific information concerning the methods used to ascertain potential adverse events. Care should be taken in extrapolating the results to patients with higher baseline risks of TEE. Am. J. Hematol. 91:594-605, 2016. © 2016 Wiley Periodicals, Inc. PMID:26973084

  7. Modulating immune responses with probiotic bacteria.

    PubMed

    Matsuzaki, T; Chin, J

    2000-02-01

    For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria. PMID:10651931

  8. Immune Response to Biologic Scaffold Materials

    PubMed Central

    Badylak, Stephen F.; Gilbert, Thomas W.

    2008-01-01

    Biologic scaffold materials composed of mammalian extracellular matrix are commonly used in regenerative medicine and in surgical procedures for the reconstruction of numerous tissue and organs. These biologic materials are typically allogeneic or xenogeneic in origin and are derived from tissues such as small intestine, urinary bladder, dermis, and pericardium. The innate and acquired host immune response to these biologic materials and the effect of the immune response upon downstream remodeling events has been largely unexplored. Variables that affect the host response include manufacturing processes, the rate of scaffold degradation, and the presence of cross species antigens. This manuscript provides an overview of studies that have evaluated the immune response to biologic scaffold materials and variables that affect this response. PMID:18083531

  9. Host innate immune responses to sepsis

    PubMed Central

    Wiersinga, Willem Joost; Leopold, Stije J; Cranendonk, Duncan R; van der Poll, Tom

    2014-01-01

    The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis. PMID:23774844

  10. Plasticity of immunity in response to eating.

    PubMed

    Luoma, Rachel L; Butler, Michael W; Stahlschmidt, Zachary R

    2016-07-01

    Following a meal, an animal can exhibit dramatic shifts in physiology and morphology, as well as a substantial increase in metabolic rate associated with the energetic costs of processing a meal (i.e. specific dynamic action, SDA). However, little is known about the effects of digestion on another important physiological and energetically costly trait: immune function. Thus, we tested two competing hypotheses. (1) Digesting animals up-regulate their immune systems (putatively in response to the increased microbial exposure associated with ingested food). (2) Digesting animals down-regulate their immune systems (presumably to allocate energy to the breakdown of food). We assayed innate immunity (lytic capacity and agglutination) in cornsnakes (Pantherophis guttatus) during and after meal digestion. Lytic capacity was higher in females, and (in support of our first hypothesis) agglutination was higher during absorption. Given its potential energetic cost, immune up-regulation may contribute to SDA. PMID:27099367

  11. Effect of cellular mobility on immune response

    NASA Astrophysics Data System (ADS)

    Pandey, R. B.; Mannion, R.; Ruskin, H. J.

    2000-08-01

    Mobility of cell types in our HIV immune response model is subject to an intrinsic mobility and an explicit directed mobility, which is governed by Pmob. We investigate how restricting the explicit mobility, while maintaining the innate mobility of a viral-infected cell, affects the model's results. We find that increasing the explicit mobility of the immune system cells leads to viral dominance for certain levels of viral mutation. We conclude that increasing immune system cellular mobility indirectly increases the virus’ inherent mobility.

  12. Mosquito immune responses to arbovirus infections

    PubMed Central

    Blair, Carol D.; Olson, Ken E.

    2014-01-01

    The principal mosquito innate immune response to virus infections, RNA interference (RNAi), differs substantially from the immune response to bacterial and fungal infections. The exo-siRNA pathway constitutes the major anti-arboviral RNAi response and its essential genetic components have been identified. Recent research has also implicated the Piwi-interacting RNA pathway in mosquito anti-arboviral immunity, but Piwi gene-family components involved are not well-defined. Arboviruses must evade or suppress RNAi without causing pathogenesis in the vector to maintain their transmission cycle, but little is known about mechanisms of arbovirus modulation of RNAi. Genetic manipulation of mosquitoes to enhance their RNAi response can limit arbovirus infection and replication and could be used in novel strategies for interruption of arbovirus transmission and greatly reduce disease. PMID:25401084

  13. Immune-mediated adverse events of anticytotoxic T lymphocyte-associated antigen 4 antibody therapy in metastatic melanoma.

    PubMed

    Quirk, Shannon K; Shure, Anna K; Agrawal, Devendra K

    2015-11-01

    Ipilimumab, an antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4; CD152), was approved by the Food and Drug Administration in 2011 for the treatment of unresectable stage III or IV malignant melanoma. Although the addition of this particular immunotherapy has broadened treatment options, immune-related adverse events (irAEs) are associated with ipilimumab therapy, including dermatologic effects, colitis and diarrhea, endocrine effects, hepatotoxicity, ocular effects, renal effects, neurologic effects, and others. In this article, a critical evaluation of the underlying mechanisms of irAEs associated with anti-CTLA-4 therapy is presented. Additionally, potentially beneficial effects of combinational therapies to alleviate ipilimumab-induced irAEs in malignant melanoma are discussed. Future research is warranted to elucidate the efficacy of such combination therapies and specific biomarkers that would help to predict a clinical response to ipilimumab in patients with malignant melanoma. PMID:26118951

  14. Vaccination Strategies for Mucosal Immune Responses

    PubMed Central

    Ogra, Pearay L.; Faden, Howard; Welliver, Robert C.

    2001-01-01

    Mucosal administration of vaccines is an important approach to the induction of appropriate immune responses to microbial and other environmental antigens in systemic sites and peripheral blood as well as in most external mucosal surfaces. The development of specific antibody- or T-cell-mediated immunologic responses and the induction of mucosally induced systemic immunologic hyporesponsiveness (oral or mucosal tolerance) depend on complex sets of immunologic events, including the nature of the antigenic stimulation of specialized lymphoid structures in the host, antigen-induced activation of different populations of regulatory T cells (Th1 versus Th2), and the expression of proinflammatory and immunoregulatory cytokines. Availability of mucosal vaccines will provide a painless approach to deliver large numbers of vaccine antigens for human immunization. Currently, an average infant will receive 20 to 25 percutaneous injections for vaccination against different childhood infections by 18 months of age. It should be possible to develop for human use effective, nonliving, recombinant, replicating, transgenic, and microbial vector- or plant-based mucosal vaccines to prevent infections. Based on the experience with many dietary antigens, it is also possible to manipulate the mucosal immune system to induce systemic tolerance against environmental, dietary, and possibly other autoantigens associated with allergic and autoimmune disorders. Mucosal immunity offers new strategies to induce protective immune responses against a variety of infectious agents. Such immunization may also provide new prophylactic or therapeutic avenues in the control of autoimmune diseases in humans. PMID:11292646

  15. The immune response to Nipah virus infection.

    PubMed

    Prescott, Joseph; de Wit, Emmie; Feldmann, Heinz; Munster, Vincent J

    2012-09-01

    Nipah virus has recently emerged as a zoonotic agent that is highly pathogenic in humans. Outbreaks have occurred regularly over the last two decades in South and Southeast Asia, where mortality rates reach as high as 100 %. The natural reservoir of Nipah virus has been identified as bats from the Pteropus family, where infection is largely asymptomatic. Human disease is characterized by both respiratory and encephalitic components, and thus far, no effective vaccine or intervention strategies are available. Little is know about how the immune response of either the reservoir host or incidental hosts responds to infection, and how this immune response is either inadequate or might contribute to disease in the dead-end host. Experimental vaccines strategies have given us some insight into the immunological requirements for protection. This review summarizes our current understanding of the immune response to Nipah virus infection and emphasizes the need for further research. PMID:22669317

  16. Studies of Immune Responses in Candida vaginitis.

    PubMed

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  17. Studies of Immune Responses in Candida vaginitis

    PubMed Central

    De Bernardis, Flavia; Arancia, Silvia; Sandini, Silvia; Graziani, Sofia; Norelli, Sandro

    2015-01-01

    The widespread occurrence of vaginal candidiasis and the development of resistance against anti-fungal agents has stimulated interest in understanding the pathogenesis of this disease. The aim of our work was to characterize, in an animal model of vaginal candidiasis, the mechanisms that play a role in the induction of mucosal immunity against C. albicans and the interaction between innate and adaptive immunity. Our studies evidenced the elicitation of cell-mediated immunity (CMIs) and antibody (Abs)-mediated immunity with a Th1 protective immunity. An immune response of this magnitude in the vagina was very encouraging to identify the proper targets for new strategies for vaccination or immunotherapy of vaginal candidiasis. Overall, our data provide clear evidence that it is possible to prevent C. albicans vaginal infection by active intravaginal immunization with aspartyl proteinase expressed as recombinant protein. This opens the way to a modality for anti-Candida protection at the mucosa. The recombinant protein Sap2 was assembled with virosomes, and a vaccine PEVION7 (PEV7) was obtained. The results have given evidence that the vaccine, constituted of virosomes and Secretory aspartyl proteinase 2 (Sap2) (PEV7), has an encouraging therapeutic potential for the treatment of recurrent vulvovaginal candidiasis. PMID:26473934

  18. Damage signals in the insect immune response

    PubMed Central

    Krautz, Robert; Arefin, Badrul; Theopold, Ulrich

    2014-01-01

    Insects and mammals share an ancient innate immune system comprising both humoral and cellular responses. The insect immune system consists of the fat body, which secretes effector molecules into the hemolymph and several classes of hemocytes, which reside in the hemolymph and of protective border epithelia. Key features of wound- and immune responses are shared between insect and mammalian immune systems including the mode of activation by commonly shared microbial (non-self) patterns and the recognition of these patterns by dedicated receptors. It is unclear how metazoan parasites in insects, which lack these shared motifs, are recognized. Research in recent years has demonstrated that during entry into the insect host, many eukaryotic pathogens leave traces that alert potential hosts of the damage they have afflicted. In accordance with terminology used in the mammalian immune systems, these signals have been dubbed danger- or damage-associated signals. Damage signals are necessary byproducts generated during entering hosts either by mechanical or proteolytic damage. Here, we briefly review the current stage of knowledge on how wound closure and wound healing during mechanical damage is regulated and how damage-related signals contribute to these processes. We also discuss how sensors of proteolytic activity induce insect innate immune responses. Strikingly damage-associated signals are also released from cells that have aberrant growth, including tumor cells. These signals may induce apoptosis in the damaged cells, the recruitment of immune cells to the aberrant tissue and even activate humoral responses. Thus, this ensures the removal of aberrant cells and compensatory proliferation to replace lost tissue. Several of these pathways may have been co-opted from wound healing and developmental processes. PMID:25071815

  19. Injury-induced immune responses in Hydra.

    PubMed

    Wenger, Yvan; Buzgariu, Wanda; Reiter, Silke; Galliot, Brigitte

    2014-08-01

    The impact of injury-induced immune responses on animal regenerative processes is highly variable, positive or negative depending on the context. This likely reflects the complexity of the innate immune system that behaves as a sentinel in the transition from injury to regeneration. Early-branching invertebrates with high regenerative potential as Hydra provide a unique framework to dissect how injury-induced immune responses impact regeneration. A series of early cellular events likely require an efficient immune response after amputation, as antimicrobial defence, epithelial cell stretching for wound closure, migration of interstitial progenitors toward the wound, cell death, phagocytosis of cell debris, or reconstruction of the extracellular matrix. The analysis of the injury-induced transcriptomic modulations of 2636 genes annotated as immune genes in Hydra identified 43 genes showing an immediate/early pulse regulation in all regenerative contexts examined. These regulations point to an enhanced cytoprotection via ROS signaling (Nrf, C/EBP, p62/SQSMT1-l2), TNFR and TLR signaling (TNFR16-like, TRAF2l, TRAF5l, jun, fos-related, SIK2, ATF1/CREB, LRRC28, LRRC40, LRRK2), proteasomal activity (p62/SQSMT1-l1, Ced6/Gulf, NEDD8-conjugating enzyme Ubc12), stress proteins (CRYAB1, CRYAB2, HSP16.2, DnaJB9, HSP90a1), all potentially regulating NF-κB activity. Other genes encoding immune-annotated proteins such as NPYR4, GTPases, Swap70, the antiproliferative BTG1, enzymes involved in lipid metabolism (5-lipoxygenase, ACSF4), secreted clotting factors, secreted peptidases are also pulse regulated upon bisection. By contrast, metalloproteinases and antimicrobial peptide genes largely follow a context-dependent regulation, whereas the protease inhibitor α2macroglobulin gene exhibits a sustained up-regulation. Hence a complex immune response to injury is linked to wound healing and regeneration in Hydra. PMID:25086685

  20. Regulation of Immune Responses by Extracellular Vesicles

    PubMed Central

    Robbins, Paul D.; Morelli, Adrian E.

    2015-01-01

    Extracellular vesicles (EVs) including exosomes, are small membrane vesicles derived from multivesicular bodies or from the plasma membrane. Most, if not all, cell types release EVs that then enter the bodily fluids. These vesicles contain a subset of proteins, lipids and nucleic acids that are derived from the parent cell. It is postulated that EVs have important roles in intercellular communication, both locally and systemically, by transferring their contents, including protein, lipids and RNAs, between cells. EVs are involved in numerous physiological processes, and vesicles from both non-immune and immune cells have important roles in immune regulation. Moreover, EV-based therapeutics are being developed and tested clinically for treatment of inflammatory and autoimmune diseases and cancer. Given the tremendous therapeutic potential of EVs this review focuses on the role of EVs in modulating immune responses and the therapeutic applications. PMID:24566916

  1. Optically Triggered Immune Response through Photocaged Oligonucleotides

    PubMed Central

    Govan, Jeane M.; Young, Douglas D.; Lively, Mark O.

    2015-01-01

    Bacterial and viral CpG oligonculeotides are unmethylated cytosine-phosphate-guanosine dinucleotide sequences and trigger an innate immune response through activation of the toll-like receptor 9 (TLR9). We have developed synthetic photocaged CpGs via site-specific incorporation of nitropiperonyloxymethyl (NPOM)-caged thymidine residues. These oligonucleotides enable the optical control of TLR9 function and thereby provide light-activation of an immune response. We provide a proof-of-concept model by applying a reporter assay in live cells and by quantification of endogenous production of interleukin 6. PMID:26034339

  2. Immune response from a resource allocation perspective

    PubMed Central

    Rauw, Wendy M.

    2012-01-01

    The immune system is a life history trait that can be expected to trade off against other life history traits. Whether or not a trait is considered to be a life history trait has consequences for the expectation on how it responds to natural selection and evolution; in addition, it may have consequences for the outcome of artificial selection when it is included in the breeding objective. The immune system involved in pathogen resistance comprises multiple mechanisms that define a host's defensive capacity. Immune resistance involves employing mechanisms that either prevent pathogens from invading or eliminate the pathogens when they do invade. On the other hand, tolerance involves limiting the damage that is caused by the infection. Both tolerance and resistance traits require (re)allocation of resources and carry physiological costs. Examples of trade-offs between immune function and growth, reproduction and stress response are provided in this review, in addition to consequences of selection for increased production on immune function and vice versa. Reaction norms are used to deal with questions of immune resistance vs. tolerance to pathogens that relate host health to infection intensity. In essence, selection for immune tolerance in livestock is a particular case of selection for animal robustness. Since breeding goals that include robustness traits are required in the implementation of more sustainable agricultural production systems, it is of interest to investigate whether immune tolerance is a robustness trait that is positively correlated with overall animal robustness. Considerably more research is needed to estimate the shapes of the cost functions of different immune strategies, and investigate trade-offs and cross-over benefits of selection for disease resistance and/or disease tolerance in livestock production. PMID:23413205

  3. Plant Immune Responses: Aphids Strike Back.

    PubMed

    Reymond, Philippe; Calandra, Thierry

    2015-07-20

    To survive and complete their life cycle, herbivorous insects face the difficult challenge of coping with the arsenal of plant defences. A new study reports that aphids secrete evolutionarily conserved cytokines in their saliva to suppress host immune responses. PMID:26196486

  4. [Modulation of immune response by bacterial lipopolysaccharides].

    PubMed

    Aldapa-Vega, Gustavo; Pastelín-Palacios, Rodolfo; Isibasi, Armando; Moreno-Eutimio, Mario A; López-Macías, Constantino

    2016-01-01

    Lipopolysaccharide (LPS) is a molecule that is profusely found on the outer membrane of Gram-negative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4) and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants. PMID:27560917

  5. Immune Response in Mussels To Environmental Pollution.

    ERIC Educational Resources Information Center

    Pryor, Stephen C.; Facher, Evan

    1997-01-01

    Describes the use of mussels in measuring the extent of chemical contamination and its variation in different coastal regions. Presents an experiment to introduce students to immune response and the effects of environmental pollution on marine organisms. Contains 14 references. (JRH)

  6. Differential regional immune response in Chagas disease.

    PubMed

    de Meis, Juliana; Morrot, Alexandre; Farias-de-Oliveira, Désio Aurélio; Villa-Verde, Déa Maria Serra; Savino, Wilson

    2009-01-01

    Following infection, lymphocytes expand exponentially and differentiate into effector cells to control infection and coordinate the multiple effector arms of the immune response. Soon after this expansion, the majority of antigen-specific lymphocytes die, thus keeping homeostasis, and a small pool of memory cells develops, providing long-term immunity to subsequent reinfection. The extent of infection and rate of pathogen clearance are thought to determine both the magnitude of cell expansion and the homeostatic contraction to a stable number of memory cells. This straight correlation between the kinetics of T cell response and the dynamics of lymphoid tissue cell numbers is a constant feature in acute infections yielded by pathogens that are cleared during the course of response. However, the regional dynamics of the immune response mounted against pathogens that are able to establish a persistent infection remain poorly understood. Herein we discuss the differential lymphocyte dynamics in distinct central and peripheral lymphoid organs following acute infection by Trypanosoma cruzi, the causative agent of Chagas disease. While the thymus and mesenteric lymph nodes undergo a severe atrophy with massive lymphocyte depletion, the spleen and subcutaneous lymph nodes expand due to T and B cell activation/proliferation. These events are regulated by cytokines, as well as parasite-derived moieties. In this regard, identifying the molecular mechanisms underlying regional lymphocyte dynamics secondary to T. cruzi infection may hopefully contribute to the design of novel immune intervention strategies to control pathology in this infection. PMID:19582140

  7. 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

  8. CXCL17 Expression Predicts Poor Prognosis and Correlates with Adverse Immune Infiltration in Hepatocellular Carcinoma

    PubMed Central

    Xu, Jing; Liu, Chao-Qun; Zhen, Zuo-Jun; Chen, Huan-Wei; Ji, Yong; Wu, Zhi-Peng; Hu, Jian-Yuan; Zheng, Limin; Lau, Wan Yee

    2014-01-01

    CXC ligand 17 (CXCL17) is a novel CXC chemokine whose clinical significance remains largely unknown. In the present study, we characterized the prognostic value of CXCL17 in patients with hepatocellular carcinoma (HCC) and evaluated the association of CXCL17 with immune infiltration. We examined CXCL17 expression in 227 HCC tissue specimens by immunohistochemical staining, and correlated CXCL17 expression patterns with clinicopathological features, prognosis, and immune infiltrate density (CD4 T cells, CD8 T cells, B cells, natural killer cells, neutrophils, macrophages). Kaplan-Meier survival analysis showed that both increased intratumoral CXCL17 (P = 0.015 for overall survival [OS], P = 0.003 for recurrence-free survival [RFS]) and peritumoral CXCL17 (P = 0.002 for OS, P<0.001 for RFS) were associated with shorter OS and RFS. Patients in the CXCL17low group had significantly lower 5-year recurrence rate compared with patients in the CXCL17high group (peritumoral: 53.1% vs. 77.7%, P<0.001, intratumoral: 58.6% vs. 73.0%, P = 0.001, respectively). Multivariate Cox proportional hazards analysis identified peritumoral CXCL17 as an independent prognostic factor for both OS (hazard ratio [HR] = 2.066, 95% confidence interval [CI] = 1.296–3.292, P = 0.002) and RFS (HR = 1.844, 95% CI = 1.218–2.793, P = 0.004). Moreover, CXCL17 expression was associated with more CD68 and less CD4 cell infiltration (both P<0.05). The combination of CXCL17 density and immune infiltration could be used to further classify patients into subsets with different prognosis for RFS. Our results provide the first evidence that tumor-infiltrating CXCL17+ cell density is an independent prognostic factor that predicts both OS and RFS in HCC. CXCL17 production correlated with adverse immune infiltration and might be an important target for anti-HCC therapies. PMID:25303284

  9. Humoral Immune Response to AAV

    PubMed Central

    Calcedo, Roberto; Wilson, James M.

    2013-01-01

    Adeno-associated virus (AAV) is a member of the family Parvoviridae that has been widely used as a vector for gene therapy because of its safety profile, its ability to transduce both dividing and non-dividing cells, and its low immunogenicity. AAV has been detected in many different tissues of several animal species but has not been associated with any disease. As a result of natural infections, antibodies to AAV can be found in many animals including humans. It has been shown that pre-existing AAV antibodies can modulate the safety and efficacy of AAV vector-mediated gene therapy by blocking vector transduction or by redirecting distribution of AAV vectors to tissues other than the target organ. This review will summarize antibody responses against natural AAV infections, as well as AAV gene therapy vectors and their impact in the clinical development of AAV vectors for gene therapy. We will also review and discuss the various methods used for AAV antibody detection and strategies to overcome neutralizing antibodies in AAV-mediated gene therapy. PMID:24151496

  10. Humoral immune responses in foetal sheep.

    PubMed Central

    Fahey, K J; Morris, B

    1978-01-01

    A total of fifty-two foetal sheep between 49 and 126 days gestation were injected with polymeric and monomeric flagellin, dinitrophenylated monomeric flagellin, chicken red blood cells, ovalbumin, ferritin, chicken gamma-globulin and the somatic antigens of Salmonella typhimurium in a variety of combinations. Immune responses were followed in these animals by taking serial blood samples from them through indwelling vascular cannulae and measuring the circulating titres of antibody. Of the antigens tested, ferritin induced immune responses in the youngest foetuses. A short time later in gestation, the majority of foetuses responded to chicken red blood cells, polymeric flagellin, monomeric flagellin and dinitrophenylated monomeric flagellin. Only older foetuses responded regularly to chicken gamma-globulin and ovalbumin. However, antibodies to all these antigens were first detected over the relatively short period of development between 64 and 82 days gestation and this made it difficult to define any precise order in the development of immune responsiveness. Of the antigens tested only the somatic antigens of S. typhimurium failed to induce a primary antibody response during foetal life. The character and magnitude of the antibody responses in foetuses changed throughout in utero development. Both the total amount of antibody produced and the duration of the response increased with foetal age. Foetuses younger than 87 days gestation did not synthesize 2-mercaptoethanol resistant antibodies or IgG1 immunoglobulin to any of the antigens tested, whereas most foetuses older than this regularly did so. PMID:711249

  11. Ovine model for studying pulmonary immune responses

    SciTech Connect

    Joel, D.D.; Chanana, A.D.

    1984-11-25

    Anatomical features of the sheep lung make it an excellent model for studying pulmonary immunity. Four specific lung segments were identified which drain exclusively to three separate lymph nodes. One of these segments, the dorsal basal segment of the right lung, is drained by the caudal mediastinal lymph node (CMLN). Cannulation of the efferent lymph duct of the CMLN along with highly localized intrabronchial instillation of antigen provides a functional unit with which to study factors involved in development of pulmonary immune responses. Following intrabronchial immunization there was an increased output of lymphoblasts and specific antibody-forming cells in efferent CMLN lymph. Continuous divergence of efferent lymph eliminated the serum antibody response but did not totally eliminate the appearance of specific antibody in fluid obtained by bronchoalveolar lavage. In these studies localized immunization of the right cranial lobe served as a control. Efferent lymphoblasts produced in response to intrabronchial antigen were labeled with /sup 125/I-iododeoxyuridine and their migrational patterns and tissue distribution compared to lymphoblasts obtained from the thoracic duct. The results indicated that pulmonary immunoblasts tend to relocate in lung tissue and reappear with a higher specific activity in pulmonary lymph than in thoracic duct lymph. The reverse was observed with labeled intestinal lymphoblasts. 35 references, 2 figures, 3 tables.

  12. Adverse events to monoclonal antibodies used for cancer therapy: Focus on hypersensitivity responses.

    PubMed

    Baldo, Brian A

    2013-10-01

    Fifteen monoclonal antibodies (mAbs) are currently registered and approved for the treatment of a range of different cancers. These mAbs are specific for a limited number of targets (9 in all). Four of these molecules are indeed directed against the B-lymphocyte antigen CD20; 3 against human epidermal growth factor receptor 2 (HER2 or ErbB2), 2 against the epidermal growth factor receptor (EGFR), and 1 each against epithelial cell adhesion molecule (EpCAM), CD30, CD52, vascular endothelial growth factor (VEGF), tumor necrosis factor (ligand) superfamily, member 11 (TNFSF11, best known as RANKL), and cytotoxic T lymphocyte-associated protein 4 (CTLA4). Collectively, the mAbs provoke a wide variety of systemic and cutaneous adverse events including the full range of true hypersensitivities: Type I immediate reactions (anaphylaxis, urticaria); Type II reactions (immune thrombocytopenia, neutopenia, hemolytic anemia); Type III responses (vasculitis, serum sickness; some pulmonary adverse events); and Type IV delayed mucocutaneous reactions as well as infusion reactions/cytokine release syndrome (IRs/CRS), tumor lysis syndrome (TLS), progressive multifocal leukoencephalopathy (PML) and cardiac events. Although the term "hypersensitivity" is widely used, no common definition has been adopted within and between disciplines and the requirement of an immunological basis for a true hypersensitivity reaction is sometimes overlooked. Consequently, some drug-induced adverse events are sometimes incorrectly described as "hypersensitivities" while others that should be described are not. PMID:24251081

  13. Vitamin E, immune response, and disease resistance.

    PubMed

    Tengerdy, R P

    1989-01-01

    Vitamin E as a dietary supplement or as part of an adjuvant vaccine formulation increases humoral and cell-mediated immunity and disease resistance in laboratory animals, farm animals, and humans. Adjuvant administration has far greater effect than dietary supplementation. Vitamin E as an antioxidant protects the cells of the immune response from peroxidative damage; possibly through a modulation of lipoxygenation of arachidonic acid, vitamin E alters cell membrane functions and cell-cell interactions. The most pronounced effect of vitamin E is on immune phagocytosis. Dietary supplementation is beneficial to animals, especially under stress, in decreasing susceptibility to infections. Vitamin E adjuvant vaccines have provided greater immunoprotection against enterotoxemia and epididymitis in sheep than conventional vaccines. PMID:2698109

  14. Consumer reporting of adverse events following immunization (AEFI): identifying predictors of reporting an AEFI.

    PubMed

    Parrella, Adriana; Gold, Michael; Braunack-Mayer, Annette; Baghurst, Peter; Marshall, Helen

    2014-01-01

    Passive reporting of adverse events following immunization (AEFI) by consumers or healthcare professionals is the primary mechanism for post-marketing surveillance of vaccine safety. Although recent initiatives have promoted consumer reporting, there is a lack of research concerning consumer reporters. Computer assisted telephone interviews (CATI) were conducted in 2011 of a cross-sectional, random, general population sample of 191 South Australian parents who stated that their children had previously experienced an AEFI. We compared awareness of surveillance, vaccine safety opinions, and demographics of parents reporting an AEFI to either healthcare professionals or surveillance authorities with those who did not report their children's AEFI. Multivariate regression analyses measured: the association between reporting and safety views; and demographic predictors of reporting an AEFI. Reporting an AEFI to a healthcare professional or a surveillance authority was not significantly associated with awareness of a surveillance system. AEFI reporters, when compared with non-reporters, were more likely to be Australian-born (OR = 4.58, [1.64, 12.78], P = 0.004); were associated with the perception that a serious reaction was more likely to occur at their children's last immunization (OR = 2.54 [95%CI 1.22, 5.30], P = 0.013); and were less accepting of the risk of febrile convulsion, (OR = 3.59 [95%CI 1.50, 8.57], P = 0.004). Although reporting an AEFI was not associated with awareness of surveillance or most socio-demographics, the results suggest some difference in safety opinions. Further studies are required to ascertain if these differences pre-date the occurrence of an AEFI or are a consequence of the AEFI and how consumers can contribute further to vaccine safety surveillance. PMID:24406315

  15. 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...

  16. Chitin Modulates Innate Immune Responses of Keratinocytes

    PubMed Central

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

    2011-01-01

    Background Chitin, after cellulose the second most abundant polysaccharide in nature, is an essential component of exoskeletons of crabs, shrimps and insects and protects these organisms from harsh conditions in their environment. Unexpectedly, chitin has been found to activate innate immune cells and to elicit murine airway inflammation. The skin represents the outer barrier of the human host defense and is in frequent contact with chitin-bearing organisms, such as house-dust mites or flies. The effects of chitin on keratinocytes, however, are poorly understood. Methodology/Principal Findings We hypothesized that chitin stimulates keratinocytes and thereby modulates the innate immune response of the skin. Here we show that chitin is bioactive on primary and immortalized keratinocytes by triggering production of pro-inflammatory cytokines and chemokines. Chitin stimulation further induced the expression of the Toll-like receptor (TLR) TLR4 on keratinocytes at mRNA and protein level. Chitin-induced effects were mainly abrogated when TLR2 was blocked, suggesting that TLR2 senses chitin on keratinocytes. Conclusions/Significance We speculate that chitin-bearing organisms modulate the innate immune response towards pathogens by upregulating secretion of cytokines and chemokines and expression of MyD88-associated TLRs, two major components of innate immunity. The clinical relevance of this mechanism remains to be defined. PMID:21383982

  17. Multiscale modeling of mucosal immune responses

    PubMed Central

    2015-01-01

    Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut

  18. Sex-dimorphic adverse drug reactions to immune suppressive agents in inflammatory bowel disease

    PubMed Central

    Zelinkova, Zuzana; Bultman, Evelien; Vogelaar, Lauran; Bouziane, Cheima; Kuipers, Ernst J; van der Woude, C Janneke

    2012-01-01

    AIM: To analyze sex differences in adverse drug reactions (ADR) to the immune suppressive medication in inflammatory bowel disease (IBD) patients. METHODS: All IBD patients attending the IBD outpatient clinic of a referral hospital were identified through the electronic diagnosis registration system. The electronic medical records of IBD patients were reviewed and the files of those patients who have used immune suppressive therapy for IBD, i.e., thiopurines, methotrexate, cyclosporine, tacrolimus and anti-tumor necrosis factor agents (anti-TNF); infliximab (IFX), adalimumab (ADA) and/or certolizumab, were further analyzed. The reported ADR to immune suppressive drugs were noted. The general definition of ADR used in clinical practice comprised the occurrence of the ADR in the temporal relationship with its disappearance upon discontinuation of the medication. Patients for whom the required information on drug use and ADR was not available in the electronic medical record and patients with only one registered contact and no further follow-up at the outpatient clinic were excluded. The difference in the incidence and type of ADR between male and female IBD patients were analyzed statistically by χ2 test. RESULTS: In total, 1009 IBD patients were identified in the electronic diagnosis registration system. Out of these 1009 patients, 843 patients were eligible for further analysis. There were 386 males (46%), mean age 42 years (range: 16-87 years) with a mean duration of the disease of 14 years (range: 0-54 years); 578 patients with Crohn’s disease, 244 with ulcerative colitis and 21 with unclassified colitis. Seventy percent (586 pts) of patients used any kind of immune suppressive agents at a certain point of the disease course, the majority of the patients (546 pts, 65%) used thiopurines, 176 pts (21%) methotrexate, 46 pts (5%) cyclosporine and one patient tacrolimus. One third (240 pts, 28%) of patients were treated with anti-TNF, the majority of patients (227

  19. 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...

  20. Humoral innate immune response and disease

    PubMed Central

    Shishido, Stephanie N.; Varahan, Sriram; Yuan, Kai; Li, Xiangdong; Fleming, Sherry D.

    2012-01-01

    The humoral innate immune response consists of multiple components, including the naturally occurring antibodies (NAb), pentraxins and the complement and contact cascades. As soluble, plasma components, these innate proteins provide key elements in the prevention and control of disease. However, pathogens and cells with altered self proteins utilize multiple humoral components to evade destruction and promote pathogy. Many studies have examined the relationship between humoral immunity and autoimmune disorders. This review focuses on the interactions between the humoral components and their role in promoting the pathogenesis of bacterial and viral infections and chronic diseases such as atherosclerosis and cancer. Understanding the beneficial and detrimental aspects of the individual components and the interactions between proteins which regulate the innate and adaptive response will provide therapeutic targets for subsequent studies. PMID:22771788

  1. Regulation of immune responses by neutrophils.

    PubMed

    Wang, Jing; Arase, Hisashi

    2014-06-01

    Neutrophils, the most abundant circulating cells in humans, are major pathogen-killing immune cells. For many years, these cells were considered to be simple killers at the "bottom" of immune responses. However, recent studies have revealed more sophisticated mechanisms associated with neutrophilic cytotoxic functions, and neutrophils have been shown to contribute to various infectious and inflammatory diseases. In this review, we discuss the key features of neutrophils during inflammatory responses, from their release from the bone marrow to their death in inflammatory loci. We also discuss the expanding roles of neutrophils that have been identified in the context of several inflammatory diseases. We further focus on the mechanisms that regulate neutrophil recruitment to inflamed tissues and neutrophil cytotoxic activities against both pathogens and host tissues. PMID:24850053

  2. Immune responses to pertussis vaccines and disease.

    PubMed

    Edwards, Kathryn M; Berbers, Guy A M

    2014-04-01

    In this article we discuss the following: (1) acellular vaccines are immunogenic, but responses vary by vaccine; (2) pertussis antibody levels rapidly wane but promptly increase after vaccination; (3) whole-cell vaccines vary in immunogenicity and efficacy; (4) whole-cell vaccines and naturally occurring pertussis generate predominantly T-helper 1 (Th1) responses, whereas acellular vaccines generate mixed Th1/Th2 responses; (5) active transplacental transport of pertussis antibody is documented; (6) neonatal immunization with diphtheria toxoid, tetanus toxoid, and acellular pertussis vaccine has been associated with some suppression of pertussis antibody, but suppression has been seen less often with acellular vaccines; (7) memory B cells persist in both acellular vaccine- and whole cell vaccine-primed children; and (8) in acellular vaccine-primed children, T-cell responses remain elevated and do not increase with vaccine boosters, whereas in whole-cell vaccine-primed children, these responses can be increased by vaccine boosting and natural exposure. Despite these findings, challenges remain in understanding the immune response to pertussis vaccines. PMID:24158958

  3. Ontology representation and analysis of vaccine formulation and administration and their effects on vaccine immune responses

    PubMed Central

    2012-01-01

    Background A vaccine is a processed material that if administered, is able to stimulate an adaptive immune response to prevent or ameliorate a disease. A vaccination process may protect the host against subsequent exposure to an infectious agent and result in reduced disease or total prevention of the disease. Vaccine formulation and administration methods may affect vaccine safety and efficacy significantly. Results In this report, the detailed classification and definitions of vaccine components and vaccine administration processes are represented using OWL within the framework of the Vaccine Ontology (VO). Different use cases demonstrate how different vaccine formulations and routes of vaccine administration affect the protection efficacy, general immune responses, and adverse events following vaccination. For example, vaccinations of mice with Brucella abortus vaccine strain RB51 using intraperitoneal or intranasal administration resulted in different protection levels. As shown in the vaccine adverse event data provided by US FDA, live attenuated and nonliving vaccines are usually administered in different routes and have different local and systematic adverse effect manifestations. Conclusions Vaccine formulation and administration route can independently or collaboratively affect host response outcomes (positive protective immunity or adverse events) after vaccination. Ontological representation of different vaccine and vaccination factors in these two areas allows better understanding and analysis of the causal effects between different factors and immune responses. PMID:23256535

  4. Staphylococcal manipulation of host immune responses

    PubMed Central

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

    2015-01-01

    Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium’s ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus. PMID:26272408

  5. Staphylococcal manipulation of host immune responses.

    PubMed

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

    2015-09-01

    Staphylococcus aureus, a bacterial commensal of the human nares and skin, is a frequent cause of soft tissue and bloodstream infections. A hallmark of staphylococcal infections is their frequent recurrence, even when treated with antibiotics and surgical intervention, which demonstrates the bacterium's ability to manipulate innate and adaptive immune responses. In this Review, we highlight how S. aureus virulence factors inhibit complement activation, block and destroy phagocytic cells and modify host B cell and T cell responses, and we discuss how these insights might be useful for the development of novel therapies against infections with antibiotic resistant strains such as methicillin-resistant S. aureus. PMID:26272408

  6. Sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral leishmaniasis with adverse consequences for Leishmania.

    PubMed

    Collin, Nicolas; Gomes, Regis; Teixeira, Clarissa; Cheng, Lily; Laughinghouse, Andre; Ward, Jerrold M; Elnaiem, Dia-Eldin; Fischer, Laurent; Valenzuela, Jesus G; Kamhawi, Shaden

    2009-05-01

    Immunity to a sand fly salivary protein protects against visceral leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-gamma at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG(2) antibody levels and significant IFN-gamma production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-gamma and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response. PMID:19461875

  7. Antiviral immune responses of bats: a review.

    PubMed

    Baker, M L; Schountz, T; Wang, L-F

    2013-02-01

    Despite being the second most species-rich and abundant group of mammals, bats are also among the least studied, with a particular paucity of information in the area of bat immunology. Although bats have a long history of association with rabies, the emergence and re-emergence of a number of viruses from bats that impact human and animal health has resulted in a resurgence of interest in bat immunology. Understanding how bats coexist with viruses in the absence of disease is essential if we are to begin to develop therapeutics to target viruses in humans and susceptible livestock and companion animals. Here, we review the current status of knowledge in the field of bat antiviral immunology including both adaptive and innate mechanisms of immune defence and highlight the need for further investigations in this area. Because data in this field are so limited, our discussion is based on both scientific discoveries and theoretical predictions. It is hoped that by provoking original, speculative or even controversial ideas or theories, this review may stimulate further research in this important field. Efforts to understand the immune systems of bats have been greatly facilitated in recent years by the availability of partial genome sequences from two species of bats, a megabat, Pteropus vampyrus, and a microbat, Myotis lucifugus, allowing the rapid identification of immune genes. Although bats appear to share most features of the immune system with other mammals, several studies have reported qualitative and quantitative differences in the immune responses of bats. These observations warrant further investigation to determine whether such differences are associated with the asymptomatic nature of viral infections in bats. PMID:23302292

  8. Ubiquitination in the Antiviral Immune Response

    PubMed Central

    Davis, Meredith E.; Gack, Michaela U.

    2016-01-01

    Ubiquitination has long been known to regulate fundamental cellular processes through the induction of proteasomal degradation of target proteins. More recently, ‘atypical’ nondegradative types of polyubiquitin chains have been appreciated as important regulatory moieties by modulating the activity or subcellular localization of key signaling proteins. Intriguingly, many of these non-degradative types of ubiquitination regulate the innate sensing pathways initiated by pattern recognition receptors (PRRs), ultimately coordinating an effective antiviral immune response. Here we discuss recent advances in understanding the functional roles of degradative and atypical types of ubiquitination in innate immunity to viral infections, with a specific focus on the signaling pathways triggered by RIG-I-like receptors, Toll-like receptors, and the intracellular viral DNA sensor cGAS. PMID:25753787

  9. Delayed Immune Mediated Adverse Effects to Hyaluronic Acid Fillers: Report of Five Cases and Review of the Literature

    PubMed Central

    Bitterman-Deutsch, Ora; Kogan, Leonid; Nasser, Faris

    2015-01-01

    Hyaluronic acid (HA) fillers in cosmetic medicine have been considered relatively safe, though fillers used in European countries and throughout the world are not necessarily approved by the Food and Drug Administration. As their use continues to expand worldwide, physicians in a wide range of medical specialties are authorized to perform HA injections, including general medicine practitioners and even dentists. An increasing number of reports have appeared regarding side effects to these products. It is now known that reactions to Hyaluronic acid are related not only to technical faults of the injections, but also to immune responses, including delayed hypersensitivity and granulomatous reactions. Herein, we describe five cases treated by a variety of treatment modalities, all with delayed reactions to different brands of hyaluronic acid fillers. As there is currently no standardization of treatment options of adverse effects, these cases accentuate the debate regarding the approach to the individual patient and the possible need for pre-testing in patients with an atopic tendency. PMID:25918619

  10. Spaceflight and Development of Immune Responses

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1996-01-01

    Evidence from both human and rodent studies has indicated that alterations in immunological parameters occur after space flight. The number of flight experiments has been small, and the full breadth of immunological alterations occurring after space flight remains to be established. Among the major effects on immune responses after space flight that have been reported are: alterations in lymphocyte blastogenesis and natural killer cell activity, alterations in production of cytokines, changes in leukocyte sub-population distribution, and decreases in the ability of bone marrow cells to respond to colony stimulating factors. Changes have been reported in immunological parameters of both humans and rodents. The significance of these alterations in relation to resistance to infection remains to be established. The objective of the studies contained in this project was to determine the effects of space flight on immune responses of pregnant rats and their offspring. The hypothesis was that space flight and the attendant period of microgravity will result in alteration of immunological parameters of both the pregnant rats as well as their offspring carried in utero during the flight. The parameters tested included: production of cytokines, composition of leukocyte sub- populations, response of bone marrow/liver cells to granulocyte/monocyte colony stimulating factor, and leukocyte blastogenesis. Changes in immune responses that could yield alterations in resistance to infection were determined. This yielded useful information for planning studies that could contribute to crew health. Additional information that could eventually prove useful to determine the potential for establishment of a permanent colony in space was obtained.

  11. Monitoring Regulatory Immune Responses in Tumor Immunotherapy Clinical Trials

    PubMed Central

    Olson, Brian M.; McNeel, Douglas G.

    2013-01-01

    While immune monitoring of tumor immunotherapy often focuses on the generation of productive Th1-type inflammatory immune responses, the importance of regulatory immune responses is often overlooked, despite the well-documented effects of regulatory immune responses in suppressing anti-tumor immunity. In a variety of malignancies, the frequency of regulatory cell populations has been shown to correlate with disease progression and a poor prognosis, further emphasizing the importance of characterizing the effects of immunotherapy on these populations. This review focuses on the role of suppressive immune populations (regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages) in inhibiting anti-tumor immunity, how these populations have been used in the immune monitoring of clinical trials, the prognostic value of these responses, and how the monitoring of these regulatory responses can be improved in the future. PMID:23653893

  12. Compartmentalization of Immune Responses in Human Tuberculosis

    PubMed Central

    Rahman, Sayma; Gudetta, Berhanu; Fink, Joshua; Granath, Anna; Ashenafi, Senait; Aseffa, Abraham; Derbew, Milliard; Svensson, Mattias; Andersson, Jan; Brighenti, Susanna Grundström

    2009-01-01

    Immune responses were assessed at the single-cell level in lymph nodes from children with tuberculous lymphadenitis. Tuberculosis infection was associated with tissue remodeling of lymph nodes as well as altered cellular composition. Granulomas were significantly enriched with CD68+ macrophages expressing the M. tuberculosis complex-specific protein antigen MPT64 and inducible nitric oxide synthase. There was a significant increase in CD8+ cytolytic T cells surrounding the granuloma; however, CD8+ T cells expressed low levels of the cytolytic and antimicrobial effector molecules perforin and granulysin in the granulomatous lesions. Quantitative real-time mRNA analysis revealed that interferon-γ, tumor necrosis factor-α, and interleukin-17 were not up-regulated in infected lymph nodes, but there was a significant induction of both transforming growth factor-β and interleukin-13. In addition, granulomas contained an increased number of CD4+FoxP3+ T cells co-expressing the immunoregulatory cytotoxic T-lymphocyte antigen-4 and glucocorticoid-induced tumor necrosis factor receptor molecules. Low numbers of CD8+ T cells in the lesions correlated with high levels of transforming growth factor-β and FoxP3+ regulatory T cells, suggesting active immunosuppression at the local infection site. Compartmentalization and skewing of the immune response toward a regulatory phenotype may result in an uncoordinated effector T-cell response that reduces granule-mediated killing of M. tuberculosis-infected cells and subsequent disease control. PMID:19435796

  13. 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

  14. 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

  15. Precision Immunization: NASA Studies Immune Response to Flu Vaccine

    NASA Video Gallery

    NASA Human Research Program Twins Study investigator Emmanuel Mignot, M.D., Ph.D, known for discovering the cause of narcolepsy is related to the immune system, is studying twin astronauts Scott an...

  16. Immune responses to coiled coil supramolecular biomaterials

    PubMed Central

    Rudra, Jai S.; Tripathi, Pulak; Hildeman, David A.; Jung, Jangwook P.; Collier, Joel H.

    2010-01-01

    Self-assembly has been increasingly utilized in recent years to create peptide-based biomaterials for 3D cell culture, tissue engineering, and regenerative medicine, but the molecular determinants of these materials' immunogenicity have remained largely unexplored. In this study, a set of molecules that self-assembled through coiled coil oligomerization was designed and synthesized, and immune responses against them were investigated in mice. Experimental groups spanned a range of oligomerization behaviors and included a peptide from the coiled coil region of mouse fibrin that did not form supramolecular structures, an engineered version of this peptide that formed coiled coil bundles, and a peptide-PEG-peptide triblock bioconjugate that formed coiled coil multimers and supramolecular aggregates. In mice, the native peptide and engineered peptide did not produce any detectable antibody response, and none of the materials elicited detectable peptide-specific T cell responses, as evidenced by the absence of IL-2 and interferon-gamma in cultures of peptide-challenged splenocytes or draining lymph node cells. However, specific antibody responses were elevated in mice injected with the multimerizing peptide-PEG-peptide. Minimal changes in secondary structure were observed between the engineered peptide and the triblock peptide-PEG-peptide, making it possible that the triblock's multimerization was responsible for this antibody response. PMID:20708258

  17. Impact of nutrition on immune function and the inflammatory response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The review utilizes data on three micronutrients (vitamin A, zinc and iron), anthropometrically defined undernutrition (stunting, wasting and underweight) and obesity to evaluate the effect on immune function, recovery of immune function in response to nutritional interventions, related health outco...

  18. Neuroendocrine and immune system responses with spaceflights.

    PubMed

    Tipton, C M; Greenleaf, J E; Jackson, C G

    1996-08-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldosterone, and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flights data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  19. Neuroendocrine and Immune System Responses with Spaceflights

    NASA Technical Reports Server (NTRS)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  20. Host immune response to infection and cancer: unexpected commonalities

    PubMed Central

    Goldszmid, Romina S.; Dzutsev, Amiran; Trinchieri, Giorgio

    2014-01-01

    Summary Both microbes and tumors activate innate resistance, tissue repair and adaptive immunity. Unlike acute infection, tumor growth is initially inapparent; however, inflammation and immunity affect all phases of tumor growth from initiation to progression and dissemination. Here, we discuss the shared features involved in the immune response to infection and cancer including modulation by commensal microbiota, reactive hematopoiesis, chronic immune responses and regulatory mechanisms to prevent collateral tissue damage. This comparative analysis of immunity to infection and cancer furthers our understanding of the basic mechanisms underlying innate resistance and adaptive immunity and their translational application to the design of new therapeutic approaches. PMID:24629336

  1. The immune response in steroid deficient mice

    PubMed Central

    Streng, Charlotte B.; Nathan, P.

    1973-01-01

    Adrenalectomy, gonadectomy and combined adrenalectomy—gonadectomy resulted in increased spleen weights, spleen cell counts and 19S plaque-forming cells following primary and secondary immunization of mice with SRBC when compared to controls. Plaque-forming cells of the 7S type in the spleen did not increase when measured on the eleventh day following the primary or the third day following secondary sensitization. Combined adrenalectomy—gonadectomy had a greater effect on spleen cell counts, spleen weights and plaque-forming cells in the primary and secondary response than either operation alone. Haemolysin titres were not significantly different between test and sham operated animals in the primary and secondary responses. In the primary responses, it appears that the increase in spleen weight and cell count is responsible for the increase in 19S plaque-forming cells. The response to a second injection of SRBC demonstrated that 19S antibody-producing cells increased three-fold in steroid depleted mice above the control values. In the test animals the 19S antibody-producing cells of the spleen were relatively enriched above that of the controls. PMID:4574579

  2. Molecular immune response of channel catfish immunized with live theronts of Ichthyophthirius multifiliis.

    PubMed

    Xu, De-Hai; Zhang, Qi-Zhong; Shoemaker, Craig A; Zhang, Dunhua; Moreira, Gabriel S A

    2016-07-01

    The parasite Ichthyophthirius multifiliis (Ich) has been reported in various freshwater fishes worldwide and results in severe losses to both food and aquarium fish production. The fish surviving natural infections or immunized with live theronts develop strong specific and non-specific immune responses. Little is known about how these immune genes are induced or how they interact and lead to specific immunity against Ichthyophthirius multifiliis in channel catfish Ictalurus punctatus. This study evaluated the differential expression of immune-related genes, including immunoglobulin, immune cell receptor, cytokine, complement factor and toll-like receptors in head kidney from channel catfish at different time points after immunization with live theronts of I. multifiliis. The immunized fish showed significantly higher anti-Ich antibody expressed as immobilization titer and ELISA titer than those of control fish. The vast majority of immunized fish (95%) survived theront challenge. Expression of IgM and IgD heavy chain genes exhibited a rapid increase from 4 hour (h4) to 2 days (d2) post immunization. Expression of immune cell receptor genes (CD4, CD8-α, MHC I, MHC II β, TcR-α, and TcR-β) showed up-regulation from h4 to d6 post immunization, indicating that different immune cells were actively involved in cellular immune response. Cytokine gene expression (IL-1βa, IL-1βb, IFN-γ and TNF-α) increased rapidly at h4 post immunization and were at an up-regulated level until d2 compared to the bovine serum albumin control. Expression of complement factor and toll-like receptor genes exhibited a rapid increase from h4 to d2 post immunization. Results of this study demonstrated differential expression of genes involved in the specific or non-specific immune response post immunization and that the vaccination against Ich resulted in protection against infection by I. multifiliis. PMID:27044331

  3. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    PubMed Central

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. PMID:25915062

  4. The immune response to resistive breathing.

    PubMed

    Vassilakopoulos, T; Roussos, C; Zakynthinos, S

    2004-12-01

    Resistive breathing is an "immune challenge" for the body, initiating an inflammatory response consisting of an elevation of plasma cytokines, and the recruitment and activation of lymphocyte subpopulations. These cytokines do not originate from monocytes, but are, instead, produced within the diaphragm, secondary to the increased muscle activation. Oxidative stress is a major stimulus for the cytokine induction, secondary to resistive breathing. The production of cytokines within the diaphragm may be mediating the diaphragm muscle fibre injury that occurs with strenuous contractions, or contributing towards the expected repair process. These cytokines may also compromise diaphragmatic contractility or contribute towards the development of muscle cachexia. They may also have systemic effects, mobilising glucose from the liver and free fatty acid from the adipose tissue to the strenuously working respiratory muscles. At the same time, they stimulate the hypothalamic-pituitary-adrenal axis, leading to production of adrenocorticotropin and beta-endorphins. The adrenocorticotropin response may represent an attempt of the organism to reduce the injury occurring in the respiratory muscles via the production of glucocorticoids and the induction of the acute phase-response proteins. The beta-endorphin response would decrease the activation of the respiratory muscles and change the pattern of breathing, which becomes more rapid and shallow, possibly in an attempt to reduce and/or prevent further injury to the respiratory muscles. PMID:15572550

  5. Ontogeny of the Bovine Immune Response 1

    PubMed Central

    Schultz, R. D.; Dunne, H. W.; Heist, C. E.

    1973-01-01

    The ontogenesis of the bovine immune response was studied in three embryos (<40 days) and 106 fetuses of various ages. In the absence of overt antigenic stimulation, fetuses had lymphoid development of the thymus at 42 days of gestation, the spleen was structurally present at 55 days, and certain peripheral lymph nodes were present at 60 days. Mesenteric lymph nodes were structurally present by 100 days of gestation, and lymphoid tissue of the gastrointestinal tract, particularly the lower ileum, was observed in histologic sections of a 175-day fetus with a bacterial infection. Pyroninophilic cells, plasma cells, and germinal centers were present in lymph node sections of antigenically stimulated fetuses. Lymphoid tissue developed more rapidly in fetuses with bacteria, viral antigens, or apparent maternal red-blood-cell antigens than in the normal fetus. Thymic and splenic indices reached maximal values in the 205- to 220-day fetal age group. Immunoglobulin M (IgM)-containing cells were first observed, by immunofluorescence, in a single fetus at 59 days of gestation. Immunoglobulin G (IgG)-containing cells were observed at 145 days of gestation in one fetus with a bacterial and viral infection. IgM-containing cells were observed in 36 fetuses and IgM and IgG cells were present in seven fetuses. Spleen, lymph nodes, thymus, bone marrow, and liver of one fetus from a dam with lymphosarcoma had immunoglobulin-containing cells. Hemal lymph nodes, blood (buffy coat), Peyer patches, and heart and lung sections from fetuses with immunoglobulin-containing cells in spleen or lymph node did not have immunoglobulin-containing cells. Antigens of the virus of bovine virus diarrhea-mucosal disease (BVD) were detected in one fetus, and antigens of infectious bovine rhinotracheitis (IBR) virus were detected in three fetuses; however, viruses were not isolated in primary bovine embryonic kidney cells. Two of the three fetuses with IBR virus antigens had neutralizing serum antibody

  6. Human immune response to Mycobacterium tuberculosis antigens.

    PubMed Central

    Havlir, D V; Wallis, R S; Boom, W H; Daniel, T M; Chervenak, K; Ellner, J J

    1991-01-01

    Little is known about the immunodominant or protective antigens of Mycobacterium tuberculosis in humans. Cell-mediated immunity is necessary for protection, and healthy tuberculin-positive individuals are relatively resistant to exogenous reinfection. We compared the targets of the cell-mediated immune response in healthy tuberculin-positive individuals to those of tuberculosis patients and tuberculin-negative persons. By using T-cell Western blotting (immunoblotting) of nitrocellulose-bound M. tuberculosis culture filtrate, peaks of T-cell blastogenic activity were identified in the healthy tuberculin reactors at 30, 37, 44, 57, 64, 71 and 88 kDa. Three of these fractions (30, 64, and 71 kDa) coincided with previously characterized proteins: antigen 6/alpha antigen, HSP60, and HSP70, respectively. The blastogenic responses to purified M. tuberculosis antigen 6/alpha antigen and BCG HSP60 were assessed. When cultured with purified antigen 6/alpha antigen, lymphocytes of healthy tuberculin reactors demonstrated greater [3H]thymidine incorporation than either healthy tuberculin-negative controls or tuberculous patients (8,113 +/- 1,939 delta cpm versus 645 +/- 425 delta cpm and 1,019 +/- 710 delta cpm, respectively; P less than 0.01). Healthy reactors also responded to HSP60, although to a lesser degree than antigen 6/alpha antigen (4,276 +/- 1,095 delta cpm; P less than 0.05). Partially purified HSP70 bound to nitrocellulose paper elicited a significant lymphocyte blastogenic response in two of six of the tuberculous patients but in none of the eight healthy tuberculin reactors. Lymphocytes of none of five tuberculin-negative controls responded to recombinant antigens at 14 or 19 kDa or to HSP70. Antibody reactivity generally was inversely correlated with blastogenic response: tuberculous sera had high titer antibody to M. tuberculosis culture filtrate in a range from 35 to 180 kDa. This is the first systematic evaluation of the human response to a panel of native

  7. Nanomaterial Induced Immune Responses and Cytotoxicity.

    PubMed

    Ali, Ashraf; Suhail, Mohd; Mathew, Shilu; Shah, Muhammad Ali; Harakeh, Steve M; Ahmad, Sultan; Kazmi, Zulqarnain; Alhamdan, Mohammed Abdul Rahman; Chaudhary, Adeel; Damanhouri, Ghazi Abdullah; Qadri, Ishtiaq

    2016-01-01

    Nanomaterials are utilized in a wide array of end user products such as pharmaceuticals, electronics, clothes and cosmetic products. Due to its size (< 100 nm), nanoparticles have the propensity to enter through the airway and skin, making its path perilous with the potential to cause damages of varying severity. Once within the body, these particles have unconstrained access to different tissues and organs including the brain, liver, and kidney. As a result, nanomaterials may cause the perturbation of the immune system eliciting an inflammatory response and cytotoxicity. This potential role is dependent on many factors such as the characteristics of the nanomaterials, presence or absence of diseases, and genetic predisposition. Cobalt and nickel nanoparticles, for example, were shown to have inflammogenic properties, while silver nanoparticles were shown to reduce allergic inflammation. Just as asbestos fibers, carbon nanotubes were shown to cause lungs damage. Some nanomaterials were shown, based on animal studies, to result in cell damage, leading to the formation of pre-cancerous lesions. This review highlights the impact of nanomaterials on immune system and its effect on human health with toxicity consideration. It recommends the development of suitable animal models to study the toxicity and bio-clearance of nanomaterials and propose safety guidelines. PMID:27398432

  8. Local Immune Response in Helicobacter pylori Infection.

    PubMed

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-05-01

    There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori-infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC).In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines-interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32-in H pylori-infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients.We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori-infected NGM group.This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  9. Malaria vaccines and human immune responses.

    PubMed

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. PMID:27262417

  10. Local Immune Response in Helicobacter pylori Infection

    PubMed Central

    Kivrak Salim, Derya; Sahin, Mehmet; Köksoy, Sadi; Adanir, Haydar; Süleymanlar, Inci

    2016-01-01

    Abstract There have been few studies concerning the cytokine profiles in gastric mucosa of Helicobacter pylori–infected patients with normal mucosa, chronic gastritis, and gastric carcinoma (GAC). In the present study, we aimed to elucidate the genomic expression levels and immune pathological roles of cytokines—interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-6, IL-10, transforming growth factor (TGF)-β, IL-17A, IL-32—in H pylori–infected patients with normal gastric mucosa (NGM; control), chronic active gastritis (CAG), and GAC. Genomic expression levels of these cytokines were assayed by real-time PCR analysis in gastric biopsy specimens obtained from 93 patients. We found that the genomic expression levels of IFN-γ, TNF-α, IL-6, IL-10, IL-17A mRNA were increased in the CAG group and those of TNF-α, IL-6, IL-10, IL-17A, TGF-β mRNA were increased in the GAC group with reference to H pylori–infected NGM group. This study is on the interest of cytokine profiles in gastric mucosa among individuals with normal, gastritis, or GAC. Our findings suggest that the immune response of gastric mucosa to infection of H pylori differs from patient to patient. For individual therapy, levels of genomic expression of IL-6 or other cytokines may be tracked in patients. PMID:27196487

  11. Adverse Effect of Nano-Silicon Dioxide on Lung Function of Rats with or without Ovalbumin Immunization

    PubMed Central

    Abrahaley, Tesfamariam; Qin, Longjuan; Wang, Li; Zheng, Yuduo; Li, Bing; Liu, Dandan; Yao, Hanchao; Yang, Jiwen; Li, Changming; Xi, Zhuge; Yang, Xu

    2011-01-01

    Background The great advances of nanomaterials have brought out broad important applications, but their possible nanotoxicity and risks have not been fully understood. It is confirmed that exposure of environmental particulate matter (PM), especially ultrafine PM, are responsible for many lung function impairment and exacerbation of pre-existing lung diseases. However, the adverse effect of nanoparticles on allergic asthma is seldom investigated and the mechanism remains undefined. For the first time, this work investigates the relationship between allergic asthma and nanosized silicon dioxide (nano-SiO2). Methodology/Principal Findings Ovalbumin (OVA)-treated and saline-treated control rats were daily intratracheally administered 0.1 ml of 0, 40 and 80 µg/ml nano-SiO2 solutions, respectively for 30 days. Increased nano-SiO2 exposure results in adverse changes on inspiratory and expiratory resistance (Ri and Re), but shows insignificant effect on rat lung dynamic compliance (Cldyn). Lung histological observation reveals obvious airway remodeling in 80 µg/ml nano-SiO2-introduced saline and OVA groups, but the latter is worse. Additionally, increased nano-SiO2 exposure also leads to more severe inflammation. With increasing nano-SiO2 exposure, IL-4 in lung homogenate increases and IFN-γ shows a reverse but insignificant change. Moreover, at a same nano-SiO2 exposure concentration, OVA-treated rats exhibit higher (significant) IL-4 and lower (not significant) IFN-γ compared with the saline-treated rats. The percentages of eosinophil display an unexpected result, in which higher exposure results lower eosinophil percentages. Conclusions/Significance This was a preliminary study which for the first time involved the effect of nano-SiO2 to OVA induced rat asthma model. The results suggested that intratracheal administration of nano-SiO2 could lead to the airway hyperresponsiveness (AHR) and the airway remolding with or without OVA immunization. This occurrence may be

  12. Essential oil of clove (Eugenia caryophyllata) augments the humoral immune response but decreases cell mediated immunity.

    PubMed

    Halder, Sumita; Mehta, Ashish K; Mediratta, Pramod K; Sharma, Krishna K

    2011-08-01

    The present study was undertaken to explore the effect of the essential oil isolated from the buds of Eugenia caryophyllata on some immunological parameters. Humoral immunity was assessed by measuring the hemagglutination titre to sheep red blood cells and delayed type hypersensitivity was assessed by measuring foot pad thickness. Clove oil administration produced a significant increase in the primary as well as secondary humoral immune response. In addition, it also produced a significant decrease in foot pad thickness compared with the control group. Thus, these results suggest that clove oil can modulate the immune response by augmenting humoral immunity and decreasing cell mediated immunity. PMID:21796701

  13. Disentangling the relationship between tumor genetic programs and immune responsiveness.

    PubMed

    Bedognetti, Davide; Hendrickx, Wouter; Ceccarelli, Michele; Miller, Lance D; Seliger, Barbara

    2016-04-01

    Correlative studies in humans have demonstrated that an active immune microenvironment characterized by the presence of a T-helper 1 immune response typifies a tumor phenotype associated with better outcome and increased responsiveness to immune manipulation. This phenotype also signifies the counter activation of immune-regulatory mechanisms. Variables modulating the development of an effective anti-tumor immune response are increasingly scrutinized as potential therapeutic targets. Genetic alterations of cancer cells that functionally influence intratumoral immune response include mutational load, specific mutations of genes involved in oncogenic pathways and copy number aberrations involving chemokine and cytokine genes. Inhibiting oncogenic pathways that prevent the development of the immune-favorable cancer phenotype may complement modern immunotherapeutic approaches. PMID:26967649

  14. Meeting report VLPNPV: Session 3: Immune responses.

    PubMed

    Morrison, Trudy G

    2014-01-01

    Virus-like particles (VLPs) and nano-particles (NP) are increasingly considered for both prophylactic and therapeutic vaccines for a wide variety of human and animal diseases. Indeed, 2 VLPs have already been licensed for use in humans, the human papilloma virus vaccine and the hepatitis B virus vaccine. (1) Reflecting this increased interest, a second international conference with a specific focus on VLPs and NP was held at the Salk Institute for Biological Studies in La Jolla, California, in June 2014. Approximately 100 attendees, hailing from many nations, came from academic institutions, research institutes, and biotech companies. A wide variety of topics were discussed, ranging from development and characterization of specific VLP and NP vaccine candidates to methods of production of these particles. Session three was focused on the general question of immune responses to VLPs. PMID:25529229

  15. Population-expression models of immune response

    NASA Astrophysics Data System (ADS)

    Stromberg, Sean P.; Antia, Rustom; Nemenman, Ilya

    2013-06-01

    The immune response to a pathogen has two basic features. The first is the expansion of a few pathogen-specific cells to form a population large enough to control the pathogen. The second is the process of differentiation of cells from an initial naive phenotype to an effector phenotype which controls the pathogen, and subsequently to a memory phenotype that is maintained and responsible for long-term protection. The expansion and the differentiation have been considered largely independently. Changes in cell populations are typically described using ecologically based ordinary differential equation models. In contrast, differentiation of single cells is studied within systems biology and is frequently modeled by considering changes in gene and protein expression in individual cells. Recent advances in experimental systems biology make available for the first time data to allow the coupling of population and high dimensional expression data of immune cells during infections. Here we describe and develop population-expression models which integrate these two processes into systems biology on the multicellular level. When translated into mathematical equations, these models result in non-conservative, non-local advection-diffusion equations. We describe situations where the population-expression approach can make correct inference from data while previous modeling approaches based on common simplifying assumptions would fail. We also explore how model reduction techniques can be used to build population-expression models, minimizing the complexity of the model while keeping the essential features of the system. While we consider problems in immunology in this paper, we expect population-expression models to be more broadly applicable.

  16. NKT Cell Immune Responses to Viral Infection

    PubMed Central

    Tessmer, Marlowe S.; Fatima, Ayesha; Paget, Christophe; Trottein, François; Brossay, Laurent

    2010-01-01

    Background Natural killer T (NKT) cells are a heterogeneous population of innate T cells that have attracted recent interest because of their potential to regulate immune responses to a variety of pathogens. The most widely studied NKT cell subset is the invariant (i)NKT cells that recognize glycolipids in the context of the CD1d molecule. The multifaceted methods of activation iNKT cells possess and their ability to produce regulatory cytokines has made them a primary target for therapeutic studies. Objective/Methods This review gives insight into the roles of iNKT cells during infectious diseases, particularly viral infections. We also highlight the different mechanisms leading to iNKT cell activation in response to pathogens. Conclusions The iNKT cell versatility allows them to detect and respond to several viral infections. However, therapeutic approaches to specifically target iNKT cells will require additional research. Notably, examination of the roles of non-invariant NKT cells in response to pathogens warrant further investigations. PMID:19236234

  17. Location, location, location: tissue-specific regulation of immune responses

    PubMed Central

    Hu, Wei; Pasare, Chandrashekhar

    2013-01-01

    Discovery of DCs and PRRs has contributed immensely to our understanding of induction of innate and adaptive immune responses. Activation of PRRs leads to secretion of inflammatory cytokines that regulate priming and differentiation of antigen-specific T and B lymphocytes. Pathogens enter the body via different routes, and although the same set of PRRs is likely to be activated, it is becoming clear that the route of immune challenge determines the nature of outcome of adaptive immunity. In addition to the signaling events initiated following innate-immune receptor activation, the cells of the immune system are influenced by the microenvironments in which they reside, and this has a direct impact on the resulting immune response. Specifically, immune responses could be influenced by specialized DCs, specific factors secreted by stromal cells, and also, by commensal microbiota present in certain organs. Following microbial detection, the complex interactions among DCs, stromal cells, and tissue-specific factors influence outcome of immune responses. In this review, we summarize recent findings on the phenotypic heterogeneity of innate and adaptive immune cells and how tissue-specific factors in the systemic and mucosal immune system influence the outcome of adaptive-immune responses. PMID:23825388

  18. Developing a national system for dealing with adverse events following immunization.

    PubMed Central

    Mehta, U.; Milstien, J. B.; Duclos, P.; Folb, P. I.

    2000-01-01

    Although vaccines are among the safest of pharmaceuticals, the occasional severe adverse event or cluster of adverse events associated with their use may rapidly become a serious threat to public health. It is essential that national monitoring and reporting systems for vaccine safety are efficient and adequately coordinated with those that conventionally deal with non-vaccine pharmaceuticals. Equally important is the need for an enlightened and informed national system to be in place to deal with public concerns and rapid evaluation of the risk to public safety when adverse events occur. Described in this article is the outcome of efforts by the WHO Global Training Network to describe a simple national system for dealing with vaccine safety and with emergencies as they arise. The goals of a training programme designed to help develop such a system are also outlined. PMID:10743281

  19. Targeting the tumor microenvironment to enhance antitumor immune responses

    PubMed Central

    Van der Jeught, Kevin; Bialkowski, Lukasz; Daszkiewicz, Lidia; Broos, Katrijn; Goyvaerts, Cleo; Renmans, Dries; Van Lint, Sandra; Heirman, Carlo; Thielemans, Kris; Breckpot, Karine

    2015-01-01

    The identification of tumor-specific antigens and the immune responses directed against them has instigated the development of therapies to enhance antitumor immune responses. Most of these cancer immunotherapies are administered systemically rather than directly to tumors. Nonetheless, numerous studies have demonstrated that intratumoral therapy is an attractive approach, both for immunization and immunomodulation purposes. Injection, recruitment and/or activation of antigen-presenting cells in the tumor nest have been extensively studied as strategies to cross-prime immune responses. Moreover, delivery of stimulatory cytokines, blockade of inhibitory cytokines and immune checkpoint blockade have been explored to restore immunological fitness at the tumor site. These tumor-targeted therapies have the potential to induce systemic immunity without the toxicity that is often associated with systemic treatments. We review the most promising intratumoral immunotherapies, how these affect systemic antitumor immunity such that disseminated tumor cells are eliminated, and which approaches have been proven successful in animal models and patients. PMID:25682197

  20. Spaceflight and immune responses of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  1. Spaceflight and Immune Responses of Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1997-01-01

    In the grant period, we perfected techniques for determination of interleukin production and leukocyte subset analysis of rhesus monkeys. These results are outlined in detail in publication number 2, appended to this report. Additionally, we participated in the ARRT restraint test to determine if restraint conditions for flight in the Space Shuttle could contribute to any effects of space flight on immune responses. All immunological parameters listed in the methods section were tested. Evaluation of the data suggests that the restraint conditions had minimal effects on the results observed, but handling of the monkeys could have had some effect. These results are outlined in detail in manuscript number 3, appended to this report. Additionally, to help us develop our rhesus monkey immunology studies, we carried out preliminary studies in mice to determine the effects of stressors on immunological parameters. We were able to show that there were gender-based differences in the response of immunological parameters to a stressor. These results are outlined in detail in manuscript number 4, appended to this report.

  2. The unfolded protein response in immunity and inflammation.

    PubMed

    Grootjans, Joep; Kaser, Arthur; Kaufman, Randal J; Blumberg, Richard S

    2016-08-01

    The unfolded protein response (UPR) is a highly conserved pathway that allows the cell to manage endoplasmic reticulum (ER) stress that is imposed by the secretory demands associated with environmental forces. In this role, the UPR has increasingly been shown to have crucial functions in immunity and inflammation. In this Review, we discuss the importance of the UPR in the development, differentiation, function and survival of immune cells in meeting the needs of an immune response. In addition, we review current insights into how the UPR is involved in complex chronic inflammatory diseases and, through its role in immune regulation, antitumour responses. PMID:27346803

  3. Q fever in pregnant goats: humoral and cellular immune responses

    PubMed Central

    2013-01-01

    Q fever is a zoonosis caused by the intracellular bacterium Coxiella burnetii. Both humoral and cellular immunity are important in the host defence against intracellular bacteria. Little is known about the immune response to C. burnetii infections in domestic ruminants even though these species are the major source of Q fever in humans. To investigate the goat’s immune response we inoculated groups of pregnant goats via inhalation with a Dutch outbreak isolate of C. burnetii. All animals were successfully infected. Phase 1 and Phase 2 IgM- and IgG-specific antibodies were measured. Cellular immune responses were investigated by interferon-gamma, enzyme-linked immunosorbent spot test (IFN-γ Elispot), lymphocyte proliferation test (LPT) and systemic cytokines. After two weeks post inoculation (wpi), a strong anti-C. burnetii Phase 2 IgM and IgG antibody response was observed while the increase in IgM anti-Phase 1 antibodies was less pronounced. IgG anti-Phase 1 antibodies started to rise at 6 wpi. Cellular immune responses were observed after parturition. Our results demonstrated humoral and cellular immune responses to C. burnetii infection in pregnant goats. Cell-mediated immune responses did not differ enough to distinguish between Coxiella-infected and non-infected pregnant animals, whereas a strong-phase specific antibody response is detected after 2 wpi. This humoral immune response may be useful in the early detection of C. burnetii-infected pregnant goats. PMID:23915213

  4. Maternal antibodies and infant immune responses to vaccines.

    PubMed

    Edwards, Kathryn M

    2015-11-25

    Infants are born with immature immune systems, making it difficult for them to effectively respond to the infectious pathogens encountered shortly after birth. Maternal antibody is actively transported across the placenta and serves to provide protection to the newborn during the first weeks to months of life. However, maternal antibody has been shown repeatedly to inhibit the immune responses of young children to vaccines. The mechanisms for this inhibition are presented and the impact on ultimate immune responses is discussed. PMID:26256526

  5. Innate immune response development in nestling tree swallows

    USGS Publications Warehouse

    Stambaugh, T.; Houdek, B.J.; Lombardo, M.P.; Thorpe, P.A.; Caldwell, Hahn D.

    2011-01-01

    We tracked the development of innate immunity in nestling Tree Swallows (Tachycineta bicolor) and compared it to that of adults using blood drawn from nestlings during days 6, 12, and 18 of the ???20-day nestling period and from adults. Innate immunity was characterized using an in vitro assay of the ability of whole blood to kill Escherichia coli. The ability of whole blood to kill E. coli increased as nestlings matured. Neither this component of innate immunity nor right wing chord length on day18 were as developed as in adults indicating that development of the innate immune system and growth both continued after fledging. Narrow sense heritability analyses suggest that females with strong immune responses produced nestlings with strong immune responses. These data suggest nestling Tree Swallows allocated sufficient energy to support rapid growth to enable fledging by day 18, but that further development of innate immunity occurred post-fledging. ?? 2011 by the Wilson Ornithological Society.

  6. Soy-Based Formula Does Not Adversely Affect Immune System Development in Neonatal Piglets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breast-fed infants are less susceptible to infections and allergic reactions than those fed formula, suggesting that diet may influence neonatal immune system development. The goal of the present study was two fold: 1. to determine the effect of formula feeding relative to breast-feeding on neonata...

  7. 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

  8. Local immune response and protection in the guinea pig keratoconjunctivitis model following immunization with Shigella vaccines.

    PubMed Central

    Hartman, A B; Van de Verg, L L; Collins, H H; Tang, D B; Bendiuk, N O; Taylor, D N; Powell, C J

    1994-01-01

    This study used the guinea pig keratoconjunctivitis model to examine the importance of route of administration (mucosal versus parenteral), frequency and timing of immunization (primary versus boosting immunization), and form of antigen given (live attenuated vaccine strain versus O-antigen-protein conjugate) on the production of protective immunity against Shigella infection. Since local immune response to the lipopolysaccharide (LPS) O-antigen of Shigella spp. is thought to be important for protection against disease, O-antigen-specific antibody-secreting cells (ASC) in the spleen and regional lymph nodes of immunized animals were measured by using an ELISPOT assay. Results indicated that protective efficacy was associated with a strong O-antigen-specific ASC response, particularly in the superficial ventral cervical lymph nodes draining the conjunctivae. In naive animals, a strong ASC response in the cervical lymph nodes and protection against challenge were detected only in animals that received a mucosal immunization. Protection in these animals was increased by a boosting mucosal immunization. While parenteral immunization alone with an O-antigen-protein conjugate vaccine did not protect naive animals against challenge, a combined parenteral-mucosal regimen elicited enhanced protection without the addition of a boosting immunization. Although O-antigen-specific serum immunoglobulin A titers were significantly higher in animals receiving a mucosal immunization, there was no apparent correlation between levels of serum antibody and protection against disease. PMID:7507892

  9. The weight of obesity on the human immune response to vaccination

    PubMed Central

    Painter, Scott D.; Ovsyannikova, Inna G.; Poland, Gregory A.

    2015-01-01

    Despite the high success of protection against several infectious diseases through effective vaccines, some sub-populations have been observed to respond poorly to vaccines, putting them at increased risk for vaccine-preventable diseases. In particular, the limited data concerning the effect of obesity on vaccine immunogenicity and efficacy suggests that obesity is a factor that increases the likelihood of a poor vaccine-induced immune response. Obesity occurs through the deposition of excess lipids into adipose tissue through the production of adipocytes, and is defined as a body-mass index (BMI) ≥ 30 kg/m2. The immune system is adversely affected by obesity, and these “immune consequences” raise concern for the lack of vaccine-induced immunity in the obese patient requiring discussion of how this sub-population might be better protected. PMID:26163925

  10. The anticancer immune response: indispensable for therapeutic success?

    PubMed Central

    Zitvogel, Laurence; Apetoh, Lionel; Ghiringhelli, François; André, Fabrice; Tesniere, Antoine; Kroemer, Guido

    2008-01-01

    Although the impact of tumor immunology on the clinical management of most cancers is still negligible, there is increasing evidence that anticancer immune responses may contribute to the control of cancer after conventional chemotherapy. Thus, radiotherapy and some chemotherapeutic agents, in particular anthracyclines, can induce specific immune responses that result either in immunogenic cancer cell death or in immunostimulatory side effects. This anticancer immune response then helps to eliminate residual cancer cells (those that fail to be killed by chemotherapy) or maintains micrometastases in a stage of dormancy. Based on these premises, in this Review we address the question, How may it be possible to ameliorate conventional therapies by stimulating the anticancer immune response? Moreover, we discuss the rationale of clinical trials to evaluate and eventually increase the contribution of antitumor immune responses to the therapeutic management of neoplasia. PMID:18523649

  11. Tipping a favorable CNS intratumoral immune response using immune stimulation combined with inhibition of tumor-mediated immune suppression.

    PubMed

    Kong, Ling-Yuan; Wei, Jun; Fuller, Gregory N; Schrand, Brett; Gabrusiewicz, Konrad; Zhou, Shouhao; Rao, Ganesh; Calin, George; Gilboa, Eli; Heimberger, Amy B

    2016-05-01

    High-grade gliomas are notoriously heterogeneous regarding antigen expression, effector responses, and immunosuppressive mechanisms. Therefore, combinational immune therapeutic approaches are more likely to impact a greater number of patients and result in longer, durable responses. We have previously demonstrated the monotherapeutic effects of miR-124, which inhibits the signal transducer and activator of transcription 3 (STAT3) immune suppressive pathway, and immune stimulatory 4-1BB aptamers against a variety of malignancies, including genetically engineered immune competent high-grade gliomas. To evaluate potential synergy, we tested an immune stimulatory aptamer together with microRNA-124 (miRNA-124), which blocks tumor-mediated immune suppression, and found survival to be markedly enhanced, including beyond that produced by monotherapy. The synergistic activity appeared to be not only secondary to enhanced CD3(+) cell numbers but also to reduced macrophage immune tumor trafficking, indicating that a greater therapeutic benefit can be achieved with approaches that both induce immune activation and inhibit tumor-mediated immune suppression within the central nervous system (CNS) tumors. PMID:27467917

  12. Biomimetic and synthetic interfaces to tune immune responses (Review)

    PubMed Central

    Garapaty, Anusha; Champion, Julie A.

    2015-01-01

    Organisms depend upon complex intercellular communication to initiate, maintain, or suppress immune responses during infection or disease. Communication occurs not only between different types of immune cells, but also between immune cells and nonimmune cells or pathogenic entities. It can occur directly at the cell–cell contact interface, or indirectly through secreted signals that bind cell surface molecules. Though secreted signals can be soluble, they can also be particulate in nature and direct communication at the cell–particle interface. Secreted extracellular vesicles are an example of native particulate communication, while viruses are examples of foreign particulates. Inspired by communication at natural immunological interfaces, biomimetic materials and designer molecules have been developed to mimic and direct the type of immune response. This review describes the ways in which native, biomimetic, and designer materials can mediate immune responses. Examples include extracellular vesicles, particles that mimic immune cells or pathogens, and hybrid designer molecules with multiple signaling functions, engineered to target and bind immune cell surface molecules. Interactions between these materials and immune cells are leading to increased understanding of natural immune communication and function, as well as development of immune therapeutics for the treatment of infection, cancer, and autoimmune disease. PMID:26178262

  13. Inflammatory Cytokines as Preclinical Markers of Adverse Responses to Chemical Stressors

    EPA Science Inventory

    Abstract: The in vivo cytokine response to chemical stressors is a promising mainstream tool used to assess potential systemic inflammation and immune function changes. Notably, new instrumentation and statistical analysis provide the selectivity and sensitivity to rapidly diff...

  14. [Therapy monitoring and management of adverse events in PD-1/PD-L1 immune checkpoint inhibition].

    PubMed

    Oppel-Heuchel, H; Grimm, M-O

    2016-05-01

    Nivolumab was recently approved as the first inhibitor of the programmed death 1 (PD-1) receptor and its ligand (PD-L1) for the treatment of urological cancer, namely metastasized renal cell carcinoma after prior therapy. The use of this new immunotherapy requires special therapy monitoring and management of side effects. An increase of immune cells around the tumor can initially mimic progression (so-called pseudoprogression). Treatment-associated side effects of higher grade according to the common terminology criteria for adverse events (CTCAE grades 3 or 4) are relatively rare; however, new immune-mediated side effects can occur and affect the skin, liver (hepatitis), kidneys (nephritis), gastrointestinal tract (diarrhea and colitis), lungs (pneumonitis) and endocrine organs (hyperthyroidism, hypothyroidism and hypophysitis). Treatment has to be delayed or discontinued depending on the kind and degree of side effects; furthermore, corticosteroids can be administered as immunosuppressants. When recognized in time and with correct management, immune-mediated side effects are basically reversible. PMID:27146870

  15. The innate immune response in the central nervous system and its role in glioma immune surveillance.

    PubMed

    Friese, M A; Steinle, A; Weller, M

    2004-10-01

    The innate immune system encompasses natural killer (NK) cells, macrophages and granulocytes, the complement system and antimicrobial peptides. Recognition pathways of the innate immune system include microbial non-self recognition, missing-self recognition and induced- self recognition. The central nervous system (CNS) participates in responses of the innate immune system. However, immune inhibitory and anti-inflammatory mechanisms physiologically outbalance and counteract immune activity and thereby limit immune-mediated tissue damage in the brain. Human gliomas appear to take advantage of this immunosuppressive milieu. Moreover, glioma cells themselves interfere with anti-tumor immune responses by expressing immune inhibitory cell surface molecules, such as HLA-G, or by releasing soluble immunosuppressants such as transforming growth factor (TGF)-beta. Yet, although glioma cells exhibit all cellular features of malignancy, these tumors very rarely metastasize outside the brain, raising the possibility of immune-mediated control of these cells outside, but not inside, the brain. Accordingly, activating the innate immune system by forcing glioma cells to express danger signals such as NKG2D ligands is a promising strategy of immunotherapy for these tumors. PMID:15585981

  16. Cumulative Adversity Sensitizes Neural Response to Acute Stress: Association with Health Symptoms

    PubMed Central

    Seo, Dongju; Tsou, Kristen A; Ansell, Emily B; Potenza, Marc N; Sinha, Rajita

    2014-01-01

    Cumulative adversity (CA) increases stress sensitivity and risk of adverse health outcomes. However, neural mechanisms underlying these associations in humans remain unclear. To understand neural responses underlying the link between CA and adverse health symptoms, the current study assessed brain activity during stress and neutral-relaxing states in 75 demographically matched, healthy individuals with high, mid, and low CA (25 in each group), and their health symptoms using the Cornell Medical Index. CA was significantly associated with greater adverse health symptoms (P=0.01) in all participants. Functional magnetic resonance imaging results indicated significant associations between CA scores and increased stress-induced activity in the lateral prefrontal cortex, insula, striatum, right amygdala, hippocampus, and temporal regions in all 75 participants (p<0.05, whole-brain corrected). In addition to these regions, the high vs low CA group comparison revealed decreased stress-induced activity in the medial orbitofrontal cortex (OFC) in the high CA group (p<0.01, whole-brain corrected). Specifically, hypoactive medial OFC and hyperactive right hippocampus responses to stress were each significantly associated with greater adverse health symptoms (p<0.01). Furthermore, an inverse correlation was found between activity in the medial OFC and right hippocampus (p=0.01). These results indicate that high CA sensitizes limbic–striatal responses to acute stress and also identifies an important role for stress-related medial OFC and hippocampus responses in the effects of CA on increasing vulnerability to adverse health consequences. PMID:24051900

  17. Transcriptional analysis of the innate immune response using the avian innate immunity microarray

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The avian innate immunity microarray (AIIM) is a genomics tool designed to study the transcriptional activity of the avian immune response (Cytogenet. Genome Res. 117:139-145, 2007). It is an avian cDNA microarray representing 4,959 avian genes spotted in triplicate. The AIIM contains 25 avian int...

  18. Immune markers and correlates of protection for vaccine induced immune responses.

    PubMed

    Thakur, Aneesh; Pedersen, Lasse E; Jungersen, Gregers

    2012-07-13

    Vaccines have been a major innovation in the history of mankind and still have the potential to address the challenges posed by chronic intracellular infections including tuberculosis, HIV and malaria which are leading causes of high morbidity and mortality across the world. Markers of an appropriate humoral response currently remain the best validated correlates of protective immunity after vaccination. Despite advancements in the field of immunology over the past few decades currently there are, however, no sufficiently validated immune correlates of vaccine induced protection against chronic infections in neither human nor veterinary medicine. Technological and conceptual advancements within cell-mediated immunology have led to a number of new immunological read-outs with the potential to emerge as correlates of vaccine induced protection. For T(H)1 type responses, antigen-specific production of interferon-gamma (IFN-γ) has been promoted as a quantitative marker of protective cell-mediated immune responses over the past couple of decades. More recently, however, evidence from several infections has pointed towards the quality of the immune response, measured through increased levels of antigen-specific polyfunctional T cells capable of producing a triad of relevant cytokines, as a better correlate of sustained protective immunity against this type of infections. Also the possibilities to measure antigen-specific cytotoxic T cells (CTL) during infection or in response to vaccination, through recombinant major histocompatibility complex (MHC) class I tetramers loaded with relevant peptides, has opened a new vista to include CTL responses in the evaluation of protective immune responses. Here, we review different immune markers and new candidates for correlates of a protective vaccine induced immune response against chronic infections and how successful they have been in defining the protective immunity in human and veterinary medicine. PMID:22658928

  19. 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

  20. Immune Response in Thyroid Cancer: Widening the Boundaries

    PubMed Central

    Ward, Laura Sterian

    2014-01-01

    The association between thyroid cancer and thyroid inflammation has been repeatedly reported and highly debated in the literature. In fact, both molecular and epidemiological data suggest that these diseases are closely related and this association reinforces that the immune system is important for thyroid cancer progression. Innate immunity is the first line of defensive response. Unlike innate immune responses, adaptive responses are highly specific to the particular antigen that induced them. Both branches of the immune system may interact in antitumor immune response. Major effector cells of the immune system that directly target thyroid cancer cells include dendritic cells, macrophages, polymorphonuclear leukocytes, mast cells, and lymphocytes. A mixture of immune cells may infiltrate thyroid cancer microenvironment and the balance of protumor and antitumor activity of these cells may be associated with prognosis. Herein, we describe some evidences that immune response may be important for thyroid cancer progression and may help us identify more aggressive tumors, sparing the vast majority of patients from costly unnecessary invasive procedures. The future trend in thyroid cancer is an individualized therapy. PMID:25328756

  1. Proteasome function shapes innate and adaptive immune responses.

    PubMed

    Kammerl, Ilona E; Meiners, Silke

    2016-08-01

    The proteasome system degrades more than 80% of intracellular proteins into small peptides. Accordingly, the proteasome is involved in many essential cellular functions, such as protein quality control, transcription, immune responses, cell signaling, and apoptosis. Moreover, degradation products are loaded onto major histocompatibility class I molecules to communicate the intracellular protein composition to the immune system. The standard 20S proteasome core complex contains three distinct catalytic active sites that are exchanged upon stimulation with inflammatory cytokines to form the so-called immunoproteasome. Immunoproteasomes are constitutively expressed in immune cells and have different proteolytic activities compared with standard proteasomes. They are rapidly induced in parenchymal cells upon intracellular pathogen infection and are crucial for priming effective CD8(+) T-cell-mediated immune responses against infected cells. Beyond shaping these adaptive immune reactions, immunoproteasomes also regulate the function of immune cells by degradation of inflammatory and immune mediators. Accordingly, they emerge as novel regulators of innate immune responses. The recently unraveled impairment of immunoproteasome function by environmental challenges and by genetic variations of immunoproteasome genes might represent a currently underestimated risk factor for the development and progression of lung diseases. In particular, immunoproteasome dysfunction will dampen resolution of infections, thereby promoting exacerbations, may foster autoimmunity in chronic lung diseases, and possibly contributes to immune evasion of tumor cells. Novel pharmacological tools, such as site-specific inhibitors of the immunoproteasome, as well as activity-based probes, however, hold promises as innovative therapeutic drugs for respiratory diseases and biomarker profiling, respectively. PMID:27343191

  2. Chemical Tools To Monitor and Manipulate Adaptive Immune Responses.

    PubMed

    Doran, Todd M; Sarkar, Mohosin; Kodadek, Thomas

    2016-05-18

    Methods to monitor and manipulate the immune system are of enormous clinical interest. For example, the development of vaccines represents one of the earliest and greatest accomplishments of the biomedical research enterprise. More recently, drugs capable of "reawakening" the immune system to cancer have generated enormous excitement. But, much remains to be done. All drugs available today that manipulate the immune system cannot distinguish between "good" and "bad" immune responses and thus drive general and systemic immune suppression or activation. Indeed, with the notable exception of vaccines, our ability to monitor and manipulate antigen-specific immune responses is in its infancy. Achieving this finer level of control would be highly desirable. For example, it might allow the pharmacological editing of pathogenic immune responses without restricting the ability of the immune system to defend against infection. On the diagnostic side, a method to comprehensively monitor the circulating, antigen-specific antibody population could provide a treasure trove of clinically useful biomarkers, since many diseases expose the immune system to characteristic molecules that are deemed foreign and elicit the production of antibodies against them. This Perspective will discuss the state-of-the-art of this area with a focus on what we consider seminal opportunities for the chemistry community to contribute to this important field. PMID:27115249

  3. Apoptosis and other immune biomarkers predict influenza vaccine responsiveness

    PubMed Central

    Furman, David; Jojic, Vladimir; Kidd, Brian; Shen-Orr, Shai; Price, Jordan; Jarrell, Justin; Tse, Tiffany; Huang, Huang; Lund, Peder; Maecker, Holden T; Utz, Paul J; Dekker, Cornelia L; Koller, Daphne; Davis, Mark M

    2013-01-01

    Despite the importance of the immune system in many diseases, there are currently no objective benchmarks of immunological health. In an effort to identifying such markers, we used influenza vaccination in 30 young (20–30 years) and 59 older subjects (60 to >89 years) as models for strong and weak immune responses, respectively, and assayed their serological responses to influenza strains as well as a wide variety of other parameters, including gene expression, antibodies to hemagglutinin peptides, serum cytokines, cell subset phenotypes and in vitro cytokine stimulation. Using machine learning, we identified nine variables that predict the antibody response with 84% accuracy. Two of these variables are involved in apoptosis, which positively associated with the response to vaccination and was confirmed to be a contributor to vaccine responsiveness in mice. The identification of these biomarkers provides new insights into what immune features may be most important for immune health. PMID:23591775

  4. 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.

  5. Tissue engineering tools for modulation of the immune response

    PubMed Central

    Boehler, Ryan M.; Graham, John G.; Shea, Lonnie D.

    2012-01-01

    Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine. PMID:21988690

  6. Subversion of the Immune Response by Rabies Virus.

    PubMed

    Scott, Terence P; Nel, Louis H

    2016-01-01

    Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses-including age, sex, cerebral lateralization and temperature-are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host's response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment. PMID:27548204

  7. Paradoxical acclimation responses in the thermal performance of insect immunity.

    PubMed

    Ferguson, Laura V; Heinrichs, David E; Sinclair, Brent J

    2016-05-01

    Winter is accompanied by multiple stressors, and the interactions between cold and pathogen stress potentially determine the overwintering success of insects. Thus, it is necessary to explore the thermal performance of the insect immune system. We cold-acclimated spring field crickets, Gryllus veletis, to 6 °C for 7 days and measured the thermal performance of potential (lysozyme and phenoloxidase activity) and realised (bacterial clearance and melanisation) immune responses. Cold acclimation decreased the critical thermal minimum from -0.5 ± 0.25 to -2.1 ± 0.18 °C, and chill coma recovery time after 72 h at -2 °C from 16.8 ± 4.9 to 5.2 ± 2.0 min. Measures of both potential and realised immunity followed a typical thermal performance curve, decreasing with decreasing temperature. However, cold acclimation further decreased realised immunity at low, but not high, temperatures; effectively, immune activity became paradoxically specialised to higher temperatures. Thus, cold acclimation induced mismatched thermal responses between locomotor and immune systems, as well as within the immune system itself. We conclude that cold acclimation in insects appears to preferentially improve cold tolerance over whole-animal immune performance at low temperatures, and that the differential thermal performance of physiological responses to multiple pressures must be considered when predicting ectotherms' response to climate change. PMID:26846428

  8. Superficial Immunity: Antimicrobial Responses Are More Than Skin Deep.

    PubMed

    Mack, Madison R; Kim, Brian S

    2016-07-19

    The skin barrier is essential for host defense, but how the skin provides protection when the barrier is breached is not well understood. In this issue of Immunity, Gallo and colleagues report that keratinocytes integrate signals from antimicrobial peptides via MAVS signaling to amplify their antiviral immune response. PMID:27438760

  9. Rotavirus immune responses and correlates of protection

    PubMed Central

    Angel, Juana; Franco, Manuel A.; Greenberg, Harry B.

    2012-01-01

    Selected topics in the field of rotavirus immunity are reviewed focusing on recent developments that may improve efficacy and safety of current and future vaccines. Rotaviruses have developed multiple mechanisms to evade interferon-mediated innate immunity. Compared to more developed regions of the world, protection induced by natural infection and vaccination is reduced in developing countries where, among other factors, high viral challenge loads are common and where infants are infected at an early age. Studies in developing countries indicate that rotavirus-specific serum IgA levels are not an optimal correlate of protection following vaccination, and better correlates need to be identified. Protection against rotavirus following vaccination is substantially heterotypic; nonetheless, a role for homotypic immunity in selection of circulating post vaccination strains needs further study. PMID:22677178

  10. Host Immune Response to Histophilus somni.

    PubMed

    Corbeil, Lynette B

    2016-01-01

    Histophilus somni is known to cause several overlapping syndromes or to be found in genital or upper respiratory carrier states in ruminants. Vaccines have been used for decades, yet efficacy is controversial and mechanisms of protective immunity are not well understood. Since H. somni survives phagocytosis, it has sometimes been considered to be a facultative intercellular parasite, implying that cell-mediated immunity would be critical in protection. However, H. somni not only inhibits phagocyte function, but also is cytotoxic for macrophages. Therefore, it does not live for long periods in healthy phagocytes. Protection of calves against H. somni pneumonia by passive immunization is also evidence that H. somni is more like an extracellular pathogen than an intracellular pathogen. Several studies showed that bovine IgG2 antibodies are more protective than IgG1 antibodies. Even the IgG2 allotypes tend to vary in protection. Of course, antigenic specificity also determines protection. So far, there is most evidence for protection by a 40 K outer membrane protein and by Immunoglobulin binding protein A fibrils. Serology and immunohistochemistry have both been used for immunodiagnosis. Many evasive mechanisms by H. somni have been defined, including decreased phagocyte function, antibodies bound by shed antigens, decreased immune stimulation, and antigenic variation. Interaction of H. somni with other bovine respiratory disease organisms is another layer of pathogenesis. Studies of bovine respiratory syncytial virus (BRSV) and H. somni in calfhood pneumonia revealed an increase in IgE antibodies to H. somni, which were associated with more severe disease of longer duration than with either agent alone. Innate immune mechanisms at the epithelial cell level are also affected by dual infection by BRSV and H. somni as compared to either pathogen alone. Although much more work needs to be done, the complex mechanisms of H. somni immunity are becoming clearer. PMID

  11. Improved immune response to recombinant influenza nucleoprotein formulated with ISCOMATRIX.

    PubMed

    Cargnelutti, Diego E; Sanchez, Maria V; Alvarez, Paula; Boado, Lorena; Glikmann, Graciela; Mattion, Nora; Scodeller, Eduardo A

    2012-03-01

    Current influenza vaccines elicit antibodies effective against homologous strains, but new strategies are urgently needed for protection against emerging epidemic or pandemic strains. Although influenza vaccine candidates based on the viral nucleoprotein (NP) or matrix protein do not elicit sterilizing immunity, they have the advantage of inducing immunity that may cover a larger number of viral strains. In this study, recombinant NP produced in Escherichia coli was purified and formulated in combination with the adjuvant ISCOMATRIX. This formulation increased a NP-specific immunity in mice, with a Th1 profile, and may constitute a promising low-cost influenza vaccine candidate, with ability to stimulate humoral and cellular immune responses.. PMID:22450799

  12. Subversion of the Immune Response by Rabies Virus

    PubMed Central

    Scott, Terence P.; Nel, Louis H.

    2016-01-01

    Rabies has affected mankind for several centuries and is one of the oldest known zoonoses. It is peculiar how little is known regarding the means by which rabies virus (RABV) evades the immune response and kills its host. This review investigates the complex interplay between RABV and the immune system, including the various means by which RABV evades, or advantageously utilizes, the host immune response in order to ensure successful replication and spread to another host. Different factors that influence immune responses—including age, sex, cerebral lateralization and temperature—are discussed, with specific reference to RABV and the effects on host morbidity and mortality. We also investigate the role of apoptosis and discuss whether it is a detrimental or beneficial mechanism of the host’s response to infection. The various RABV proteins and their roles in immune evasion are examined in depth with reference to important domains and the downstream effects of these interactions. Lastly, an overview of the means by which RABV evades important immune responses is provided. The research discussed in this review will be important in determining the roles of the immune response during RABV infections as well as to highlight important therapeutic target regions and potential strategies for rabies treatment. PMID:27548204

  13. Regulation of Immune Responses by mTOR

    PubMed Central

    Powell, Jonathan D.; Pollizzi, Kristen N.; Heikamp, Emily B.; Horton, Maureen R.

    2013-01-01

    mTOR is an evolutionarily conserved serine/threonine kinase that plays a central role in integrating environmental cues in the form of growth factors, amino acids, and energy. In the study of the immune system, mTOR is emerging as a critical regulator of immune function because of its role in sensing and integrating cues from the immune microenvironment. With the greater appreciation of cellular metabolism as an important regulator of immune cell function, mTOR is proving to be a vital link between immune function and metabolism. In this review, we discuss the ability of mTOR to direct the adaptive immune response. Specifically, we focus on the role of mTOR in promoting differentiation, activation, and function in T cells, B cells, and antigen-presenting cells. PMID:22136167

  14. Virus-like nanostructures for tuning immune response

    NASA Astrophysics Data System (ADS)

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-11-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system.

  15. Virus-like nanostructures for tuning immune response

    PubMed Central

    Mammadov, Rashad; Cinar, Goksu; Gunduz, Nuray; Goktas, Melis; Kayhan, Handan; Tohumeken, Sehmus; Topal, Ahmet E.; Orujalipoor, Ilghar; Delibasi, Tuncay; Dana, Aykutlu; Ide, Semra; Tekinay, Ayse B.; Guler, Mustafa O.

    2015-01-01

    Synthetic vaccines utilize viral signatures to trigger immune responses. Although the immune responses raised against the biochemical signatures of viruses are well characterized, the mechanism of how they affect immune response in the context of physical signatures is not well studied. In this work, we investigated the ability of zero- and one-dimensional self-assembled peptide nanostructures carrying unmethylated CpG motifs (signature of viral DNA) for tuning immune response. These nanostructures represent the two most common viral shapes, spheres and rods. The nanofibrous structures were found to direct immune response towards Th1 phenotype, which is responsible for acting against intracellular pathogens such as viruses, to a greater extent than nanospheres and CpG ODN alone. In addition, nanofibers exhibited enhanced uptake into dendritic cells compared to nanospheres or the ODN itself. The chemical stability of the ODN against nuclease-mediated degradation was also observed to be enhanced when complexed with the peptide nanostructures. In vivo studies showed that nanofibers promoted antigen-specific IgG production over 10-fold better than CpG ODN alone. To the best of our knowledge, this is the first report showing the modulation of the nature of an immune response through the shape of the carrier system. PMID:26577983

  16. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes.

    PubMed

    Toor, Amir A; Sabo, Roy T; Roberts, Catherine H; Moore, Bonny L; Salman, Salman R; Scalora, Allison F; Aziz, May T; Shubar Ali, Ali S; Hall, Charles E; Meier, Jeremy; Thorn, Radhika M; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B; McCarty, John M; Chung, Harold M; Manjili, Masoud H; Neale, Michael C

    2015-07-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3(+) cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3(+) at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  17. Dynamical System Modeling of Immune Reconstitution after Allogeneic Stem Cell Transplantation Identifies Patients at Risk for Adverse Outcomes

    PubMed Central

    Toor, Amir A.; Sabo, Roy T.; Roberts, Catherine H.; Moore, Bonny L.; Salman, Salman R.; Scalora, Allison F.; Aziz, May T.; Shubar Ali, Ali S.; Hall, Charles E.; Meier, Jeremy; Thorn, Radhika M.; Wang, Elaine; Song, Shiyu; Miller, Kristin; Rizzo, Kathryn; Clark, William B.; McCarty, John M.; Chung, Harold M.; Manjili, Masoud H.; Neale, Michael C.

    2016-01-01

    Systems that evolve over time and follow mathematical laws as they evolve are called dynamical systems. Lymphocyte recovery and clinical outcomes in 41 allograft recipients conditioned using antithymocyte globulin (ATG) and 4.5-Gy total body irradiation were studied to determine if immune reconstitution could be described as a dynamical system. Survival, relapse, and graft-versus-host disease (GVHD) were not significantly different in 2 cohorts of patients receiving different doses of ATG. However, donor-derived CD3+ cell reconstitution was superior in the lower ATG dose cohort, and there were fewer instances of donor lymphocyte infusion (DLI). Lymphoid recovery was plotted in each individual over time and demonstrated 1 of 3 sigmoid growth patterns: Pattern A (n = 15) had rapid growth with high lymphocyte counts, pattern B (n = 14) had slower growth with intermediate recovery, and pattern C (n = 10) had poor lymphocyte reconstitution. There was a significant association between lymphocyte recovery patterns and both the rate of change of donor-derived CD3+ at day 30 after stem cell transplantation (SCT) and clinical outcomes. GVHD was observed more frequently with pattern A, relapse and DLI more so with pattern C, with a consequent survival advantage in patients with patterns A and B. We conclude that evaluating immune reconstitution after SCT as a dynamical system may differentiate patients at risk of adverse outcomes and allow early intervention to modulate that risk. PMID:25849208

  18. Transcriptional Profiling of the Immune Response to Marburg Virus Infection

    PubMed Central

    Yen, Judy; Caballero, Ignacio S.; Garamszegi, Sara; Malhotra, Shikha; Lin, Kenny; Hensley, Lisa; Goff, Arthur J.

    2015-01-01

    ABSTRACT Marburg virus is a genetically simple RNA virus that causes a severe hemorrhagic fever in humans and nonhuman primates. The mechanism of pathogenesis of the infection is not well understood, but it is well accepted that pathogenesis is appreciably driven by a hyperactive immune response. To better understand the overall response to Marburg virus challenge, we undertook a transcriptomic analysis of immune cells circulating in the blood following aerosol exposure of rhesus macaques to a lethal dose of Marburg virus. Using two-color microarrays, we analyzed the transcriptomes of peripheral blood mononuclear cells that were collected throughout the course of infection from 1 to 9 days postexposure, representing the full course of the infection. The response followed a 3-stage induction (early infection, 1 to 3 days postexposure; midinfection, 5 days postexposure; late infection, 7 to 9 days postexposure) that was led by a robust innate immune response. The host response to aerosolized Marburg virus was evident at 1 day postexposure. Analysis of cytokine transcripts that were overexpressed during infection indicated that previously unanalyzed cytokines are likely induced in response to exposure to Marburg virus and further suggested that the early immune response is skewed toward a Th2 response that would hamper the development of an effective antiviral immune response early in disease. Late infection events included the upregulation of coagulation-associated factors. These findings demonstrate very early host responses to Marburg virus infection and provide a rich data set for identification of factors expressed throughout the course of infection that can be investigated as markers of infection and targets for therapy. IMPORTANCE Marburg virus causes a severe infection that is associated with high mortality and hemorrhage. The disease is associated with an immune response that contributes to the lethality of the disease. In this study, we investigated how the

  19. SURVIVAL AND IMMUNE RESPONSE OF COHO SALMON EXPOSED TO COPPER

    EPA Science Inventory

    Vaccination with Vibrio anguillarum by oral administration during copper exposure and intraperitoneal injection prior to copper exposure was employed to investigate the effects of copper upon survival and the immune response of juvenile coho salmon (Oncorhynchus kisutch). Followi...

  20. Role of nutrients in the development of neonatal immune response

    PubMed Central

    Cunningham-Rundles, Susanna; Lin, Hong; Ho-Lin, Deborah; Dnistrian, Ann; Cassileth, Barrie R; Perlman, Jeffrey M

    2015-01-01

    Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures. PMID:19906219

  1. DNA Damage Response and Immune Defense: Links and Mechanisms

    PubMed Central

    Nakad, Rania; Schumacher, Björn

    2016-01-01

    DNA damage plays a causal role in numerous human pathologies including cancer, premature aging, and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signaling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signaling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signaling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans. PMID:27555866

  2. Heat-Based Tumor Ablation: Role of the Immune Response.

    PubMed

    Wu, Feng

    2016-01-01

    The ideal cancer therapy not only induces the death of all localized tumor cells with less damage to surrounding normal tissue, but also activates a systemic antitumor immunity. Heat-based tumor ablation has the potential to be such a treatment as it can minimal-invasively ablate a targeted tumor below the skin surface, and may subsequently augment host antitumor immunity. This chapter primarily introduces increasing pre-clinical and clinical evidence linking antitumor immune response to thermal tumor ablation, and then discusses the potential mechanisms involved in ablation-enhanced host antitumor immunity. The seminal studies performed so far indicate that although it is not possible to make definite conclusions on the connection between thermal ablation and antitumor immune response, it is nonetheless important to conduct extensive studies on the subject in order to elucidate the processes involved. PMID:26486336

  3. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    2005-09-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self-antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely, gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system’s search for antibodies, a balance has evolved between binding affinity and specificity.

  4. Role of nutrients in the development of neonatal immune response.

    PubMed

    Cunningham-Rundles, Susanna; Lin, Hong; Ho-Lin, Deborah; Dnistrian, Ann; Cassileth, Barrie R; Perlman, Jeffrey M

    2009-11-01

    Nutrients exert unique regulatory effects in the perinatal period that mold the developing immune system. The interactions of micronutrients and microbial and environmental antigens condition the post-birth maturation of the immune system, influencing reactions to allergens, fostering tolerance towards the emerging gastrointestinal flora and ingested antigens, and defining patterns of host defense against potential pathogens. The shared molecular structures that are present on microbes or certain plants, but not expressed by human cells, are recognized by neonatal innate immune receptors. Exposure to these activators in the environment through dietary intake in early life can modify the immune response to allergens and prime the adaptive immune response towards pathogens that express the corresponding molecular structures. PMID:19906219

  5. Assessment of attitudes towards adverse events following immunization with oral poliovirus vaccine: a pilot study among high school students of Kinshasa, the Democratic Republic of Congo

    PubMed Central

    Kinuani, Léon; Nzolo, Didier Bomene; Aloni, Michel Ntetani; Makolo, Pavel; Ntamabyaliro, Nsengi; Ntamba, Yves Lula; Kazadi, Crispin; Nyembwe, Michel; Ekila, Mathilde Bothale; Mesia, Gauthier Kahunu

    2014-01-01

    Objective: The aim of this study is to evaluate the reaction of students to adverse events following immunization in order to offer a baseline for developing a communication and risk management plan. Method: This is a cross-sectional study conducted in Kinshasa. A survey was conducted between the third and the fourth rounds of Supplementary Immunization Activity. Nine hundred and fifty questionnaires were used and addressed students who attended this university from 1 to 10 June 2011. Results: Completed questionnaires were received from 848 students, with 485 females (57.2%), 343 males (40.4%), and 20 unknown (2.4%); 46.9% of students were from the faculty of medicine and 24.7% was from the third graduate degree. From those who completed the questionnaire, 136 (16.4%) reported experiencing an adverse events following immunization. Concerning the attitude of students towards adverse events following immunization, 79 students (58.5%) did nothing; 54 (40.0%) opted for self-medication; 2 (1.5%) went to the hospital. Conclusion: The main finding of our study is the low rate of people referring to health-care providers for vaccine-related problems, more specially for adverse events following immunization. A risk management plan should be focused in strategies to increase communication between population and health-care providers. PMID:25237792

  6. Intravenous immune globulin and thromboembolic adverse events in patients with hematologic malignancy.

    PubMed

    Ammann, Eric M; Jones, Michael P; Link, Brian K; Carnahan, Ryan M; Winiecki, Scott K; Torner, James C; McDowell, Bradley D; Fireman, Bruce H; Chrischilles, Elizabeth A

    2016-01-14

    In patients with hypogammaglobulinemia secondary to chronic lymphocytic leukemia (CLL) or multiple myeloma (MM), intravenous immune globulin (IVIg) may be administered to reduce the risk of infection. Since 2013, IVIg products have carried a boxed safety warning about the risk of thromboembolic events (TEEs), with TEEs reported in 0.5% to 15% of patients treated with IVIg. In this retrospective cohort study of older patients with CLL or MM identified from the Surveillance, Epidemiology, and End Results-Medicare Linked Database, we assessed rates of clinically serious TEEs in 2724 new users of IVIg and a propensity-matched comparison group of 8035 nonusers. For the primary end point, arterial TEE, we observed a transient increased risk of TEE during the day of an IVIg infusion and the day afterward (hazard ration = 3.40; 95% confidence interval [CI]: 1.25, 9.25); this risk declined over the remainder of the 30-day treatment cycle. When considered in terms of absolute risk averaged over a 1-year treatment period, the increase in risk attributable to IVIg was estimated to be 0.7% (95% CI: -0.2%, 2.0%) compared with a baseline risk of 1.8% for the arterial TEE end point. A statistically nonsignificant risk increase of 0.3% (95% CI: -0.4%, 1.5%) compared with a baseline risk of 1.1% was observed for the venous TEE end point. Further research is needed to establish the generalizability of these results to patients receiving higher doses of IVIg for other indications. PMID:26443622

  7. Systemic Effector and Regulatory Immune Responses to Chlamydial Antigens in Trachomatous Trichiasis

    PubMed Central

    Gall, Alevtina; Horowitz, Amir; Joof, Hassan; Natividad, Angels; Tetteh, Kevin; Riley, Eleanor; Bailey, Robin L.; Mabey, David C. W.; Holland, Martin J.

    2010-01-01

    Trachomatous trichiasis (TT) caused by repeated or chronic ocular infection with Chlamydia trachomatis is the result of a pro-fibrotic ocular immune response. At the conjunctiva, the increased expression of both inflammatory (IL1B, TNF) and regulatory cytokines (IL10) have been associated with adverse clinical outcomes. We measured in vitro immune responses of peripheral blood to a number of chlamydial antigens. Peripheral blood effector cells (CD4, CD69, IFNγ, IL-10) and regulatory cells (CD4, CD25, FOXP3, CTLA4/GITR) were readily stimulated by C. trachomatis antigens but neither the magnitude (frequency or stimulation index) or the breadth and amount of cytokines produced in vitro [IL-5, IL-10, IL-12 (p70), IL-13, IFNγ, and TNFα] were significantly different between TT cases and their non-diseased controls. Interestingly we observed that CD4+ T cells account for <50% of the IFNγ positive cells induced following stimulation. Further investigation in individuals selected from communities where exposure to ocular infection with C. trachomatis is endemic indicated that CD3−CD56+ (classical natural killer cells) were a major early source of IFNγ production in response to C. trachomatis elementary body stimulation and that the magnitude of this response increased with age. Future efforts to unravel the contribution of the adaptive immune response to conjunctival fibrosis should focus on the early events following infection and the interaction with innate immune mediated mechanisms of inflammation in the conjunctiva. PMID:21747780

  8. Modeling the interactions between pathogenic bacteria, bacteriophage and immune response

    NASA Astrophysics Data System (ADS)

    Leung, Chung Yin (Joey); Weitz, Joshua S.

    The prevalence of antibiotic-resistant strains of pathogenic bacteria has led to renewed interest in the use of bacteriophage (phage), or virus that infects bacteria, as a therapeutic agent against bacterial infections. However, little is known about the theoretical mechanism by which phage therapy may work. In particular, interactions between the bacteria, the phage and the host immune response crucially influences the outcome of the therapy. Few models of phage therapy have incorporated all these three components, and existing models suffer from unrealistic assumptions such as unbounded growth of the immune response. We propose a model of phage therapy with an emphasis on nonlinear feedback arising from interactions with bacteria and the immune response. Our model shows a synergistic effect between the phage and the immune response which underlies a possible mechanism for phage to catalyze the elimination of bacteria even when neither the immune response nor phage could do so alone. We study the significance of this effect for different parameters of infection and immune response, and discuss its implications for phage therapy.

  9. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    PubMed Central

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  10. Ontogeny of Intestinal Epithelial Innate Immune Responses

    PubMed Central

    Hornef, Mathias W.; Fulde, Marcus

    2014-01-01

    Emerging evidence indicates that processes during postnatal development might significantly influence the establishment of mucosal host-microbial homeostasis. Developmental and adaptive immunological processes but also environmental and microbial exposure early after birth might thus affect disease susceptibility and health during adult life. The present review aims at summarizing the current understanding of the intestinal epithelial innate immune system and its developmental and adaptive changes after birth. PMID:25346729

  11. Mucosal immune responses following intestinal nematode infection

    PubMed Central

    Zaph, C; Cooper, P J; Harris, N L

    2014-01-01

    In most natural environments, the large majority of mammals harbour parasitic helminths that often live as adults within the intestine for prolonged periods (1–2 years) 1. Although these organisms have been eradicated to a large extent within westernized human populations, those living within rural areas of developing countries continue to suffer from high infection rates. Indeed, recent estimates indicate that approximately 2·5 billion people worldwide, mainly children, currently suffer from infection with intestinal helminths (also known as geohelminths and soil-transmitted helminths) 2. Paradoxically, the eradication of helminths is thought to contribute to the increased incidence of autoimmune diseases and allergy observed in developed countries. In this review, we will summarize our current understanding of host–helminth interactions at the mucosal surface that result in parasite expulsion or permit the establishment of chronic infections with luminal dwelling adult worms. We will also provide insight into the adaptive immune mechanisms that provide immune protection against re-infection with helminth larvae, a process that is likely to be key to the future development of successful vaccination strategies. Lastly, the contribution of helminths to immune modulation and particularly to the treatment of allergy and inflammatory bowel disease will be discussed. PMID:25201407

  12. Charon Mediates Immune Deficiency-Driven PARP-1-Dependent Immune Responses in Drosophila.

    PubMed

    Ji, Yingbiao; Thomas, Colin; Tulin, Nikita; Lodhi, Niraj; Boamah, Ernest; Kolenko, Vladimir; Tulin, Alexei V

    2016-09-15

    Regulation of NF-κB nuclear translocation and stability is central to mounting an effective innate immune response. In this article, we describe a novel molecular mechanism controlling NF-κB-dependent innate immune response. We show that a previously unknown protein, termed as Charon, functions as a regulator of antibacterial and antifungal immune defense in Drosophila Charon is an ankyrin repeat-containing protein that mediates poly(ADP-ribose) polymerase-1 (PARP-1)-dependent transcriptional responses downstream of the innate immune pathway. Our results demonstrate that Charon interacts with the NF-κB ortholog Relish inside perinuclear particles and delivers active Relish to PARP-1-bearing promoters, thus triggering NF-κB/PARP-1-dependent transcription of antimicrobial peptides. Ablating the expression of Charon prevents Relish from targeting promoters of antimicrobial genes and effectively suppresses the innate immune transcriptional response. Taken together, these results implicate Charon as an essential mediator of PARP-1-dependent transcription in the innate immune pathway. Thus, to our knowledge, our results are the first to describe the molecular mechanism regulating translocation of the NF-κB subunit from cytoplasm to chromatin. PMID:27527593

  13. Autophagy-associated immune responses and cancer immunotherapy

    PubMed Central

    Xu, Yinghua; Han, Weidong; Lou, Fang; Fei, Weiqiang; Liu, Shuiping; Jing, Zhao; Sui, Xinbing

    2016-01-01

    Autophagy is an evolutionarily conserved catabolic process by which cellular components are sequestered into a double-membrane vesicle and delivered to the lysosome for terminal degradation and recycling. Accumulating evidence suggests that autophagy plays a critical role in cell survival, senescence and homeostasis, and its dysregulation is associated with a variety of diseases including cancer, cardiovascular disease, neurodegeneration. Recent studies show that autophagy is also an important regulator of cell immune response. However, the mechanism by which autophagy regulates tumor immune responses remains elusive. In this review, we will describe the role of autophagy in immune regulation and summarize the possible molecular mechanisms that are currently well documented in the ability of autophagy to control cell immune response. In addition, the scientific and clinical hurdles regarding the potential role of autophagy in cancer immunotherapy will be discussed. PMID:26788909

  14. Cancer immunotherapy and immune-related response assessment: the role of radiologists in the new arena of cancer treatment

    PubMed Central

    Nishino, Mizuki; Tirumani, Sree H.; Ramaiya, Nikhil H.; Hodi, F. Stephen

    2015-01-01

    The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists’ awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions. PMID:25937524

  15. Cancer immunotherapy and immune-related response assessment: The role of radiologists in the new arena of cancer treatment.

    PubMed

    Nishino, Mizuki; Tirumani, Sree H; Ramaiya, Nikhil H; Hodi, F Stephen

    2015-07-01

    The recent advances in the clinical application of anti-cancer immunotherapeutic agents have opened a new arena for the treatment of advanced cancers. Cancer immunotherapy is associated with a variety of important radiographic features in the assessments of tumor response and immune-related adverse events, which calls for radiologists' awareness and in-depth knowledge on the topic. This article will provide the state-of-the art review and perspectives of cancer immunotherapy, including its molecular mechanisms, the strategies for immune-related response assessment on imaging and their pitfalls, and the emerging knowledge of radiologic manifestations of immune-related adverse events. The cutting edge clinical and radiologic investigations are presented to provide future directions. PMID:25937524

  16. Maternal immunity enhances Mycoplasma hyopneumoniae vaccination induced cell-mediated immune responses in piglets

    PubMed Central

    2014-01-01

    Background Passively acquired maternal derived immunity (MDI) is a double-edged sword. Maternal derived antibody-mediated immunity (AMI) and cell-mediated immunity (CMI) are critical immediate defenses for the neonate; however, MDI may interfere with the induction of active immunity in the neonate, i.e. passive interference. The effect of antigen-specific MDI on vaccine-induced AMI and CMI responses to Mycoplasma hyopneumoniae (M. hyopneumoniae) was assessed in neonatal piglets. To determine whether CMI and AMI responses could be induced in piglets with MDI, piglets with high and low levels of maternal M. hyopneumoniae-specific immunity were vaccinated against M. hyopneumoniae at 7 d of age. Piglet M. hyopneumoniae-specific antibody, lymphoproliferation, and delayed type hypersensitivity (DTH) responses were measured 7 d and 14 d post vaccination. Results Piglets with M. hyopneumoniae-specific MDI failed to show vaccine-induced AMI responses; there was no rise in M. hyopneumoniae antibody levels following vaccination of piglets in the presence of M. hyopneumoniae-specific MDI. However, piglets with M. hyopneumoniae-specific MDI had primary (antigen-specific lymphoproliferation) and secondary (DTH) M. hyopneumoniae-specific CMI responses following vaccination. Conclusions In this study neonatal M. hyopneumoniae-specific CMI was not subject to passive interference by MDI. Further, it appears that both maternal derived and endogenous CMI contribute to M. hyopneumoniae-specific CMI responses in piglets vaccinated in the face of MDI. PMID:24903770

  17. Concurrent decrease in IL-10 with development of immune-related adverse events in a patient treated with anti-CTLA-4 therapy

    PubMed Central

    Sun, Jingjing; Schiffman, Jade; Raghunath, Anitha; Ng Tang, Derek; Chen, Hong

    2008-01-01

    The cytotoxic T lymphocyte antigen-4 (CTLA-4) molecule on T cells acts to maintain homeostasis by regulating the proliferation of recently activated T cells. Blockade of CTLA-4 by anti-CTLA-4 antibody enhances T cell responses and has elicited significant tumor regression in some cancer patients. Clinical trials are ongoing to investigate the efficacy of anti-CTLA-4 antibody as a cancer therapeutic. Reports from several clinical trials have documented the occurrence of adverse events in patients treated with anti-CTLA-4 antibody which have some similarities with autoimmune conditions and have been termed immune-related adverse events (irAEs). Most irAEs are reversible with corticosteroid therapy. Some investigators suggest that irAEs occur in the same patients who have anti-tumor responses as a result of the anti-CTLA-4 antibody. Immunologic mechanisms to explain why irAEs occur in some patients have not been reported. Here we report that bladder cancer patients treated with anti-CTLA-4 antibody have increased levels of the Th1 cytokine IFN-γ detected in plasma samples. Although IFN-γ is a potent anti-tumor and inflammatory cytokine, increased levels of IFN-γ were not associated with irAEs in our patients. However, in one patient who experienced an irAE consisting of ischemic papillopathy and optic neuritis, we documented high pre-therapy levels of the Th2 cytokine IL-10 which decreased after treatment with anti-CTLA-4 antibody. The decrease in plasma IL-10 concentration coincided with the patient's irAE. We propose that decreased levels of IL-10 after treatment with anti-CTLA-4 therapy may be responsible for irAEs in some patients and needs to be further investigated in larger studies. PMID:18503261

  18. A Cognitive Computational Model Inspired by the Immune System Response

    PubMed Central

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective. PMID:25003131

  19. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  20. Agouron and immune response to commercialize remune immune-based treatment.

    PubMed

    James, J S

    1998-06-19

    Agouron Pharmaceuticals agreed in June to collaborate with The Immune Response Corporation on the final development and marketing of an immune-based treatment for HIV. Remune, the vaccine developed by Dr. Jonas Salk, is currently in Phase III randomized trials with 2,500 patients, and the trials are expected to be completed in April 1999. Immune-based treatments have been difficult to test, as there is no surrogate marker, like viral load, to determine if the drug is working. Agouron agreed to participate in the joint venture after reviewing encouraging results from preliminary trials in which remune was taken in combination with highly active antiretroviral drugs. PMID:11365593

  1. Determining adaptive and adverse oxidative stress responses in human bronical epithelial cells exposed to zinc

    EPA Science Inventory

    Determining adaptive and adverse oxidative stress responses in human bronchial epithelial cells exposed to zincJenna M. Currier1,2, Wan-Yun Cheng1, Rory Conolly1, Brian N. Chorley1Zinc is a ubiquitous contaminant of ambient air that presents an oxidant challenge to the human lung...

  2. Mapping immune response profiles: the emerging scenario from helminth immunology.

    PubMed

    Díaz, Alvaro; Allen, Judith E

    2007-12-01

    Metazoan parasites of mammals (helminths) belong to highly divergent animal groups and yet induce a stereotypical host response: Th2-type immunity. It has long been debated whether this response benefits the host or the parasite. We review the current literature and suggest that Th2 immunity is an evolutionarily appropriate response to metazoan invaders both in terms of controlling parasites and repairing the damage they inflict. However, successful parasites induce regulatory responses, which become superimposed with, and control, Th2 responses. Beyond helminth infection, this superimposition of response profiles may be the norm: both Th1 and Th2 responses coexist with regulatory responses or, on the contrary, with the inflammatory Th17 responses. Thus, typical responses to helminth infections may differ from Th2-dominated allergic reactions in featuring not only a stronger regulatory component but also a weaker Th17 component. The similarity of immune response profiles to phylogenetically distinct helminths probably arises from mammalian evolution having hard-wired diverse worm molecules, plus tissue-damage signals, to the beneficial Th2 response, and from the convergent evolution of different helminths to elicit regulatory responses. We speculate that initiation of both Th2 and regulatory responses involves combinatorial signaling, whereby TLR-mediated signals are modulated by signals from other innate receptors, including lectins. PMID:18000958

  3. Sedimentation rapidly induces an immune response and depletes energy stores in a hard coral

    NASA Astrophysics Data System (ADS)

    Sheridan, C.; Grosjean, Ph.; Leblud, J.; Palmer, C. V.; Kushmaro, A.; Eeckhaut, I.

    2014-12-01

    High sedimentation rates have been linked to reduced coral health within multiple systems; however, whether this is a direct result of compromised coral immunity has not been previously investigated. The potential effects of sedimentation on immunity of the hard coral Montipora patula were examined by comparing physiological responses of coral fragments inoculated with sterilized marine sediments and those under control conditions. Sediments were collected from terrestrial runoff-affected reefs in SW Madagascar and applied cyclically for a total of 24 h at a rate observed during precipitation-induced sedimentation events. Coral health was determined 24 h after the onset of the sedimentation stress through measuring metabolic proxies of O2 budget and lipid ratios. Immune response of the melanin synthesis pathway was measured by quantifying phenoloxidase activity and melanin deposits. Sedimentation induced both immune and metabolic responses in M. patula. Both phenoloxidase activity and melanin deposition were significantly higher in the sediment treatment compared to controls, indicating an induced immune response. Sediment-treated corals also showed a tendency towards increased respiration (during the night) and decreased photosynthesis (during the day) and a significant depletion of energy reserves as compared to controls. These data highlight that short-term (24 h) sedimentation, free of live microorganisms, compromises the health of M. patula. The energetically costly immune response, potentially elicited by residual endotoxins and other inflammatory particles associated with the sterile sediments, likely contributes to the energy depletion. Overall, exposure to sedimentation adversely affects coral health and continued exposure may lead to resource depletion and an increased susceptibility to disease.

  4. [Effect of anabolic steroid on immune response].

    PubMed

    Yamagishi, H; Kobayashi, M; Konosu, H; Kurioka, H; Naito, K; Sonoyama, T; Nishimoto, T; Hashimoto, I

    1984-03-01

    Using lymphocyte, monocyte and eosinophil counts of the peripheral blood, PHA-blastoid transformation, immunoglobulin and beta 2-microglobulin, the influence of anabolic steroid on the immune reactivity of the host was dissected by administration of Deca-Durabolin ( nandrolone decanoate) to both tumor-bearing host and tumor-free host after operation for alimentary tract. The number of peripheral lymphocytes and monocytes, the PHA-blastoid transformation of peripheral lymphocytes and the IgG level were increased, and the beta 2-microglobulin level showed the tendency of decrease after the administration of Deca-Durabolin. PMID:6367663

  5. Genetic immunization in the lung induces potent local and systemic immune responses.

    PubMed

    Song, Kaimei; Bolton, Diane L; Wei, Chih-Jen; Wilson, Robert L; Camp, Jeremy V; Bao, Saran; Mattapallil, Joseph J; Herzenberg, Leonore A; Herzenberg, Leonard A; Andrews, Charla A; Sadoff, Jerald C; Goudsmit, Jaap; Pau, Maria Grazia; Seder, Robert A; Kozlowski, Pamela A; Nabel, Gary J; Roederer, Mario; Rao, Srinivas S

    2010-12-21

    Successful vaccination against respiratory infections requires elicitation of high levels of potent and durable humoral and cellular responses in the lower airways. To accomplish this goal, we used a fine aerosol that targets the entire lung surface through normal respiration to deliver replication-incompetent recombinant adenoviral vectors expressing gene products from several infectious pathogens. We show that this regimen induced remarkably high and stable lung T-cell responses in nonhuman primates and that it also generated systemic and respiratory tract humoral responses of both IgA and IgG isotypes. Moreover, strong immunogenicity was achieved even in animals with preexisting antiadenoviral immunity, overcoming a critical hurdle to the use of these vectors in humans, who commonly are immune to adenoviruses. The immunogenicity profile elicited with this regimen, which is distinct from either intramuscular or intranasal delivery, has highly desirable properties for protection against respiratory pathogens. We show that it can be used repeatedly to generate mucosal humoral, CD4, and CD8 T-cell responses and as such may be applicable to other mucosally transmitted pathogens such as HIV. Indeed, in a lethal challenge model, we show that aerosolized recombinant adenoviral immunization completely protects ferrets against H5N1 highly pathogenic avian influenza virus. Thus, genetic immunization in the lung offers a powerful platform approach to generating protective immune responses against respiratory pathogens. PMID:21135247

  6. Modulation of Innate Immune Responses via Covalently Linked TLR Agonists

    PubMed Central

    2015-01-01

    We present the synthesis of novel adjuvants for vaccine development using multivalent scaffolds and bioconjugation chemistry to spatially manipulate Toll-like receptor (TLR) agonists. TLRs are primary receptors for activation of the innate immune system during vaccination. Vaccines that contain a combination of small and macromolecule TLR agonists elicit more directed immune responses and prolong responses against foreign pathogens. In addition, immune activation is enhanced upon stimulation of two distinct TLRs. Here, we synthesized combinations of TLR agonists as spatially defined tri- and di-agonists to understand how specific TLR agonist combinations contribute to the overall immune response. We covalently conjugated three TLR agonists (TLR4, 7, and 9) to a small molecule core to probe the spatial arrangement of the agonists. Treating immune cells with the linked agonists increased activation of the transcription factor NF-κB and enhanced and directed immune related cytokine production and gene expression beyond cells treated with an unconjugated mixture of the same three agonists. The use of TLR signaling inhibitors and knockout studies confirmed that the tri-agonist molecule activated multiple signaling pathways leading to the observed higher activity. To validate that the TLR4, 7, and 9 agonist combination would activate the immune response to a greater extent, we performed in vivo studies using a vaccinia vaccination model. Mice vaccinated with the linked TLR agonists showed an increase in antibody depth and breadth compared to mice vaccinated with the unconjugated mixture. These studies demonstrate how activation of multiple TLRs through chemically and spatially defined organization assists in guiding immune responses, providing the potential to use chemical tools to design and develop more effective vaccines. PMID:26640818

  7. Transgenerational effects enhance specific immune response in a wild passerine

    PubMed Central

    Soriguer, Ramon C.; Figuerola, Jordi

    2016-01-01

    Vertebrate mothers transfer diverse compounds to developing embryos that can affect their development and final phenotype (i.e., maternal effects). However, the way such effects modulate offspring phenotype, in particular their immunity, remains unclear. To test the impact of maternal effects on offspring development, we treated wild breeding house sparrows (Passer domesticus) in Sevilla, SE Spain with Newcastle disease virus (NDV) vaccine. Female parents were vaccinated when caring for first broods, eliciting a specific immune response to NDV. The immune response to the same vaccine, and to the PHA inflammatory test were measured in 11-day-old chicks from their following brood. Vaccinated chicks from vaccinated mothers developed a stronger specific response that was related to maternal NDV antibody concentration while rearing their chicks. The chicks’ carotenoid concentration and total antioxidant capacity in blood were negatively related to NDV antibody concentration, whereas no relation with PHA response was found. Specific NDV antibodies could not be detected in 11-day-old control chicks from vaccinated mothers, implying that maternally transmitted antibodies are not directly involved but may promote offspring specific immunity through a priming effect, while other immunity components remain unaffected. Maternally transmitted antibodies in the house sparrow are short-lived, depend on maternal circulation levels and enhance pre-fledging chick specific immunity when exposed to the same pathogens as the mothers. PMID:27069782

  8. Behavioural trait covaries with immune responsiveness in a wild passerine.

    PubMed

    Sild, Elin; Sepp, Tuul; Hõrak, Peeter

    2011-10-01

    Immune system is highly integrated with the nervous and endocrine systems, which is thought to result in covariation between behavioural syndromes and stress- and immune-associated diseases. Very little is known about the associations between behaviour and immune traits in wild animals. Here we describe such an association in passerine birds, the greenfinches (Carduelis chloris). When wild-caught greenfinches are brought into captivity, some individuals damage their tail feathers against cage walls due to excited behaviour, while others retain their feathers in intact condition. We show that damage to tail feathers was associated with flapping flight movements and the frequency of such flapping bouts was individually consistent over 57 days. Birds with intact tails, i.e., relatively 'calm' individuals mounted stronger antibody response to a novel Brucella abortus antigen and their circulating phagocytes were capable of producing stronger oxidative burst in response to stimulation with bacterial lipopolysaccharide in vitro. As the behavioural trait was assessed 13-25 days before measuring immune responsiveness, our results demonstrate that individuals' coping styles with captivity predicted how these individuals would respond to forthcoming immune challenges. This is a novel evidence about covariation between immune responsiveness and a behavioural trait in a wild-caught animal. PMID:21473910

  9. 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

  10. Innate immune responses to microbial agonist stimulations in heterophils and monocytes from young commercial turkeys

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The innate immune system recognizes microbial pathogens and pathogen associated molecular patterns and incites inflammatory immune responses to control the infection. Here, we examined functional innate immune responses of turkey heterophils and monocytes to microbial agonist stimulations by measur...

  11. Balancing Immune Protection and Immune Pathology by CD8+ T-Cell Responses to Influenza Infection

    PubMed Central

    Duan, Susu; Thomas, Paul G.

    2016-01-01

    Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8+ cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID:26904022

  12. Balancing Immune Protection and Immune Pathology by CD8(+) T-Cell Responses to Influenza Infection.

    PubMed

    Duan, Susu; Thomas, Paul G

    2016-01-01

    Influenza A virus (IAV) is a significant human pathogen causing annual epidemics and periodic pandemics. CD8(+) cytotoxic T lymphocyte (CTL)-mediated immunity contributes to the clearance of virus-infected cells, and CTL immunity targeting the conserved internal proteins of IAVs is a key protection mechanism when neutralizing antibodies are absent during heterosubtypic IAV infection. However, CTL infiltration into the airways, its cytotoxicity, and the effects of produced proinflammatory cytokines can cause severe lung tissue injury, thereby contributing to immunopathology. Studies have discovered complicated and exquisite stimulatory and inhibitory mechanisms that regulate CTL magnitude and effector activities during IAV infection. Here, we review the state of knowledge on the roles of IAV-specific CTLs in immune protection and immunopathology during IAV infection in animal models, highlighting the key findings of various requirements and constraints regulating the balance of immune protection and pathology involved in CTL immunity. We also discuss the evidence of cross-reactive CTL immunity as a positive correlate of cross-subtype protection during secondary IAV infection in both animal and human studies. We argue that the effects of CTL immunity on protection and immunopathology depend on multiple layers of host and viral factors, including complex host mechanisms to regulate CTL magnitude and effector activity, the pathogenic nature of the IAV, the innate response milieu, and the host historical immune context of influenza infection. Future efforts are needed to further understand these key host and viral factors, especially to differentiate those that constrain optimally effective CTL antiviral immunity from those necessary to restrain CTL-mediated non-specific immunopathology in the various contexts of IAV infection, in order to develop better vaccination and therapeutic strategies for modifying protective CTL immunity. PMID:26904022

  13. The immune response against Candida spp. and Sporothrix schenckii.

    PubMed

    Martínez-Álvarez, José A; Pérez-García, Luis A; Flores-Carreón, Arturo; Mora-Montes, Héctor M

    2014-01-01

    Candida albicans is the main causative agent of systemic candidiasis, a condition with high mortality rates. The study of the interaction between C. albicans and immune system components has been thoroughly studied and nowadays there is a model for the anti-C. albicans immune response; however, little is known about the sensing of other pathogenic species of the Candida genus. Sporothrix schenckii is the causative agent of sporotrichosis, a subcutaneous mycosis, and thus far there is limited information about its interaction with the immune system. In this paper, we review the most recent information about the immune sensing of species from genus Candida and S. schenckii. Thoroughly searches in scientific journal databases were performed, looking for papers addressing either Candida- or Sporothrix-immune system interactions. There is a significant advance in the knowledge of non-C. albicans species of Candida and Sporothrix immune sensing; however, there are still relevant points to address, such as the specific contribution of pathogen-associated molecular patterns (PAMPs) for sensing by different immune cells and the immune receptors involved in such interactions. This manuscript is part of the series of works presented at the "V International Workshop: Molecular genetic approaches to the study of human pathogenic fungi" (Oaxaca, Mexico, 2012). PMID:24252829

  14. Functional genomic analysis of the Drosophila immune response.

    PubMed

    Valanne, Susanna

    2014-01-01

    Drosophila melanogaster has been widely used as a model organism for over a century now, and also as an immunological research model for over 20 years. With the emergence of RNA interference (RNAi) in Drosophila as a robust tool to silence genes of interest, large-scale or genome-wide functional analysis has become a popular way of studying the Drosophila immune response in cell culture. Drosophila immunity is composed of cellular and humoral immunity mechanisms, and especially the systemic, humoral response pathways have been extensively dissected using the functional genomic approach. Although most components of the main immune pathways had already been found using traditional genetic screening techniques, important findings including pathway components, positive and negative regulators and modifiers have been made with RNAi screening. Additionally, RNAi screening has produced new information on host-pathogen interactions related to the pathogenesis of many microbial species. PMID:23707784

  15. Activation and Regulation of DNA-Driven Immune Responses

    PubMed Central

    2015-01-01

    SUMMARY The innate immune system provides early defense against infections and also plays a key role in monitoring alterations of homeostasis in the body. DNA is highly immunostimulatory, and recent advances in this field have led to the identification of the innate immune sensors responsible for the recognition of DNA as well as the downstream pathways that are activated. Moreover, information on how cells regulate DNA-driven immune responses to avoid excessive inflammation is now emerging. Finally, several reports have demonstrated how defects in DNA sensing, signaling, and regulation are associated with susceptibility to infections or inflammatory diseases in humans and model organisms. In this review, the current literature on DNA-stimulated innate immune activation is discussed, and important new questions facing this field are proposed. PMID:25926682

  16. [Bone marrow stromal damage mediated by immune response activity].

    PubMed

    Vojinović, J; Kamenov, B; Najman, S; Branković, Lj; Dimitrijević, H

    1994-01-01

    The aim of this work was to estimate influence of activated immune response on hematopoiesis in vitro, using the experimental model of BCG immunized BALB/c mice and in patients with chronic immunoactivation: long-lasting infections, autoimmunity or malignancy. We correlated changes in long term bone marrow cultures (Dexter) and NBT reduction with appearance of anemia in patients and experimental model of immunization by BCG. Increased spontaneous NBT reduction pointed out role of macrophage activation in bone marrow stroma damage. Long-term bone marrow cultures showed reduced number of hematopoietic cells, with predomination of fibroblasts and loss of fat cells. This results correlated with anemia and leucocytosis with stimulated myelopoiesis in peripheral blood. Activation of immune response, or acting of any agent that directly changes extracellular matrix and cellularity of bone marrow, may result in microenviroment bone marrow damage that modify hematopoiesis. PMID:18173180

  17. Respiratory and immune response to maximal physical exertion following exposure to secondhand smoke in healthy adults.

    PubMed

    Flouris, Andreas D; Metsios, Giorgos S; Carrillo, Andres E; Carrill, Andres E; Jamurtas, Athanasios Z; Stivaktakis, Polychronis D; Tzatzarakis, Manolis N; Tsatsakis, Aristidis M; Koutedakis, Yiannis

    2012-01-01

    We assessed the cardiorespiratory and immune response to physical exertion following secondhand smoke (SHS) exposure through a randomized crossover experiment. Data were obtained from 16 (8 women) non-smoking adults during and following a maximal oxygen uptake cycling protocol administered at baseline and at 0-, 1-, and 3- hours following 1-hour of SHS set at bar/restaurant carbon monoxide levels. We found that SHS was associated with a 12% decrease in maximum power output, an 8.2% reduction in maximal oxygen consumption, a 6% increase in perceived exertion, and a 6.7% decrease in time to exhaustion (P<0.05). Moreover, at 0-hours almost all respiratory and immune variables measured were adversely affected (P<0.05). For instance, FEV(1) values at 0-hours dropped by 17.4%, while TNF-α increased by 90.1% (P<0.05). At 3-hours mean values of cotinine, perceived exertion and recovery systolic blood pressure in both sexes, IL4, TNF-α and IFN-γ in men, as well as FEV(1)/FVC, percent predicted FEV(1), respiratory rate, and tidal volume in women remained different compared to baseline (P<0.05). It is concluded that a 1-hour of SHS at bar/restaurant levels adversely affects the cardiorespiratory and immune response to maximal physical exertion in healthy nonsmokers for at least three hours following SHS. PMID:22355401

  18. Pathogenesis of necrotizing enterocolitis: modeling the innate immune response.

    PubMed

    Tanner, Scott M; Berryhill, Taylor F; Ellenburg, James L; Jilling, Tamas; Cleveland, Dava S; Lorenz, Robin G; Martin, Colin A

    2015-01-01

    Necrotizing enterocolitis (NEC) is a major cause of morbidity and mortality in premature infants. The pathophysiology is likely secondary to innate immune responses to intestinal microbiota by the premature infant's intestinal tract, leading to inflammation and injury. This review provides an updated summary of the components of the innate immune system involved in NEC pathogenesis. In addition, we evaluate the animal models that have been used to study NEC with regard to the involvement of innate immune factors and histopathological changes as compared to those seen in infants with NEC. Finally, we discuss new approaches to studying NEC, including mathematical models of intestinal injury and the use of humanized mice. PMID:25447054

  19. Modulation of Immune Response Using Engineered Nanoparticle Surfaces.

    PubMed

    Moyano, Daniel F; Liu, Yuanchang; Peer, Dan; Rotello, Vincent M

    2016-01-01

    Nanoparticles (NPs) coated with a monolayer of ligands can be recognized by different components of the immune system, opening new doors for the modulation of immunological responses. By the use of different physical or chemical properties at the NP surface (such as charge, functional groups, and ligand density), NPs can be designed to have distinct cellular uptake, cytokine secretion, and immunogenicity, factors that influence the distribution and clearance of these particles. Understanding these immunological responses is critical for the development of new NP-based carriers for the delivery of therapeutic molecules, and as such several studies have been performed to understand the relationships between immune responses and NP surface functionality. In this review, we will discuss recent reports of these structure-activity relationships, and explore how these motifs can be controlled to elicit therapeutically useful immune responses. PMID:26618755

  20. Harnessing DNA-induced immune responses for improving cancer vaccines

    PubMed Central

    Herrada, Andrés A.; Rojas-Colonelli, Nicole; González-Figueroa, Paula; Roco, Jonathan; Oyarce, César; Ligtenberg, Maarten A.; Lladser, Alvaro

    2012-01-01

    DNA vaccines have emerged as an attractive strategy to promote protective cellular and humoral immunity against the encoded antigen. DNA vaccines are easy to generate, inexpensive to produce and purify at large-scale, highly stable and safe. In addition, plasmids used for DNA vaccines act as powerful “danger signals” by stimulating several DNA-sensing innate immune receptors that promote the induction of protective adaptive immunity. The induction of tumor-specific immune responses represents a major challenge for DNA vaccines because most of tumor-associated antigens are normal non-mutated self-antigens. As a consequence, induction of potentially self-reactive T cell responses against such poorly immunogenic antigens is controlled by mechanisms of central and peripheral tolerance as well as tumor-induced immunosuppression. Although several DNA vaccines against cancer have reached clinical testing, disappointing results have been observed. Therefore, the development of new adjuvants that strongly stimulate the induction of antitumor T cell immunity and counteract immune-suppressive regulation is an attractive approach to enhance the potency of DNA vaccines and overcome tumor-associated tolerance. Understanding the DNA-sensing signaling pathways of innate immunity that mediate the induction of T cell responses elicited by DNA vaccines represents a unique opportunity to develop novel adjuvants that enhance vaccine potency. The advance of DNA adjuvants needs to be complemented with the development of potent delivery systems, in order to step toward successful clinical application. Here, we briefly discuss recent evidence showing how to harness DNA-induced immune response to improve the potency of cancer vaccines and counteract tumor-associated tolerance. PMID:23111166

  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. Innate Immune Response to Intramammary Mycoplasma bovis Infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mastitis caused by Mycoplasma bovis is a growing concern for the dairy industry. M. bovis intramammary infection commonly results in an untreatable case of chronic mastitis. The innate immune system is responsible for initial recognition of, and immediate host responses to, infectious pathogens. ...

  3. Innate immune responses of temperamental and calm cattle after transportation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective was to investigate measures of cellular innate immune responses among calm and temperamental Brahman bulls in response to handling and transportation. Sixteen Brahman bulls (344 ± 37 days of age; 271.6 ± 45.5 kg BW) classified as either calm (n = 8) or temperamental (n = 8) were loaded...

  4. How Neutrophils Shape Adaptive Immune Responses

    PubMed Central

    Leliefeld, Pieter H. C.; Koenderman, Leo; Pillay, Janesh

    2015-01-01

    Neutrophils are classically considered as cells pivotal for the first line of defense against invading pathogens. In recent years, evidence has accumulated that they are also important in the orchestration of adaptive immunity. Neutrophils rapidly migrate in high numbers to sites of inflammation (e.g., infection, tissue damage, and cancer) and are subsequently able to migrate to draining lymph nodes (LNs). Both at the site of inflammation as well as in the LNs, neutrophils can engage with lymphocytes and antigen-presenting cells. This crosstalk occurs either directly via cell–cell contact or via mediators, such as proteases, cytokines, and radical oxygen species. In this review, we will discuss the current knowledge regarding locations and mechanisms of interaction between neutrophils and lymphocytes in the context of homeostasis and various pathological conditions. In addition, we will highlight the complexity of the microenvironment that is involved in the generation of suppressive or stimulatory neutrophil phenotypes. PMID:26441976

  5. Arginine and Citrulline and the Immune Response in Sepsis

    PubMed Central

    Wijnands, Karolina A.P.; Castermans, Tessy M.R.; Hommen, Merel P.J.; Meesters, Dennis M.; Poeze, Martijn

    2015-01-01

    Arginine, a semi-essential amino acid is an important initiator of the immune response. Arginine serves as a precursor in several metabolic pathways in different organs. In the immune response, arginine metabolism and availability is determined by the nitric oxide synthases and the arginase enzymes, which convert arginine into nitric oxide (NO) and ornithine, respectively. Limitations in arginine availability during inflammatory conditions regulate macrophages and T-lymfocyte activation. Furthermore, over the past years more evidence has been gathered which showed that arginine and citrulline deficiencies may underlie the detrimental outcome of inflammatory conditions, such as sepsis and endotoxemia. Not only does the immune response contribute to the arginine deficiency, also the impaired arginine de novo synthesis in the kidney has a key role in the eventual observed arginine deficiency. The complex interplay between the immune response and the arginine-NO metabolism is further underscored by recent data of our group. In this review we give an overview of physiological arginine and citrulline metabolism and we address the experimental and clinical studies in which the arginine-citrulline NO pathway plays an essential role in the immune response, as initiator and therapeutic target. PMID:25699985

  6. Antigen-specific immune responses to influenza vaccine in utero

    PubMed Central

    Rastogi, Deepa; Wang, Chaodong; Mao, Xia; Lendor, Cynthia; Rothman, Paul B.; Miller, Rachel L.

    2007-01-01

    Initial immune responses to allergens may occur before birth, thereby modulating the subsequent development of atopy. This paradigm remains controversial, however, due to the inability to identify antigen-specific T cells in cord blood. The advent of MHC tetramers has revolutionized the detection of antigen-specific T cells. Tetramer staining of cord blood after CMV infection has demonstrated that effective CD8+ antigen-specific immune responses can follow intrauterine viral infections. We hypothesized that sensitization to antigens occurs in utero in humans. We studied cord blood B and T cell immune responses following vaccination against influenza during pregnancy. Anti-Fluzone and anti-matrix protein IgM antibodies were detected in 38.5% (27 of 70) and 40.0% (28 of 70), respectively, of cord blood specimens. Using MHC tetramers, HA-specific CD4+ T cells were detected among 25.0% (3 of 12) and 42.9% (6 of 14) of cord blood specimens possessing DRB1*0101 and DRB1*0401 HLA types, respectively, and were detected even when the DRB1 HLA type was inherited from the father. Matrix protein–specific CD8+ T cells were detected among 10.0% (2 of 20) of HLA-A*0201+ newborns. These results suggest that B and T cell immune responses occur in the fetus following vaccination against influenza and have important implications for determining when immune responses to environmental exposures begin. PMID:17549258

  7. Modulation of immune responses in stress by Yoga

    PubMed Central

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-01-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress. PMID:21829284

  8. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies.

    PubMed

    Guillerey, Camille; Nakamura, Kyohei; Vuckovic, Slavica; Hill, Geoffrey R; Smyth, Mark J

    2016-04-01

    Multiple myeloma (MM) is a tumor of terminally differentiated B cells that arises in the bone marrow. Immune interactions appear as key determinants of MM progression. While myeloid cells foster myeloma-promoting inflammation, Natural Killer cells and T lymphocytes mediate protective anti-myeloma responses. The profound immune deregulation occurring in MM patients may be involved in the transition from a premalignant to a malignant stage of the disease. In the last decades, the advent of stem cell transplantation and new therapeutic agents including proteasome inhibitors and immunoregulatory drugs has dramatically improved patient outcomes, suggesting potentially key roles for innate and adaptive immunity in disease control. Nevertheless, MM remains largely incurable for the vast majority of patients. A better understanding of the complex interplay between myeloma cells and their immune environment should pave the way for designing better immunotherapies with the potential of very long term disease control. Here, we review the immunological microenvironment in myeloma. We discuss the role of naturally arising anti-myeloma immune responses and their potential corruption in MM patients. Finally, we detail the numerous promising immune-targeting strategies approved or in clinical trials for the treatment of MM. PMID:26801219

  9. LIGHT May Improve Immune Checkpoint Blockade Response.

    PubMed

    2016-06-01

    A new study suggests that insufficient T-cell infiltration may explain why a majority of patients do not respond to immunotherapy. Combining PD-L1 inhibitors with antibody-guided LIGHT, a protein that recruits tumor-infiltrating lymphocytes, increased antitumor response in mice, and may have the potential to improve patient response rates to immunotherapy. PMID:27080334

  10. Immune responses to Aeromonas hydrophila in catfish (Heteropneustis fossilis) exposed to cadmium and hexachlorocyclohexane

    SciTech Connect

    Saxena, M.P.; Gopal, K.; Jones, W.; Ray, P.K. )

    1992-02-01

    Fishes are poikilothermic vertebrates hence all the body functions including immunological defense may be susceptible to adverse changes in the aquatic environment. Environmental pollutants, especially heavy metals and pesticides are known to contribute to outbreaks of infectious bacterial diseases in fishes. Pesticides enter the aquatic environment through intentional application, aerial drift or runoff from applications or accidental release and then become rapidly distributed. Major routes of pesticide movement into water are agricultural runoff from fields and grazing lands. Several investigators have evaluated the toxicity of hexachlorocyclohexane (HCH) in fishes, however, only sporadic observations on the humoral immune responses have been made. Cadmium has been demonstrated to affect the immune system of teleost. The effects of sublethal concentrations of methylmercury and copper on the immune response of blue gourami (Trichogaster trichopterus) have also been studied. Attempts have been made to investigate the effect of the HCH and cadmium on the humoral immune responses to bacterial antigen using H. fossilis as test species. Attempt is also made to evaluate the vascular function at sublethal doses.

  11. Immunization with Immune Complexes Modulates the Fine Specificity of Antibody Responses to a Flavivirus Antigen

    PubMed Central

    Tsouchnikas, Georgios; Zlatkovic, Juergen; Jarmer, Johanna; Strauß, Judith; Vratskikh, Oksana; Kundi, Michael; Stiasny, Karin

    2015-01-01

    ABSTRACT The antibody response to proteins may be modulated by the presence of preexisting antigen-specific antibodies and the formation of immune complexes (ICs). Effects such as a general increase or decrease of the response as well as epitope-specific phenomena have been described. In this study, we investigated influences of IC immunization on the fine specificity of antibody responses in a structurally well-defined system, using the envelope (E) protein of tick-borne encephalitis (TBE) virus as an immunogen. TBE virus occurs in Europe and Asia and—together with the yellow fever, dengue, West Nile, and Japanese encephalitis viruses—represents one of the major human-pathogenic flaviviruses. Mice were immunized with a dimeric soluble form of E (sE) alone or in complex with monoclonal antibodies specific for each of the three domains of E, and the antibody response induced by these ICs was compared to that seen after immunization with sE alone. Immunoassays using recombinant domains and domain combinations of TBE virus sE as well as the distantly related West Nile virus sE allowed the dissection and quantification of antibody subsets present in postimmunization sera, thus generating fine-specificity patterns of the polyclonal responses. There were substantially different responses with two of the ICs, and the differences could be mechanistically related to (i) epitope shielding and (ii) antibody-mediated structural changes leading to dissociation of the sE dimer. The phenomena described may also be relevant for polyclonal responses upon secondary infections and/or booster immunizations and may affect antibody responses in an individual-specific way. IMPORTANCE Infections with flaviviruses such as yellow fever, dengue, Japanese encephalitis, West Nile, and tick-borne encephalitis (TBE) viruses pose substantial public health problems in different parts of the world. Antibodies to viral envelope protein E induced by natural infection or vaccination were shown to

  12. Age-dependent immune responses and immune protection after avian coronavirus vaccination.

    PubMed

    van Ginkel, Frederik W; Padgett, Justin; Martinez-Romero, Gisela; Miller, Matthew S; Joiner, Kellye S; Gulley, Stephen L

    2015-05-28

    Infectious bronchitis virus (IBV) is an endemic disease of chickens and a major contributor to economic losses for the poultry industry despite vaccination. Recent observations indicated that chicks may have an immature immune system immediately after hatching when vaccinated for IBV. Therefore we hypothesized that early IBV vaccination will generate an immature, poorly protective IBV-specific immune response contributing to immune escape and persistence of IBV. To test this hypothesis the IBV-specific immune response and immune protection were measured in chicks vaccinated at different ages. This demonstrated a delayed production of IgG and IgA plasma antibodies in the 1, 7 and 14-day-old vaccination groups and also lower IgA antibody levels were observed in plasma of the 1-day-old group. Similar observations were made for antibodies in tears. In addition, IgG antibodies from the 1-day-old group had lower avidity indices than day 28 vaccinated birds. The delayed and/or lower antibody response combined with lower IgG avidity indices coincided with increased tracheal inflammation and depletion of tracheal epithelia cells and goblet cells upon IBV field strain challenge. The lack of vaccine-mediated protection was most pronounced in the 1-day-old vaccination group and to a lesser extent the 7-day-old group, while the 14-day-old and older chickens were protected. These data strongly support IBV vaccination after day 7 post hatch. PMID:25910920

  13. Bacterial Outer Membrane Vesicles Induce Plant Immune Responses.

    PubMed

    Bahar, Ofir; Mordukhovich, Gideon; Luu, Dee Dee; Schwessinger, Benjamin; Daudi, Arsalan; Jehle, Anna Kristina; Felix, Georg; Ronald, Pamela C

    2016-05-01

    Gram-negative bacteria continuously pinch off portions of their outer membrane, releasing membrane vesicles. These outer membrane vesicles (OMVs) are involved in multiple processes including cell-to-cell communication, biofilm formation, stress tolerance, horizontal gene transfer, and virulence. OMVs are also known modulators of the mammalian immune response. Despite the well-documented role of OMVs in mammalian-bacterial communication, their interaction with plants is not well studied. To examine whether OMVs of plant pathogens modulate the plant immune response, we purified OMVs from four different plant pathogens and used them to treat Arabidopsis thaliana. OMVs rapidly induced a reactive oxygen species burst, medium alkalinization, and defense gene expression in A. thaliana leaf discs, cell cultures, and seedlings, respectively. Western blot analysis revealed that EF-Tu is present in OMVs and that it serves as an elicitor of the plant immune response in this form. Our results further show that the immune coreceptors BAK1 and SOBIR1 mediate OMV perception and response. Taken together, our results demonstrate that plants can detect and respond to OMV-associated molecules by activation of their immune system, revealing a new facet of plant-bacterial interactions. PMID:26926999

  14. Probiotics, antibiotics and the immune responses to vaccines

    PubMed Central

    Praharaj, Ira; John, Sushil M.; Bandyopadhyay, Rini; Kang, Gagandeep

    2015-01-01

    Orally delivered vaccines have been shown to perform poorly in developing countries. There are marked differences in the structure and the luminal environment of the gut in developing countries resulting in changes in immune and barrier function. Recent studies using newly developed technology and analytic methods have made it increasingly clear that the intestinal microbiota activate a multitude of pathways that control innate and adaptive immunity in the gut. Several hypotheses have been proposed for the underperformance of oral vaccines in developing countries, and modulation of the intestinal microbiota is now being tested in human clinical trials. Supplementation with specific strains of probiotics has been shown to have modulatory effects on intestinal and systemic immune responses in animal models and forms the basis for human studies with vaccines. However, most studies published so far that have evaluated the immune response to vaccines in children and adults have been small and results have varied by age, antigen, type of antibody response and probiotic strain. Use of anthelminthic drugs in children has been shown to possibly increase immunogenicity following oral cholera vaccination, lending further support to the rationale for modulation of the immune response to oral vaccination through the intestinal microbiome. PMID:25964456

  15. Immune responses of ducks infected with duck Tembusu virus

    PubMed Central

    Li, Ning; Wang, Yao; Li, Rong; Liu, Jiyuan; Zhang, Jinzhou; Cai, Yumei; Liu, Sidang; Chai, Tongjie; Wei, Liangmeng

    2015-01-01

    Duck Tembusu virus (DTMUV) can cause serious disease in ducks, characterized by reduced egg production. Although the virus has been isolated and detection methods developed, the host immune responses to DTMUV infection are unclear. Therefore, we systematically examined the expression of immune-related genes and the viral distribution in DTMUV-infected ducks, using quantitative real-time PCR. Our results show that DTMUV replicates quickly in many tissues early in infection, with the highest viral titers in the spleen 1 day after infection. Rig-1, Mda5, and Tlr3 are involved in the host immune response to DTMUV, and the expression of proinflammatory cytokines (Il-1β, –2, –6, Cxcl8) and antiviral proteins (Mx, Oas, etc.) are also upregulated early in infection. The expression of Il-6 increased most significantly in the tissues tested. The upregulation of Mhc-I was observed in the brain and spleen, but the expression of Mhc-II was upregulated in the brain and downregulated in the spleen. The expression of the interferons was also upregulated to different degrees in the spleen but that of the brain was various. Our study suggests that DTMUV replicates rapidly in various tissues and that the host immune responses are activated early in infection. However, the overexpression of cytokines may damage the host. These results extend our understanding of the immune responses of ducks to DTMUV infection, and provide insight into the pathogenesis of DTMUV attributable to host factors. PMID:26005441

  16. Crosstalk between microbiota, pathogens and the innate immune responses.

    PubMed

    Günther, Claudia; Josenhans, Christine; Wehkamp, Jan

    2016-08-01

    Research in the last decade has convincingly demonstrated that the microbiota is crucial in order to prime and orchestrate innate and adaptive immune responses of their host and influence barrier function as well as multiple developmental and metabolic parameters of the host. Reciprocally, host reactions and immune responses instruct the composition of the microbiota. This review summarizes recent evidence from experimental and human studies which supports these arms of mutual relationship and crosstalk between host and resident microbiota, with a focus on innate immune responses in the gut, the role of cell death pathways and antimicrobial peptides. We also provide some recent examples on how dysbiosis and pathogens can act in concert to promote intestinal infection, inflammatory pathologies and cancer. The future perspectives of these combined research efforts include the discovery of protective species within the microbiota and specific traits and factors of microbes that weaken or enforce host intestinal homeostasis. PMID:26996809

  17. Mucosal Immune Responses and Protection against Tetanus Toxin after Intranasal Immunization with Recombinant Lactobacillus plantarum

    PubMed Central

    Grangette, Corinne; Müller-Alouf, Heide; Goudercourt, Denise; Geoffroy, Marie-Claude; Turneer, Mireille; Mercenier, Annick

    2001-01-01

    The use of live microorganisms as an antigen delivery system is an effective means to elicit local immune responses and thus represents a promising strategy for mucosal vaccination. In this respect, lactic acid bacteria represent an original and attractive approach, as they are safe organisms that are used as food starters and probiotics. To determine whether an immune response could be elicited by intranasal delivery of recombinant lactobacilli, a Lactobacillus plantarum strain of human origin (NCIMB8826) was selected as the expression host. Cytoplasmic production of the 47-kDa fragment C of tetanus toxin (TTFC) was achieved at different levels depending on the plasmid construct. All recombinant strains proved to be immunogenic by the intranasal route in mice and able to elicit very high systemic immunoglobulin G (IgG1, IgG2b, and IgG2a) responses which correlated to the antigen dose. No significant differences in enzyme-linked immunosorbent assay IgG titers were observed when mice were immunized with live or mitomycin C-treated recombinant lactobacilli. Nevertheless, protection against the lethal effect of tetanus toxin was obtained only with the strains producing the highest dose of antigen and was greater following immunization with live bacteria. Significant TTFC-specific mucosal IgA responses were measured in bronchoalveolar lavage fluids, and antigen-specific T-cell responses were detected in cervical lymph nodes, both responses being higher in mice receiving a double dose of bacteria (at a 24-h interval) at each administration. These results demonstrate that recombinant lactobacilli can induce specific humoral (protective) and mucosal antibodies and cellular immune response against protective antigens upon nasal administration. PMID:11179325

  18. Acute psychological stress induces short-term variable immune response.

    PubMed

    Breen, Michael S; Beliakova-Bethell, Nadejda; Mujica-Parodi, Lilianne R; Carlson, Joshua M; Ensign, Wayne Y; Woelk, Christopher H; Rana, Brinda K

    2016-03-01

    In spite of advances in understanding the cross-talk between the peripheral immune system and the brain, the molecular mechanisms underlying the rapid adaptation of the immune system to an acute psychological stressor remain largely unknown. Conventional approaches to classify molecular factors mediating these responses have targeted relatively few biological measurements or explored cross-sectional study designs, and therefore have restricted characterization of stress-immune interactions. This exploratory study analyzed transcriptional profiles and flow cytometric data of peripheral blood leukocytes with physiological (endocrine, autonomic) measurements collected throughout the sequence of events leading up to, during, and after short-term exposure to physical danger in humans. Immediate immunomodulation to acute psychological stress was defined as a short-term selective up-regulation of natural killer (NK) cell-associated cytotoxic and IL-12 mediated signaling genes that correlated with increased cortisol, catecholamines and NK cells into the periphery. In parallel, we observed down-regulation of innate immune toll-like receptor genes and genes of the MyD88-dependent signaling pathway. Correcting gene expression for an influx of NK cells revealed a molecular signature specific to the adrenal cortex. Subsequently, focusing analyses on discrete groups of coordinately expressed genes (modules) throughout the time-series revealed immune stress responses in modules associated to immune/defense response, response to wounding, cytokine production, TCR signaling and NK cell cytotoxicity which differed between males and females. These results offer a spring-board for future research towards improved treatment of stress-related disease including the impact of stress on cardiovascular and autoimmune disorders, and identifies an immune mechanism by which vulnerabilities to these diseases may be gender-specific. PMID:26476140

  19. Compartmentalization of the mucosal immune responses to commensal intestinal bacteria.

    PubMed

    Macpherson, Andrew J; Uhr, Therese

    2004-12-01

    Mammals coexist with a luxuriant load of bacteria in the lower intestine (up to 10(12) organisms/g of intestinal contents). Although these bacteria do not cause disease if they remain within the intestinal lumen, they contain abundant immunostimulatory molecules that trigger immunopathology if the bacteria penetrate the body in large numbers. The physical barrier consists only of a single epithelial cell layer with overlying mucus, but comparisons between animals kept in germ-free conditions and those colonized with bacteria show that bacteria induce both mucosal B cells and some T cell subsets; these adaptations are assumed to function as an immune barrier against bacterial penetration, but the mechanisms are poorly understood. In mice with normal intestinal flora, but no pathogens, there is a secretory IgA response against bacterial membrane proteins and other cell wall components. Whereas induction of IgA against cholera toxin is highly T help dependent, secretory IgA against commensal bacteria is induced by both T independent and T dependent pathways. When animals are kept in clean conditions and free of pathogens, there is still a profound intestinal secretory IgA response against the commensal intestinal flora. However, T dependent serum IgG responses against commensal bacteria do not occur in immunocompetent animals unless they are deliberately injected intravenously with 10(4) to 10(6) organisms. In other words, unmanipulated pathogen-free mice are systemically ignorant but not tolerant of their commensal flora despite the mucosal immune response to these organisms. In mice that are challenged with intestinal doses of commensal bacteria, small numbers of commensals penetrate the epithelial cell layer and survive within dendritic cells (DC). These commensal-loaded DC induce IgA, but because they are confined within the mucosal immune system by the mesenteric lymph nodes, they do not induce systemic immune responses. In this way the mucosal immune responses

  20. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids

    PubMed Central

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas’ disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts’ immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host’s immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite–host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites–hosts–vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  1. Control of the Adaptive Immune Response by Tumor Vasculature

    PubMed Central

    Mauge, Laetitia; Terme, Magali; Tartour, Eric; Helley, Dominique

    2014-01-01

    The endothelium is nowadays described as an entire organ that regulates various processes: vascular tone, coagulation, inflammation, and immune cell trafficking, depending on the vascular site and its specific microenvironment as well as on endothelial cell-intrinsic mechanisms like epigenetic changes. In this review, we will focus on the control of the adaptive immune response by the tumor vasculature. In physiological conditions, the endothelium acts as a barrier regulating cell trafficking by specific expression of adhesion molecules enabling adhesion of immune cells on the vessel, and subsequent extravasation. This process is also dependent on chemokine and integrin expression, and on the type of junctions defining the permeability of the endothelium. Endothelial cells can also regulate immune cell activation. In fact, the endothelial layer can constitute immunological synapses due to its close interactions with immune cells, and the delivery of co-stimulatory or co-inhibitory signals. In tumor conditions, the vasculature is characterized by an abnormal vessel structure and permeability, and by a specific phenotype of endothelial cells. All these abnormalities lead to a modulation of intra-tumoral immune responses and contribute to the development of intra-tumoral immunosuppression, which is a major mechanism for promoting the development, progression, and treatment resistance of tumors. The in-depth analysis of these various abnormalities will help defining novel targets for the development of anti-tumoral treatments. Furthermore, eventual changes of the endothelial cell phenotype identified by plasma biomarkers could secondarily be selected to monitor treatment efficacy. PMID:24734218

  2. Escaping Deleterious Immune Response in Their Hosts: Lessons from Trypanosomatids.

    PubMed

    Geiger, Anne; Bossard, Géraldine; Sereno, Denis; Pissarra, Joana; Lemesre, Jean-Loup; Vincendeau, Philippe; Holzmuller, Philippe

    2016-01-01

    The Trypanosomatidae family includes the genera Trypanosoma and Leishmania, protozoan parasites displaying complex digenetic life cycles requiring a vertebrate host and an insect vector. Trypanosoma brucei gambiense, Trypanosoma cruzi, and Leishmania spp. are important human pathogens causing human African trypanosomiasis (HAT or sleeping sickness), Chagas' disease, and various clinical forms of Leishmaniasis, respectively. They are transmitted to humans by tsetse flies, triatomine bugs, or sandflies, and affect millions of people worldwide. In humans, extracellular African trypanosomes (T. brucei) evade the hosts' immune defenses, allowing their transmission to the next host, via the tsetse vector. By contrast, T. cruzi and Leishmania sp. have developed a complex intracellular lifestyle, also preventing several mechanisms to circumvent the host's immune response. This review seeks to set out the immune evasion strategies developed by the different trypanosomatids resulting from parasite-host interactions and will focus on: clinical and epidemiological importance of diseases; life cycles: parasites-hosts-vectors; innate immunity: key steps for trypanosomatids in invading hosts; deregulation of antigen-presenting cells; disruption of efficient specific immunity; and the immune responses used for parasite proliferation. PMID:27303406

  3. Role of DNA repair in host immune response and inflammation.

    PubMed

    Fontes, Fabrícia Lima; Pinheiro, Daniele Maria Lopes; Oliveira, Ana Helena Sales de; Oliveira, Rayssa Karla de Medeiros; Lajus, Tirzah Braz Petta; Agnez-Lima, Lucymara Fassarella

    2015-01-01

    In recent years, the understanding of how DNA repair contributes to the development of innate and acquired immunity has emerged. The DNA damage incurred during the inflammatory response triggers the activation of DNA repair pathways, which are required for host-cell survival. Here, we reviewed current understanding of the mechanism by which DNA repair contributes to protection against the oxidized DNA damage generated during infectious and inflammatory diseases and its involvement in innate and adaptive immunity. We discussed the functional role of DNA repair enzymes in the immune activation and the relevance of these processes to: transcriptional regulation of cytokines and other genes involved in the inflammatory response; V(D)J recombination; class-switch recombination (CSR); and somatic hypermutation (SHM). These three last processes of DNA damage repair are required for effective humoral adaptive immunity, creating genetic diversity in developing T and B cells. Furthermore, viral replication is also dependent on host DNA repair mechanisms. Therefore, the elucidation of the pathways of DNA damage and its repair that activate innate and adaptive immunity will be important for a better understanding of the immune and inflammatory disorders and developing new therapeutic interventions for treatment of these diseases and for improving their outcome. PMID:25795123

  4. Mitochondrial DNA in the regulation of innate immune responses.

    PubMed

    Fang, Chunju; Wei, Xiawei; Wei, Yuquan

    2016-01-01

    Mitochondrion is known as the energy factory of the cell, which is also a unique mammalian organelle and considered to be evolved from aerobic prokaryotes more than a billion years ago. Mitochondrial DNA, similar to that of its bacterial ancestor’s, consists of a circular loop and contains significant number of unmethylated DNA as CpG islands. The innate immune system plays an important role in the mammalian immune response. Recent research has demonstrated that mitochondrial DNA (mtDNA) activates several innate immune pathways involving TLR9, NLRP3 and STING signaling, which contributes to the signaling platforms and results in effector responses. In addition to facilitating antibacterial immunity and regulating antiviral signaling, mounting evidence suggests that mtDNA contributes to inflammatory diseases following cellular damage and stress. Therefore, in addition to its well-appreciated roles in cellular metabolism and energy production,mtDNA appears to function as a key member in the innate immune system. Here, we highlight the emerging roles of mtDNA in innate immunity. PMID:26498951

  5. Mycobacterial infection induces a specific human innate immune response

    PubMed Central

    Blischak, John D.; Tailleux, Ludovic; Mitrano, Amy; Barreiro, Luis B.; Gilad, Yoav

    2015-01-01

    The innate immune system provides the first response to infection and is now recognized to be partially pathogen-specific. Mycobacterium tuberculosis (MTB) is able to subvert the innate immune response and survive inside macrophages. Curiously, only 5–10% of otherwise healthy individuals infected with MTB develop active tuberculosis (TB). We do not yet understand the genetic basis underlying this individual-specific susceptibility. Moreover, we still do not know which properties of the innate immune response are specific to MTB infection. To identify immune responses that are specific to MTB, we infected macrophages with eight different bacteria, including different MTB strains and related mycobacteria, and studied their transcriptional response. We identified a novel subset of genes whose regulation was affected specifically by infection with mycobacteria. This subset includes genes involved in phagosome maturation, superoxide production, response to vitamin D, macrophage chemotaxis, and sialic acid synthesis. We suggest that genetic variants that affect the function or regulation of these genes should be considered candidate loci for explaining TB susceptibility. PMID:26586179

  6. Bacterial RNA: An Underestimated Stimulus for Innate Immune Responses.

    PubMed

    Eigenbrod, Tatjana; Dalpke, Alexander H

    2015-07-15

    Although DNA of bacterial and viral origin, as well as viral RNA, have been intensively studied as triggers of innate immune responses, the stimulatory properties of bacterial RNA and its role during infections have just begun to be deciphered. Bacterial RNA is a strong inducer of type I IFN and NF-κB-dependent cytokines, and it also can activate the Nlrp3 inflammasome. In this review, we focus on the receptors and signaling pathways involved in innate immune activation by bacterial RNA and analyze the physiological relevance of bacterial RNA recognition during infections. Furthermore, we present the concept that RNA modifications can impair RNA-dependent immune activation. RNA modifications differ between eukaryotes and prokaryotes; thus, they can serve to define the innate pattern that is recognized. In this regard, we discuss the role of ribose 2'-O-methylation as a potential immune-escape mechanism. PMID:26138638

  7. Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

    PubMed Central

    Ludington, Jacob G.; Ward, Honorine D.

    2015-01-01

    Cryptosporidium spp is a major cause of diarrheal disease worldwide, particularly in malnourished children and untreated AIDS patients in developing countries in whom it can cause severe, chronic and debilitating disease. Unfortunately, there is no consistently effective drug for these vulnerable populations and no vaccine, partly due to a limited understanding of both the parasite and the host immune response. In this review, we will discuss our current understanding of the systemic and mucosal immune responses to Cryptosporidium infection, discuss the feasibility of developing a Cryptosporidium vaccine and evaluate recent advances in Cryptosporidium vaccine development strategies PMID:26279971

  8. Nanotechnology, neuromodulation & the immune response: discourse, materiality & ethics.

    PubMed

    Fins, Joseph J

    2015-04-01

    Drawing upon the American Pragmatic tradition in philosophy and the more recent work of philosopher Karen Barad, this paper examines how scientific problems are both obscured, and resolved by our use of language describing the natural world. Using the example of the immune response engendered by neural implants inserted in the brain, the author explains how this discourse has been altered by the advent of nanotechnology methods and devices which offer putative remedies that might temper the immune response in the central nervous system. This emergent nanotechnology has altered this problem space and catalyzed one scientific community to acknowledge a material reality that was always present, if not fully acknowledged. PMID:25681046

  9. Immunization with Single Oral Dose of Alginate-Encapsulated BCG Elicits Effective and Long-Lasting Mucosal Immune Responses.

    PubMed

    Hosseini, M; Dobakhti, F; Pakzad, S R; Ajdary, S

    2015-12-01

    Effective vaccination against pathogens, which enter the body through mucosal surfaces, requires the induction of both mucosal and systemic immune responses. Here, mucosal as well as systemic immune responses in the lung and spleen of BALB/c mice which were orally vaccinated with a single dose of alginate-encapsulated bacille Calmette-Guerin (BCG) were evaluated. Twenty weeks after immunization, the vaccinated mice were challenged intranasally with BCG. Twelve weeks after immunization and 5 weeks after challenge, the immune responses were evaluated. Moreover, immune responses were compared with those of mice that were vaccinated with free BCG by subcutaneous (sc) and oral routes. Twelve weeks after the immunization, serum IgG level was higher in the sc-immunized mice, while serum IgA level was higher in the orally immunized mice with encapsulated BCG. Significant productions of both IgG and IgA were only detected in lungs of mice orally immunized with encapsulated BCG. Proliferative and delayed-type hypersensitivity responses and IFN-γ production were significantly higher in mice immunized orally with encapsulated BCG, compared to mice immunized orally with free BCG. After challenge, the levels of IFN-γ were comparable between sc-immunized mice with free BCG and orally immunized with encapsulated BCG; however, significantly less IL-4 was detected in mice which had received encapsulated BCG via oral route. Moreover, significant control of the bacilli growth in the lung of the immunized mice after intranasal challenge with BCG was documented in mice vaccinated with encapsulated BCG. These results suggest that oral immunization with alginate-encapsulated BCG is an effective mean of inducing mucosal and systemic specific immune responses. PMID:26286252

  10. Adverse health consequences of US Government responses to the 2001 terrorist attacks.

    PubMed

    Levy, Barry S; Sidel, Victor W

    2011-09-01

    In response to the attacks on Sept 11, 2001 (9/11), and the related security concerns, the USA and its coalition partners began a war in Afghanistan and subsequently invaded Iraq. The wars caused many deaths of non-combatant civilians, further damaged the health-supporting infrastructure and the environment (already adversely affected by previous wars), forced many people to migrate, led to violations of human rights, and diverted resources away from important health needs. After 9/11 and the anthrax outbreak shortly afterwards, the USA and other countries have improved emergency preparedness and response capabilities, but these actions have often diverted attention and resources from more urgent health issues. The documentation and dissemination of information about the adverse health effects of these wars and about the diversion of resources could help to mitigate these consequences and prevent their recurrence. PMID:21890059

  11. The innate and adaptive immune response induced by alveolar macrophages exposed to ambient particulate matter

    SciTech Connect

    Miyata, Ryohei; Eeden, Stephan F. van

    2011-12-15

    Emerging epidemiological evidence suggests that exposure to particulate matter (PM) air pollution increases the risk of cardiovascular events but the exact mechanism by which PM has adverse effects is still unclear. Alveolar macrophages (AM) play a major role in clearing and processing inhaled PM. This comprehensive review of research findings on immunological interactions between AM and PM provides potential pathophysiological pathways that interconnect PM exposure with adverse cardiovascular effects. Coarse particles (10 {mu}m or less, PM{sub 10}) induce innate immune responses via endotoxin-toll-like receptor (TLR) 4 pathway while fine (2.5 {mu}m or less, PM{sub 2.5}) and ultrafine particles (0.1 {mu}m or less, UFP) induce via reactive oxygen species generation by transition metals and/or polyaromatic hydrocarbons. The innate immune responses are characterized by activation of transcription factors [nuclear factor (NF)-{kappa}B and activator protein-1] and the downstream proinflammatory cytokine [interleukin (IL)-1{beta}, IL-6, and tumor necrosis factor-{alpha}] production. In addition to the conventional opsonin-dependent phagocytosis by AM, PM can also be endocytosed by an opsonin-independent pathway via scavenger receptors. Activation of scavenger receptors negatively regulates the TLR4-NF-{kappa}B pathway. Internalized particles are subsequently subjected to adaptive immunity involving major histocompatibility complex class II (MHC II) expression, recruitment of costimulatory molecules, and the modulation of the T helper (Th) responses. AM show atypical antigen presenting cell maturation in which phagocytic activity decreases while both MHC II and costimulatory molecules remain unaltered. PM drives AM towards a Th1 profile but secondary responses in a Th1- or Th-2 up-regulated milieu drive the response in favor of a Th2 profile.

  12. Photodynamic therapy for cancer and activation of immune response

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Huang, Ying-Ying; Hamblin, Michael R.

    2010-02-01

    Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors (TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.

  13. Immune responses in DNA vaccine formulated with PMMA following immunization and after challenge with Leishmania major.

    PubMed

    Zarrati, Somayeh; Mahdavi, Mehdi; Tabatabaie, Fatemeh

    2016-06-01

    Leishmaniasis is a major infectious disease caused by protozoan parasites of the genus Leishmania. Despite of many efforts toward vaccine against Leishmania no effective vaccine has been approved yet. DNA vaccines can generate more powerful and broad immune responses than conventional vaccines. In order to increase immunity, the DNA vaccine has been supplemented with adjuvant. In this study a new nano-vaccine containing TSA recombinant plasmid and poly(methylmethacrylate) nanoparticles (act as adjuvant) was designed and its immunogenicity tested on BALB/c mouse. After three intramuscular injection of nano-vaccine (100 μg), the recombinant TSA protein (20 μg) was injected subcutaneously. Finally as a challenge animals were infected by Leishmania major. After the last injection of nano-vaccine, after protein booster injection, and also after challenge, cellular immune and antibody responses were evaluated by ELISA method. The findings of this study showed the new nano-vaccine was capable of induction both cytokines secretion and specific antibody responses, but predominant Th1 immune response characterized by IFN-γ production compared to control groups. Moreover, results revealed that nano-vaccine was effective in reducing parasite burden in the spleen of Leishmania major-infected BALB/c mice. Base on results, current candidate vaccine has potency for further studies. PMID:27413316

  14. The Challenge for Gene Therapy: Innate Immune Response to Adenoviruses

    PubMed Central

    Thaci, Bart; Ulasov, Ilya V.; Wainwright, Derek A.; Lesniak, Maciej S.

    2011-01-01

    Adenoviruses are the most commonly used vectors for gene therapy. Despite the promising safety profile demonstrated in clinical trials, the efficacy of using adenoviruses for gene therapy is poor. A major hurdle to adenoviral-mediated gene therapy is the innate immune system. Cell-mediated recognition of viruses via capsid components or nucleic acids has received significant attention, principally thought to be regulated by the toll-like receptors (TLRs). Antiviral innate immune responses are initiated by the infected cell, which activates the interferon (IFN) response to block viral replication, while simultaneously releasing chemokines to attract neutrophils, mononuclear- and natural killer-cells. While the IFN and cellular recruitment pathways are activated and regulated independently of each other, both are required to overcome immune escape mechanisms by adenoviruses. Recent work has shown that the generation of adenoviral vectors lacking specific transcriptionally-active regions decreases immune system activation and increases the chance for immune escape. In this review, we elucidate how adenoviral vector modifications alter the IFN and innate inflammatory pathway response and propose future targets with clinically-translational relevance. PMID:21399236

  15. Immune Responses and Protection of Aotus Monkeys Immunized with Irradiated Plasmodium vivax Sporozoites

    PubMed Central

    Jordán-Villegas, Alejandro; Perdomo, Anilza Bonelo; Epstein, Judith E.; López, Jesús; Castellanos, Alejandro; Manzano, María R.; Hernández, Miguel A.; Soto, Liliana; Méndez, Fabián; Richie, Thomas L.; Hoffman, Stephen L.; Arévalo-Herrera, Myriam; Herrera, Sócrates

    2011-01-01

    A non-human primate model for the induction of protective immunity against the pre-erythrocytic stages of Plasmodium vivax malaria using radiation-attenuated P. vivax sporozoites may help to characterize protective immune mechanisms and identify novel malaria vaccine candidates. Immune responses and protective efficacy induced by vaccination with irradiated P. vivax sporozoites were evaluated in malaria-naive Aotus monkeys. Three groups of six monkeys received two, five, or ten intravenous inoculations, respectively, of 100,000 irradiated P. vivax sporozoites; control groups received either 10 doses of uninfected salivary gland extract or no inoculations. Immunization resulted in the production low levels of antibodies that specifically recognized P. vivax sporozoites and the circumsporozoite protein. Additionally, immunization induced low levels of antigen-specific IFN-γ responses. Intravenous challenge with viable sporozoites resulted in partial protection in a dose-dependent manner. These findings suggest that the Aotus monkey model may be able to play a role in preclinical development of P. vivax pre-erythrocytic stage vaccines. PMID:21292877

  16. Immune response in the lungs following oral immunization with bacterial lysates of respiratory pathogens.

    PubMed Central

    Ruedl, C; Frühwirth, M; Wick, G; Wolf, H

    1994-01-01

    We have investigated the local immune response of the BALB/c mouse respiratory tract after oral immunization with a bacterial lysate of seven common respiratory pathogens. After two immunization on five consecutive days, we examined the immunoglobulin (immunoglobulin G [IgG], IgM, and IgA) secretion rates of cells isolated from the lungs and compared them with those of spleen cells of orally immunized and nonimmunized animals by using a new test system based on time-resolved fluorescence. The procedure followed the principle of the classical ELISPOT test with nitrocellulose-bottomed microtiter plates, but europium (Eu3+)-linked streptavidin rather than enzyme-conjugated streptavidin was used, with the advantage of quantifying secreted immunoglobulins instead of detecting single antibody-secreting cells. Lymphocytes isolated from the lungs of treated animals revealed significant increases in total and antigen-specific IgA synthesis compared with the rates of the controls, whereas IgG and IgM production rates showed no remarkable differences. In addition, the sera of treated mice revealed higher antigen-specific IgA titers but not increased IgM and IgG levels. We conclude that priming the gut-associated lymphoid tissue with bacterial antigens of pneumotropic microorganisms can elicit an enhanced IgA response in a distant mucosal effector site, such as the respiratory tract, according to the concept of a common mucosa-associated immune system. PMID:7496936

  17. Verification of immune response optimality through cybernetic modeling.

    PubMed

    Batt, B C; Kompala, D S

    1990-02-01

    An immune response cascade that is T cell independent begins with the stimulation of virgin lymphocytes by antigen to differentiate into large lymphocytes. These immune cells can either replicate themselves or differentiate into plasma cells or memory cells. Plasma cells produce antibody at a specific rate up to two orders of magnitude greater than large lymphocytes. However, plasma cells have short life-spans and cannot replicate. Memory cells produce only surface antibody, but in the event of a subsequent infection by the same antigen, memory cells revert rapidly to large lymphocytes. Immunologic memory is maintained throughout the organism's lifetime. Many immunologists believe that the optimal response strategy calls for large lymphocytes to replicate first, then differentiate into plasma cells and when the antigen has been nearly eliminated, they form memory cells. A mathematical model incorporating the concept of cybernetics has been developed to study the optimality of the immune response. Derived from the matching law of microeconomics, cybernetic variables control the allocation of large lymphocytes to maximize the instantaneous antibody production rate at any time during the response in order to most efficiently inactivate the antigen. A mouse is selected as the model organism and bacteria as the replicating antigen. In addition to verifying the optimal switching strategy, results showing how the immune response is affected by antigen growth rate, initial antigen concentration, and the number of antibodies required to eliminate an antigen are included. PMID:2338827

  18. Immune Responses to Low Back Pain Risk Factors

    PubMed Central

    Splittstoesser, Riley E.; Marras, William S.; Best, Thomas M.

    2013-01-01

    Objective Investigate effects of interactions between biomechanical, psychosocial and individual risk factors on the body’s immune inflammatory responses. Background Current theories for low back pain causation do not fully account for the body’s response to tissue loading and tissue trauma. Methods Two groups possessing a preference for the sensor or intuitor personality trait performed repetitive lifting combined with high or low mental workload on separate occasions. Spinal loading was assessed using an EMG-assisted subject-specific biomechanical model and immune markers were collected before and after exposure. Results Mental workload was associated with a small decrease in AP shear. Both conditions were characterized by a regulated time-dependent immune response making use of markers of inflammation, tissue trauma and muscle damage. Intuitors’ creatine kinase levels were increased following low mental workload compared to that observed in Sensors with the opposite trend occurring for high mental workload. Conclusions A temporally regulated immune response to lifting combined with mental workload exists. This response is influenced by personality and mental workload. PMID:22317743

  19. Elevated EBNA1 Immune Responses Predict Conversion to Multiple Sclerosis

    PubMed Central

    Lünemann, Jan D.; Tintoré, Mar; Messmer, Brady; Strowig, Till; Rovira, Álex; Perkal, Héctor; Caballero, Estrella; Münz, Christian; Montalban, Xavier; Comabella, Manuel

    2009-01-01

    Objective The aims of the study were to determine the immune responses to candidate viral triggers of multiple sclerosis (MS) in patients with clinically isolated syndromes (CIS), and to evaluate their potential value in predicting conversion to MS. Methods Immune responses to Epstein-Barr virus (EBV), human herpesvirus 6, cytomegalovirus (HCMV), and measles were determined in a cohort of 147 CIS patients with a mean follow-up of 7 years and compared with 50 demographically matched controls. Results Compared to controls, CIS patients showed increased humoral (p<0.0001) and cellular (p=0.007) immune responses to the EBV-encoded nuclear antigen-1 (EBNA1), but not to other EBV-derived proteins. IgG responses to other virus antigens and frequencies of T cells specific for HCMV and influenza virus gene products were unchanged in CIS patients. EBNA1 was the only viral antigen towards which immune responses correlated with number of T2 lesions (p=0.006) and number of Barkhof criteria (p=0.001) at baseline, and with number of T2 lesions (p=0.012 both at 1 and 5 years), presence of new T2 lesions (p=0.003 and p=0.028 at 1 and 5 years), and EDSS (p=0.015 and p=0.010 at 1 and 5 years) during follow-up. In a univariate Cox regression model, increased EBNA1-specific IgG responses predicted conversion to MS based on McDonald criteria [hazard ratio (95% confidence interval), 2.2 (1.2–4.3); p=0.003]. Interpretation Our results indicate that elevated immune responses towards EBNA1 are selectively increased in CIS patients and suggest that EBNA1-specific IgG titers could be used as a prognostic marker for disease conversion and disability progression. PMID:20225269

  20. Adjuvant effects of saponins on animal immune responses*

    PubMed Central

    Rajput, Zahid Iqbal; Hu, Song-hua; Xiao, Chen-wen; Arijo, Abdullah G.

    2007-01-01

    Vaccines require optimal adjuvants including immunopotentiator and delivery systems to offer long term protection from infectious diseases in animals and man. Initially it was believed that adjuvants are responsible for promoting strong and sustainable antibody responses. Now it has been shown that adjuvants influence the isotype and avidity of antibody and also affect the properties of cell-mediated immunity. Mostly oil emulsions, lipopolysaccharides, polymers, saponins, liposomes, cytokines, ISCOMs (immunostimulating complexes), Freund’s complete adjuvant, Freund’s incomplete adjuvant, alums, bacterial toxins etc., are common adjuvants under investigation. Saponin based adjuvants have the ability to stimulate the cell mediated immune system as well as to enhance antibody production and have the advantage that only a low dose is needed for adjuvant activity. In the present study the importance of adjuvants, their role and the effect of saponin in immune system is reviewed. PMID:17323426

  1. HIV-1 and the immune response to TB

    PubMed Central

    Walker, Naomi F; Meintjes, Graeme; Wilkinson, Robert J

    2013-01-01

    TB causes 1.4 million deaths annually. HIV-1 infection is the strongest risk factor for TB. The characteristic immunological effect of HIV is on CD4 cell count. However, the risk of TB is elevated in HIV-1 infected individuals even in the first few years after HIV acquisition and also after CD4 cell counts are restored with antiretroviral therapy. In this review, we examine features of the immune response to TB and how this is affected by HIV-1 infection and vice versa. We discuss how the immunology of HIV–TB coinfection impacts on the clinical presentation and diagnosis of TB, and how antiretroviral therapy affects the immune response to TB, including the development of TB immune reconstitution inflammatory syndrome. We highlight important areas of uncertainty and future research needs. PMID:23653664

  2. 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

  3. Incidence of adverse drug reactions in human immune deficiency virus-positive patients using highly active antiretroviral therapy.

    PubMed

    Srikanth, B Akshaya; Babu, S Chandra; Yadav, Harlokesh Narayan; Jain, Sunil Kumar

    2012-01-01

    To estimate the incidence of adverse drug reactions (ADRs) in Human immune deficiency virus (HIV) patients on highly active antiretroviral therapy (HAART). To identify the risk factors associated with ADRs in HIV patients. To analyze reported ADRs based on various parameters like causality, severity, predictability, and preventability. Retrospective case-control study. An 18-month retrospective case-control study of 208 patients newly registered in ART center, RIMS hospital, Kadapa, were intensively monitored for ADRs to HAART. Predictability was calculated based on the history of previous exposure to drug. Multivariate logistic regressions were used to identify the risk factors for ADRs. Data were analyzed using the chi-square test for estimating the correlation between ADRs and different variables. All statistical calculations were performed using EpiInfo version 3.5.3. Monitoring of 208 retrospective patients by active Pharmacovigilance identified 105 ADRs that were identified in 71 patients. Skin rash and anemia were the most commonly observed ADRs. The organ system commonly affected by ADR was skin and appendages (31.57%). The ADRs that were moderate were 90.14% of cases. The incidence of ADRs (53.52%) was higher with Zidovudine + Lamivudine + Nevirapine combination. CD4 cell count less than <250 cells/μl were 80.28%, male gender were observed to be the risk factors for ADRs. Our study finding showed that there is a need of active pharmaceutical care with intensive monitoring for ADRs in Indian HIV-positive patients who are illiterate, of male and female gender, with CD4 count ≤250 cells/mm(3) with comorbid conditions. PMID:22470896

  4. A Drosophila immune response against Ras-induced overgrowth

    PubMed Central

    Hauling, Thomas; Krautz, Robert; Markus, Robert; Volkenhoff, Anne; Kucerova, Lucie; Theopold, Ulrich

    2014-01-01

    ABSTRACT Our goal is to characterize the innate immune response against the early stage of tumor development. For this, animal models where genetic changes in specific cells and tissues can be performed in a controlled way have become increasingly important, including the fruitfly Drosophila melanogaster. Many tumor mutants in Drosophila affect the germline and, as a consequence, also the immune system itself, making it difficult to ascribe their phenotype to a specific tissue. Only during the past decade, mutations have been induced systematically in somatic cells to study the control of tumorous growth by neighboring cells and by immune cells. Here we show that upon ectopic expression of a dominant-active form of the Ras oncogene (RasV12), both imaginal discs and salivary glands are affected. Particularly, the glands increase in size, express metalloproteinases and display apoptotic markers. This leads to a strong cellular response, which has many hallmarks of the granuloma-like encapsulation reaction, usually mounted by the insect against larger foreign objects. RNA sequencing of the fat body reveals a characteristic humoral immune response. In addition we also identify genes that are specifically induced upon expression of RasV12. As a proof-of-principle, we show that one of the induced genes (santa-maria), which encodes a scavenger receptor, modulates damage to the salivary glands. The list of genes we have identified provides a rich source for further functional characterization. Our hope is that this will lead to a better understanding of the earliest stage of innate immune responses against tumors with implications for mammalian immunity. PMID:24659248

  5. Immune responses to exercising in a cold environment.

    PubMed

    LaVoy, Emily C P; McFarlin, Brian K; Simpson, Richard J

    2011-12-01

    Cold temperature and exercise independently impose stress on the human body that can lead to circulatory and metabolic changes, and depress the immune system. Multiple stressors applied together may amplify this immunodepression, causing greater immune impairment and heightened infection risk than with either stressor alone. As such, winter athletes and other persons who work or physically exert themselves in cold temperatures may have greater levels of stress-induced immune impairment than would be expected under mild temperatures. This review examines the literature regarding changes to physiological and immunological parameters arising from exposure to cold temperatures and to exercise. Even brief exposure to cold leads to increased levels of norepinephrine and cortisol, lymphocytosis, decreased lymphoproliferative responses, decreased levels of TH1 cytokines and salivary IgA, and increased lactate levels during exercise. Whether these changes lead to increased susceptibility to infection, as suggested by some epidemiological reports, remains to be determined. Although there is some evidence that exercising in temperatures near 5°C leads to greater immune impairment compared to exercising in milder temperatures, there is a need to explore the effects of exercise on immunity in the subfreezing conditions typically encountered by winter athletes. This is required to fully determine the extent to which performing vigorous exercise in subfreezing temperatures amplifies exercise-induced immune impairment and infection risk. PMID:21982757

  6. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases.

    PubMed

    Middleton, Elizabeth A; Weyrich, Andrew S; Zimmerman, Guy A

    2016-10-01

    Platelets are essential for physiological hemostasis and are central in pathological thrombosis. These are their traditional and best known activities in health and disease. In addition, however, platelets have specializations that broaden their functional repertoire considerably. These functional capabilities, some of which are recently discovered, include the ability to sense and respond to infectious and immune signals and to act as inflammatory effector cells. Human platelets and platelets from mice and other experimental animals can link the innate and adaptive limbs of the immune system and act across the immune continuum, often also linking immune and hemostatic functions. Traditional and newly recognized facets of the biology of platelets are relevant to defensive, physiological immune responses of the lungs and to inflammatory lung diseases. The emerging view of platelets as blood cells that are much more diverse and versatile than previously thought further predicts that additional features of the biology of platelets and of megakaryocytes, the precursors of platelets, will be discovered and that some of these will also influence pulmonary immune defenses and inflammatory injury. PMID:27489307

  7. Radiation, Inflammation, and Immune Responses in Cancer

    PubMed Central

    Multhoff, Gabriele; Radons, Jürgen

    2012-01-01

    Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR. PMID:22675673

  8. Altered Innate and Lymphocytic Immune Responses in Mouse Splenocytes Post-Flight

    NASA Technical Reports Server (NTRS)

    Hwang, ShenAn; Crucian, Brian E.; Sams, Clarence F.; Actor, Jeffrey K.

    2011-01-01

    Space flight is known to affect immune responses of astronauts and animals, decreasing lymphocytic responses to mitogenic stimuli, delayed typed hypersensitivity reactions, and T-cell activation. Despite changes in immune suppression, there are no reports of consistent adverse clinical events post flight. To further investigate the spectrum of affected immune responses, murine splenocytes were stimulated immediately post-shuttle flight (14 days on STS-135) with T-cell stimulators or toll-like receptor agonists. Comparisons were made to ground control splenocytes from age-matched mice. Cell phenotypes were assessed, as well as activation markers and associated cytokine production. The CD4+ population decreased with no concurrent decrease in CD8+ cells from shuttle mice post flight compared to ground controls. Regarding antigen presenting cell populations, the number of CD11c+ cells were slightly elevated post flight, compared to ground controls, with increased MHC Class I expression (I-A(sup b)) and no change in Class II expression (H-2K(sup b)). CD86+ populations were also significantly diminished. However, the decreased markers did not correlate with activity. Stimulation of splenocytes post flight showed significant increase in bead uptake, increased Class I expression, increased TNF-alpha and IL-6 production in response to TLR-2 (zymosan) and TLR-4 (LPS) agonists. While most activated (ConA or anti-CD3/anti-CD28) CD4+ cells showed markedly diminished responses (reduced IL-2 production), non-specific T cell responses to superantigen (SEA/SEB) increased post flight as determined by expression of early activation markers. Production of additional cytokines was also dysregulated postflight. Overall, persistent immune changes during space flight could represent unique clinical risks for exploration class missions. The consequences of pathogenic encounter remain an important concern that should be addressed.

  9. Immune response in mice to ingested soya protein: antibody production, oral tolerance and maternal transfer.

    PubMed

    Christensen, Hanne R; Brix, Susanne; Frøkiaer, Hanne

    2004-05-01

    While allergic reactions to soya are increasingly investigated, the normal immune response to ingested soya is scarcely described. In the present study, we wanted to characterise the soya-specific immune response in healthy mice ingesting soya protein. Mice fed a soya-containing diet (F0) and mice of the first (F1) and second (F2) offspring generation bred on a soya protein-free diet were used either directly or were transferred between the soya-containing and soya protein-free diet during pregnancy or neonatal life. The mice were compared as to levels of naturally occurring specific antibodies analysed by ELISA, and to the presence of oral tolerance detected as a suppressed antibody and cell-proliferation response upon immunisation with soya protein. F0 mice generated soya-specific antibodies, while oral tolerance to the same soya proteins was also clearly induced. When F0 dams were transferred to soya protein-free feed before mating, the F1 and F2 offspring generations showed no significantly different response, indicating that soya-specific immune components were not maternally transmitted. However, the ingestion of dietary soya protein by F1 mice during late pregnancy and lactation caused a lasting antibody response in the offspring, but in this case in the absence of oral tolerance. This indicates that, under certain conditions, factors involved in spontaneous antibody production can be transmitted from mother to offspring. Understanding the immune response to soya protein ingested under healthy conditions is important in the assessment of adverse effects of soya protein and in the use of animal allergy models. The present results add to this understanding. PMID:15137924

  10. Veni, vidi, vici: in vivo molecular imaging of immune response.

    PubMed

    Gross, Shimon; Moss, Britney L; Piwnica-Worms, David

    2007-10-01

    "I came, I saw, I conquered," Julius Caesar proclaimed, highlighting the importance of direct visualization as a winning strategy. Continuing the "From the Field" series (see Editorial [2007] 26, 131), Gross et al. summarize how modern molecular imaging techniques can successfully dissect the complexities of immune response in vivo. PMID:17967405

  11. DEVELOPMENT OF MOLECULAR BIOMARKERS TO MEASURE ENVIRONMENTALLY INDUCED IMMUNE RESPONSES

    EPA Science Inventory

    This study will generate a panel of sensitive molecular biomarkers to measure environmentally induced changes in systemic and local immune responses within small biological samples. Once tested and characterized, these reagents can be immediately incorporated as a part of the...

  12. Eicosanoids mediate Galaleria mellonella cellular immune response to viral infection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Nodulation is the predominant insect cellular immune response to bacterial and fungal infections and it can also be induced by viral infection. Treating seventh instar larvae of greater wax moth Galleria mellonella with Bovine herpes simplex virus-1 (BHSV-1) induced nodulation reactions in a dose-d...

  13. ASSESSMENT OF ALLERGIC IMMUNE RESPONSES TO INDOOR AIR FUNGAL CONTAMINANTS

    EPA Science Inventory

    We are using a mouse model to assess immune and inflammatory responses as well as changes in respiratory function and pathology characteristic of allergic asthma to fungal extracts M. anisopliae (MACA), S. chartarum (SCE), and P. chrysogenum (PCE). This model will be useful to a...

  14. Human genes in TB infection: their role in immune response.

    PubMed

    Lykouras, D; Sampsonas, F; Kaparianos, A; Karkoulias, K; Tsoukalas, G; Spiropoulos, K

    2008-03-01

    Tuberculosis (TB) caused by the human pathogen Mycobacterium tuberculosis, is the leading cause of morbidity and mortality caused by infectious agents worldwide. Recently, there has been an ongoing concern about the clarification of the role of specific human genes and their polymorphisms involved in TB infection. In the vast majority of individuals, innate immune pathways and T-helper 1 (Th1) cell mediated immunity are activated resulting in the lysis of the bacterium. Firstly, PTPN22 R620W polymorphism is involved in the response to cases of infection. The Arg753Gln polymorphism in TLR-2 leads to a weaker response against the M. tuberculosis. The gene of the vitamin D receptor (VDR) has a few polymorphisms (BsmI, ApaI, Taq1, FokI) whose mixed genotypes alter the immune response. Solute carrier family 11 member (SLC11A1) is a proton/divalent cation antiporter that is more familiar by its former name NRAMP1 (natural resistance associated macrophage protein 1) and can affect M. tuberculosis growth. Polymorphisms of cytokines such as IL-10, IL-6, IFN-g, TNF-a, TGF-b1 can affect the immune response in various ways. Finally, a major role is played by M. tuberculosis antigens and the Ras-associated small GTP-ase 33A. As far as we know this is the first review that collates all these polymorphisms in order to give a comprehensive image of the field, which is currently evolving. PMID:18507196

  15. Primary immune response to blood group antigens in burned children.

    PubMed

    Bacon, N; Patten, E; Vincent, J

    1991-01-01

    Delayed hemolytic transfusion reactions (DHTRs) are generally attributed to an anamnestic immune response. Case reports of DHTRs due to a primary immune response are rare. Transfusion reactions occurring in patients on the pediatric burn unit from 1981 to September 1988 were reviewed, and additional information was obtained for patients for whom a DHTR was documented. Of 62 transfusion reactions, 11 were classified as a primary immune response (DHTR), with either a positive antibody screen, a positive direct antiglobulin test (DAT), or both. None of the 11 patients included in the study had been previously tranfused or pregnant. The average number of units transfused prior to antibody identification was 19. The average time elapsed between the first transfusion and antibody identification was 3.6 weeks. Anti-K and anti-E were the most frequently identified. Three patients had a decrease in hemoglobin (average 1.5 g/dL) and hematocrit at the time that a positive DAT was detected. Such changes could not be demonstrated for the remaining eight patients. The conclusion was that a DHTR may he caused by a primary immune response in burned children more often than expected, but DHTR signs and symptoms are often not apparent due to the complications of burn trauma. PMID:15946011

  16. Nitric oxide and redox mechanisms in the immune response

    PubMed Central

    Wink, David A.; Hines, Harry B.; Cheng, Robert Y. S.; Switzer, Christopher H.; Flores-Santana, Wilmarie; Vitek, Michael P.; Ridnour, Lisa A.; Colton, Carol A.

    2011-01-01

    The role of redox molecules, such as NO and ROS, as key mediators of immunity has recently garnered renewed interest and appreciation. To regulate immune responses, these species trigger the eradication of pathogens on the one hand and modulate immunosuppression during tissue-restoration and wound-healing processes on the other. In the acidic environment of the phagosome, a variety of RNS and ROS is produced, thereby providing a cauldron of redox chemistry, which is the first line in fighting infection. Interestingly, fluctuations in the levels of these same reactive intermediates orchestrate other phases of the immune response. NO activates specific signal transduction pathways in tumor cells, endothelial cells, and monocytes in a concentration-dependent manner. As ROS can react directly with NO-forming RNS, NO bioavailability and therefore, NO response(s) are changed. The NO/ROS balance is also important during Th1 to Th2 transition. In this review, we discuss the chemistry of NO and ROS in the context of antipathogen activity and immune regulation and also discuss similarities and differences between murine and human production of these intermediates. PMID:21233414

  17. Optimal control strategy for abnormal innate immune response.

    PubMed

    Tan, Jinying; Zou, Xiufen

    2015-01-01

    Innate immune response plays an important role in control and clearance of pathogens following viral infection. However, in the majority of virus-infected individuals, the response is insufficient because viruses are known to use different evasion strategies to escape immune response. In this study, we use optimal control theory to investigate how to control the innate immune response. We present an optimal control model based on an ordinary-differential-equation system from a previous study, which investigated the dynamics and regulation of virus-triggered innate immune signaling pathways, and we prove the existence of a solution to the optimal control problem involving antiviral treatment or/and interferon therapy. We conduct numerical experiments to investigate the treatment effects of different control strategies through varying the cost function and control efficiency. The results show that a separate treatment, that is, only inhibiting viral replication (u1(t)) or enhancing interferon activity (u2(t)), has more advantages for controlling viral infection than a mixed treatment, that is, controlling both (u1(t)) and (u2(t)) simultaneously, including the smallest cost and operability. These findings would provide new insight for developing effective strategies for treatment of viral infectious diseases. PMID:25949271

  18. Aberrant Immune Responses in a Mouse with Behavioral Disorders

    PubMed Central

    Gao, Donghong; Miller, Veronica M.; Lawrence, David A.

    2011-01-01

    BTBR T+tf/J (BTBR) mice have recently been reported to have behaviors that resemble those of autistic individuals, in that this strain has impairments in social interactions and a restricted repetitive and stereotyped pattern of behaviors. Since immune responses, including autoimmune responses, are known to affect behavior, and individuals with autism have aberrant immune activities, we evaluated the immune system of BTBR mice, and compared their immunity and degree of neuroinflammation with that of C57BL/6 (B6) mice, a highly social control strain, and with F1 offspring. Mice were assessed at postnatal day (pnd) 21 and after behavioral analysis at pnd70. BTBR mice had significantly higher amounts of serum IgG and IgE, of IgG anti-brain antibodies (Abs), and of IgG and IgE deposited in the brain, elevated expression of cytokines, especially IL-33 IL-18, and IL-1β in the brain, and an increased proportion of MHC class II-expressing microglia compared to B6 mice. The F1 mice had intermediate levels of Abs and cytokines as well as social activity. The high Ab levels of BTBR mice are in agreement with their increased numbers of CD40hi/I-Ahi B cells and IgG-secreting B cells. Upon immunization with KLH, the BTBR mice produced 2–3 times more anti-KLH Abs than B6 mice. In contrast to humoral immunity, BTBR mice are significantly more susceptible to listeriosis than B6 or BALB/c mice. The Th2-like immune profile of the BTBR mice and their constitutive neuroinflammation suggests that an autoimmune profile is implicated in their aberrant behaviors, as has been suggested for some humans with autism. PMID:21799730

  19. HTLV-1, Immune Response and Autoimmunity

    PubMed Central

    Quaresma, Juarez A S; Yoshikawa, Gilberto T; Koyama, Roberta V L; Dias, George A S; Fujihara, Satomi; Fuzii, Hellen T

    2015-01-01

    Human T-lymphotropic virus type-1 (HTLV-1) infection is associated with adult T-cell leukemia/lymphoma (ATL). Tropical spastic paraparesis/HTLV-1-associated myelopathy (PET/HAM) is involved in the development of autoimmune diseases including Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE), and Sjögren’s Syndrome (SS). The development of HTLV-1-driven autoimmunity is hypothesized to rely on molecular mimicry, because virus-like particles can trigger an inflammatory response. However, HTLV-1 modifies the behavior of CD4+ T cells on infection and alters their cytokine production. A previous study showed that in patients infected with HTLV-1, the activity of regulatory CD4+ T cells and their consequent expression of inflammatory and anti-inflammatory cytokines are altered. In this review, we discuss the mechanisms underlying changes in cytokine release leading to the loss of tolerance and development of autoimmunity. PMID:26712781

  20. Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Deem, Michael

    2006-03-01

    The immune system normally protects the human host against death by infection. However, when an immune response is mistakenly directed at self antigens, autoimmune disease can occur. We describe a model of protein evolution to simulate the dynamics of the adaptive immune response to antigens. Computer simulations of the dynamics of antibody evolution show that different evolutionary mechanisms, namely gene segment swapping and point mutation, lead to different evolved antibody binding affinities. Although a combination of gene segment swapping and point mutation can yield a greater affinity to a specific antigen than point mutation alone, the antibodies so evolved are highly cross-reactive and would cause autoimmune disease, and this is not the chosen dynamics of the immune system. We suggest that in the immune system a balance has evolved between binding affinity and specificity in the mechanism for searching the amino acid sequence space of antibodies. Our model predicts that chronic infection may lead to autoimmune disease as well due to cross-reactivity and suggests a broad distribution for the time of onset of autoimmune disease due to chronic exposure. The slow search of antibody sequence space by point mutation leads to the broad of distribution times.

  1. TRAUMA AND IMMUNE RESPONSE – EFFECT OF GENDER DIFFERENCES

    PubMed Central

    Choudhry, Mashkoor A.; Bland, Kirby I.; Chaudry, Irshad H.

    2009-01-01

    A major consequence of traumatic injury is the immunosuppression. Findings from previous studies suggest that the depression of immune functions is severe in young males, ovariectomized and aged females. In contrast, the immune functions in proestrus females following trauma-hemorrhage are maintained. Studies have also shown that the survival rate in proestrus females following trauma-hemorrhage and the induction of subsequent sepsis is significantly higher than in age-matched males and ovariectomized females. Furthermore, administration of female sex hormone 17β-estradiol in males and ovariectomized females after trauma-hemorrhage prevents the suppression of immune response. Thus, these findings suggest that sex hormones play a significant role in shaping the host response following trauma. This article reviews studies delineating the mechanism by which sex hormones regulate immune cell functions in the experimental model of trauma-hemorrhage. The findings from the studies reviewed in this article suggest that sex steroids can be synthesized by the immune cell. The findings further indicate that T cell and macrophages express receptors for androgen and estrogen. Since these cells are also the cells that produce cytokines, local synthesis of active steroids in these cells may become the significant factor in modulating their cytokine production. PMID:18048037

  2. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    NASA Astrophysics Data System (ADS)

    Godina-Nava, J. J.; Segura, M. A. Rodríguez; Cadena, S. Reyes; Sierra, L. C. Gaitán

    2008-08-01

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

  3. Immune Response to Electromagnetic Fields through Cybernetic Modeling

    SciTech Connect

    Godina-Nava, J. J.; Segura, M. A. Rodriguez; Cadena, S. Reyes; Sierra, L. C. Gaitan

    2008-08-11

    We study the optimality of the humoral immune response through a mathematical model, which involves the effect of electromagnetic fields over the large lymphocytes proliferation. Are used the so called cybernetic variables in the context of the matching law of microeconomics or mathematical psychology, to measure the large lymphocytes population and to maximize the instantaneous antibody production rate in time during the immunologic response in order to most efficiently inactivate the antigen.

  4. Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model

    PubMed Central

    Guzman-Bautista, Edgar R; Garcia-Ruiz, Carlos E; Gama-Espinosa, Alicia L; Ramirez-Estudillo, Carmen; Rojas-Gomez, Oscar I; Vega-Lopez, Marco A

    2014-01-01

    Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA)-specific MatAb on the anti-OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti-OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination. PMID:24754050

  5. Humoural immune response and pathological analysis in patients with false immune diagnosis of cystic echinococcosis

    PubMed Central

    Chen, X; Zhang, J; Feng, X; Chen, X; Yin, S; Wen, H; Zheng, S

    2014-01-01

    The patients with false immune diagnosis of hydatid disease were investigated for the humoural immune response to analyse the possible reasons and mechanism leading to false immune diagnosis. Two hundred and thirty-nine patients with nature-unknown cysts and 30 healthy controls were detected by immunological assays (four hydatid antigen-based immunogold filtration assay and enzyme-linked immune absorbent assay) and ultrasound. Sensitivity of and specificity of immunological assay and ultrasound were calculated, respectively. The serological diagnosis was compared with surgical pathology to screen the patients with false immune diagnosis for the immunoglobulin measurement and pathological analysis. The history and cyst characteristics were also reviewed. The results indicate the immunoglobulin has little influence on false immunodiagnosis. The false-negative immunodiagnosis was caused by the cysts' inactive status while the false positive caused by previous rupture, antigen cross-reaction. The clinical diagnosis of cystic echinococcosis requires a combination of immunodiagnosis and ultrasonography, which is the necessary complementary confirmation. PMID:24372157

  6. Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses

    PubMed Central

    Verma, Saguna; Hoffmann, FuKun W.; Kumar, Mukesh; Huang, Zhi; Roe, Kelsey; Nguyen-Wu, Elizabeth; Hashimoto, Ann S.; Hoffmann, Peter R.

    2011-01-01

    Selenoprotein K (Sel K) is a selenium-containing protein for which no function has been identified. We found that Sel K is an endoplasmic reticulum (ER) transmembrane protein expressed at relatively high levels in immune cells and is regulated by dietary selenium. Sel K−/− mice were generated and found to be similar to WT controls regarding growth and fertility. Immune system development was not affected by Sel K deletion, but specific immune cell defects were found in Sel K−/− mice. Receptor-mediated Ca2+ flux was decreased in T cells, neutrophils, and macrophages from Sel K−/− mice compare to controls. Ca2+-dependent functions including T cell proliferation, T cell and neutrophil migration, and Fcγ-receptor-mediated oxidative burst in macrophages were decreased in cells from Sel K−/− mice compared to controls. West Nile virus (WNV) infections were performed and Sel K−/− mice exhibited decreased viral clearance in the periphery and increased viral titers in brain. Furthermore, WNV-infected Sel K−/− mice demonstrated significantly lower survival (2/23; 8.7%) compared to WT controls (10/26; 38.5%). These results establish Sel K as an ER-membrane protein important for promoting effective Ca2+ flux during immune cell activation and provide insight into molecular mechanisms by which dietary selenium enhances immune responses. PMID:21220695

  7. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer.

    PubMed

    Mehnert, Janice M; Panda, Anshuman; Zhong, Hua; Hirshfield, Kim; Damare, Sherri; Lane, Katherine; Sokol, Levi; Stein, Mark N; Rodriguez-Rodriquez, Lorna; Kaufman, Howard L; Ali, Siraj; Ross, Jeffrey S; Pavlick, Dean C; Bhanot, Gyan; White, Eileen P; DiPaola, Robert S; Lovell, Ann; Cheng, Jonathan; Ganesan, Shridar

    2016-06-01

    Antibodies that target the immune checkpoint receptor programmed cell death protein 1 (PD-1) have resulted in prolonged and beneficial responses toward a variety of human cancers. However, anti-PD-1 therapy in some patients provides no benefit and/or results in adverse side effects. The factors that determine whether patients will be drug sensitive or resistant are not fully understood; therefore, genomic assessment of exceptional responders can provide important insight into patient response. Here, we identified a patient with endometrial cancer who had an exceptional response to the anti-PD-1 antibody pembrolizumab. Clinical grade targeted genomic profiling of a pretreatment tumor sample from this individual identified a mutation in DNA polymerase epsilon (POLE) that associated with an ultramutator phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that the presence of POLE mutation associates with high mutational burden and elevated expression of several immune checkpoint genes. Together, these data suggest that cancers harboring POLE mutations are good candidates for immune checkpoint inhibitor therapy. PMID:27159395

  8. Immune activation and response to pembrolizumab in POLE-mutant endometrial cancer

    PubMed Central

    Mehnert, Janice M.; Panda, Anshuman; Zhong, Hua; Hirshfield, Kim; Damare, Sherri; Lane, Katherine; Sokol, Levi; Stein, Mark N.; Rodriguez-Rodriquez, Lorna; Kaufman, Howard L.; Ali, Siraj; Ross, Jeffrey S.; Pavlick, Dean C.; Bhanot, Gyan; White, Eileen P.; DiPaola, Robert S.; Lovell, Ann; Cheng, Jonathan

    2016-01-01

    Antibodies that target the immune checkpoint receptor programmed cell death protein 1 (PD-1) have resulted in prolonged and beneficial responses toward a variety of human cancers. However, anti–PD-1 therapy in some patients provides no benefit and/or results in adverse side effects. The factors that determine whether patients will be drug sensitive or resistant are not fully understood; therefore, genomic assessment of exceptional responders can provide important insight into patient response. Here, we identified a patient with endometrial cancer who had an exceptional response to the anti–PD-1 antibody pembrolizumab. Clinical grade targeted genomic profiling of a pretreatment tumor sample from this individual identified a mutation in DNA polymerase epsilon (POLE) that associated with an ultramutator phenotype. Analysis of The Cancer Genome Atlas (TCGA) revealed that the presence of POLE mutation associates with high mutational burden and elevated expression of several immune checkpoint genes. Together, these data suggest that cancers harboring POLE mutations are good candidates for immune checkpoint inhibitor therapy. PMID:27159395

  9. Repeated Administration of Hyaluronic Acid Coated Liposomes with Improved Pharmacokinetics and Reduced Immune Response.

    PubMed

    Zhang, Quan; Deng, Caifeng; Fu, Yao; Sun, Xun; Gong, Tao; Zhang, Zhirong

    2016-06-01

    PEGylated liposomes (PEG-Lip) have been widely used as a drug carrier for their good stealth property in blood circulation. However, the second injection of PEG-Lip was reported to result in the accelerated blood clearance (ABC) phenomenon and trigger hypersensitivity reactions in sensitive individuals for its complement activation effect. To avoid adverse immune responses, HA was selected to modify liposomes to afford HA modified liposomes (HA-Lip). Repeated administrations of PEG-Lip and HA-Lip were performed in rats. Our results showed that PEG-Lip induced the ABC phenomenon accompanied by a greatly increased accumulation of PEG-Lip in the liver. In contrast, HA-Lip showed good stealth property without inducing either the ABC phenomenon or an increase in liver uptake. Moreover, HA-Lip did not trigger complement activation in human serum in vitro and in rat blood in vivo. Consequently, HA modification represents a viable strategy to prolong the blood circulation time of liposomes without inducing the ABC phenomenon and adverse immune responses. PMID:27112287

  10. Effect of season of inoculation on immune response to rubella vaccine in children.

    PubMed

    Linder, Nehama; Abudi, Yair; Abdalla, Wafa; Badir, Mursi; Amitai, Yona; Samuels, Justin; Mendelson, Ella; Levy, Itzhak

    2011-08-01

    The yearly seasons are marked by changes in the amount of sunlight. Ultraviolet radiation (UVR) is known to adversely affect the course of viral infections, immunologic memory and cellular and humoral immune responses. Our objectives were to investigate potential differences in the immune response of the rubella vaccine after 3-4 years by season of inoculation. Children aged 4-5 years attending four kindergartens in villages in northern Israel, all of whom had been vaccinated at 1 year of age, were enrolled in the study. Participants were divided into three groups by season of the year in which the inoculation was performed: summer (N = 63), winter (N = 36) and intermediate (N = 104). Main outcome measures were mean geometrical titer of rubella antibodies and complete, partial or no immunity to rubella by season of inoculation. Of the 203 children tested, 186 (91.6%) had adequate antibody levels, 7 (3.4%) had equivocal levels and 10 (4.9%) had inadequate levels. Significantly higher mean geometrical titers were found in the winter-inoculated compared with the summer-inoculated group (73.0 ± 2.6 vs 47.6 ± 2.8; p < 0.05). The same tendency was noted in the percent of infants properly immunized. This preliminary study shows a strong correlation between the immune response to rubella vaccine and the season of vaccination. Immunogenicity may be improved by inoculating children during seasons of less sunlight or by reducing the children's exposure to sunlight following inoculation. This practice is especially important in areas with extreme seasonal variability in solar radiation and tropical areas. Further studies are needed to corroborate and expand these findings. PMID:19889749

  11. Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

    PubMed Central

    Turroni, Francesca; Taverniti, Valentina; Ruas-Madiedo, Patricia; Duranti, Sabrina; Guglielmetti, Simone; Lugli, Gabriele Andrea; Gioiosa, Laura; Palanza, Paola; Margolles, Abelardo; van Sinderen, Douwe

    2014-01-01

    Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF-κB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. PMID:24242237

  12. Reprogramming immune responses via microRNA modulation

    PubMed Central

    Cubillos-Ruiz, Juan R.; Rutkowski, Melanie R; Tchou, Julia; Conejo-Garcia, Jose R.

    2013-01-01

    It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. PMID:25285232

  13. Immunization with Brucella VirB Proteins Reduces Organ Colonization in Mice through a Th1-Type Immune Response and Elicits a Similar Immune Response in Dogs

    PubMed Central

    Pollak, Cora N.; Wanke, María Magdalena; Estein, Silvia M.; Delpino, M. Victoria; Monachesi, Norma E.; Comercio, Elida A.; Fossati, Carlos A.

    2014-01-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. PMID:25540276

  14. Immunization with Brucella VirB proteins reduces organ colonization in mice through a Th1-type immune response and elicits a similar immune response in dogs.

    PubMed

    Pollak, Cora N; Wanke, María Magdalena; Estein, Silvia M; Delpino, M Victoria; Monachesi, Norma E; Comercio, Elida A; Fossati, Carlos A; Baldi, Pablo C

    2015-03-01

    VirB proteins from Brucella spp. constitute the type IV secretion system, a key virulence factor mediating the intracellular survival of these bacteria. Here, we assessed whether a Th1-type immune response against VirB proteins may protect mice from Brucella infection and whether this response can be induced in the dog, a natural host for Brucella. Splenocytes from mice immunized with VirB7 or VirB9 responded to their respective antigens with significant and specific production of gamma interferon (IFN-γ), whereas interleukin-4 (IL-4) was not detected. Thirty days after an intraperitoneal challenge with live Brucella abortus, the spleen load of bacteria was almost 1 log lower in mice immunized with VirB proteins than in unvaccinated animals. As colonization reduction seemed to correlate with a Th1-type immune response against VirB proteins, we decided to assess whether such a response could be elicited in the dog. Peripheral blood mononuclear cells (PBMCs) from dogs immunized with VirB proteins (three subcutaneous doses in QuilA adjuvant) produced significantly higher levels of IFN-γ than cells from control animals upon in vitro stimulation with VirB proteins. A skin test to assess specific delayed-type hypersensitivity was positive in 4 out of 5 dogs immunized with either VirB7 or VirB9. As both proteins are predicted to locate in the outer membrane of Brucella organisms, the ability of anti-VirB antibodies to mediate complement-dependent bacteriolysis of B. canis was assessed in vitro. Sera from dogs immunized with either VirB7 or VirB9, but not from those receiving phosphate-buffered saline (PBS), produced significant bacteriolysis. These results suggest that VirB-specific responses that reduce organ colonization by Brucella in mice can be also elicited in dogs. PMID:25540276

  15. B cell regulation of anti-tumor immune response.

    PubMed

    Zhang, Yu; Morgan, Richard; Podack, Eckhard R; Rosenblatt, Joseph

    2013-12-01

    Our laboratory has been investigating the role of B cells on tumor immunity. We have studied the immune response in mice that are genetically lacking in B cells (BCDM) using a variety of syngeneic mouse tumors and compared immune responses in BCDM with those seen in wild type (WT) immunocompetent mice (ICM). A variety of murine tumors are rejected or inhibited in their growth in BCDM, compared with ICM, including the EL4 thymoma, and the MC38 colon carcinoma in C57BL/6 mice, as well as the EMT-6 breast carcinoma in BALB/c mice. In all three murine models, tumors show reduced growth in BCDM which is accompanied by increased T cell and NK cell infiltration, and a more vigorous Th1 cytokine response, and increased cytolytic T cell response in the absence of B cells. Reconstitution of the mice with B cells results in augmented tumor growth due to a diminished anti-tumor immune response and in reduction in CD8+ T cell and NK cell infiltration. Studies involving BCR transgenic mice indicated that B cells inhibit anti-tumor T cell responses through antigen non-specific mechanisms. More recent studies using the EMT-6 model demonstrated that both the number and function of Treg cells in ICM was increased relative to that seen in BCDM. Increased expansion of Treg cells was evident following EMT-6 implantation in ICM relative to that seen in non-tumor-bearing mice or BCDM. The percentage and number of Tregs in spleen, tumor draining lymph nodes, and the tumor bed are increased in ICM compared with BCDM. Treg functional capacity as measured by suppression assays appears to be reduced in BCDM compared with ICM. In contrast to other described types of B regulatory activity, adoptive transfer of B cells can rescue tumor growth independently of the ability of B cells to secrete IL-10, and also independently of MHC-II expression. In experiments using the MC38 adenocarcinoma model, BCDM reconstituted with WT B cells support tumor growth while tumor growth continues to be inhibited

  16. Host Immune Status and Response to Hepatitis E Virus Infection

    PubMed Central

    Krain, Lisa J.; Nelson, Kenrad E.

    2014-01-01

    SUMMARY Hepatitis E virus (HEV), identified over 30 years ago, remains a serious threat to life, health, and productivity in developing countries where access to clean water is limited. Recognition that HEV also circulates as a zoonotic and food-borne pathogen in developed countries is more recent. Even without treatment, most cases of HEV-related acute viral hepatitis (with or without jaundice) resolve within 1 to 2 months. However, HEV sometimes leads to acute liver failure, chronic infection, or extrahepatic symptoms. The mechanisms of pathogenesis appear to be substantially immune mediated. This review covers the epidemiology of HEV infection worldwide, the humoral and cellular immune responses to HEV, and the persistence and protection of antibodies produced in response to both natural infection and vaccines. We focus on the contributions of altered immune states (associated with pregnancy, human immunodeficiency virus [HIV], and immunosuppressive agents used in cancer and transplant medicine) to the elevated risks of chronic infection (in immunosuppressed/immunocompromised patients) and acute liver failure and mortality (among pregnant women). We conclude by discussing outstanding questions about the immune response to HEV and interactions with hormones and comorbid conditions. These questions take on heightened importance now that a vaccine is available. PMID:24396140

  17. Fluid phase recognition molecules in neutrophil-dependent immune responses.

    PubMed

    Jaillon, Sébastien; Ponzetta, Andrea; Magrini, Elena; Barajon, Isabella; Barbagallo, Marialuisa; Garlanda, Cecilia; Mantovani, Alberto

    2016-04-01

    The innate immune system comprises both a cellular and a humoral arm. Neutrophils are key effector cells of the immune and inflammatory responses and have emerged as a major source of humoral pattern recognition molecules (PRMs). These molecules, which include collectins, ficolins, and pentraxins, are specialised in the discrimination of self versus non-self and modified-self and share basic multifunctional properties including recognition and opsonisation of pathogens and apoptotic cells, activation and regulation of the complement cascade and tuning of inflammation. Neutrophils act as a reservoir of ready-made soluble PRMs, such as the long pentraxin PTX3, the peptidoglycan recognition protein PGRP-S, properdin and M-ficolin, which are stored in neutrophil granules and are involved in neutrophil effector functions. In addition, other soluble PRMs, such as members of the collectin family, are not expressed in neutrophils but can modulate neutrophil-dependent immune responses. Therefore, soluble PRMs are an essential part of the innate immune response and retain antibody-like effector functions. Here, we will review the expression and general function of soluble PRMs, focusing our attention on molecules involved in neutrophil effector functions. PMID:27021644

  18. The Effect of Radiation on the Immune Response to Cancers

    PubMed Central

    Park, Bonggoo; Yee, Cassian; Lee, Kyung-Mi

    2014-01-01

    In cancer patients undergoing radiation therapy, the beneficial effects of radiation can extend beyond direct cytotoxicity to tumor cells. Delivery of localized radiation to tumors often leads to systemic responses at distant sites, a phenomenon known as the abscopal effect which has been attributed to the induction and enhancement of the endogenous anti-tumor innate and adaptive immune response. The mechanisms surrounding the abscopal effect are diverse and include trafficking of lymphocytes into the tumor microenvironment, enhanced tumor recognition and killing via up-regulation of tumor antigens and antigen presenting machinery and, induction of positive immunomodulatory pathways. Here, we discuss potential mechanisms of radiation-induced enhancement of the anti-tumor response through its effect on the host immune system and explore potential combinational immune-based strategies such as adoptive cellular therapy using ex vivo expanded NK and T cells as a means of delivering a potent effector population in the context of radiation-enhanced anti-tumor immune environment. PMID:24434638

  19. Immunization with avian metapneumovirus harboring chicken Fc induces higher immune responses.

    PubMed

    Paudel, Sarita; Easwaran, Maheswaran; Jang, Hyun; Jung, Ho-Kyoung; Kim, Joo-Hun; Shin, Hyun-Jin

    2016-07-15

    In this study, we evaluated the immune responses of avian metapneumovirus harboring chicken Fc molecule. Stable Vero cells expressing chicken Fc chimera on its surface (Vero-cFc) were established, and we confirmed that aMPV grown in Vero-cFc incorporated host derived chimera Fc into the aMPV virions. Immunization of chicken with aMPV-cFc induced higher level of antibodies and inflammatory cytokines; (Interferon (IFN)-γ and Interleukin (IL)-1β) compared to those of aMPV. The increased levels of antibodies and inflammatory cytokines in chicken immunized with aMPV-cFc were statistically significantly (p<0.05) to that of aMPV and control. The aMPV-cFc group also generated the highest neutralizing antibody response. After challenges, chickens immunized with aMPV-cFc showed much less pathological signs in nasal turbinates and trachea so that we could confirm aMPV-cFc induced higher protection than that of aMPV. The greater ability of aMPV harboring chicken Fc to that of aMPV presented it as a possible vaccine candidate. PMID:27130629

  20. Profiling the host immune response to tuberculosis vaccines.

    PubMed

    Fletcher, Helen A

    2015-09-29

    There is an urgent need for improved vaccines for protection against tuberculosis (TB) disease and an immune correlate of protection would aid in the design, development and testing of a new TB vaccine candidates. The immune response to TB is likely to be multi-factorial and transcriptional profiling is a potentially useful tool for the simultaneous measurement of multiple immune processes. Although there are 16 candidate TB vaccines in clinical development the only published transcriptomics studies are from the MVA85A trials. With the publication of transcriptional signatures from the South African adolescent cohort study and the GC6 consortium also expected in 2015 the next year could see an increase of interest in the use of transcriptomics in TB vaccine development. PMID:26241949

  1. NF-κB in the Immune Response of Drosophila

    PubMed Central

    Hetru, Charles; Hoffmann, Jules A.

    2009-01-01

    The nuclear factor κB (NF-κB) pathways play a major role in Drosophila host defense. Two recognition and signaling cascades control this immune response. The Toll pathway is activated by Gram-positive bacteria and by fungi, whereas the immune deficiency (Imd) pathway responds to Gram-negative bacterial infection. The basic mechanisms of recognition of these various types of microbial infections by the adult fly are now globally understood. Even though some elements are missing in the intracellular pathways, numerous proteins and interactions have been identified. In this article, we present a general picture of the immune functions of NF-κB in Drosophila with all the partners involved in recognition and in the signaling cascades. PMID:20457557

  2. Genomics of immune response to typhoid and cholera vaccines

    PubMed Central

    Majumder, Partha P.

    2015-01-01

    Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways. PMID:25964454

  3. Genomics of immune response to typhoid and cholera vaccines.

    PubMed

    Majumder, Partha P

    2015-06-19

    Considerable variation in antibody response (AR) was observed among recipients of an injectable typhoid vaccine and an oral cholera vaccine. We sought to find whether polymorphisms in genes of the immune system, both innate and adaptive, were associated with the observed variation in response. For both vaccines, we were able to discover and validate several polymorphisms that were significantly associated with immune response. For the typhoid vaccines, these polymorphisms were on genes that belonged to pathways of polysaccharide recognition, signal transduction, inhibition of T-cell proliferation, pro-inflammatory signalling and eventual production of antimicrobial peptides. For the cholera vaccine, the pathways included epithelial barrier integrity, intestinal homeostasis and leucocyte recruitment. Even though traditional wisdom indicates that both vaccines should act as T-cell-independent antigens, our findings reveal that the vaccines induce AR using different pathways. PMID:25964454

  4. Immune Responses Associated with Resistance to Haemonchosis in Sheep

    PubMed Central

    Alba-Hurtado, Fernando; Muñoz-Guzmán, Marco Antonio

    2013-01-01

    This paper examines the known immunological and genetic factors associated with sheep resistance to infection by Haemonchus contortus. Such resistance is an inheritable genetic trait (h2, 0.22–0.63) associated with certain sheep breeds. Resistant sheep do not completely reject the disease; they only harbor fewer parasites than susceptible sheep and therefore have a lower fecal egg count. Protective immune response to haemonchosis is an expression of genetic resistance. Genes associated with resistance and susceptibility are described. Genetically resistant sheep have nonspecific mechanisms that block the initial colonization by Haemonchus contortus larvae. These sheep also have an efficacious Th2 type response (e.g., increases in blood and tissue eosinophils, specific IgE class antibodies, mast cells, IL-5, IL-13, and TNFα) that protects them against the infection; in contrast, susceptible sheep do not efficiently establish this type of immune response. Finally, the main reported antigens of H. contortus were reviewed. PMID:23509684

  5. Adaptive immune response during hepatitis C virus infection

    PubMed Central

    Larrubia, Juan Ramón; Moreno-Cubero, Elia; Lokhande, Megha Uttam; García-Garzón, Silvia; Lázaro, Alicia; Miquel, Joaquín; Perna, Cristian; Sanz-de-Villalobos, Eduardo

    2014-01-01

    Hepatitis C virus (HCV) infection affects about 170 million people worldwide and it is a major cause of liver cirrhosis and hepatocellular carcinoma. HCV is a hepatotropic non-cytopathic virus able to persist in a great percentage of infected hosts due to its ability to escape from the immune control. Liver damage and disease progression during HCV infection are driven by both viral and host factors. Specifically, adaptive immune response carries out an essential task in controlling non-cytopathic viruses because of its ability to recognize infected cells and to destroy them by cytopathic mechanisms and to eliminate the virus by non-cytolytic machinery. HCV is able to impair this response by several means such as developing escape mutations in neutralizing antibodies and in T cell receptor viral epitope recognition sites and inducing HCV-specific cytotoxic T cell anergy and deletion. To impair HCV-specific T cell reactivity, HCV affects effector T cell regulation by modulating T helper and Treg response and by impairing the balance between positive and negative co-stimulatory molecules and between pro- and anti-apoptotic proteins. In this review, the role of adaptive immune response in controlling HCV infection and the HCV mechanisms to evade this response are reviewed. PMID:24707125

  6. Cellular Immune Responses to Neisseria meningitidis in Children

    PubMed Central

    Pollard, Andrew J.; Galassini, Rachel; Rouppe van der Voort, Eileene M.; Hibberd, Martin; Booy, Robert; Langford, Paul; Nadel, Simon; Ison, Catherine; Kroll, J. Simon; Poolman, Jan; Levin, Michael

    1999-01-01

    There is an urgent need for effective vaccines against serogroup B Neisseria meningitidis. Current experimental vaccines based on the outer membrane proteins (OMPs) of this organism provide a measure of protection in older children but have been ineffective in infants. We postulated that the inability of OMP vaccines to protect infants might be due to age-dependent defects in cellular immunity. We measured proliferation and in vitro production of gamma interferon (IFN-γ), tumor necrosis factor alpha, and interleukin-10 (IL-10) in response to meningococcal antigens by peripheral blood mononuclear cells (PBMCs) from children convalescing from meningococcal disease and from controls. After meningococcal infection, the balance of cytokine production by PBMCs from the youngest children was skewed towards a TH1 response (low IL-10/IFN-γ ratio), while older children produced more TH2 cytokine (higher IL-10/IFN-γ ratio). There was a trend to higher proliferative responses by PBMCs from older children. These responses were not influenced by the presence or subtype of class 1 (PorA) OMP or by the presence of class 2/3 (PorB) or class 4 OMP. Even young infants might be expected to develop adequate cellular immune responses to serogroup B N. meningitidis vaccines if a vaccine preparation can be formulated to mimic the immune stimulus of invasive disease, which may include stimulation of TH2 cytokine production. PMID:10225908

  7. Immune responses to Mycoplasma bovis proteins formulated with different adjuvants.

    PubMed

    Prysliak, Tracy; Perez-Casal, Jose

    2016-06-01

    Most vaccines for protection against Mycoplasma bovis disease are made of bacterins, and they offer varying degrees of protection. Our focus is on the development of a subunit-based protective vaccine, and to that end, we have identified 10 novel vaccine candidates. After formulation of these candidates with TriAdj, an experimental tri-component novel vaccine adjuvant developed at VIDO-InterVac, we measured humoral and cell-mediated immune responses in vaccinated animals. In addition, we compared the immune responses after formulation with TriAdj with the responses measured in animals vaccinated with a mix of a commercial adjuvant (Emulsigen™) and 2 of the components of the TriAdj, namely polyinosinic:polycytidylic acid (poly I:C) and the cationic innate defense regulator (IDR) peptide 1002 (VQRWLIVWRIRK). In this latter trial, we detected significant IgG1 humoral immune responses to 8 out of 10 M. bovis proteins, and IgG2 responses to 7 out of 10 proteins. Thus, we concluded that the commercial adjuvant formulated with poly I:C and the IDR peptide 1002 is the best formulation for the experimental vaccine. PMID:27105454

  8. Immune responses of wild birds to emerging infectious diseases.

    PubMed

    Staley, M; Bonneaud, C

    2015-05-01

    Over the past several decades, outbreaks of emerging infectious diseases (EIDs) in wild birds have attracted worldwide media attention, either because of their extreme virulence or because of alarming spillovers into agricultural animals or humans. The pathogens involved have been found to infect a variety of bird hosts ranging from relatively few species (e.g. Trichomonas gallinae) to hundreds of species (e.g. West Nile Virus). Here we review and contrast the immune responses that wild birds are able to mount against these novel pathogens. We discuss the extent to which these responses are associated with reduced clinical symptoms, pathogen load and mortality, or conversely, how they can be linked to worsened pathology and reduced survival. We then investigate how immune responses to EIDs can evolve over time in response to pathogen-driven selection using the illustrative case study of the epizootic outbreak of Mycoplasma gallisepticum in wild North American house finches (Haemorhous mexicanus). We highlight the need for future work to take advantage of the substantial inter- and intraspecific variation in disease progression and outcome following infections with EID to elucidate the extent to which immune responses confer increased resistance through pathogen clearance or may instead heighten pathogenesis. PMID:25847450

  9. Phenytoin promotes Th2 type immune response in mice

    PubMed Central

    Okada, K; Sugiura, T; Kuroda, E; Tsuji, S; Yamashita, U

    2001-01-01

    The effects of chronic administration of phenytoin, a common anticonvulsive drug, on immune responses were studied in mice. Anti-keyhole limpet haemocyanin (KLH) IgE antibody response after KLH-immunization was enhanced in phenytoin-treated mice. Proliferative responses of spleen cells induced with KLH, concanavalin A (ConA), lipopolysaccharide and anti-CD3 antibody were reduced in phenytoin-treated mice. Accessory function of spleen adherent cells on ConA-induced T cell proliferative response was reduced in phenytoin-treated mice. KLH-induced IL-4 production of spleen cells was enhanced, while IFN-γ production was reduced in phenytoin-treated mice. In addition, production of IL-1α, but not IL-6 and IL-12 by spleen adherent cells from phenytoin-treated mice was reduced. Natural killer cell activity was reduced in phenytoin-treated mice. These results suggest that phenytoin treatment preferentially induces a Th2 type response. We also observed that plasma ACTH and corticosterone levels were increased in phenytoin-treated mice, and speculated that phenytoin might act directly and indirectly, through HPA axis activation, on the immune system to modulate Th1/Th2 balance. PMID:11472401

  10. Abnormal immune responses of Bloom's syndrome lymphocytes in vitro.

    PubMed Central

    Hütteroth, T H; Litwin, S D; German, J

    1975-01-01

    Bloom's syndrome is a rare autosmal recessive disorder, first characterized by growth retardation and asum-sensitive facial telangiectasia and more recently demonstarted to have increased chromosome instability, a predisposition to malignancy, and increased susecptibitily to infection. The present report ocncern the immune function of Bloom's syndrom lymphoctes in vitro. Four affected homozgotes and five heterozygotes were studied. An abnormal serum concentartion of at least one class of immunoglobin was present in three out of four homozgotes. Affected homozgotes were shown capable of both a humoral and cellular response after antigenic challenge, the responses in general being weak but detectable. Blood lymphocytes from Bloom's syndrome individuals were cultured in impaired proliferavite response and synthesized less immunoglobulin at the end of 5 days than did normal controls. In contrast, they had a normal proliferative response to phytohemagglutinin except at highest concentrations of the mitogen. In the mixed lymphocte culture, Bloom's syndrome lymphocytes proved to be poor responder cells but normal stimulator cells. Lmyphoctes from the heterozgotes produced normal responses in these three systems. Distrubed immunity appears to be on of several major consequences of homozygosity for the Bloom's syndrome gene. Although the explanation for this pleiotropism is at present obscure, the idea was advanced that the aberrant immune function is, along with the major clincial feature-small body size, amanifestation of defect in cellular proliferation. PMID:124745

  11. No apparent cost of evolved immune response in Drosophila melanogaster.

    PubMed

    Gupta, Vanika; Venkatesan, Saudamini; Chatterjee, Martik; Syed, Zeeshan A; Nivsarkar, Vaishnavi; Prasad, Nagaraj G

    2016-04-01

    Maintenance and deployment of the immune system are costly and are hence predicted to trade-off with other resource-demanding traits, such as reproduction. We subjected this longstanding idea to test using laboratory experimental evolution approach. In the present study, replicate populations of Drosophila melanogaster were subjected to three selection regimes-I (Infection with Pseudomonas entomophila), S (Sham-infection with MgSO4 ), and U (Unhandled Control). After 30 generations of selection flies from the I regime had evolved better survivorship upon infection with P. entomophila compared to flies from U and S regimes. However, contrary to expectations and previous reports, we did not find any evidence of trade-offs between immunity and other life history related traits, such as longevity, fecundity, egg hatchability, or development time. After 45 generations of selection, the selection was relaxed for a set of populations. Even after 15 generations, the postinfection survivorship of populations under relaxed selection regime did not decline. We speculate that either there is a negligible cost to the evolved immune response or that trade-offs occur on traits such as reproductive behavior or other immune mechanisms that we have not investigated in this study. Our research suggests that at least under certain conditions, life-history trade-offs might play little role in maintaining variation in immunity. PMID:26932243

  12. [Immune response in experimental animals immunized with Burkholderia pseudomallei surface antigens].

    PubMed

    Avrorova, I V; Piven', N N; Zhukova, S I; Viktorov, D V; Khrapova, N P; Popov, S F

    2004-01-01

    The influence of the chromatographic fractions of B. pseudomallei surface antigenic complex (C, C1, D, H) on immune response in white rats and white mice was under study. These antigenic complexes were noted to produce perceptible stimulating effect on the immune system of white rats, in contrast to that of white mice. The immunization of the mice the above-mentioned fractions suppressed the phagocytic activity of peritoneal macrophages (PM) and slightly enhanced cell-mediated immunity. In experiments on white rats, fraction C induced the growth of specific antibody titers and stimulated the phagocytic activity of PM, as well as the indices of delayed hypersensitivity (DH). Fraction D showed a lower level of the induction of the phagocytic activity of PM and was inactive in the manifestation of cell-mediated immunity, but induced a high level of humoral immunity. Antigenic complexes C1 and H increased the phagocytic activity of PM and DH characteristics with a low level of antibody production. The studied fractions of the causative agent of melioidosis decreased the content of bactericidal cationic proteins (BCP) in rat blood neutrophils, and in mice a decreased content of BCP in phagocytes was registered. The fractions increased the activity of myeloperoxidase in blood neutrophils in mice and rats. As revealed with the use of immunoelectrophoresis, SDS PAAG electrophoresis and immunoblotting, the surface antigenic complex contained proteins of 18, 22, 39 kD and glycoproteins 42, 55, 90 kD. The latter glycoprotein was found in all the fractions under study, having protective properties. PMID:15554321

  13. Immune response to measles vaccine in Peruvian children.

    PubMed Central

    Bautista-López, N. L.; Vaisberg, A.; Kanashiro, R.; Hernández, H.; Ward, B. J.

    2001-01-01

    OBJECTIVE: To evaluate the immune response in Peruvian children following measles vaccination. METHODS: Fifty-five Peruvian children received Schwarz measles vaccine (about 10(3) plaque forming units) at about 9 months of age. Blood samples were taken before vaccination, then twice after vaccination: one sample at between 1 and 4 weeks after vaccination and the final sample 3 months post vaccination for evaluation of immune cell phenotype and lymphoproliferative responses to measles and non-measles antigens. Measles-specific antibodies were measured by plaque reduction neutralization. FINDINGS: The humoral response developed rapidly after vaccination; only 4 of the 55 children (7%) had plaque reduction neutralization titres <200 mlU/ml 3 months after vaccination. However, only 8 out of 35 children tested (23%) had lymphoproliferative responses to measles antigens 3-4 weeks after vaccination. Children with poor lymphoproliferative responses to measles antigens had readily detectable lymphoproliferative responses to other antigens. Flow cytometric analysis of peripheral blood mononuclear cells revealed diffuse immune system activation at the time of vaccination in most children. The capacity to mount a lymphoproliferative response to measles antigens was associated with expression of CD45RO on CD4+ T-cells. CONCLUSION: The 55 Peruvian children had excellent antibody responses after measles vaccination, but only 23% (8 out of 35) generated detectable lymphoproliferative responses to measles antigens (compared with 55-67% in children in the industrialized world). This difference may contribute to the less than uniform success of measles vaccination programmes in the developing world. PMID:11731811

  14. Enteric immunization with live adenovirus type 21 vaccine. II. Systemic and local immune responses following immunization.

    PubMed

    Scott, R M; Dudding, B A; Romano, S V; Russell, P K

    1972-03-01

    Studies of the immunologic responses following administration of a live, enteric-coated adenovirus (ADV) type 21 vaccine showed that nine of ten vaccinees and none of five controls developed neutralizing antibody. Antibody activity of serum and secretory immunoglobulins was assayed by using a (14)C-labeled ADV-21 antigen in a radioimmunodiffusion system. Increases in immunoglobulin M, A and G (IgM, IgA, IgG) activity were detected in sera from vaccinees but not in those from controls. IgA copro antibody activity was also shown in vaccinees but not in controls. Nasal secretions showed no detectable IgA antibody responses by this method. These studies show marked differences in serum and local IgA antibody activity in induced enteric ADV infection compared to previously reported responses after natural infection. The protective role of secretory IgA in adenovirus infections is obscure. However, absence of nasal IgA responses may indicate that protection against disease with enteric ADV vaccines depends primarily upon humoral antibody. PMID:4629075

  15. 41 CFR 102-78.40 - What responsibilities do Federal agencies have when an undertaking adversely affects a historic...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... guidance on the protection of historic and cultural properties in 36 CFR part 800. ... Federal agencies have when an undertaking adversely affects a historic or cultural property? 102-78.40...-78.40 What responsibilities do Federal agencies have when an undertaking adversely affects a...

  16. The Immune Response to Tumors as a Tool toward Immunotherapy

    PubMed Central

    Pandolfi, F.; Cianci, R.; Pagliari, D.; Casciano, F.; Bagalà, C.; Astone, A.; Landolfi, R.; Barone, C.

    2011-01-01

    Until recently cancer medical therapy was limited to chemotherapy that could not differentiate cancer cells from normal cells. More recently with the remarkable mushroom of immunology, newer tools became available, resulting in the novel possibility to attack cancer with the specificity of the immune system. Herein we will review some of the recent achievement of immunotherapy in such aggressive cancers as melanoma, prostatic cancer, colorectal carcinoma, and hematologic malignancies. Immunotherapy of tumors has developed several techniques: immune cell transfer, vaccines, immunobiological molecules such as monoclonal antibodies that improve the immune responses to tumors. This can be achieved by blocking pathways limiting the immune response, such as CTLA-4 or Tregs. Immunotherapy may also use cytokines especially proinflammatory cytokines to enhance the activity of cytotoxic T cells (CTLs) derived from tumor infiltrating lymphocytes (TILs). The role of newly discovered cytokines remains to be investigated. Alternatively, an other mechanism consists in enhancing the expression of TAAs on tumor cells. Finally, monoclonal antibodies may be used to target oncogenes. PMID:22190975

  17. Impact on allergic immune response after treatment with vitamin A

    PubMed Central

    Matheu, Victor; Berggård, Karin; Barrios, Yvelise; Barrios, Ysamar; Arnau, Maria-Rosa; Zubeldia, Jose M; Baeza, Maria L; Back, Ove; Issazadeh-Navikas, Shohreh

    2009-01-01

    Background Vitamin A may have some influence on the immune system, but the role in allergy modulation is still unclear. Objective To clarify whether high levels of retinoic acid (RA) affects allergic response in vivo, we used a murine experimental model of airway allergic disease. Methods Ovalbumin (OVA)-immunization/OVA-challenge (OVA/OVA) and house dust mite (HDM)-immunization/HDM-challenge (HDM/HDM) experimental murine models of allergic airway disease, using C57Bl.10/Q groups of mice (n = 10) treated subcutaneously with different concentrations of all-trans RA (0, 50, 500 and 2,500 ug) every 2-days were used to assess the allergic immune response. Results Levels of total and specific-IgE in sera were increased in all groups of RA treated OVA/OVA and HDM/HDM mice. Percentage and total amount of recruited eosinophil in airways by bronchoalveolar lavage fluid (BALF) were significantly enhanced in groups treated with 50, 500 and 2,500 ug of RA compared to non-treated mice. However, the group of mice treated with 2,500 ug had less eosinophil recruitment than the other two groups (50 and 500 ug). In parallel, levels of IL-5 and total IgE in BALF were also significantly diminished in the group treated with 2,500 ug compared to the other 2 groups (50 and 500 ug). Finally, total lung resistance was decreased in group treated with 2,500 ug compared to non-treated mice. Conclusion Our results suggest that retinoic acid directly enhances allergic response in vivo, but in higher doses may produce of immune suppression. PMID:19852821

  18. Myeloid IKKβ promotes antitumor immunity by modulating CCL11 and the innate immune response.

    PubMed

    Yang, Jinming; Hawkins, Oriana E; Barham, Whitney; Gilchuk, Pavlo; Boothby, Mark; Ayers, Gregory D; Joyce, Sebastian; Karin, Michael; Yull, Fiona E; Richmond, Ann

    2014-12-15

    Myeloid cells are capable of promoting or eradicating tumor cells and the nodal functions that contribute to their different roles are still obscure. Here, we show that mice with myeloid-specific genetic loss of the NF-κB pathway regulatory kinase IKKβ exhibit more rapid growth of cutaneous and lung melanoma tumors. In a BRAF(V600E/PTEN(-/-)) allograft model, IKKβ loss in macrophages reduced recruitment of myeloid cells into the tumor, lowered expression of MHC class II molecules, and enhanced production of the chemokine CCL11, thereby negatively regulating dendritic-cell maturation. Elevated serum and tissue levels of CCL11 mediated suppression of dendritic-cell differentiation/maturation within the tumor microenvironment, skewing it toward a Th2 immune response and impairing CD8(+) T cell-mediated tumor cell lysis. Depleting macrophages or CD8(+) T cells in mice with wild-type IKKβ myeloid cells enhanced tumor growth, where the myeloid cell response was used to mediate antitumor immunity against melanoma tumors (with less dependency on a CD8(+) T-cell response). In contrast, myeloid cells deficient in IKKβ were compromised in tumor cell lysis, based on their reduced ability to phagocytize and digest tumor cells. Thus, mice with continuous IKKβ signaling in myeloid-lineage cells (IKKβ(CA)) exhibited enhanced antitumor immunity and reduced melanoma outgrowth. Collectively, our results illuminate new mechanisms through which NF-κB signaling in myeloid cells promotes innate tumor surveillance. PMID:25336190

  19. Humoral and cellular immune responses to influenza vaccination in children with cancer receiving chemotherapy

    PubMed Central

    WONG-CHEW, ROSA MARÍA; FRÍAS, MARGARITA NAVA; GARCÍA-LEÓN, MIGUEL LEONARDO; ARRIAGA-PIZANO, LOURDES; SANSON, AURORA MEDINA; LOPEZ-MACÍAS, CONSTANTINO; ISIBASI, ARMANDO; SANTOS-PRECIADO, JOSÉ IGNACIO

    2012-01-01

    The immune response to influenza vaccination in children with cancer is controversial. The objective of this study was to characterize the cellular and humoral immune responses to an influenza vaccine in children with cancer who were receiving chemotherapy. In this study, children with cancer, who were not previously immunized, received an influenza vaccine via intramuscular injection. Blood samples were obtained prior to and at 4 weeks after immunization. Antibodies were measured using a hemagglutination inhibition (HI) assay. Cell-mediated immunity was measured by specific lymphoproliferation with 3H-thymidine incorporation and by measuring cell frequencies following staining with monoclonal antibodies (CD8, CD4, CD19, CD45RA and CD27) using flow cytometry following incubation with the influenza antigen for 5 days. Geometric mean titers (GMT), mean counts per minute (cpm), cell frequencies prior to and following vaccination and percentage patient responses were compared using the Mann-Whitney non-parametric U and Chi-square tests; where p<0.05 was considered to indicate a statistically significant result. A total of 56 children were included. Their mean age was 6.64±3.61 years. Acute lymphoblastic leukemia (ALL) was diagnosed in 75, solid tumors in 23 and lymphoma in 2% of the children. Subjects with titers ≥40 hemagglutination units (HU) increased from 43% prior to vaccination to 73% following vaccination (p=0.01), whereas the GMT increased from 31.35 [95% confidence interval (CI), 29–111] to 143.45 HU (95% CI, 284–640) following vaccination (p<0.001). An increase in CD45RA expression in CD8+ T cells was observed following vaccination (p=0.01). An increase in CD27 expression was observed in the CD4/8-negative cell population stimulated with the influenza antigen following vaccination (p<0.05). No serious adverse effects were observed. An increase in the seropositivity rate and GMT values following influenza vaccination were also observed. Influenza

  20. Host immune responses to rhinovirus: Mechanisms in asthma

    PubMed Central

    Kelly, John T.; Busse, William W.

    2014-01-01

    Viral respiratory infections can have a profound effect on many aspects of asthma including its inception, exacerbations, and, possibly, severity. Of the many viral respiratory infections that influence asthma, the common cold virus, rhinovirus, has emerged as the most frequent illness associated with exacerbations and other aspects of asthma. The mechanisms by which rhinovirus influences asthma are not fully established, but current evidence indicates that the immune response to this virus is critical in this process. Many airway cell types are involved in the immune response to rhinovirus, but most important are respiratory epithelial cells and possibly macrophages. Infection of epithelial cells generates a variety of proinflammatory mediators to attract inflammatory cells to the airway with a subsequent worsening of underlying disease. Furthermore, there is evidence that the epithelial airway antiviral response to rhinovirus may be defective in asthma. Therefore, understanding the immune response to rhinovirus is a key step in defining mechanisms of asthma, exacerbations, and, perhaps most importantly, improved treatment. PMID:19014757

  1. Inhibition of the immune response to experimental fresh osteoarticular allografts

    SciTech Connect

    Rodrigo, J.J.; Schnaser, A.M.; Reynolds, H.M. Jr.; Biggart, J.M. 3d.; Leathers, M.W.; Chism, S.E.; Thorson, E.; Grotz, T.; Yang, Q.M. )

    1989-06-01

    The immune response to osteoarticular allografts is capable of destroying the cartilage--a tissue that has antigens on its cells identical to those on the bone and marrow cells. Osteoarticular allografts of the distal femur were performed in rats using various methods to attempt to temporarily inhibit the antibody response. The temporary systemic immunosuppressant regimens investigated were cyclophosphamide, azathioprine and prednisolone, cyclosporine A, and total lymphoid irradiation. The most successful appeared to be cyclosporine A, but significant side effects were observed. To specifically inhibit the immune response in the allograft antigens without systemically inhibiting the entire immune system, passive enhancement and preadministration of donor blood were tried. Neither was as effective as coating the donor bone with biodegradable cements, a method previously found to be successful. Cyclosporine A was investigated in dogs in a preliminary study of medial compartmental knee allografts and was found to be successful in inhibiting the antibody response and in producing a more successful graft; however, some significant side effects were similarly observed.

  2. Acidic chitinase primes the protective immune response to gastrointestinal nematodes.

    PubMed

    Vannella, Kevin M; Ramalingam, Thirumalai R; Hart, Kevin M; de Queiroz Prado, Rafael; Sciurba, Joshua; Barron, Luke; Borthwick, Lee A; Smith, Allen D; Mentink-Kane, Margaret; White, Sandra; Thompson, Robert W; Cheever, Allen W; Bock, Kevin; Moore, Ian; Fitz, Lori J; Urban, Joseph F; Wynn, Thomas A

    2016-05-01

    Acidic mammalian chitinase (AMCase) is known to be induced by allergens and helminths, yet its role in immunity is unclear. Using AMCase-deficient mice, we show that AMCase deficiency reduced the number of group 2 innate lymphoid cells during allergen challenge but was not required for establishment of type 2 inflammation in the lung in response to allergens or helminths. In contrast, AMCase-deficient mice showed a profound defect in type 2 immunity following infection with the chitin-containing gastrointestinal nematodes Nippostrongylus brasiliensis and Heligmosomoides polygyrus bakeri. The impaired immunity was associated with reduced mucus production and decreased intestinal expression of the signature type 2 response genes Il13, Chil3, Retnlb, and Clca1. CD103(+) dendritic cells, which regulate T cell homing, were also reduced in mesenteric lymph nodes of infected AMCase-deficient mice. Thus, AMCase functions as a critical initiator of protective type 2 responses to intestinal nematodes but is largely dispensable for allergic responses in the lung. PMID:27043413

  3. The Immune Response to Blood-Group Substances

    PubMed Central

    Holborow, E. J.; Loewi, G.

    1962-01-01

    Guinea pigs were immunized with purified human A and Lea blood-group substances. Skin testing revealed a delayed hypersensitivity response to A and Lea and other human blood-group substances, showing a very marked degree of cross-reactivity, irrespective of the immunizing antigen. Circulating antibody was tested for by eliciting systemic anaphylaxis, by direct cutaneous anaphylaxis using a dye-spreading method, and by the passive cutaneous anaphylaxis test of Ovary. Precipitation and red-cell agglutination tests were also employed. It was found that immunization with A substance consistently produced a major specific anti-A antibody and a minor separate antibody specific for Lea. Immunization with Lea substance did not consistently give rise to detectable circulating antibody. In those animals, however, in which antibody to Lea was found, a reaction with A substance could also be shown. These results could be explained in terms of a small amount of Lea activity in A substance, as revealed by agglutination-inhibition and P.C.A. tests. The results indicate that the polypeptide part of blood-group mucopolysaccharides is the entity chiefly concerned in producing and eliciting delayed hypersensitivity to these substances. The cross-reactivity of the delayed response supports the view that the different human blood-group mucopolysaccharides share a similar polypeptide component. The more precise nature of the circulating antibody is explicable in terms of a response to the specific polysaccharide entity of blood-group substances. These findings are considered in the light of previous work on the relationship of delayed hypersensitivity to the circulating antibody response. The question of a possible delayed response to carbohydrate antigen is left unanswered. PMID:13908295

  4. Homotypic and heterotypic immune responses to group A rotaviruses in parenterally immunized sheep.

    PubMed

    Beards, G M; King, J A; Mazhar, S; Landon, J; Desselberger, U

    1993-01-01

    Immune responses to human rotaviruses were investigated in sheep with a view to obtaining antibodies for passive immunotherapy of humans. Eighteen adult sheep with previous natural exposure to rotavirus serotypes G3 and G6 were immunized parenterally with purified preparations of either individual rotavirus serotypes G1, G2, G3, G4 and G8, or a mixture thereof. Two additional sheep were kept as control animals with the flock. The antibody responses were measured on serial serum samples by neutralization tests. The homotypic antibody response ranged from 100-fold (rarely) up to 100,000-fold increases in titre. Heterotypic responses against serotypes G3 and G6 were demonstrated in 7/12 and 15/18 sheep, respectively, but the increases in titre were lower than the homotypic responses, ranging from 10- to 100-fold in most cases and were 1000-fold in two sheep. Interestingly, no heterotypic response against the human rotavirus serotypes was raised after 3 months; moderate titres of cross-neutralizing antibodies for the human serotypes were only observed after a third inoculation. PMID:8382420

  5. Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines.

    PubMed

    Klein, Katja; Mann, Jamie F S; Rogers, Paul; Shattock, Robin J

    2014-06-10

    Protective mucosal immune responses are thought best induced by trans-mucosal vaccination, providing greater potential to generate potent local immune responses than conventional parenteral vaccination. However, poor trans-mucosal permeability of large macromolecular antigens limits bioavailability to local inductive immune cells. This study explores the utility of polymeric penetration enhancers to promote trans-mucosal bioavailability of insulin, as a biomarker of mucosal absorption, and two vaccine candidates: recombinant HIV-1 envelope glycoprotein (CN54gp140) and tetanus toxoid (TT). Responses to vaccinating antigens were assessed by measurement of serum and the vaginal humoral responses. Polyethyleneimine (PEI), Dimethyl-β-cyclodextrin (DM-β-CD) and Chitosan enhanced the bioavailability of insulin following intranasal (IN), sublingual (SL), intravaginal (I.Vag) and intrarectal (IR) administration. The same penetration enhancers also increased antigen-specific IgG and IgA antibody responses to the model vaccine antigens in serum and vaginal secretions following IN and SL application. Co-delivery of both antigens with PEI or Chitosan showed the highest increase in systemic IgG and IgA responses following IN or SL administration. However the highest IgA titres in vaginal secretions were achieved after IN immunisations with PEI and Chitosan. None of the penetration enhancers were able to increase antibody responses to gp140 after I.Vag immunisations, while in contrast PEI and Chitosan were able to induce TT-specific systemic IgG levels following I.Vag administration. In summary, we present supporting data that suggest appropriate co-formulation of vaccine antigens with excipients known to influence mucosal barrier functions can increase the bioavailability of mucosally applied antigens promoting the induction of mucosal and systemic antibody responses. PMID:24657807

  6. Flagellin from Marinobacter algicola and Vibrio vulnificus activates the innate immune response of gilthead seabream.

    PubMed

    Montero, Jana; Gómez-Casado, Eduardo; García-Alcázar, Alicia; Meseguer, José; Mulero, Victoriano

    2014-11-01

    Adjuvants have emerged as the best tools to enhance the efficacy of vaccination. However, the traditional adjuvants used in aquaculture may cause adverse alterations in fish making necessary the development of new adjuvants able to stimulate the immune system and offer strong protection against infectious pathogens with minimal undesirable effects. In this respect, flagellin seems an attractive candidate due to its ability to strongly stimulate the immune response of fish. In the present study, we have evaluated the ability of recombinant flagellin from Marinobacter algicola (MA) and Vibrio vulnificus (Vvul), a non-pathogenic and a pathogenic bacteria, respectively, to stimulate the innate immune system of gilthead seabream (Sparus aurata L.) and compare the effect with that of the classical flagellin from Salmonella enterica serovar Typhimurium (Salmonella Typhimurium, STF). Intraperitoneal injection of MA and Vvul resulted in a strong inflammatory response characterized by increased reactive oxygen species production and the infiltration of acidophilic granulocytes at the injection site. Interestingly, however, only flagellin from MA consistently induced the expression of the gene encoding pro-inflammatory interleukin-1β. These effects were further confirmed in vitro, where a dose-dependent activation of macrophages and acidophilic granulocytes by MA and Vvul flagellins was observed. In contrast, STF flagellin was found to be less potent in both in vivo and in vitro experiments. Our results suggest the potential use of MA and Vvul flagellins as immunostimulants and adjuvants for fish vaccination. PMID:25020195

  7. Cell-mediated immune responses after immunization of healthy seronegative children with varicella vaccine: kinetics and specificity.

    PubMed

    Watson, B; Keller, P M; Ellis, R W; Starr, S E

    1990-10-01

    Humoral and cell-mediated immune responses were determined in seronegative children immunized with live attenuated Oka strain varicella vaccine. At 2 weeks after immunization, 80% of children had detectable lymphocyte proliferation to varicella-zoster virus (VZV) antigens, while only 40% had antibodies to VZV as detected by ELISA. By 6 weeks after immunization, 97% of children seroconverted, and 95% of these responded to VZV antigens in the proliferation assay. A high proportion of immunized children also responded in the proliferation assay to purified glycoproteins I, II, and III of VZV. These results indicate that most children develop a broad cell-mediated immune response to VZV antigens within weeks after immunization with varicella vaccine. PMID:2169495

  8. Anti-tumor immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Castano, Ana P.; Wu, Mei X.; Kung, Andrew L.; Hamblin, Michael R.

    2009-06-01

    Anti-tumor immunity is stimulated after PDT due a number of factors including: the acute inflammatory response caused by PDT, release of antigens from PDT-damaged tumor cells, priming of the adaptive immune system to recognize tumor-associated antigens (TAA), and induction of heat-shock proteins. The induction of specific CD8+ T-lymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy as it would allow the treatment of tumors that may have already metastasized. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. We have carried out in vivo PDT with a BPD-mediated vascular regimen using a pair of BALB/c mouse colon carcinomas: CT26 wild type expressing the naturally occurring retroviral antigen gp70 and CT26.CL25 additionally expressing beta-galactosidase (b-gal) as a model tumor rejection antigen. PDT of CT26.CL25 cured 100% of tumors but none of the CT26WT tumors (all recurred). Cured CT26.CL25 mice were resistant to rechallenge. Moreover mice with two bilateral CT26.CL25 tumors that had only one treated with PDT demonstrated spontaneous regression of 70% of untreated contralateral tumors. T-lymphocytes were isolated from lymph nodes of PDT cured mice that recognized a particular peptide specific to b-gal antigen. T-lymphocytes from LN were able to kill CT26.CL25 target cells in vitro but not CT26WT cells as shown by a chromium release assay. CT26.CL25 tumors treated with PDT and removed five days later had higher levels of Th1 cytokines than CT26 WT tumors showing a higher level of immune response. When mice bearing CT26WT tumors were treated with a regimen of low dose cyclophosphamide (CY) 2 days before, PDT led to 100% of cures (versus 0% without CY) and resistance to rechallenge. Low dose CY is thought to deplete regulatory T-cells (Treg, CD4+CD25+foxp

  9. 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.

  10. Immune responses in humans after 60 days of confinement

    NASA Technical Reports Server (NTRS)

    Schmitt, D. A.; Peres, C.; Sonnenfeld, G.; Tkackzuk, J.; Arquier, M.; Mauco, G.; Ohayon, E.

    1995-01-01

    A confinement experiment in a normobaric diving chamber was undertaken to better understand the effect of confinement and isolation on human psychology and physiology. Pre- and postconfinement blood samples were obtained from four test subjects and control donors to analyze immune responses. No modification in the levels of CD2+, CD3+, CD4+, CD8+, CD19+, and CD56+ cells was observed after confinement. Mitogen-induced T-lymphocyte proliferation and interleukin-2 receptor expression were not altered significantly. Whole blood interferon-alpha and gamma-induction and plasma cortisol levels were also unchanged, as was natural killer cell activity. These data suggest that in humans, no specific components of the immune response are affected by a 2-month isolation and confinement of a small group.

  11. Curcumin prevents human dendritic cell response to immune stimulants

    SciTech Connect

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2008-09-26

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14{sup +} monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing CD4{sup +} T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant.

  12. Immune responses to final exams in healthy and asthmatic adolescents.

    PubMed

    Kang, D H; Coe, C L; McCarthy, D O; Ershler, W B

    1997-01-01

    Immune responses to an academic stressor were examined in healthy and asthmatic adolescents with regard to their illness symptom reports. Eighty-seven high school students completed a health diary for 2 weeks and provided three blood samples during midsemester, final-exam, and postexam periods. During exam week, all students showed significant immunological alterations from baseline. Natural killer cell activity was significantly lower, whereas lymphocyte proliferation and neutrophil superoxide release were significantly higher. These immune changes tended to return toward baseline during the postexam period, but the enhanced neutrophil reactivity continued to rise. Overall, immunological responses were similar between asthmatic subjects and controls. Appropriate medical management may have accounted for this similarity. However, subtle group differences in the postexam recovery pattern and a continuous activation of inflammatory cell function following a stressor may warrant further investigation. PMID:9024419

  13. Viral dynamics model with CTL immune response incorporating antiretroviral therapy.

    PubMed

    Wang, Yan; Zhou, Yicang; Brauer, Fred; Heffernan, Jane M

    2013-10-01

    We present two HIV models that include the CTL immune response, antiretroviral therapy and a full logistic growth term for uninfected CD4+ T-cells. The difference between the two models lies in the inclusion or omission of a loss term in the free virus equation. We obtain critical conditions for the existence of one, two or three steady states, and analyze the stability of these steady states. Through numerical simulation we find substantial differences in the reproduction numbers and the behaviour at the infected steady state between the two models, for certain parameter sets. We explore the effect of varying the combination drug efficacy on model behaviour, and the possibility of reconstituting the CTL immune response through antiretroviral therapy. Furthermore, we employ Latin hypercube sampling to investigate the existence of multiple infected equilibria. PMID:22930342

  14. Effect of onion extract on immune response in rabbits.

    PubMed

    Chisty, M M; Quddus, R; Islam, B; Khan, B R

    1996-08-01

    A total of 40 NZW rabbits were selected for this study to see the effect of onion extract on immune response following antigenic challenge. These animals were randomly divided into four groups, each composed of ten rabbits. Group I and II were challenged with typhoid H (TH) antigen and groups III and IV with sheep red blood cells (SRBC). Groups I and III were considered as control and II and IV as treated groups. The latter two groups were treated with onion extract orally. The immunosuppressive effect of onion extract was evaluated by estimating antibody levels by Widal test and hemolysin titer. It was found that mean antibody titers were significantly lower in the treated groups than in controls. The weights of thymus and lymph nodes were higher and of adrenal glands were lower in the control groups than in the treated groups. It appeared from the current study that onion extract has an inhibitory effect on immune response. PMID:9103661

  15. Changes in macrophage phenotype as the immune response evolves

    PubMed Central

    Lichtnekert, Julia; Kawakami, Takahisa; Parks, William C.; Duffield, Jeremy S.

    2013-01-01

    Mononuclear phagocytic cells, including macrophages and dendritic cells, are widely distributed throughout our organs where they perform important homeostatic, surveillance and regenerative tasks. In response to infection or injury, the composition and number of mononuclear phagocytic cells changes remarkably, in part due to the recruitment of inflammatory monocytes from bone marrow. In infection or injury, macrophages and dendritic cells perform important innate and adaptive immune roles from the initial insult through repair and regeneration of the tissue and resolution of inflammation. Evidence from mouse models of disease has shown increasing complexity and subtlety to the mononuclear phagocytic system, which will be reviewed here. New studies show that in addition to monocytes, the resident populations of mononuclear phagocytes expand in disease states and play distinct but important roles in the immune response. Finally, new insights into these functionally diverse cells are now translating into therapeutics to treat human disease. PMID:23747023

  16. Curcumin prevents human dendritic cell response to immune stimulants

    PubMed Central

    Shirley, Shawna A.; Montpetit, Alison J.; Lockey, R.F.; Mohapatra, Shyam S.

    2012-01-01

    Curcumin, a compound found in the Indian spice turmeric, has anti-inflammatory and immunomodulatory properties, though the mechanism remains unclear. Dendritic cells (DCs) are important to generating an immune response and the effect of curcumin on human DCs has not been explored. The role curcumin in the DC response to bacterial and viral infection was investigated in vitro using LPS and Poly I:C as models of infection. CD14+ monocytes, isolated from human peripheral blood, were cultured in GM-CSF- and IL-4-supplemented medium to generate immature DCs. Cultures were incubated with curcumin, stimulated with LPS or Poly I:C and functional assays were performed. Curcumin prevents DCs from responding to immunostimulants and inducing naïve CD4+ T cell proliferation by blocking maturation marker, cytokine and chemokine expression and reducing both migration and endocytosis. These data suggest a therapeutic role for curcumin as an immune suppressant. PMID:18639521

  17. 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

  18. Assessing humoral and cell-mediated immune response in Hawaiian green turtles, Chelonia mydas

    USGS Publications Warehouse

    Work, T.M.; Balazs, G.H.; Rameyer, R.A.; Chang, S.P.; Berestecky, J.

    2000-01-01

    Seven immature green turtles, Chelonia mydas, captured from Kaneohe Bay on the island of Oahu were used to evaluate methods for assessing their immune response. Two turtles each were immunized intramuscularly with egg white lysozyme (EWL) in Freunda??s complete adjuvant, Gerbu, or ISA-70; a seventh turtle was immunized with saline only and served as a control. Humoral immune response was measured with an indirect enzyme linked immunosorbent assay (ELISA). Cell-mediated immune response was measured using in vitro cell proliferation assays (CPA) using whole blood or peripheral blood mononuclear cells (PBM) cultured with concanavalin A (ConA), phytohaemagglutinin (PHA), or soluble egg EWL antigen. All turtles, except for one immunized with Gerbu and the control, produced a detectable humoral immune response by 6 weeks which persisted for at least 14 weeks after a single immunization. All turtles produced an anamnestic humoral immune response after secondary immunization. Antigen specific cell-mediated immune response in PBM was seen in all turtles either after primary or secondary immunization, but it was not as consistent as humoral immune response; antigen specific cell-mediated immune response in whole blood was rarely seen. Mononuclear cells had significantly higher stimulation indices than whole blood regardless of adjuvant, however, results with whole blood had lower variability. Both Gerbu and ISA-70 appeared to potentiate the cell-mediated immune response when PBM or whole blood were cultured with PHA. This is the first time cell proliferation assays have been compared between whole blood and PBM for reptiles. This is also the first demonstration of antigen specific cell-mediated response in reptiles. Cell proliferation assays allowed us to evaluate the cell-mediated immune response of green turtles. However, CPA may be less reliable than ELISA for detecting antigen specific immune response. Either of the three adjuvants appears suitable to safely elicit a

  19. History of Childhood Adversity is Positively Associated with Ventral Striatal Dopamine Responses to Amphetamine

    PubMed Central

    Oswald, Lynn M.; Wand, Gary S.; Kuwabara, Hiroto; Wong, Dean F.; Zhu, Shijun; Brasic, James R.

    2014-01-01

    Childhood exposure to severe or chronic trauma is an important risk factor for the later development of adult mental health problems, such as substance abuse. Even in nonclinical samples of healthy adults, persons with a history of significant childhood adversity seem to experience greater psychological distress than those without this history. Evidence from rodent studies suggests that early life stress may impair dopamine function in ways that increase risks for drug abuse. However, the degree to which these findings translate to other species remains unclear. This study was conducted to examine associations between childhood adversity and dopamine and subjective responses to amphetamine in humans. Following intake assessment, 28 healthy male and female adults, ages 18–29 years, underwent two consecutive 90-minute positron emission tomography (PET) studies with high specific activity [11C]raclopride. The first scan was preceded by intravenous saline; the second by amphetamine (AMPH 0.3 mg/kg). Consistent with prior literature, findings showed positive associations between childhood trauma and current levels of perceived stress. Moreover, greater number of traumatic events and higher levels of perceived stress were each associated with higher ventral striatal dopamine responses to AMPH. Findings of mediation analyses further showed that a portion of the relationship between childhood trauma and dopamine release may be mediated by perceived stress. Overall, results are consistent with preclinical findings suggesting that early trauma may lead to enhanced sensitivity to psychostimulants and that this mechanism may underlie increased vulnerability for drug abuse. PMID:24448898

  20. Immune surveillance and response to JC virus infection and PML

    PubMed Central

    Beltrami, Sarah; Gordon, Jennifer

    2014-01-01

    The ubiquitous human polyomavirus JC virus (JCV) is the established etiological agent of the debilitating and often fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Most healthy individuals have been infected with JCV and generate an immune response to the virus, yet remain persistently infected at subclinical levels. The onset of PML is rare in the general population, but has become an increasing concern in immunocompromised patients, where reactivation of JCV leads to uncontrolled replication in the CNS. Understanding viral persistence and the normal immune response to JCV provides insight into the circumstances which could lead to viral resurgence. Further, clues on the potential mechanisms of reactivation may be gleaned from the crosstalk among JCV and HIV-1, as well as the impact of monoclonal antibody therapies used for the treatment of autoimmune disorders, including multiple sclerosis, on the development of PML. In this review, we will discuss what is known about viral persistence and the immune response to JCV replication in immunocompromised individuals to elucidate the deficiencies in viral containment that permit viral reactivation and spread. PMID:24297501

  1. Mice Lacking Endoglin in Macrophages Show an Impaired Immune Response

    PubMed Central

    Ojeda-Fernández, Luisa; Recio-Poveda, Lucía; Aristorena, Mikel; Lastres, Pedro; Blanco, Francisco J.; Sanz-Rodríguez, Francisco; Gallardo-Vara, Eunate; de las Casas-Engel, Mateo; Corbí, Ángel; Arthur, Helen M.; Bernabeu, Carmelo; Botella, Luisa M.

    2016-01-01

    Endoglin is an auxiliary receptor for members of the TGF-β superfamily and plays an important role in the homeostasis of the vessel wall. Mutations in endoglin gene (ENG) or in the closely related TGF-β receptor type I ACVRL1/ALK1 are responsible for a rare dominant vascular dysplasia, the Hereditary Hemorrhagic Telangiectasia (HHT), or Rendu-Osler-Weber syndrome. Endoglin is also expressed in human macrophages, but its role in macrophage function remains unknown. In this work, we show that endoglin expression is triggered during the monocyte-macrophage differentiation process, both in vitro and during the in vivo differentiation of blood monocytes recruited to foci of inflammation in wild-type C57BL/6 mice. To analyze the role of endoglin in macrophages in vivo, an endoglin myeloid lineage specific knock-out mouse line (Engfl/flLysMCre) was generated. These mice show a predisposition to develop spontaneous infections by opportunistic bacteria. Engfl/flLysMCre mice also display increased survival following LPS-induced peritonitis, suggesting a delayed immune response. Phagocytic activity is impaired in peritoneal macrophages, altering one of the main functions of macrophages which contributes to the initiation of the immune response. We also observed altered expression of TGF-β1 target genes in endoglin deficient peritoneal macrophages. Overall, the altered immune activity of endoglin deficient macrophages could help to explain the higher rate of infectious diseases seen in HHT1 patients. PMID:27010826

  2. Evolutionary immune response to conserved domains in parasites and aeroallergens.

    PubMed

    Bielory, Brett Phillip; Mainardi, Timothy; Rottem, Menachem

    2013-01-01

    The immune response based on immunoglobulin E (IgE) evolved as a defense against specific parasitic infections. In the absence of active helminthic infections, the immune system has redirected its IgE epitopes toward innocuous environmental antigens. Helminths and aeroallergens have a similar stereotypical IgE response to unique antigens that can not be explained by chance alone. This study was designed to evaluate potential homology between conserved protein domains embedded in parasitic organisms and aeroallergens. Search and retrieval systems for nucleotide and protein sequences (Entrez, BLAST, and National Center for Biotechnology Information) were searched to identify conserved domains between allergens and certain parasites. A total score was developed that correlated positively with homology between compared sequences. Over 2000 domains were examined. We found matches with a high total score (>100) that signified a strong positive correlation between sequences in allergens (n = 30) and parasites (n = 13). Multiple shared conserved domains were identified between parasites and allergens. Parasite-allergen combinations with the most significant homology (greatest total score) were Plasmodium falciparum enolase and Hev b9 (total score, 612), Schistosoma mansoni albumin and Fel d 2 (total score, 991), Ascaris lumbricoides tropomyosin and Ani s3 (total score, 531), and Wuchereria bancrofti trypsin and Blo t3 (138). Homologous conserved domains exist in specific parasites and allergens, consistent with the theory that the human IgE-eosinophil immune response to common allergens is a direct consequence of stimulation by parasitic organisms. PMID:23406942

  3. Protective and pathologic immune responses in human tegumentary leishmaniasis.

    PubMed

    Carvalho, Lucas P; Passos, Sara; Schriefer, Albert; Carvalho, Edgar M

    2012-01-01

    Studies in the recent years have advanced the knowledge of how host and parasite factors contribute to the pathogenesis of human tegumentary leishmaniasis. Polymorphism within populations of Leishmania from the same species has been documented; indicating that infection with different strains may lead to distinct clinical pictures and can also interfere in the response to treatment. Moreover, detection of parasite genetic tags for the precise identification of strains will improve diagnostics and therapy against leishmaniasis. On the host side, while a predominant Th1 type immune response is important to control parasite growth, it does not eradicate Leishmania and, in some cases, does not prevent parasite dissemination. Evidence has accumulated showing the participation of CD4(+) and CD8(+) T cells, as well as macrophages, in the pathology associated with L. braziliensis, L. guayanensis, and L. major infection. The discovery that a large percentage of individuals that are infected with Leishmania do not develop disease will help to understand how the host controls Leishmania infection. As these individuals have a weaker type 1 immune response than patients with cutaneous leishmaniasis, it is possible that control of parasite replication in these individuals is dependent, predominantly, on innate immunity, and studies addressing the ability of neutrophils, macrophages, and NK cells to kill Leishmania should be emphasized. PMID:23060880

  4. Mouse macrophage innate immune response to chikungunya virus infection

    PubMed Central

    2012-01-01

    Background Infection with Chikungunya alphavirus (CHIKV) can cause severe arthralgia and chronic arthritis in humans with persistence of the virus in perivascular macrophages of the synovial membrane by mechanisms largely ill-characterized. Findings We herein analysed the innate immune response (cytokine and programmed cell death) of RAW264.7 mouse macrophages following CHIKV infection. We found that the infection was restrained to a small percentage of cells and was not associated with a robust type I IFN innate immune response (IFN-α4 and ISG56). TNF-α, IL-6 and GM-CSF expression were upregulated while IFN-γ, IL-1α, IL-2, IL-4, IL-5, IL-10 or IL-17 expression could not be evidenced prior to and after CHIKV exposure. Although CHIKV is known to drive apoptosis in many cell types, we found no canonical signs of programmed cell death (cleaved caspase-3, -9) in infected RAW264.7 cells. Conclusion These data argue for the capacity of CHIKV to infect and drive a specific innate immune response in RAW264.7 macrophage cell which seems to be polarized to assist viral persistence through the control of apoptosis and IFN signalling. PMID:23253140

  5. Immune response and histology of humoral rejection in kidney transplantation.

    PubMed

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. PMID:27267916

  6. New concepts in immunity to Neisseria gonorrhoeae: innate responses and suppression of adaptive immunity favor the pathogen, not the host.

    PubMed

    Liu, Yingru; Feinen, Brandon; Russell, Michael W

    2011-01-01

    It is well-known that gonorrhea can be acquired repeatedly with no apparent development of protective immunity arising from previous episodes of infection. Symptomatic infection is characterized by a purulent exudate, but the host response mechanisms are poorly understood. While the remarkable antigenic variability displayed by Neisseria gonorrhoeae and its capacity to inhibit complement activation allow it to evade destruction by the host's immune defenses, we propose that it also has the capacity to avoid inducing specific immune responses. In a mouse model of vaginal gonococcal infection, N. gonorrhoeae elicits Th17-driven inflammatory-immune responses, which recruit innate defense mechanisms including an influx of neutrophils. Concomitantly, N. gonorrhoeae suppresses Th1- and Th2-dependent adaptive immunity, including specific antibody responses, through a mechanism involving TGF-β and regulatory T cells. Blockade of TGF-β alleviates the suppression of specific anti-gonococcal responses and allows Th1 and Th2 responses to emerge with the generation of immune memory and protective immunity. Genital tract tissues are naturally rich in TGF-β, which fosters an immunosuppressive environment that is important in reproduction. In exploiting this niche, N. gonorrhoeae exemplifies a well-adapted pathogen that proactively elicits from its host innate responses that it can survive and concomitantly suppresses adaptive immunity. Comprehension of these mechanisms of gonococcal pathogenesis should allow the development of novel approaches to therapy and facilitate the development of an effective vaccine. PMID:21833308

  7. Humoral immune responses in periodontal disease may have mucosal and systemic immune features

    PubMed Central

    Kinane, D F; Lappin, D F; Koulouri, O; Buckley, A

    1999-01-01

    The humoral immune response, especially IgG and IgA, is considered to be protective in the pathogenesis of periodontal disease, but the precise mechanisms are still unknown. Immunoglobulins arriving at the periodontal lesion are from both systemic and local tissue sources. In order to understand better the local immunoglobulin production, we examined biopsy tissue from periodontitis lesions for the expression of IgM, IgG, IgA, IgE and in addition the IgG and IgA subclasses and J-chain by in situ hybridization. Tissues examined were superficial inflamed gingiva and the deeper granulation tissue from periodontal sites. These data confirm that IgM, and IgG and IgA subclass proteins and J-chain can be locally produced in the periodontitis tissues. IgG1 mRNA-expressing cells were predominant in the granulation tissues and in the gingiva, constituting approx. 65% of the total IgG-expressing plasma cells. There was a significantly increased proportion of IgA-expressing plasma cells in the gingiva compared with the granulation tissue (P < 0.01). Most of the IgA-expressing plasma cells were IgA1, but a greater proportion expressed IgA2 mRNA and J-chain mRNA in the gingival tissues (30.5% and 7.5%, respectively) than in the periodontal granulation tissues (19% and 0–4%, respectively). The J-chain or dimeric IgA2-expressing plasma cells were located adjacent to the epithelial cells, suggesting that this tissue demonstrates features consistent with a mucosal immune response. Furthermore, we were able to detect the secretory component in gingival and junctional epithelial cells, demonstrating that the periodontal epithelium shares features with mucosal epithelium. In contrast, deeper tissues had more plasma cells that expressed IgM, and less expressing IgA, a response which appears more akin to the systemic immune response. In conclusion, this study suggests that immune mechanisms involved in the pathogenesis of periodontitis may involve features of both the mucosal and

  8. Injury and immune response: applying the danger theory to mosquitoes

    PubMed Central

    Moreno-García, Miguel; Recio-Tótoro, Benito; Claudio-Piedras, Fabiola; Lanz-Mendoza, Humberto

    2014-01-01

    The insect immune response can be activated by the recognition of both non-self and molecular by-products of tissue damage. Since pathogens and tissue damage usually arise at the same time during infection, the specific mechanisms of the immune response to microorganisms, and to tissue damage have not been unraveled. Consequently, some aspects of damage caused by microorganisms in vector-borne arthropods have been neglected. We herein reassess the Anopheles–Plasmodium interaction, incorporating Matzinger’s danger/damage hypothesis and George Salt’s injury assumptions. The invasive forms of the parasite cross the peritrophic matrix and midgut epithelia to reach the basal lamina and differentiate into an oocyst. The sporozoites produced in the oocyst are released into the hemolymph, and from there enter the salivary gland. During parasite development, wounds to midgut tissue and the basement membrane are produced. We describe the response of the different compartments where the parasite interacts with the mosquito. In the midgut, the response includes the expression of antimicrobial peptides, production of reactive oxygen species, and possible activation of midgut regenerative cells. In the basal membrane, wound repair mainly involves the production of molecules and the recruitment of hemocytes. We discuss the susceptibility to damage in tissues, and how the place and degree of damage may influence the differential response and the expression of damage associated molecular patterns (DAMPs). Knowledge about damage caused by parasites may lead to a deeper understanding of the relevance of tissue damage and the immune response it generates, as well as the origins and progression of infection in this insect–parasite interaction. PMID:25250040

  9. Control of the Immune Response by Pro-Angiogenic Factors

    PubMed Central

    Voron, Thibault; Marcheteau, Elie; Pernot, Simon; Colussi, Orianne; Tartour, Eric; Taieb, Julien; Terme, Magali

    2014-01-01

    The progressive conversion of normal cells into cancer cells is characterized by the acquisition of eight hallmarks. Among these criteria, the capability of the cancer cell to avoid the immune destruction has been noted. Thus, tumors develop mechanisms to become invisible to the immune system, such as the induction of immunosuppressive cells, which are able to inhibit the development of an efficient immune response. Molecules produced in the tumor microenvironment are involved in the occurrence of an immunosuppressive microenvironment. Recently, it has been shown that vascular endothelial growth factor A (VEGF-A) exhibits immunosuppressive properties in addition to its pro-angiogenic activities. VEGF-A can induce the accumulation of immature dendritic cells, myeloid-derived suppressor cells, regulatory T cells, and inhibit the migration of T lymphocytes to the tumor. Other pro-angiogenic factors such as placental growth factor (PlGF) could also participate in tumor-induced immunosuppression, but only few works have been performed on this point. Here, we review the impact of pro-angiogenic factors (especially VEGF-A) on immune cells. Anti-angiogenic molecules, which target VEGF-A/VEGFR axis, have been developed in the last decades and are commonly used to treat cancer patients. These drugs have anti-angiogenic properties but can also counteract the tumor-induced immunosuppression. Based on these immunomodulatory properties, anti-angiogenic molecules could be efficiently associated with immunotherapeutic strategies in preclinical models. These combinations are currently under investigation in cancer patients. PMID:24765614

  10. Royal Decree: Gene Expression in Trans-Generationally Immune Primed Bumblebee Workers Mimics a Primary Immune Response.

    PubMed

    Barribeau, Seth M; Schmid-Hempel, Paul; Sadd, Ben M

    2016-01-01

    Invertebrates lack the cellular and physiological machinery of the adaptive immune system, but show specificity in their immune response and immune priming. Functionally, immune priming is comparable to immune memory in vertebrates. Individuals that have survived exposure to a given parasite are better protected against subsequent exposures. Protection may be cross-reactive, but demonstrations of persistent and specific protection in invertebrates are increasing. This immune priming can cross generations ("trans-generational" immune priming), preparing offspring for the prevailing parasite environment. While these phenomena gain increasing support, the mechanistic foundations underlying such immune priming, both within and across generations, remain largely unknown. Using a transcriptomic approach, we show that exposing bumblebee queens with an injection of heat-killed bacteria, known to induce trans-generational immune priming, alters daughter (worker) gene expression. Daughters, even when unexposed themselves, constitutively express a core set of the genes induced upon direct bacterial exposure, including high expression of antimicrobial peptides, a beta-glucan receptor protein implicated in bacterial recognition and the induction of the toll signaling pathway, and slit-3 which is important in honeybee immunity. Maternal exposure results in a distinct upregulation of their daughters' immune system, with a signature overlapping with the induced individual response to a direct exposure. This will mediate mother-offspring protection, but also associated costs related to reconfiguration of constitutive immune expression. Moreover, identification of conserved immune pathways in memory-like responses has important implications for our understanding of the innate immune system, including the innate components in vertebrates, which share many of these pathways. PMID:27442590

  11. Royal Decree: Gene Expression in Trans-Generationally Immune Primed Bumblebee Workers Mimics a Primary Immune Response

    PubMed Central

    Schmid-Hempel, Paul; Sadd, Ben M.

    2016-01-01

    Invertebrates lack the cellular and physiological machinery of the adaptive immune system, but show specificity in their immune response and immune priming. Functionally, immune priming is comparable to immune memory in vertebrates. Individuals that have survived exposure to a given parasite are better protected against subsequent exposures. Protection may be cross-reactive, but demonstrations of persistent and specific protection in invertebrates are increasing. This immune priming can cross generations ("trans-generational" immune priming), preparing offspring for the prevailing parasite environment. While these phenomena gain increasing support, the mechanistic foundations underlying such immune priming, both within and across generations, remain largely unknown. Using a transcriptomic approach, we show that exposing bumblebee queens with an injection of heat-killed bacteria, known to induce trans-generational immune priming, alters daughter (worker) gene expression. Daughters, even when unexposed themselves, constitutively express a core set of the genes induced upon direct bacterial exposure, including high expression of antimicrobial peptides, a beta-glucan receptor protein implicated in bacterial recognition and the induction of the toll signaling pathway, and slit-3 which is important in honeybee immunity. Maternal exposure results in a distinct upregulation of their daughters’ immune system, with a signature overlapping with the induced individual response to a direct exposure. This will mediate mother-offspring protection, but also associated costs related to reconfiguration of constitutive immune expression. Moreover, identification of conserved immune pathways in memory-like responses has important implications for our understanding of the innate immune system, including the innate components in vertebrates, which share many of these pathways. PMID:27442590

  12. The Ocular Conjunctiva as a Mucosal Immunization Route: A Profile of the Immune Response to the Model Antigen Tetanus Toxoid

    PubMed Central

    Belij, Sandra; Marinkovic, Emilija; Stojicevic, Ivana; Montanaro, Jacqueline; Stein, Elisabeth; Bintner, Nora; Stojanovic, Marijana

    2013-01-01

    Background In a quest for a needle-free vaccine administration strategy, we evaluated the ocular conjunctiva as an alternative mucosal immunization route by profiling and comparing the local and systemic immune responses to the subcutaneous or conjunctival administration of tetanus toxoid (TTd), a model antigen. Materials and methods BALB/c and C57BL/6 mice were immunized either subcutaneously with TTd alone or via the conjunctiva with TTd alone, TTd mixed with 2% glycerol or TTd with merthiolate-inactivated whole-cell B. pertussis (wBP) as adjuvants. Mice were immunized on days 0, 7 and 14 via both routes, and an evaluation of the local and systemic immune responses was performed two weeks after the last immunization. Four weeks after the last immunization, the mice were challenged with a lethal dose (2 × LD50) of tetanus toxin. Results The conjunctival application of TTd in BALB/c mice induced TTd-specific secretory IgA production and skewed the TTd-specific immune response toward a Th1/Th17 profile, as determined by the stimulation of IFNγ and IL-17A secretion and/or the concurrent pronounced reduction of IL-4 secretion, irrespective of the adjuvant. In conjunctivaly immunized C57BL/6 mice, only TTd administered with wBP promoted the establishment of a mixed Th1/Th17 TTd-specific immune response, whereas TTd alone or TTd in conjunction with glycerol initiated a dominant Th1 response against TTd. Immunization via the conjunctiva with TTd plus wBP adjuvant resulted in a 33% survival rate of challenged mice compared to a 0% survival rate in non-immunized animals (p<0.05). Conclusion Conjunctival immunization with TTd alone or with various adjuvants induced TTd-specific local and systemic immune responses, predominantly of the Th1 type. The strongest immune responses developed in mice that received TTd together with wBP, which implies that this alternative route might tailor the immune response to fight intracellular bacteria or viruses more effectively. PMID

  13. Immune responses to viral infections: relevance for asthma.

    PubMed

    Martin, James G; Siddiqui, Sana; Hassan, Muhannad

    2006-01-01

    Severe respiratory viral infections in childhood are associated with the development of asthma later in life. Rhinovirus, respiratory syncytial virus and metapneumovirus are of particular importance as triggers of asthma. Effects of virus infection on dendritic cell function in the airways may predispose children to allergic sensitization. Asthmatic subjects may have impaired interferon responses to viral infection that also predispose to allergic sensitization. Difference in Toll-like receptor expression on airway epithelial cells is a potential mechanism for the altered immune responses of asthmatic children. PMID:16798536

  14. [Gold antirheumatic drug: desired and adverse effects of Au(I) and Au(III) [corrected] on the immune system.

    PubMed

    Griem, P; Gleichmann, E

    1996-01-01

    Three new findings are reviewed that help to understand the mechanisms of action of anti-rheumatic gold drugs, such as disodium aurothiomalate (Na2Au(I)TM): i) We found that Na2Au(I)TM selectively inhibits T-cell receptor-mediated antigen recognition by murine CD4+ T-cell hybridomas specific for antigenic peptides containing at least two cysteine residues. Presumably, Au(I) acts as a chelating agent forming linear complexes (Cys-Au(I)-Cys) which prevents correct antigen-processing and/or peptide recognition by the T-cell receptor, ii) We were able to show that Au(I) is oxidized to Au(III) in mononuclear phagocytes, such as macrophages. Because Au(III) rapidly oxidizes protein and itself is re-reduced to Au(I), this may introduce an Au(I)/Au(III) redox system into phagocytes which scavenges reactive oxygen species, such as hypochlorous acid (HOCl) and inactivates lysosomal enzymes, iii) Pretreatment with Au(III) of a model protein antigen, bovine ribonuclease A (RNase A), induced novel antigenic determinants recognized by CD4+ T lymphocytes. Analysis of the fine specificity of these "Au(III)-specific" T-cells revealed that they react to RNase peptides that are not presented to T-cells when the native protein, i.e., not treated with Au(III), is used as antigen. The T-cell recognition of these cryptic peptides did not require the presence of gold. This finding has important implications for understanding the pathogenesis of allergic and autoimmune responses induced by gold drugs. Taken together, our findings indicate that Au(I) and Au(III) each exert specific effects on several distinct functions of macrophages and the activation of T-cells. These effects may explain both the desired anti-inflammatory and the adverse effects of antirheumatic gold drugs. PMID:9036720

  15. Phylogeny of immune recognition: antigen processing/presentation in channel catfish immune responses to hemocyanins.

    PubMed

    Vallejo, A N; Miller, N W; Jørgensen, T; Clem, L W

    1990-10-15

    Studies were conducted to address the role(s) of antigen (Ag) processing/presentation in channel catfish immune responses. Vigorous and specific secondary in vitro proliferative and antibody (Ab) responses were obtained to keyhole limpet and Limulus polyphemus hemocyanins with peripheral blood leukocytes (PBL) from catfish previously primed in vivo with Ag. In addition, such antigen-specific in vitro proliferative and Ab responses were efficiently elicited by antigen-pulsed and subsequently paraformaldehyde-fixed autologous PBL used as putative antigen-presenting cells (APC) but not by APC fixed prior to Ag pulsing. Treatment of these putative APC with lysosomotropic agents, protease inhibitors, or the ionophore monensin prior to or during pulsing with Ag significantly inhibited both in vitro responses. Furthermore, the use of radiolabeled protein indicated that both untreated and inhibitor-treated PBL but not erythrocytes take up Ag; however, only untreated PBL were able to degrade Ag. Immune restriction was indicated by the use of allogeneic PBL as APC in that only strong MLRs were generated with no detectable antibodies produced in vitro. Finally, the employment of isolated leukocyte subpopulations demonstrated that both catfish B (sIg+) lymphocytes and monocytes were efficient Ag presentors. PMID:2208303

  16. DNA and Protein Co-Immunization Improves the Magnitude and Longevity of Humoral Immune Responses in Macaques

    PubMed Central

    Jalah, Rashmi; Kulkarni, Viraj; Patel, Vainav; Rosati, Margherita; Alicea, Candido; Bear, Jenifer; Yu, Lei; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D.; LaBranche, Celia; Montefiori, David C.; Prattipati, Rajasekhar; Pinter, Abraham; Bess, Julian; Lifson, Jeffrey D.; Reed, Steven G.; Sardesai, Niranjan Y.; Venzon, David J.; Valentin, Antonio; Pavlakis, George N.; Felber, Barbara K.

    2014-01-01

    We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques. PMID:24626482

  17. DNA and protein co-immunization improves the magnitude and longevity of humoral immune responses in macaques.

    PubMed

    Jalah, Rashmi; Kulkarni, Viraj; Patel, Vainav; Rosati, Margherita; Alicea, Candido; Bear, Jenifer; Yu, Lei; Guan, Yongjun; Shen, Xiaoying; Tomaras, Georgia D; LaBranche, Celia; Montefiori, David C; Prattipati, Rajasekhar; Pinter, Abraham; Bess, Julian; Lifson, Jeffrey D; Reed, Steven G; Sardesai, Niranjan Y; Venzon, David J; Valentin, Antonio; Pavlakis, George N; Felber, Barbara K

    2014-01-01

    We tested the concept of combining DNA with protein to improve anti-HIV Env systemic and mucosal humoral immune responses. Rhesus macaques were vaccinated with DNA, DNA&protein co-immunization or DNA prime followed by protein boost, and the magnitude and mucosal dissemination of the antibody responses were monitored in both plasma and mucosal secretions. We achieved induction of robust humoral responses by optimized DNA vaccination delivered by in vivo electroporation. These responses were greatly increased upon administration of a protein boost. Importantly, a co-immunization regimen of DNA&protein injected in the same muscle at the same time induced the highest systemic binding and neutralizing antibodies to homologous or heterologous Env as well as the highest Env-specific IgG in saliva. Inclusion of protein in the vaccine resulted in more immunized animals with Env-specific IgG in rectal fluids. Inclusion of DNA in the vaccine significantly increased the longevity of systemic humoral immune responses, whereas protein immunization, either as the only vaccine component or as boost after DNA prime, was followed by a great decline of humoral immune responses overtime. We conclude that DNA&protein co-delivery in a simple vaccine regimen combines the strength of each vaccine component, resulting in improved magnitude, extended longevity and increased mucosal dissemination of the induced antibodies in immunized rhesus macaques. PMID:24626482

  18. Tissue communication in a systemic immune response of Drosophila.

    PubMed

    Yang, Hairu; Hultmark, Dan

    2016-07-01

    Several signaling pathways, including the JAK/STAT and Toll pathways, are known to activate blood cells (hemocytes) in Drosophila melanogaster larvae. They are believed to regulate the immune response against infections by parasitoid wasps, such as Leptopilina boulardi, but how these pathways control the hemocytes is not well understood. Here, we discuss the recent discovery that both muscles and fat body take an active part in this response. Parasitoid wasp infection induces Upd2 and Upd3 secretion from hemocytes, leading to JAK/STAT activation mainly in hemocytes and in skeletal muscles. JAK/STAT activation in muscles, but not in hemocytes, is required for an efficient encapsulation of wasp eggs. This suggests that Upd2 and Upd3 are important cytokines, coordinating different tissues for the cellular immune response in Drosophila. In the fat body, Toll signaling initiates a systemic response in which hemocytes are mobilized and activated hemocytes (lamellocytes) are generated. However, the contribution of Toll signaling to the defense against wasps is limited, probably because the wasps inject inhibitors that prevent the activation of the Toll pathway. In conclusion, parasite infection induces a systemic response in Drosophila larvae involving major organ systems and probably the physiology of the entire organism. PMID:27116253

  19. Multi-scale modeling of the CD8 immune response

    NASA Astrophysics Data System (ADS)

    Barbarroux, Loic; Michel, Philippe; Adimy, Mostafa; Crauste, Fabien

    2016-06-01

    During the primary CD8 T-Cell immune response to an intracellular pathogen, CD8 T-Cells undergo exponential proliferation and continuous differentiation, acquiring cytotoxic capabilities to address the infection and memorize the corresponding antigen. After cleaning the organism, the only CD8 T-Cells left are antigen-specific memory cells whose role is to respond stronger and faster in case they are presented this very same antigen again. That is how vaccines work: a small quantity of a weakened pathogen is introduced in the organism to trigger the primary response, generating corresponding memory cells in the process, giving the organism a way to defend himself in case it encounters the same pathogen again. To investigate this process, we propose a non linear, multi-scale mathematical model of the CD8 T-Cells immune response due to vaccination using a maturity structured partial differential equation. At the intracellular scale, the level of expression of key proteins is modeled by a delay differential equation system, which gives the speeds of maturation for each cell. The population of cells is modeled by a maturity structured equation whose speeds are given by the intracellular model. We focus here on building the model, as well as its asymptotic study. Finally, we display numerical simulations showing the model can reproduce the biological dynamics of the cell population for both the primary response and the secondary responses.

  20. “Prepandemic” Immunization for Novel Influenza Viruses, “Swine Flu” Vaccine, Guillain-Barré Syndrome, and the Detection of Rare Severe Adverse Events

    PubMed Central

    Evans, David; Cauchemez, Simon; Hayden, Frederick G

    2010-01-01

    The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against “swine” influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or “priming” of populations in the so-called “prepandemic” (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against “swine flu” and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting. PMID:19563262

  1. "Prepandemic" immunization for novel influenza viruses, "swine flu" vaccine, Guillain-Barré syndrome, and the detection of rare severe adverse events.

    PubMed

    Evans, David; Cauchemez, Simon; Hayden, Frederick G

    2009-08-01

    The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against "swine" influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or "priming" of populations in the so-called "prepandemic" (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against "swine flu" and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting. PMID:19563262

  2. Hypocretin/orexin loss changes the hypothalamic immune response.

    PubMed

    Tanaka, Susumu; Takizawa, Nae; Honda, Yoshiko; Koike, Taro; Oe, Souichi; Toyoda, Hiromi; Kodama, Tohru; Yamada, Hisao

    2016-10-01

    Hypocretin, also known as orexin, maintains the vigilance state and regulates various physiological processes, such as arousal, sleep, food intake, energy expenditure, and reward. Previously, we found that when wild-type mice and hypocretin/ataxin-3 littermates (which are depleted of hypothalamic hypocretin-expressing neurons postnatally) were administered lipopolysaccharide (LPS), the two genotypes exhibited significant differences in their sleep/wake cycle, including differences in the degree of increase in sleep periods and in recovery from sickness behaviour. In the present study, we examined changes in the hypothalamic vigilance system and in the hypothalamic expression of inflammatory factors in response to LPS in hypocretin/ataxin-3 mice. Peripheral immune challenge with LPS affected the hypothalamic immune response and vigilance states. This response was altered by the loss of hypocretin. Hypocretin expression was inhibited after LPS injection in both hypocretin/ataxin-3 mice and their wild-type littermates, but expression was completely abolished only in hypocretin/ataxin-3 mice. Increases in the number of histidine decarboxylase (HDC)-positive cells and in Hdc mRNA expression were found in hypocretin/ataxin-3 mice, and this increase was suppressed by LPS. Hypocretin loss did not impact the change in expression of hypothalamic inflammatory factors in response to LPS, except for interferon gamma and colony stimulating factor 3. The number of c-Fos-positive/HDC-positive cells in hypocretin/ataxin-3 mice administered LPS injections was elevated, even during the rest period, in all areas, suggesting that there is an increase in the activity of histaminergic neurons in hypocretin/ataxin-3 mice following LPS injection. Taken together, our results suggest a novel role for hypocretin in the hypothalamic response to peripheral immune challenge. Our findings contribute to the understanding of the pathophysiology of narcolepsy. PMID:27318095

  3. Effects of anti-schistosomal chemotherapy on immune responses, protection and immunity. II. Concomitant immunity and immunization with irradiated cercariae

    SciTech Connect

    Tawfik, A.F.; Colley, D.G.

    1986-01-01

    Resistance of mice to challenge infections of Schistosoma mansoni was evaluated before and after elimination of their primary, established S. mansoni infections with the chemotherapeutic drug praziquantel. Mice treated after either 10 or 20 weeks of primary infection were challenged 6 or 10 weeks after treatment. Mice infected for for 10 weeks prior to treatment expressed progressively less resistance 6 and 10 weeks after treatment. By 10 weeks after treatment significant levels of protection were no longer observed. Resistance waned more slowly if mice were treated 20 weeks after infection, and there was still significant expression of resistance to challenge 10 weeks after treatment. A separate set of experiments evaluated the use of highly irradiated cercariae as a vaccine in mice that had been previously infected with S. mansoni and cured with praziquantel. It was observed that effective immunizations were possible in previously infected mice. These studies demonstrate that established resistance waned after treatment and the rate of loss of protection was dependent upon the duration of infection prior to treatment. Furthermore, the irradiated cercarial vaccine studies indicate that in the murine model induction of immunological resistance was feasible following chemotherapeutic treatment of infected populations.

  4. Redox rhythm reinforces the circadian clock to gate immune response

    PubMed Central

    Zhou, Mian; Wang, Wei; Karapetyan, Sargis; Mwimba, Musoki; Marqués, Jorge; Buchler, Nicolas E.; Dong, Xinnian

    2015-01-01

    Recent studies have shown that in addition to the transcriptional circadian clock, many organisms, including Arabidopsis, have a circadian redox rhythm driven by the organism’s metabolic activities1–3. It has been hypothesized that the redox rhythm is linked to the circadian clock, but the mechanism and the biological significance of this link have only begun to be investigated4–7. Here we report that the master immune regulator NPR1 (non-expressor of pathogenesis-related gene 1) of Arabidopsis is a sensor of the plant’s redox state and regulates transcription of core circadian clock genes even in the absence of pathogen challenge. Surprisingly, acute perturbation in the redox status triggered by the immune signal salicylic acid (SA) does not compromise the circadian clock but rather leads to its reinforcement. Mathematical modelling and subsequent experiments show that NPR1 reinforces the circadian clock without changing the period by regulating both the morning and the evening clock genes. This balanced network architecture helps plants gate their immune responses towards the morning and minimize costs on growth at night. Our study demonstrates how a sensitive redox rhythm interacts with a robust circadian clock to ensure proper responsiveness to environmental stimuli without compromising fitness of the organism. PMID:26098366

  5. Analysis of a successful immune response against hepatitis C virus.

    PubMed

    Cooper, S; Erickson, A L; Adams, E J; Kansopon, J; Weiner, A J; Chien, D Y; Houghton, M; Parham, P; Walker, C M

    1999-04-01

    To investigate the type of immunity responsible for resolution of hepatitis C virus (HCV) infection, we monitored antibody and intrahepatic cytotoxic T lymphocyte (CTL) responses during acute (<20 weeks) infection in chimpanzees. Two animals who terminated infection made strong CTL but poor antibody responses. In both resolvers, CTL targeted at least six viral regions. In contrast, animals developing chronic hepatitis generated weaker acute CTL responses. Extensive analysis of the fine specificity of the CTL in one resolver revealed nine peptide epitopes and restriction by all six MHC class I allotypes. Every specificity shown during acute hepatitis persisted in normal liver tissue more than 1 yr after resolution. These results suggest that CD8+CTL are better correlated with protection against HCV infection than antibodies. PMID:10229187

  6. Glucosinolate Metabolites Required for an Arabidopsis Innate Immune Response*

    PubMed Central

    Clay, Nicole K.; Adio, Adewale M.; Denoux, Carine; Jander, Georg; Ausubel, Frederick M.

    2008-01-01

    Summary The perception of pathogen or microbe-associated molecular pattern molecules by plants triggers a basal defense response analogous to animal innate immunity, and is defined in part by the deposition of the glucan polymer callose at the cell wall at the site of pathogen contact. Transcriptional and metabolic profiling in Arabidopsis mutants, coupled with the monitoring of pathogen triggered callose deposition, have identified major roles in pathogen response for the plant hormone ethylene and the secondary metabolite 4-methoxy-indol-3-ylmethylglucosinolate. Two genes, PEN2 and PEN3, are also necessary for resistance to pathogens and are required for both callose deposition and glucosinolate activation, suggesting that the pathogen triggered callose response is required for resistance to microbial pathogens. Our study shows that well-studied plant metabolites, previously identified as important in avoiding damage by herbivores, are also required as a component of the plant defense response against microbial pathogens. PMID:19095898

  7. Specificity and signaling in the Drosophila immune response

    PubMed Central

    Silverman, N; Paquette, N; Aggarwal, K

    2011-01-01

    The Drosophila immune response is characterized by the rapid and robust production of a battery of antimicrobial peptides immediately following infection. The genes encoding these antimicrobial peptides are controlled by two NF-κB signaling pathways that respond to microbial infection. The IMD pathway is triggered by DAP-type peptidoglycan, from the cell wall of most Gram-negative and certain Gram-positive bacteria, and activates the NF-κB precursor protein Relish. The Toll pathway, on the other hand, is stimulated by lysine-type peptidoglycan from many Gram-positive bacteria, β 1,3 glucans from many fungi, as well as by microbial proteases. Toll signaling leads to the activation and nuclear translocation of DIF or Dorsal, two other NF-κB homologs. This review presents our current understanding of the molecular mechanisms involved in microbial recognition and signal transduction in these two innate immune pathways. PMID:21625362

  8. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  9. The Lung Immune Response to Nontypeable Haemophilus influenzae (Lung Immunity to NTHi)

    PubMed Central

    King, Paul T.; Sharma, Roleen

    2015-01-01

    Haemophilus influenzae is divided into typeable or nontypeable strains based on the presence or absence of a polysaccharide capsule. The typeable strains (such as type b) are an important cause of systemic infection, whilst the nontypeable strains (designated as NTHi) are predominantly respiratory mucosal pathogens. NTHi is present as part of the normal microbiome in the nasopharynx, from where it may spread down to the lower respiratory tract. In this context it is no longer a commensal and becomes an important respiratory pathogen associated with a range of common conditions including bronchitis, bronchiectasis, pneumonia, and particularly chronic obstructive pulmonary disease. NTHi induces a strong inflammatory response in the respiratory tract with activation of immune responses, which often fail to clear the bacteria from the lung. This results in recurrent/persistent infection and chronic inflammation with consequent lung pathology. This review will summarise the current literature about the lung immune response to nontypeable Haemophilus influenzae, a topic that has important implications for patient management. PMID:26114124

  10. Murine immune responses to oral BCG immunization in the presence or absence of prior BCG sensitization.

    PubMed

    Cross, Martin L; Lambeth, Matthew R; Aldwell, Frank E

    2010-02-01

    Oral delivery of live Mycobacterium bovis BCG in a lipid matrix invokes cell-mediated immune (CMI) responses in mice and consequent protection against pulmonary challenge with virulent mycobacteria. To investigate the influence of prior BCG sensitization on oral vaccine efficacy, we assessed CMI responses and BCG colonization of the alimentary tract lymphatics 5 months after oral vaccination, in both previously naive mice and in mice that had been sensitized to BCG by injection 6 months previously. CMI responses did not differ significantly between mice that received subcutaneous BCG followed by oral BCG and those that received either injected or oral BCG alone. In vivo BCG colonization was predominant in the mesenteric lymph nodes after oral vaccination; this colonizing ability was not influenced by prior BCG sensitization. From this murine model study, we conclude that although prior parenteral-route BCG sensitization does not detrimentally affect BCG colonization after oral vaccination, there is no significant immune-boosting effect of the oral vaccine either. PMID:19918257

  11. Quantitative Determination of the Human Immune Response to Immunization with Meningococcal Vaccines

    PubMed Central

    Gotschlich, Emil C.; Rey, Michel; Triau, Rene; Sparks, Kenneth J.

    1972-01-01

    Radioactive antigen binding tests have been developed to measure quantitatively the antibody response of 167 adults, 84 children, and 51 infants to several different preparations of group A and group C meningococcal polysaccharides. Almost all the adults injected responded and the geometric mean responses were approximately 15 μg/ml of antibody protein in individuals vaccinated subcutaneously with two preparations of group A vaccine. The geometric mean antibody concentration after immunization with two preparations of group C vaccine was approximately 35 μg/ml. Most children aged 7 yr responded to immunization with two group A vaccines, and their mean response was only slightly less than that seen in adults. There was no difference between the subcutaneous and the intradermal route if both were given with jet gun. The majority of infants aged 6-13 months responded to a preparation of group A vaccine and the geometric mean titer was approximately 1.2 μg/ml. Adults, children, and infants responded significantly less to a preparation of group A polysaccharide which was of low molceular weight. PMID:4621363

  12. Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish

    PubMed Central

    Chatterjee, Arunita; Roy, Debasish; Patnaik, Esha

    2016-01-01

    ABSTRACT Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual. PMID:27101844

  13. Innate Cellular Immune Responses in Aedes caspius (Diptera: Culicidae) Mosquitoes.

    PubMed

    Soliman, D E; Farid, H A; Hammad, R E; Gad, A M; Bartholomay, L C

    2016-03-01

    Mosquitoes transmit a variety of pathogens that have devastating consequences for global public and veterinary health. Despite their capacity to serve as vectors, these insects have a robust capacity to respond to invading organisms with strong cellular and humoral immune responses. In Egypt, Aedes caspius (Pallas, 1771) has been suspected to act as a bridge vector of Rift Valley Fever virus between animals and humans. Microscopic analysis of Ae. caspius hemolymph revealed the presence of phagocytic cells called granulocytes. We further evaluated cellular immune responses produced by Ae. caspius as a result of exposure to a Gram-negative, and Gram-positive bacterium, and to latex beads. After challenge, a rapid and strong phagocytic response against either a natural or synthetic invader was evident. Hemocyte integrity in bacteria-inoculated mosquitoes was not morphologically affected. The number of circulating granulocytes decreased with age, reducing the overall phagocytic capacity of mosquitoes over time. The magnitude and speed of the phagocytic response suggested that granulocytes act as an important force in the battle against foreign invaders, as has been characterized in other important mosquito vector species. PMID:26792848

  14. Mitochondrial DNA Stress Primes the Antiviral Innate Immune Response

    PubMed Central

    West, A. Phillip; Khoury-Hanold, William; Staron, Matthew; Tal, Michal C.; Pineda, Cristiana M.; Lang, Sabine M.; Bestwick, Megan; Duguay, Brett A.; Raimundo, Nuno; MacDuff, Donna A.; Kaech, Susan M.; Smiley, James R.; Means, Robert E.; Iwasaki, Akiko; Shadel, Gerald S.

    2014-01-01

    Mitochondrial DNA (mtDNA) is normally present at thousands of copies per cell and is packaged into several hundred higher-order structures termed nucleoids1. The abundant mtDNA-binding protein, transcription factor A mitochondrial (TFAM), regulates nucleoid architecture, abundance, and segregation2. Complete mtDNA depletion profoundly impairs oxidative phosphorylation (OXPHOS), triggering calcium-dependent stress signaling and adaptive metabolic responses3. However, the cellular responses to mtDNA instability, a physiologically relevant stress observed in many human diseases and aging, remain ill-defined4. Here we show that moderate mtDNA stress elicited by TFAM deficiency engages cytosolic antiviral signaling to enhance the expression of a subset of interferon-stimulated genes (ISG). Mechanistically, we have found that aberrant mtDNA packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor cGAS and promotes STING-IRF3-dependent signaling to elevate ISG expression, potentiate type I interferon responses, and confer broad viral resistance. Furthermore, we demonstrate that herpesviruses induce mtDNA stress, which potentiates antiviral signaling and type I interferon responses during infection. Our results further demonstrate that mitochondria are central participants in innate immunity, identify mtDNA stress as a cell-intrinsic trigger of antiviral signaling, and suggest that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully license antiviral innate immunity. PMID:25642965

  15. Mitochondrial DNA stress primes the antiviral innate immune response.

    PubMed

    West, A Phillip; Khoury-Hanold, William; Staron, Matthew; Tal, Michal C; Pineda, Cristiana M; Lang, Sabine M; Bestwick, Megan; Duguay, Brett A; Raimundo, Nuno; MacDuff, Donna A; Kaech, Susan M; Smiley, James R; Means, Robert E; Iwasaki, Akiko; Shadel, Gerald S

    2015-04-23

    Mitochondrial DNA (mtDNA) is normally present at thousands of copies per cell and is packaged into several hundred higher-order structures termed nucleoids. The abundant mtDNA-binding protein TFAM (transcription factor A, mitochondrial) regulates nucleoid architecture, abundance and segregation. Complete mtDNA depletion profoundly impairs oxidative phosphorylation, triggering calcium-dependent stress signalling and adaptive metabolic responses. However, the cellular responses to mtDNA instability, a physiologically relevant stress observed in many human diseases and ageing, remain poorly defined. Here we show that moderate mtDNA stress elicited by TFAM deficiency engages cytosolic antiviral signalling to enhance the expression of a subset of interferon-stimulated genes. Mechanistically, we find that aberrant mtDNA packaging promotes escape of mtDNA into the cytosol, where it engages the DNA sensor cGAS (also known as MB21D1) and promotes STING (also known as TMEM173)-IRF3-dependent signalling to elevate interferon-stimulated gene expression, potentiate type I interferon responses and confer broad viral resistance. Furthermore, we demonstrate that herpesviruses induce mtDNA stress, which enhances antiviral signalling and type I interferon responses during infection. Our results further demonstrate that mitochondria are central participants in innate immunity, identify mtDNA stress as a cell-intrinsic trigger of antiviral signalling and suggest that cellular monitoring of mtDNA homeostasis cooperates with canonical virus sensing mechanisms to fully engage antiviral innate immunity. PMID:25642965

  16. Role of natural and immune IgM antibodies in immune responses.

    PubMed

    Boes, M

    2000-12-01

    IgM antibodies constitute the major component of the natural antibodies and is also the first class of antibodies produced during a primary antibody response. The IgM-type antibodies differ from other classes of antibodies in that they are predominantly produced by B1 cells, in the absence of apparent stimulation by specific antigens. In addition, IgM antibodies are mostly encoded by germline V gene segments and have low affinities but broad specificites to both foreign and self structures. New developments regarding the function of both immune IgM antibodies and natural IgM antibodies will be examined here. PMID:11451419

  17. [Local Immune response in rabbits following enteral immunization with live attenuated bacterial Enterobacteriaceae vaccines].

    PubMed

    Dentschev, W; Marinova, S; Sumerska, T; Nenkov, P; Koitschev, T; Trifonowa, A

    1980-01-01

    Streptomycin-dependent and inactivated Shigella flexneri 2a and Shigella sonnei strains were intra-intestinally applied to rabbits for immunisation. Rosette and plaque tests and well as indirect haemagglutination gave short-time secretion of low titres of specific copro-antibody, following monovaccines and bivaccines. High titres of secretory antibody were induced, depending on doses, by re-immunisation. No antigen competition was established. The localised immune response caused by Shigella live vaccines was found to be much stronger than that induced by inactivated vaccines PMID:6998404

  18. Immune Response to Sipuleucel-T in Prostate Cancer

    PubMed Central

    Thara, Eddie; Dorff, Tanya B.; Averia-Suboc, Monica; Luther, Michael; Reed, Mary E.; Pinski, Jacek K.; Quinn, David I.

    2012-01-01

    Historically, chemotherapy has remained the most commonly utilized therapy in patients with metastatic cancers. In prostate cancer, chemotherapy has been reserved for patients whose metastatic disease becomes resistant to first line castration or androgen deprivation. While chemotherapy palliates, decreases serum prostate specific antigen and improves survival, it is associated with significant side effects and is only suitable for approximately 60% of patients with castrate-resistant prostate cancer. On that basis, exploration of other therapeutic options such as active secondary hormone therapy, bone targeted treatments and immunotherapy are important. Until recently, immunotherapy has had no role in the treatment of solid malignancies aside from renal cancer and melanoma. The FDA-approved autologous cellular immunotherapy sipuleucel-T has demonstrated efficacy in improving overall survival in patients with metastatic castrate-resistant prostate cancer in randomized clinical trials. The proposed mechanism of action is reliant on activating the patients’ own antigen presenting cells (APCs) to prostatic acid phosphatase (PAP) fused with granulocyte-macrophage colony stimulating factor (GM-CSF) and subsequent triggered T-cell response to PAP on the surface of prostate cancer cells in the patients body. Despite significant prolongation of survival in Phase III trials, the challenge to health care providers remains the dissociation between objective changes in serum PSA or on imaging studies after sipleucel-T and survival benefit. On that basis there is an unmet need for markers of outcome and a quest to identify immunologic or clinical surrogates to fill this role. This review focuses on the impact of sipuleucel-T on the immune system, the T and B cells, and their responses to relevant antigens and prostate cancer. Other therapeutic modalities such as chemotherapy, corticosteroids and GM-CSF and host factors can also affect immune response. The optimal timing for

  19. Introducing seasonal influenza vaccine in low-income countries: an adverse events following immunization survey in the Lao People's Democratic Republic

    PubMed Central

    Phengxay, Manilay; Mirza, Sara A; Reyburn, Rita; Xeuatvongsa, Anonh; Winter, Christian; Lewis, Hannah; Olsen, Sonja J; Tsuyuoka, Reiko; Khanthamaly, Viengphone; Palomeque, Francisco S; Bresee, Joseph S; Moen, Ann C; Corwin, Andrew L

    2015-01-01

    Objective In 2012, Lao PDR introduced seasonal influenza vaccine in pregnant women, persons aged ≥50 years, persons with chronic diseases, and healthcare personnel. We assessed adverse events following immunization (AEFI). Methods We used a multistage randomized cluster sample design to interview vaccine recipients. Findings Between April and May 2012, 355 902 were vaccinated. Of 2089 persons interviewed, 261 (12·5%) reported one or more AEFI. The most commonly reported AEFIs were local reactions. No hospitalizations or deaths were reported; 16% sought medical care. Acceptance and awareness of vaccination were high. Conclusions Following the introduction of seasonal influenza vaccine in Lao PDR, self-reported adverse events were mild. PMID:25598475

  20. Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide

    NASA Astrophysics Data System (ADS)

    Wu, Qiuli; Zhao, Yunli; Fang, Jianpeng; Wang, Dayong

    2014-05-01

    Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO toxicity and accumulation in the intestine and maintained the relatively normal immune response of animals. The severe accumulation of OP50 in the intestine might be partially due to the damage by GO on the development and function of AVL and DVB neurons controlling defecation behavior. Reduction of chronic GO toxicity by PEG surface modification largely resulted from the inhibition of OP50 accumulation in the intestine and the maintenance of normal immune response. Our results highlight the key role of innate immunity in regulating in vivo chronic GO toxicity, which will be helpful for our understanding of the interactions between nanomaterials and biological systems during the long-term development of animals.Graphene oxide (GO) shows great promise as a nanomaterial for medical applications; however, the mechanism for its long-term adverse effects is still largely unclear. Here, we show that chronic GO exposure not only caused damage on the function of both primary and secondary targeted organs but also induced severe accumulation of pathogenic microbial food (OP50) in the intestine of Caenorhabditis elegans, a non-mammalian alternative toxicity assay system. GO accumulated in the intestine could be largely co-localized with OP50 and induced decreased immune response of animals. In contrast, feeding with UV-treated OP50 suppressed GO

  1. The effect of nutritional status on immune capacity and immune responses in preschool children in a rural community in India*

    PubMed Central

    Kielmann, A. A.; Uberoi, I. S.; Chandra, R. K.; Mehra, V. L.

    1976-01-01

    Cell-mediated immune response (CMI) and several aspects of humoral immune status and response were measured and related to nutritional status in preschool children in north India. CMI was measured by means of postvaccinal (BCG) tuberculin sensitivity and leucocytic blast cell transformation. Humoral immune response was measured by means of tetanus antibody production following vaccination with diphtheria—pertussis—tetanus vaccine. Immunoglobulins A, G, and M and complement (C3) were also determined. CMI, serum IgA, and C3 were found to be directly correlated with weight-for-age status. PMID:1088398

  2. Yersinia type III effectors perturb host innate immune responses

    PubMed Central

    Pha, Khavong; Navarro, Lorena

    2016-01-01

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  3. Yersinia type III effectors perturb host innate immune responses.

    PubMed

    Pha, Khavong; Navarro, Lorena

    2016-02-26

    The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type III secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The three human pathogenic Yersinia spp. (Y. pestis, Y. enterocolitica, and Y. pseudotuberculosis) are Gram-negative bacteria that share in common a 70 kb virulence plasmid which encodes the T3SS. Translocation of the Yersinia effector proteins (YopE, YopH, YopT, YopM, YpkA/YopO, and YopP/J) into the target host cell results in disruption of the actin cytoskeleton to inhibit phagocytosis, downregulation of proinflammatory cytokine/chemokine production, and induction of cellular apoptosis of the target cell. Over the past 25 years, studies on the Yersinia effector proteins have unveiled tremendous knowledge of how the effectors enhance Yersinia virulence. Recently, the long awaited crystal structure of YpkA has been solved providing further insights into the activation of the YpkA kinase domain. Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia

  4. Ribavirin stimulates the immune response of Atlantic salmon.

    PubMed

    Rivas-Aravena, A; Guajardo, S; Valenzuela, B; Cartagena, J; Imarai, M I; Spencer, E; Sandino, A M

    2015-03-15

    Ribavirin is a synthetic nucleotide analog capable of inhibiting or even preventing some viral infections in mammals and also in fish. It has been seen by others that ribavirin by itself is able to stimulate the immune system of mammals, causing a differentiation of T-cells to T helper 1 cells (Th)-1. In this work, we evaluated the immune effect of ribavirin in vitro on kidney cells from Atlantic salmon and in vivo by oral administration of ribavirin to Atlantic salmon. For this purpose, the transcripts of immune molecules Tbet, GATA3, CD8, CD4, IFNα, IFNγ, IL-4/13, IL-10, IL-12, IL-15 and TGF-B were quantified. The results show that ribavirin administered orally in food to Atlantic salmon increased IFNγ and CD4 transcripts in the in vivo assays and, in addition, increased IL-12, IL-15 and CD8 in the in vitro analyses, indicating that the treatment stimulates a Th1 type response in salmon. PMID:25631788

  5. Stress, Nutrition, and Intestinal Immune Responses in Pigs - A Review.

    PubMed

    Lee, In Kyu; Kye, Yoon Chul; Kim, Girak; Kim, Han Wool; Gu, Min Jeong; Umboh, Johnny; Maaruf, Kartini; Kim, Sung Woo; Yun, Cheol-Heui

    2016-08-01

    Modern livestock production became highly intensive and large scaled to increase production efficiency. This production environment could add stressors affecting the health and growth of animals. Major stressors can include environment (air quality and temperature), nutrition, and infection. These stressors can reduce growth performance and alter immune systems at systemic and local levels including the gastrointestinal tract. Heat stress increases the permeability, oxidative stress, and inflammatory responses in the gut. Nutritional stress from fasting, antinutritional compounds, and toxins induces the leakage and destruction of the tight junction proteins in the gut. Fasting is shown to suppress pro-inflammatory cytokines, whereas deoxynivalenol increases the recruitment of intestinal pro-inflammatory cytokines and the level of lymphocytes in the gut. Pathogenic and viral infections such as Enterotoxigenic E. coli (ETEC) and porcine epidemic diarrhea virus can lead to loosening the intestinal epithelial barrier. On the other hand, supplementation of Lactobacillus or Saccharaomyces reduced infectious stress by ETEC. It was noted that major stressors altered the permeability of intestinal barriers and profiles of genes and proteins of pro-inflammatory cytokines and chemokines in mucosal system in pigs. However, it is not sufficient to fully explain the mechanism of the gut immune system in pigs under stress conditions. Correlation and interaction of gut and systemic immune system under major stressors should be better defined to overcome aforementioned obstacles. PMID:27189643

  6. Feliform carnivores have a distinguished constitutive innate immune response

    PubMed Central

    Heinrich, Sonja K.; Wachter, Bettina; Aschenborn, Ortwin H. K.; Thalwitzer, Susanne; Melzheimer, Jörg; Hofer, Heribert; Czirják, Gábor Á.

    2016-01-01

    ABSTRACT Determining the immunological phenotype of endangered and threatened populations is important to identify those vulnerable to novel pathogens. Among mammals, members of the order Carnivora are particularly threatened by diseases. We therefore examined the constitutive innate immune system, the first line of protection against invading microbes, of six free-ranging carnivore species; the black-backed jackal (Canis mesomelas), the brown hyena (Hyena brunnea), the caracal (Caracal caracal), the cheetah (Acinonyx jubatus), the leopard (Panthera pardus) and the lion (Panthera leo) using a bacterial killing assay. The differences in immune responses amongst the six species were independent of their foraging behaviour, body mass or social organisation but reflected their phylogenetic relatedness. The bacterial killing capacity of black-backed jackals, a member of the suborder Caniformia, followed the pattern established for a wide variety of vertebrates. In contrast, the five representatives of the suborder Feliformia demonstrated a killing capacity at least an order of magnitude higher than any species reported previously, with a particularly high capacity in caracals and cheetahs. Our results suggest that the immunocompetence of threatened felids such as the cheetah has been underestimated and its assessment ought to consider both innate and adaptive components of the immune system. PMID:27044323

  7. Feliform carnivores have a distinguished constitutive innate immune response.

    PubMed

    Heinrich, Sonja K; Wachter, Bettina; Aschenborn, Ortwin H K; Thalwitzer, Susanne; Melzheimer, Jörg; Hofer, Heribert; Czirják, Gábor Á

    2016-01-01

    Determining the immunological phenotype of endangered and threatened populations is important to identify those vulnerable to novel pathogens. Among mammals, members of the order Carnivora are particularly threatened by diseases. We therefore examined the constitutive innate immune system, the first line of protection against invading microbes, of six free-ranging carnivore species; the black-backed jackal (Canis mesomelas), the brown hyena (Hyena brunnea), the caracal (Caracal caracal), the cheetah (Acinonyx jubatus), the leopard (Panthera pardus) and the lion (Panthera leo) using a bacterial killing assay. The differences in immune responses amongst the six species were independent of their foraging behaviour, body mass or social organisation but reflected their phylogenetic relatedness. The bacterial killing capacity of black-backed jackals, a member of the suborder Caniformia, followed the pattern established for a wide variety of vertebrates. In contrast, the five representatives of the suborder Feliformia demonstrated a killing capacity at least an order of magnitude higher than any species reported previously, with a particularly high capacity in caracals and cheetahs. Our results suggest that the immunocompetence of threatened felids such as the cheetah has been underestimated and its assessment ought to consider both innate and adaptive components of the immune system. PMID:27044323

  8. Humoral and Cellular Immune Response in Canine Hypothyroidism.

    PubMed

    Miller, J; Popiel, J; Chełmońska-Soyta, A

    2015-07-01

    Hypothyroidism is one of the most common endocrine diseases in dogs and is generally considered to be autoimmune in nature. In human hypothyroidism, the thyroid gland is destroyed by both cellular (i.e. autoreactive helper and cytotoxic T lymphocytes) and humoral (i.e. autoantibodies specific for thyroglobulin, thyroxine and triiodothyronine) effector mechanisms. Other suggested factors include impaired peripheral immune suppression (i.e. the malfunction of regulatory T cells) or an additional pro-inflammatory effect of T helper 17 lymphocytes. The aim of this study was to evaluate immunological changes in canine hypothyroidism. Twenty-eight clinically healthy dogs, 25 hypothyroid dogs without thyroglobulin antibodies and eight hypothyroid dogs with these autoantibodies were enrolled into the study. There were alterations in serum proteins in hypothyroid dogs compared with healthy controls (i.e. raised concentrations of α-globulins, β2- and γ-globulins) as well as higher concentration of acute phase proteins and circulating immune complexes. Hypothyroid animals had a lower CD4:CD8 ratio in peripheral blood compared with control dogs and diseased dogs also had higher expression of interferon γ (gene and protein expression) and CD28 (gene expression). Similar findings were found in both groups of hypothyroid dogs. Canine hypothyroidism is therefore characterized by systemic inflammation with dominance of a cellular immune response. PMID:25958183

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

    PubMed

    Delvaeye, Mieke; Conway, Edward M

    2009-09-17

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

  10. Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

    PubMed Central

    Davis, Elysia Poggi; Pfaff, Donald

    2014-01-01

    During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

  11. Gelam Honey Scavenges Peroxynitrite During the Immune Response

    PubMed Central

    Kassim, Mustafa; Mansor, Marzida; Suhaimi, Anwar; Ong, Gracie; Yusoff, Kamaruddin Mohd

    2012-01-01

    Monocytes and macrophages are part of the first-line defense against bacterial, fungal, and viral infections during host immune responses; they express high levels of proinflammatory cytokines and cytotoxic molecules, including nitric oxide, reactive oxygen species, and their reaction product peroxynitrite. Peroxynitrite is a short-lived oxidant and a potent inducer of cell death. Honey, in addition to its well-known sweetening properties, is a natural antioxidant that has been used since ancient times in traditional medicine. We examined the ability of Gelam honey, derived from the Gelam tree (Melaleuca spp.), to scavenge peroxynitrite during immune responses mounted in the murine macrophage cell line RAW 264.7 when stimulated with lipopolysaccharide/interferon-γ (LPS/IFN-γ) and in LPS-treated rats. Gelam honey significantly improved the viability of LPS/IFN-γ-treated RAW 264.7 cells and inhibited nitric oxide production—similar to the effects observed with an inhibitor of inducible nitric oxide synthase (1400W). Furthermore, honey, but not 1400W, inhibited peroxynitrite production from the synthetic substrate 3-morpholinosydnonimine (SIN-1) and prevented the peroxynitrite-mediated conversion of dihydrorhodamine 123 to its fluorescent oxidation product rhodamine 123. Honey inhibited peroxynitrite synthesis in LPS-treated rats. Thus, honey may attenuate inflammatory responses that lead to cell damage and death, suggesting its therapeutic uses for several inflammatory disorders. PMID:23109904

  12. Innate immune inflammatory response in the acutely ischemic myocardium.

    PubMed

    Deftereos, Spyridon; Angelidis, Christos; Bouras, Georgios; Raisakis, Konstantinos; Gerckens, Ulrich; Cleman, Michael W; Giannopoulos, Georgios

    2014-01-01

    The "holy grail" of modern interventional cardiology is the salvage of viable myocardial tissue in the distribution of an acutely occluded coronary artery. Thrombolysis and percutaneous coronary interventions, provided they can be delivered on time, can interrupt the occlusion and save tissue. At the same time restoring the patency of the coronary vessels and providing the ischemic myocardium with blood can cause additional tissue damage. A key element of ischemic and reperfusion injury and major determinant of the evolution of damage in the injured myocardium is the inflammatory response. The innate immune system initiates and directs this response which is a prerequisite for subsequent healing. The complement cascade is set in motion following the release of subcellular membrane constituents. Endogenous 'danger' signals known as danger-associated molecular patterns (DAMPs) released from ischemic and dying cells alert the innate immune system and activate several signal transduction pathways through interactions with the highly conserved Toll like receptors (TLRs). Reactive oxygen species (ROS) generation directly induces pro-inflammatory cascades and triggers formation of the inflammasome. The challenge lies into designing strategies that specifically block the inflammatory cascades responsible for tissue damage without affecting those concerned with tissue healing. PMID:25102201

  13. Uncontrolled immune response in acute myocardial infarction: unraveling the thread.

    PubMed

    Bodi, Vicente; Sanchis, Juan; Nunez, Julio; Mainar, Luis; Minana, Gema; Benet, Isabel; Solano, Carlos; Chorro, Francisco J; Llacer, Angel

    2008-12-01

    Recently, the theory that hyperinflammation is the body's primary response to potent stimulus has been challenged. Indeed, a deregulation of the immune system could be the cause of multiple organ failure. So far, clinicians have focused on the last steps of the inflammatory cascade. However, little attention has been paid to lymphocytes, which play an important role as strategists of the inflammatory response. Experimental evidence suggests a crucial role of T lymphocytes in the pathophysiology of atherosclerosis and acute myocardial infarction (AMI). In summary, from the bottom of an imaginary inverted pyramid, a few regulatory T-cells control the upper parts represented by the wide spectrum of the inflammatory cascade. In AMI, a loss of regulation of the inflammatory system occurs in patients with a decreased activity of regulatory T-cells. As a consequence, aggressive T-cells boost and anti-inflammatory T-cells drop. A pleiotropic proinflammatory imbalance with damaging effects in terms of left ventricular performance and patient outcome is the result of this uncontrolled immune response. It is needed to unravel the thread of the inflammatory cells to better understand the pathophysiology as well as to open innovative therapeutic options in AMI. PMID:19033000

  14. Immunological aspects of the immune response induced by mosquito allergens.

    PubMed

    Cantillo, José Fernando; Fernández-Caldas, Enrique; Puerta, Leonardo

    2014-01-01

    Allergies caused by mosquito bites may produce local or systemic reactions. The inhalation of mosquito allergens may also cause asthma and/or allergic rhinoconjunctivitis in sensitized individuals. The mechanisms implicated in the development of these immune responses involve IgE antibodies, different subtypes of IgG and proinflammatory cytokines as well as basophils, eosinophils and mast cells. Several allergenic components have been identified in the saliva and bodies of mosquitoes and some of these are present in different mosquito species. The most common species implicated in allergic reactions belong to the genera Aedes, Culex and Anopheles. Several Aedes aegypti allergens have been cloned and sequenced. The recombinant molecules show IgE reactivity similar to that of the native allergens, making them good candidates for the diagnosis of mosquito allergies. Allergen-specific immunotherapy with mosquito extracts induces a protective response characterized by a decreased production of IgE antibodies, increased IgG levels, a reduction in the severity of cutaneous and respiratory symptoms and the need for medication. The aims of this review are to summarize the progress made in the characterization of mosquito allergens and discuss the types of immune responses induced by mosquito bites and the inhalation of mosquito allergens in atopic individuals. PMID:25661054

  15. Immune response triggered by Brucella abortus following infection or vaccination.

    PubMed

    Dorneles, Elaine M S; Teixeira-Carvalho, Andréa; Araújo, Márcio S S; Sriranganathan, Nammalwar; Lage, Andrey P

    2015-07-17

    Brucella abortus live vaccines have been used successfully to control bovine brucellosis worldwide for decades. However, due to some limitations of these live vaccines, efforts are being made for the development of new safer and more effective vaccines that could also be used in other susceptible species. In this context, understanding the protective immune responses triggered by B. abortus is critical for the development of new vaccines. Such understandings will enhance our knowledge of the host/pathogen interactions and enable to develop methods to evaluate potential vaccines and innovative treatments for animals or humans. At present, almost all the knowledge regarding B. abortus specific immunological responses comes from studies in mice. Active participation of macrophages, dendritic cells, IFN-γ producing CD4(+) T-cells and cytotoxic CD8(+) T-cells are vital to overcome the infection. In this review, we discuss the characteristics of the immune responses triggered by vaccination versus infection by B. abortus, in different hosts. PMID:26048781

  16. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization

    NASA Astrophysics Data System (ADS)

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J. P.; Kendall, Mark Anthony Fernance

    2016-06-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30–90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm2 to flat-shaped protrusions at 8,000 per cm2, whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination.

  17. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization.

    PubMed

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J P; Kendall, Mark Anthony Fernance

    2016-01-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30-90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm(2) to flat-shaped protrusions at 8,000 per cm(2), whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination. PMID:27251567

  18. The changing shape of vaccination: improving immune responses through geometrical variations of a microdevice for immunization

    PubMed Central

    Crichton, Michael Lawrence; Muller, David Alexander; Depelsenaire, Alexandra Christina Isobel; Pearson, Frances Elizabeth; Wei, Jonathan; Coffey, Jacob; Zhang, Jin; Fernando, Germain J. P.; Kendall, Mark Anthony Fernance

    2016-01-01

    Micro-device use for vaccination has grown in the past decade, with the promise of ease-of-use, painless application, stable solid formulations and greater immune response generation. However, the designs of the highly immunogenic devices (e.g. the gene gun, Nanopatch or laser adjuvantation) require significant energy to enter the skin (30–90 mJ). Within this study, we explore a way to more effectively use energy for skin penetration and vaccination. These modifications change the Nanopatch projections from cylindrical/conical shapes with a density of 20,000 per cm2 to flat-shaped protrusions at 8,000 per cm2, whilst maintaining the surface area and volume that is placed within the skin. We show that this design results in more efficient surface crack initiations, allowing the energy to be more efficiently be deployed through the projections into the skin, with a significant overall increase in penetration depth (50%). Furthermore, we measured a significant increase in localized skin cell death (>2 fold), and resultant infiltrate of cells (monocytes and neutrophils). Using a commercial seasonal trivalent human influenza vaccine (Fluvax 2014), our new patch design resulted in an immune response equivalent to intramuscular injection with approximately 1000 fold less dose, while also being a practical device conceptually suited to widespread vaccination. PMID:27251567

  19. The implicated and the immune: cultural responses to AIDS.

    PubMed

    Goldstein, R

    1990-01-01

    Unlike previous epidemics in American history, AIDS has spawned a host of creative works in the arts and mass media. Representations in the fine arts have emphasized perspectives of the insider or the "implicated," i.e., people with AIDS, while commercial programs and performers in popular culture have adopted the vantage point of the "immune," viewing AIDS as emblematic of a stigmatized "other." These cultural responses embody tensions between contemporary and traditional approaches to social life. Some television and commercial films are beginning to portray AIDS from the "implicated" perspective, however; this tentative change suggests that the epidemic is becoming more broadly experienced in the United States. PMID:2381387

  20. The effect of selenium supplementation on vaccination response and immune function in adult horses.

    PubMed

    Brummer, M; Hayes, S; Adams, A A; Horohov, D W; Dawson, K A; Lawrence, L M

    2013-08-01

    AS, SP, and SS (P < 0.05). Whole blood mRNA expression of IL-10 was greater for SS compared with LS, AS, and SP (P = 0.043). Although the OVA and influenza vaccination responses were unaffected by Se status, other measures of immune function did indicate that low Se status could adversely affect cell-mediated immunity. PMID:23658361

  1. Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

    PubMed Central

    Wu, Tianxia; Zhang, Nannan; Kosa, Peter; Komori, Mika; Blake, Andrew; Browne, Sarah K.; Rosen, Lindsey B.; Hagen, Ferry; Meis, Jacques; Levitz, Stuart M.; Quezado, Martha; Hammoud, Dima; Bennett, John E.; Bielekova, Bibi; Williamson, Peter R.

    2015-01-01

    The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-γ as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell

  2. Immune response to 60-day head-down bed rest

    NASA Astrophysics Data System (ADS)

    Song, Jinping; Guo, Aihua; Zhong, Ping; Zhang, Hongyu; Wu, Feng; Wan, Yumin; Bai, Yanqiang; Chen, Shanguang; Li, Yinghui

    Introduction: Exposure of humans to spaceflight has resulted in disregulation of the immune system. Head-down bed rest (HDBR) has been extensively used as an earth-bound analog to study physiologic effects mimicking those occurring in weightlessness during spaceflight. It is uncertain how a prolonged period of bed rest affect human immune responses. The objective of this study was to investigate the effects of 60-day HDBR on immune function and EB virus reactivation in seven male volunteers. Methods: There were seven healthy male volunteers who were subjected to HDBR for 60d. Immunological parameters including leukocyte subset distribution, lymphocyte proliferation to mitogens, secreted cytokine profiles and EB virus reactivation were monitored. Results: Total WBC conunts increased significantly 10d post-HDBR as compared with pre-HDBR. At the same time, the relative percentage of neutrophils was also higher than pre-HDBR but not significant. MFI of CD11b in neutrophils was reduced obviously at thd end of HDBR. T Lymphocyte proliferations to PHA reduced at HDBR 30, HDBR 60 and 10d post-HDBR while IL-2 production decreased significantly at the same time. IFN-and IL-4 production trended to decrease at HDBR 30 and HDBR 60. The relative percentage of T lymphocyte subset, B lymphocyte and NK cells were not altered. EBV EA (early antigen) were negative and EBV VCA titers had no changes through HDBR. Conclusion: The results indicate that several immunological parameters (mainly cellular immunity) are altered significantly by prolonged HDBR, and these changes were similar to those happened in spaceflight.

  3. Teriflunomide effect on immune response to influenza vaccine in patients with multiple sclerosis

    PubMed Central

    Freedman, Mark S.; Kremenchutzky, Marcelo; Menguy-Vacheron, Françoise; Bauer, Deborah; Jodl, Stefan; Truffinet, Philippe; Benamor, Myriam; Chambers, Scott; O’Connor, Paul W.

    2013-01-01

    Objective: To investigate the effect of teriflunomide on the efficacy and safety of seasonal influenza vaccine. Methods: The 2011/2012 seasonal influenza vaccine (containing H1N1, H3N2, and B strains) was administered to patients with relapsing forms of multiple sclerosis (RMS) treated for ≥6 months with teriflunomide 7 mg (n = 41) or 14 mg (n = 41), or interferon-β-1 (IFN-β-1; n = 46). The primary endpoint was the proportion of patients with influenza strain–specific antibody titers ≥40, 28 days postvaccination. Results: More than 90% of patients achieved postvaccination antibody titers ≥40 for H1N1 and B in all groups. For H3N2, titers ≥40 were achieved in ≥90% of patients in the 7 mg and IFN-β-1 groups, and in 77% of the 14-mg group, respectively. A high proportion of patients already had detectable antibodies for each influenza strain at baseline. Geometric mean titer ratios (post/prevaccination) were ≥2.5 for all groups and strains, except for H1N1 in the 14-mg group (2.3). The proportion of patients with a prevaccination titer <40 achieving seroprotection was ≥61% across the 3 treatment groups and 3 influenza strains. However, fewer patients in the 14-mg than the 7-mg or IFN-β-1 groups exhibited seroprotection to H3N2 (61% vs 78% and 82%, respectively). Conclusion: Teriflunomide-treated patients generally mounted effective immune responses to seasonal influenza vaccination, consistent with preservation of protective immune responses. Classification of evidence: This study provides Class II evidence that teriflunomide generally does not adversely impact the ability of patients with RMS to mount immune responses to influenza vaccination. PMID:23851964

  4. Regulation of Heliothis virescens Innate Immune Responses to the Endoparasitoid Campoletis sonorensis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insect immune responses play important roles in host defense against pathogens and parasitoids. In this study, we propose that the regulation of host immune responses may determine the successful parasitization of Campoletis sonorensis in the host. To investigate the regulation of innate immune resp...

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  7. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease

    PubMed Central

    Carrillo, Eugenia; Martorell, Susanna; Todolí, Felicitat; Martínez-Flórez, Alba; Urniza, Alicia; Moreno, Javier

    2016-01-01

    Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease. PMID:27171409

  8. Compartmentalized Immune Response in Leishmaniasis: Changing Patterns throughout the Disease.

    PubMed

    Rodríguez-Cortés, Alhelí; Carrillo, Eugenia; Martorell, Susanna; Todolí, Felicitat; Ojeda, Ana; Martínez-Flórez, Alba; Urniza, Alicia; Moreno, Javier; Alberola, Jordi

    2016-01-01

    Visceral leishmaniasis (VL) is characterized by loss of T-cell responsiveness and absence of Leishmania-specific IFN-γ production by peripheral blood mononuclear cells. However, the expressions of IFN-γ and TNF-α are up-regulated in the tissues and plasma of VL patients. There is a paucity of information regarding the cytokine profile expressed by different target tissues in the same individual and the changes it undergoes throughout the course of infection. In this work we evaluated IFN-γ, TNF-α, IL-10, and TGF-β mRNA expression using real-time RT-PCR in 5 target tissues at 6 months and 16 months post-infection (PI) in a canine experimental model which mimics many aspects of human VL. The spleen and liver of Leishmania infantum experimentally-infected dogs elicited a pro- and anti- inflammatory response and high parasite density at 6 and 16 months PI. The popliteal lymph node, however, showed an up-regulation of IFN-γ cytokin at commencement of the study and was at the chronic phase when the IL-10 and TGF-β expression appeared. In spite of skin parasite invasion, local cytokine response was absent at 6 months PI. Parasite growth and onset of clinical disease both correlated with dermal up-regulation of all the studied cytokines. Our VL model suggests that central target organs, such as the spleen and liver, present a mixed cytokine immune response early on infection. In contrast, an anti-inflammatory/regulatory immune response in peripheral tissues is activated in the later chronic-patent stages of the disease. PMID:27171409

  9. Factors influencing adverse skin responses in rats receiving repeated subcutaneous injections and potential impact on neurobehavior

    PubMed Central

    Levoe, S. Nikki; Flannery, Brenna M.; Brignolo, Laurie; Imai, Denise M.; Koehne, Amanda; Austin, Adam T.; Bruun, Donald A.; Tancredi, Daniel J.; Lein, Pamela J.

    2015-01-01

    Repeated subcutaneous (s.c.) injection is a common route of administration in chronic studies of neuroactive compounds. However, in a pilot study we noted a significant incidence of skin abnormalities in adult male Long-Evans rats receiving daily s.c. injections of peanut oil (1.0 ml/kg) in the subscapular region for 21 d. Histopathological analyses of the lesions were consistent with a foreign body reaction. Subsequent studies were conducted to determine factors that influenced the incidence or severity of skin abnormalities, and whether these adverse skin reactions influenced a specific neurobehavioral outcome. Rats injected daily for 21 d with food grade peanut oil had an earlier onset and greater incidence of skin abnormalities relative to rats receiving an equal volume (1.0 ml/kg/d) of reagent grade peanut oil or triglyceride of coconut oil. Skin abnormalities in animals injected daily with peanut oil were increased in animals housed on corncob versus paper bedding. Comparison of animals obtained from different barrier facilities exposed to the same injection paradigm (reagent grade peanut oil, 1.0 ml/kg/d s.c.) revealed significant differences in the severity of skin abnormalities. However, animals from different barrier facilities did not perform differently in a Pavlovian fear conditioning task. Collectively, these data suggest that environmental factors influence the incidence and severity of skin abnormalities following repeated s.c. injections, but that these adverse skin responses do not significantly influence performance in at least one test of learning and memory. PMID:25705100

  10. Modified cellular immune responses in dogs infected with Echinococcus multilocularis.

    PubMed

    Kato, Naoko; Nonaka, Nariaki; Oku, Yuzaburo; Kamiya, Masao

    2005-03-01

    Parasite-specific antigen responses and lymphocyte blastogenesis in dogs orally inoculated with Echinococcus multilocuralis metacestodes were examined. Serum IgG1 (Th2-oriented) and IgG2 (Th 1-oriented) levels against somatic and excretory-secretory (ES) antigens of protoscoleces and adult worms increased from 7 days post-infection (DPI), with the highest responses against protoscolex excretory-secretory antigen (PES). Specific blastogenesis of peripheral blood mononuclear cells (PBMC) against the parasite antigens was not observed during the 21-day infection period, but Peyer's patches cells from one out of two dogs at 21 DPI showed blastogenesis against PES (stimulation index: 4.65). Interestingly, only at 7 DPI were concanavalin A (ConA)-induce proliferative responses of PBMC reduced. Moreover, ConA-induced proliferative responses of lymphocytes from various origins were suppressed by the addition of parasite antigens, especially with PES. These data suggest that although both Th1- and Th2-oriented humoral immune responses were observed in E. multilocularis infected dogs, the parasite antigens, especially PES, may have incompletely suppressed lymphocyte responses in these dogs. PMID:15719262

  11. The responses of immune cells to iron oxide nanoparticles.

    PubMed

    Xu, Yaolin; Sherwood, Jennifer A; Lackey, Kimberly H; Qin, Ying; Bao, Yuping

    2016-04-01

    Immune cells play an important role in recognizing and removing foreign objects, such as nanoparticles. Among various parameters, surface coatings of nanoparticles are the first contact with biological system, which critically affect nanoparticle interactions. Here, surface coating effects on nanoparticle cellular uptake, toxicity and ability to trigger immune response were evaluated on a human monocyte cell line using iron oxide nanoparticles. The cells were treated with nanoparticles of three types of coatings (negatively charged polyacrylic acid, positively charged polyethylenimine and neutral polyethylene glycol). The cells were treated at various nanoparticle concentrations (5, 10, 20, 30, 50 μg ml(-1) or 2, 4, 8, 12, 20 μg cm(-2)) with 6 h incubation or treated at a nanoparticle concentration of 50 μg ml(-1) (20 μg cm(-2)) at different incubation times (6, 12, 24, 48 or 72 h). Cell viability over 80% was observed for all nanoparticle treatment experiments, regardless of surface coatings, nanoparticle concentrations and incubation times. The much lower cell viability for cells treated with free ligands (e.g. ~10% for polyethylenimine) suggested that the surface coatings were tightly attached to the nanoparticle surfaces. The immune responses of cells to nanoparticles were evaluated by quantifying the expression of toll-like receptor 2 and tumor necrosis factor-α. The expression of tumor necrosis factor-α and toll-like receptor 2 were not significant in any case of the surface coatings, nanoparticle concentrations and incubation times. These results provide useful information to select nanoparticle surface coatings for biological and biomedical applications. PMID:26817529

  12. Modulation of cellular immune response against hepatitis C virus nonstructural protein 3 by cationic liposome encapsulated DNA immunization.

    PubMed

    Jiao, Xuanmao; Wang, Richard Y-H; Feng, Zhiming; Alter, Harvey J; Shih, James Wai-Kuo

    2003-02-01

    A vaccine strategy directed to increase Th1 cellular immune responses, particularly to hepatitis C virus (HCV) nonstructural protein 3 (NS3), has considerable potential to overcome the infection with HCV. DNA vaccination can induce both humoral and cellular immune responses, but it became apparent that the cellular uptake of naked DNA injected into muscle was not very efficient, as much of the DNA is degraded by interstitial nucleases before it reaches the nucleus for transcription. In this paper, cationic liposomes composed of different cationic lipids, such as dimethyl-dioctadecylammonium bromide (DDAB), 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), or 1,2-dioleoyl-sn-glycerol-3-ethylphosphocholine (DOEPC), were used to improve DNA immunization in mice, and their efficiencies were compared. It was found that cationic liposome-mediated DNA immunization induced stronger HCV NS3-specific immune responses than immunization with naked DNA alone. Cationic liposomes composed of DDAB and equimolar of a neutral lipid, egg yolk phosphatidylcholine (EPC), induced the strongest antigen-specific Th1 type immune responses among the cationic liposome investigated, whereas the liposomes composed of 2 cationic lipids, DDAB and DOEPC, induced an antigen-specific Th2 type immune response. All cationic liposomes used in this study triggered high-level, nonspecific IL-12 production in mice, a feature important for the development of maximum Th1 immune responses. In conclusion, the cationic liposome-mediated gene delivery is a viable HCV vaccine strategy that should be further tested in the chimpanzee model. PMID:12540796

  13. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors.

    PubMed

    Metcalf, Talibah U; Cubas, Rafael A; Ghneim, Khader; Cartwright, Michael J; Grevenynghe, Julien Van; Richner, Justin M; Olagnier, David P; Wilkinson, Peter A; Cameron, Mark J; Park, Byung S; Hiscott, John B; Diamond, Michael S; Wertheimer, Anne M; Nikolich-Zugich, Janko; Haddad, Elias K

    2015-06-01

    Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections. PMID:25728020

  14. Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors

    PubMed Central

    Metcalf, Talibah U; Cubas, Rafael A; Ghneim, Khader; Cartwright, Michael J; Grevenynghe, Julien Van; Richner, Justin M; Olagnier, David P; Wilkinson, Peter A; Cameron, Mark J; Park, Byung S; Hiscott, John B; Diamond, Michael S; Wertheimer, Anne M; Nikolich-Zugich, Janko; Haddad, Elias K

    2015-01-01

    Aging leads to dysregulation of multiple components of the immune system that results in increased susceptibility to infections and poor response to vaccines in the aging population. The dysfunctions of adaptive B and T cells are well documented, but the effect of aging on innate immunity remains incompletely understood. Using a heterogeneous population of peripheral blood mononuclear cells (PBMCs), we first undertook transcriptional profiling and found that PBMCs isolated from old individuals (≥ 65 years) exhibited a delayed and altered response to stimulation with TLR4, TLR7/8, and RIG-I agonists compared to cells obtained from adults (≤ 40 years). This delayed response to innate immune agonists resulted in the reduced production of pro-inflammatory and antiviral cytokines and chemokines including TNFα, IL-6, IL-1β, IFNα, IFNγ, CCL2, and CCL7. While the major monocyte and dendritic cell subsets did not change numerically with aging, activation of specific cell types was altered. PBMCs from old subjects also had a lower frequency of CD40+ monocytes, impaired up-regulation of PD-L1 on monocytes and T cells, and increased expression of PD-L2 and B7-H4 on B cells. The defective immune response to innate agonists adversely affected adaptive immunity as TLR-stimulated PBMCs (minus CD3 T cells) from old subjects elicited significantly lower levels of adult T-cell proliferation than those from adult subjects in an allogeneic mixed lymphocyte reaction (MLR). Collectively, these age-associated changes in cytokine, chemokine and interferon production, as well as co-stimulatory protein expression could contribute to the blunted memory B- and T-cell immune responses to vaccines and infections. PMID:25728020

  15. Bullous pemphigoid, an autoantibody-mediated disease, is a novel immune-related adverse event in patients treated with anti-programmed cell death 1 antibodies.

    PubMed

    Hwang, Shelley J E; Carlos, Giuliana; Chou, Shaun; Wakade, Deepal; Carlino, Matteo S; Fernandez-Penas, Pablo

    2016-08-01

    Anti-programmed cell death 1 (anti-PD1) antibodies such as pembrolizumab have shown improved progression-free and overall survival in patients with advanced melanoma. Of 124 patients reviewed in Westmead Hospital from May 2012 to November 2015, treated with pembrolizumab for advanced melanoma, we encountered three cases of bullous pemphigoid (BP). We have previously reported a case of BP. In two recent cases, BP was diagnosed early and treated promptly with potent topical or oral steroid. Patients on anti-PD1 antibodies are at a higher risk of developing cutaneous immune-related adverse events such as lichenoid reactions, eczema and vitiligo. No cases of BP were encountered in the previously published cohort of 260 melanoma patients treated with BRAF inhibitors; as such, it appears that BP is associated with anti-PD1 treatment rather than metastatic melanoma. BP appears to be another immune-related adverse event, and clinicians should have a low threshold for performing cutaneous biopsies and immunofluorescence studies in patients on anti-PD1 therapies. PMID:27031539

  16. Innate Immune Responses in House Dust Mite Allergy

    PubMed Central

    Jacquet, Alain

    2013-01-01

    Sensitizations to house dust mites (HDM) trigger strong exacerbated allergen-induced inflammation of the skin and airways mucosa from atopic subjects resulting in atopic dermatitis as well as allergic rhinitis and asthma. Initially, the Th2-biased HDM allergic response was considered to be mediated only by allergen B- and T-cell epitopes to promote allergen-specific IgE production as well as IL-4, IL-5, and IL-13 to recruit inflammatory cells. But this general molecular model of HDM allergenicity must be revisited as a growing literature suggests that stimulations of innate immune activation pathways by HDM allergens offer new answers to the following question: what makes an HDM allergen an allergen? Indeed, HDM is a carrier not only for allergenic proteins but also microbial adjuvant compounds, both of which are able to stimulate innate signaling pathways leading to allergy. This paper will describe the multiple ways used by HDM allergens together with microbial compounds to control the initiation of the allergic response through engagement of innate immunity. PMID:23724247

  17. Autophagy suppresses host adaptive immune responses toward Borrelia burgdorferi.

    PubMed

    Buffen, Kathrin; Oosting, Marije; Li, Yang; Kanneganti, Thirumala-Devi; Netea, Mihai G; Joosten, Leo A B

    2016-09-01

    We have previously demonstrated that inhibition of autophagy increased the Borrelia burgdorferi induced innate cytokine production in vitro, but little is known regarding the effect of autophagy on in vivo models of Borrelia infection. Here, we showed that ATG7-deficient mice that were intra-articular injected with Borrelia spirochetes displayed increased joint swelling, cell influx, and enhanced interleukin-1β and interleukin-6 production by inflamed synovial tissue. Because both interleukin-1β and interleukin-6 are linked to the development of adaptive immune responses, we examine the function of autophagy on Borrelia induced adaptive immunity. Human peripheral blood mononuclear cells treated with autophagy inhibitors showed an increase in interleukin-17, interleukin-22, and interferon-γ production in response to exposure to Borrelia burgdorferi. Increased IL-17 production was dependent on IL-1β release but, interestingly, not on interleukin-23 production. In addition, cytokine quantitative trait loci in ATG9B modulate the Borrelia induced interleukin-17 production. Because high levels of IL-17 have been found in patients with confirmed, severe, chronic borreliosis, we propose that the modulation of autophagy may be a potential target for anti-inflammatory therapy in patients with persistent Lyme disease. PMID:27101991

  18. 7 alpha-hydroxy-dehydroepiandrosterone and immune response.

    PubMed

    Morfin, R; Lafaye, P; Cotillon, A C; Nato, F; Chmielewski, V; Pompon, D

    2000-01-01

    In human and murine lymphoid organs, circulating 3 beta-hydroxysteroids, including pregnenolone (PREG), dehydroepiandrosterone (DHEA), and epiandrosterone (EPIA), are 7 alpha-hydroxylated by a cytochrome P450 identified in the hippocampus as P4507B1. Mouse and human lymphoid organs produced different patterns of 3 beta-hydroxysteroid 7 alpha-hydroxylation with the absence of pregnenolone and epiandrosterone hydroxylation in human and mouse, respectively. Both 7 alpha-hydroxy-DHEA and 7 alpha-hydroxy-EPIA triggered a significant increase of antitetanus toxoid and anti-Bordetella pertussis toxins IgGs production in cultures of activated B + T cells derived from human tonsils, whereas both 7 alpha-hydroxy-PREG and 7 alpha-hydroxy-DHEA increased the immune response in mouse. Paracrine action of 7 alpha-hydroxysteroids resulted from their production in cells of the lymphoid organs. Comparison of P4507B1 sequences in rat, human, and two mouse species showed that one amino acid change might explain important differences in KM for 7 alpha-hydroxylation, and suggested that such differences might contribute to the extent of immune response. PMID:11268429

  19. Photodynamic therapy induces an immune response against a bacterial pathogen

    PubMed Central

    Huang, Ying-Ying; Tanaka, Masamitsu; Vecchio, Daniela; Garcia-Diaz, Maria; Chang, Julie; Morimoto, Yuji; Hamblin, Michael R

    2012-01-01

    Photodynamic therapy (PDT) employs the triple combination of photosensitizers, visible light and ambient oxygen. When PDT is used for cancer, it has been observed that both arms of the host immune system (innate and adaptive) are activated. When PDT is used for infectious disease, however, it has been assumed that the direct antimicrobial PDT effect dominates. Murine arthritis caused by methicillin-resistant Staphylococcus aureus in the knee failed to respond to PDT with intravenously injected Photofrin®. PDT with intra-articular Photofrin produced a biphasic dose response that killed bacteria without destroying host neutrophils. Methylene blue was the optimum photosensitizer to kill bacteria while preserving neutrophils. We used bioluminescence imaging to noninvasively monitor murine bacterial arthritis and found that PDT with intra-articular methylene blue was not only effective, but when used before infection, could protect the mice against a subsequent bacterial challenge. The data emphasize the importance of considering the host immune response in PDT for infectious disease. PMID:22882222

  20. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity

    PubMed Central

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  1. Innate and Adaptive Immune Response to Fungal Products and Allergens.

    PubMed

    Williams, P Brock; Barnes, Charles S; Portnoy, Jay M

    2016-01-01

    Exposure to fungi and their products is practically ubiquitous, yet most of this is of little consequence to most healthy individuals. This is because there are a number of elaborate mechanisms to deal with these exposures. Most of these mechanisms are designed to recognize and neutralize such exposures. However, in understanding these mechanisms it has become clear that many of them overlap with our ability to respond to disruptions in tissue function caused by trauma or deterioration. These responses involve the innate and adaptive immune systems usually through the activation of nuclear factor kappa B and the production of cytokines that are considered inflammatory accompanied by other factors that can moderate these reactivities. Depending on different genetic backgrounds and the extent of activation of these mechanisms, various pathologies with resulting symptoms can ensue. Complicating this is the fact that these mechanisms can bias toward type 2 innate and adaptive immune responses. Thus, to understand what we refer to as allergens from fungal sources, we must first understand how they influence these innate mechanisms. In doing so it has become clear that many of the proteins that are described as fungal allergens are essentially homologues of our own proteins that signal or cause tissue disruptions. PMID:26755096

  2. The immune response in cattle infected with Tritrichomonas foetus.

    PubMed

    Soto, P; Parma, A E

    1989-10-01

    Holando-Argentina calves (males and females) were experimentally infected with Tritrichomonas foetus var. Belfast (T. foetus) by introducing 10(7) protozoa into the preputial and vaginal cavities, in order to analyse the course of the immune response to infection. Samples of serum, vaginal mucus and preputial secretion were taken periodically and assayed by means of microagglutination of living protozoa. The serum antibody titre, which averaged 32 before infection and was equivalent to titres in a non-infected group, increased to 512 in the heifers 11 weeks later and to 128 in the bulls 4 months post-infection. Agglutinating antibodies were not detected in the preputial cavity, but heifers showed antibodies in the vaginal mucus and became trichomoniasis free after 4 months. Conversely, genital secretions from the bulls gave rise to positive cultures during the whole period of experimentation. The intradermal sensitivity was checked using a soluble antigen from T. foetus. The diameter of the papula increased up to three times in heifers, while in bulls the results were no different than those from the non-infected group. Serum antibodies were of the IgG2 subclass, while those isolated from vaginal mucus were characterized as IgG1, an opsonizing antibody. Heifers were refractory to challenge infection after 1 year. The poor immune response in bulls is consistent with their role as carriers of T. foetus. PMID:2683348

  3. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity.

    PubMed

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin; Henriques-Normark, Birgitta; Olliver, Marie

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  4. Antitumor immune responses induced by photodynamic immunotherapy in rats

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Robinson, Karen E.; Adams, Robert L.; Singhal, Anil K.; Nordquist, Robert E.

    1998-05-01

    A new laser immunotherapy was used to treat metastatic mammary rat tumors. This new modality consists of three components: a near-infrared diode laser, a photosensitizer, and an immunoadjuvant. The sensitizer-adjuvant solution was injected directly to the tumor, followed by a non-invasive laser application. The new method resulted in total eradication of the treated primary tumors and eradication of untreated metastases at remote sites. Observed was the long-term survival of treated tumor-bearing rats: up to 120 days after tumor inoculation, a 300% increase in survival length compared with untreated control tumor-bearing rats. In addition, the successfully treated rats were refractory to tumor rechallenge with 10 times of the original tumor dose. Fluorescein and peroxidase immunochemical assays were also performed using sera from cured rats as the primary antibody. Strong antibody binding to both live and preserved tumor cells was observed. Western blot analysis, using the cured rat serum as primary antibody also showed distinctive protein binding, suggesting the induction of tumor-specific humoral immune response. These results indicated that an immune response was induced by the treatment of laser, photosensitizer and immunoadjuvant.

  5. Polyphasic innate immune responses to acute and chronic LCMV infection

    PubMed Central

    Norris, Brian A.; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A.; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Summary Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after infection, there was an increase in Ly6Chi monocytic and Gr-1hi neutrophilic cells in lymphoid organs and blood. This expansion in cell numbers was enhanced and sustained in C13 infection, whereas it occurred only transiently with ARM infection. These cells resembled myeloid-derived suppressor cells, and potently suppressed T cell proliferation. The reduction of monocytic cells in Ccr2−/− mice or after Gr-1 antibody depletion enhanced anti-viral T cell function. Thus, innate cells have an important immunomodulatory role throughout chronic infection. PMID:23438822

  6. The Immune System Strikes Back: Cellular Immune Responses against Indoleamine 2,3-dioxygenase

    PubMed Central

    Sørensen, Rikke Bæk; Berge-Hansen, Linda; Junker, Niels; Hansen, Christina Aaen; Hadrup, Sine Reker; Schumacher, Ton N. M.; Svane, Inge Marie; Becker, Jürgen C.; Straten, Per thor; Andersen, Mads Hald

    2009-01-01

    Background The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. Methods and Findings The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T lymphocytes (CTL) from the peripheral blood of cancer patients were cloned and expanded. The functional capacity of the established CTL clones was examined by chrome release assays. The study unveiled spontaneous cytotoxic T-cell reactivity against IDO in peripheral blood as well as in the tumor microenvironment of different cancer patients. We demonstrate that these IDO reactive T cells are indeed peptide specific, cytotoxic effector cells. Hence, IDO reactive T cells are able to recognize and kill tumor cells including directly isolated AML blasts as well as IDO-expressing dendritic cells, i.e. one of the major immune suppressive cell populations. Conclusion IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals, IDO-based immunotherapy holds the promise to boost anti-cancer immunotherapy in general. PMID:19738905

  7. Neonate Intestinal Immune Response to CpG Oligodeoxynucleotide Stimulation

    PubMed Central

    Lacroix-Lamandé, Sonia; Rochereau, Nicolas; Mancassola, Roselyne; Barrier, Mathieu; Clauzon, Amandine; Laurent, Fabrice

    2009-01-01

    Background The development of mucosal vaccines is crucial to efficiently control infectious agents for which mucosae are the primary site of entry. Major drawbacks of these protective strategies are the lack of effective mucosal adjuvant. Synthetic oligodeoxynucleotides that contain several unmethylated cytosine-guanine dinucleotide (CpG-ODN) motifs are now recognized as promising adjuvants displaying mucosal adjuvant activity through direct activation of TLR9-expressing cells. However, little is known about the efficacy of these molecules in stimulating the intestinal immune system in neonates. Methodology/Principal Findings First, newborn mice received CpG-ODN orally, and the intestinal cytokine and chemokine response was measured. We observed that oral administration of CpG-ODN induces CXC and CC chemokine responses and a cellular infiltration in the intestine of neonates as detected by immunohistochemistry. We next compared the efficiency of the oral route to intraperitoneal administration in stimulating the intestinal immune responses of both adults and neonates. Neonates were more responsive to TLR9-stimulation than adults whatever the CpG-ODN administration route. Their intestinal epithelial cells (IECs) indirectly responded to TLR9 stimulation and contributed to the CXC chemokine response, whereas other TLR9-bearing cells of the lamina-propria produced CC chemokines and Th1-type cytokines. Moreover, we showed that the intestine of adult exhibited a significantly higher level of IL10 at homeostasis than neonates, which might be responsible for the unresponsiveness to TLR9-stimulation, as confirmed by our findings in IL10-deficient mice. Conclusions/Significance This is the first report that deciphers the role played by CpG-ODN in the intestine of neonates. This work clearly demonstrates that an intraperitoneal administration of CpG-ODN is more efficient in neonates than in adults to stimulate an intestinal chemokine response due to their lower IL-10

  8. [Immune response to sheep erythrocytes fixed in formaldehyde].

    PubMed

    Kostadinov, D

    1978-01-01

    Treatment of sheep erythrocytes with 1.5% of formaldehyde alter their immunogenic properties. On the background of immune response to nonfixed erythrocytes, the performed studies showed the following peculiarities in the reaction of mice to fixed erythrocytes: 1) the primary response of animals, in ected with fixed erythrocytes, was rather weak after its determination by the number of rosette forming cells (RFC), antibody forming cells (AFC) in the spleen and by the of hemagglutinins (HA) in serum; 2) in contrast to the primary response the fixed erythrocytes induced a good secondary response, which was considerably higher/according to the number of RFC and titre of HA/in mice sensibilized by nonfixed erytrocytes in advance than in those presensibilized by fixed cells. Therefore the fixed erythrocytes were weaker inducers of immunologic memory than the nonfixed under equal other conditions. 3) In contrast to the nonfixed the fixed erythrocytes did not induce the formation of large amounts of direct AFC during the secondary response as well even then when the animals were presensibilized by nonfixed form of the antigen. PMID:77759

  9. Immune response in mice and cattle after immunization with a Boophilus microplus DNA vaccine containing bm86 gene.

    PubMed

    Ruiz, Lina María; Orduz, Sergio; López, Elkin D; Guzmán, Fanny; Patarroyo, Manuel E; Armengol, Gemma

    2007-03-15

    Plasmid pBMC2 encoding antigen Bm86 from a Colombian strain of cattle tick Boophilus microplus, was used for DNA-mediated immunization of BALB/c mice, employing doses of 10 and 50microg, delivered by intradermic and intramuscular routes. Anti-Bm86 antibody levels were significantly higher compared to control mice treated with PBS. In the evaluation of immunoglobulin isotypes, significant levels of IgG2a and IgG2b were observed in mice immunized with 50microg of pBMC2. Measurement of interleukine (IL) levels (IL-4, IL-5, IL-12(p40)) and interferon-gamma (IFN-gamma) in the sera of mice immunized with pBMC2 indicated high levels of IL-4 and IL-5, although there were also significant levels of IFN-gamma. Mice immunized with pBMC2 showed antigen-specific stimulation of splenocytes according to the incorporation of bromodeoxyuridine and IFN-gamma secretion. In all trials, mice injected intramuscularly with 50microg of pBMC2 presented the highest immune response. Moreover, cattle immunized with this DNA vaccine showed antibody production significantly different to the negative control. In conclusion, these results suggest the potential of DNA immunization with pBMC2 to induce humoral and cellular immune responses against B. microplus. PMID:17055651

  10. Cell-mediated immune responses to respiratory syncytial virus infection

    PubMed Central

    Geevarghese, Bessey; Weinberg, Adriana

    2014-01-01

    We evaluated the cell-mediated immune (CMI) response to RSV acute infection including the magnitude, kinetics and correlates with morbidity and age. Twenty-nine RSV-infected patients with mean ± SD age of 15 ± 14 months were enrolled during their first week of disease. Th1, Th2, Th9, Th17 and Th22 responses were measured at entry and 2 and 6 weeks later. All subjects were hospitalized for a median (range) of 5 (3–11) days. RSV-specific effector and memory Th1 CMI measured by lymphocyte proliferation and IFNγ ELISPOT significantly increased over time (P ≤ 0.03). In contrast, Th22 responses decreased over time (P ≤ 0.03). Other changes did not reach statistical significance. The severity of RSV disease measured by the length of hospitalization positively correlated with the magnitude of Th9, Th22 and TNFα inflammatory responses (rho ≥ 0.4; P ≤ 0.04) and negatively with memory CMI (rho = –0.45; P = 0.04). The corollary of this observation is that robust Th1 and/or low Th9, Th22, and TNFα inflammatory responses may be associated with efficient clearance of RSV infection and therefore desirable characteristics of an RSV vaccine. Young age was associated with low memory and effector Th1 responses (rho ≥ 0.4; P ≤ 0.04) and high Th2, Th9, Th17, Th22 and TNFα inflammatory responses (rho ≤ –0.4; P ≤ 0.04), indicating that age at vaccination may be a major determinant of the CMI response pattern. PMID:24513666

  11. 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. ...

  12. 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 ...

  13. 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. ...

  14. Long flights do not influence immune responses of a long-distance migrant bird: a wind-tunnel experiment.

    PubMed

    Hasselquist, Dennis; Lindström, Ake; Jenni-Eiermann, Susi; Koolhaas, Anita; Piersma, Theunis

    2007-04-01

    Heavy physical work can result in physiological stress and suppressed immune function. Accordingly, long-distance migrant birds that fly for thousands of km within days can be expected to show immunosuppression, and hence be more vulnerable to infections en route. The red knot Calidris canutus Linnaeus is a long-distance migrant shorebird. We flew red knots the equivalent of 1500 km over 6 days in a wind tunnel. The humoral and cell-mediated immune responses of the flyers were compared to those of non-flying controls. Humoral immunity was measured as antibody production against injected diphtheria and tetanus antigens, and cell-mediated response as phytohemagglutinin-induced wing-web swelling. Blood corticosterone levels, which may modulate immune function, were measured in parallel. The long flights had no detectable effects on humoral or cell-mediated immune responses, or on corticosterone levels. Thus, flight performance per se may not be particularly stressful or immunosuppressive in red knots. Some birds assigned as flyers refused to fly for extended periods. Before flights started, these non-flyers had significantly lower antibody responses against tetanus than the birds that carried out the full flight program. This suggests that only birds in good physical condition may be willing to take on heavy exercise. We conclude that these long-distance migrants appear well adapted to the work load induced by long flights, enabling them to cope with long flight distances without increased stress levels and suppression of immunity. Whether this also applies in the wild, where the migrating birds may face adverse weather and food conditions, remains to be investigated. PMID:17371911

  15. Immune response of postpartum dairy cows fed flaxseed.

    PubMed

    Lessard, M; Gagnon, N; Petit, H V

    2003-08-01

    concentrations in serum due to dietary treatment and physiological status influenced systemic immunity as shown by reduced proliferative response. However, other mechanisms must be considered and are discussed to explain dietary effect on lymphocyte proliferative response to mitogenic stimulation and other immune functions. PMID:12939089

  16. Mosquito immune responses and malaria transmission: lessons from insect model systems and implications for vertebrate innate immunity and vaccine development.

    PubMed

    Barillas-Mury, C; Wizel, B; Han, Y S

    2000-06-01

    The introduction of novel biochemical, genetic, molecular and cell biology tools to the study of insect immunity has generated an information explosion in recent years. Due to the biodiversity of insects, complementary model systems have been developed. The conceptual framework built based on these systems is used to discuss our current understanding of mosquito immune responses and their implications for malaria transmission. The areas of insect and vertebrate innate immunity are merging as new information confirms the remarkable extent of the evolutionary conservation, at a molecular level, in the signaling pathways mediating these responses in such distant species. Our current understanding of the molecular language that allows the vertebrate innate immune system to identify parasites, such as malaria, and direct the acquired immune system to mount a protective immune response is very limited. Insect vectors of parasitic diseases, such as mosquitoes, could represent excellent models to understand the molecular responses of epithelial cells to parasite invasion. This information could broaden our understanding of vertebrate responses to parasitic infection and could have extensive implications for anti-malarial vaccine development. PMID:10802234

  17. Desensitization and immune tolerance induction in children with severe factor IX deficiency; inhibitors and adverse reactions to replacement therapy: a case-report and literature review.

    PubMed

    Bon, Andrea; Morfini, Massimo; Dini, Alessandro; Mori, Francesca; Barni, Simona; Gianluca, Sottilotta; de Martino, Maurizio; Novembre, Elio

    2015-01-01

    Hemophilia B is a rare X-linked recessive disorder with plasma factor IX (FIX) deficiency. 1-3% of patients treated with exogenous FIX-containing products develop inhibitors (i.e. polyclonal high affinity immunoglobulins) that neutralize the procoagulant activity of a specific coagulation factor. Although the incidence of inhibitors in hemophilia B patients is low, most are "high titer" and frequently associated with the development of severe allergic or anaphylactic reactions. Immune tolerance induction as a strategy for inhibitor eradication was first described in 1984. Unfortunately, the overall reported success of immune tolerance induction in FIX deficiency with inhibitors is approximately 25-40%.We report the case of a 2-year-old boy with hemophilia B severe FIX deficiency (<1%), inhibitor antibodies to FIX development, and a history of adverse reactions to FIX infusions, who underwent a successful desensitization and immune tolerance induction with a daily FIX infusion. With this regimen the inhibitor titer decreased with effective bleeding prevention. PMID:25887512

  18. Detection of Innate Immune Response Modulating Impurities in Therapeutic Proteins

    PubMed Central

    Haile, Lydia Asrat; Puig, Montserrat; Kelley-Baker, Logan; Verthelyi, Daniela

    2015-01-01

    Therapeutic proteins can contain multiple impurities, some of which are variants of the product, while others are derived from the cell substrate and the manufacturing process. Such impurities, even when present at trace levels, have the potential to activate innate immune cells in peripheral blood or embedded in tissues causing expression of cytokines and chemokines, increasing antigen uptake, facilitating processing and presentation by antigen presenting cells, and fostering product immunogenicity. Currently, while products are tested for host cell protein content, assays to control innate immune response modulating impurities (IIRMIs) in products are focused mainly on endotoxin and nucleic acids, however, depending on the cell substrate and the manufacturing process, numerous other IIRMI could be present. In these studies we assess two approaches that allow for the detection of a broader subset of IIRMIs. In the first, we use commercial cell lines transfected with Toll like receptors (TLR) to detect receptor-specific agonists. This method is sensitive to trace levels of IIRMI and provides information of the type of IIRMIs present but is limited by the availability of stably transfected cell lines and requires pre-existing knowledge of the IIRMIs likely to be present in the product. Alternatively, the use of a combination of macrophage cell lines of human and mouse origin allows for the detection of a broader spectrum of impurities, but does not identify the source of the activation. Importantly, for either system the lower limit of detection (LLOD) of impurities was similar to that of PBMC and it was not modified by the therapeutic protein tested, even in settings where the product had inherent immune modulatory properties. Together these data indicate that a cell-based assay approach could be used to screen products for the presence of IIRMIs and inform immunogenicity risk assessments, particularly in the context of comparability exercises. PMID:25901912

  19. Allopurinol induces innate immune responses through mitogen-activated protein kinase signaling pathways in HL-60 cells.

    PubMed

    Nakajima, Akira; Oda, Shingo; Yokoi, Tsuyoshi

    2016-09-01

    Allopurinol, an inhibitor of xanthine oxidase, is a frequent cause of severe cutaneous adverse reactions (SCARs) in humans, including drug rash with eosinophilia and systemic symptoms, Stevens-Johnson syndrome and toxic epidermal necrolysis. Although SCARs have been suspected to be immune-mediated, the mechanisms of allopurinol-induced SCARs remain unclear. In this study, we examined whether allopurinol has the ability to induce innate immune responses in vitro using human dendritic cell (DC)-like cell lines, including HL-60, THP-1 and K562, and a human keratinocyte cell line, HaCaT. In this study, we demonstrate that treatment of HL-60 cells with allopurinol significantly increased the mRNA expression levels of interleukin-8, monocyte chemotactic protein-1 and tumor necrosis factor α in a time- and concentration-dependent manner. Furthermore, allopurinol induced the phosphorylation of mitogen-activated protein kinases (MAPK), such as c-Jun N-terminal kinase and extracellular signal-regulated kinase, which regulate cytokine production in DC. In addition, allopurinol-induced increases in cytokine expression were inhibited by co-treatment with the MAPK inhibitors. Collectively, these results suggest that allopurinol has the ability to induce innate immune responses in a DC-like cell line through activation of the MAPK signaling pathways. These results indicate that innate immune responses induced by allopurinol might be involved in the development of allopurinol-induced SCARs. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26641773

  20. Role of Innate Immunity against Human Papillomavirus (HPV) Infections and Effect of Adjuvants in Promoting Specific Immune Response

    PubMed Central

    Amador-Molina, Alfredo; Hernández-Valencia, José Fernando; Lamoyi, Edmundo; Contreras-Paredes, Adriana; Lizano, Marcela

    2013-01-01

    During the early stages of human papillomavirus (HPV) infections, the innate immune system creates a pro-inflammatory microenvironment by recruiting innate immune cells to eliminate the infected cells, initiating an effective acquired immune response. However, HPV exhibits a wide range of strategies for evading immune-surveillance, generating an anti-inflammatory microenvironment. The administration of new adjuvants, such as TLR (Toll-like receptors) agonists and alpha-galactosylceramide, has been demonstrated to reverse the anti-inflammatory microenvironment by down-regulating a number of adhesion molecules and chemo-attractants and activating keratinocytes, dendritic (DC), Langerhans (LC), natural killer (NK) or natural killer T (NKT) cells; thus, promoting a strong specific cytotoxic T cell response. Therefore, these adjuvants show promise for the treatment of HPV generated lesions and may be useful to elucidate the unknown roles of immune cells in the natural history of HPV infection. This review focuses on HPV immune evasion mechanisms and on the proposed response of the innate immune system, suggesting a role for the surrounding pro-inflammatory microenvironment and the NK and NKT cells in the clearance of HPV infections. PMID:24169630

  1. Immune and non-immune responses to hepatitis C virus infection

    PubMed Central

    Sun, Jiaren; Rajsbaum, Ricardo; Yi, MinKyung

    2015-01-01

    The host innate and adaptive immune systems are involved in nearly every step of hepatitis C virus (HCV) infection. In patients, the outcome is determined by a series of complex host-virus interactions, whether it is a natural infection or results from clinical intervention. Strong and persistent CD8+ and CD4+ T-cell responses are critical in HCV clearance, as well as cytokine-induced factors that can directly inhibit virus replication. Newly available direct-acting antivirals (DAAs) are very effective in viral clearance in patients. DAA treatment may further result in the down-regulation of programmed death-1, leading to rapid restoration of HCV-specific CD8+ T cell functions. In this review, we focus on recent studies that address the host responses critical for viral clearance and disease resolution. Additional discussion is devoted to the prophylactic vaccine development as well as to current efforts aimed at understanding the host innate responses against HCV infection. Current theories on how the ubiquitin system and interferon-stimulated genes may affect HCV replication are also discussed. PMID:26478666

  2. Schistosoma infection inhibits cellular immune responses to core HCV peptides.

    PubMed

    Farid, A; Al-Sherbiny, M; Osman, A; Mohamed, N; Saad, A; Shata, M T; Lee, D-H; Prince, A M; Strickland, G T

    2005-05-01

    Patients coinfected with hepatitis C virus (HCV) and the trematode, Schistosoma mansoni, have an increased incidence of viral persistence and accelerated fibrosis. To investigate immunological mechanisms responsible for this more aggressive natural history of HCV, the core HCV-specific T-cell responses were analysed in 44 donated blood units rejected because they had antibodies to HCV (anti-HCV). Half also had anti-S. mansoni antibodies, evidence of past or active infection. HCV-specific ELISPOT responses were examined using pools of 180 overlapping 9-mer peptides with offsets of one covering the core of HCV genotype 4a. Comparison of T-cell responses in blood units positive for both anti-HCV and anti-Schistosoma antibodies with blood units positive only for anti-HCV antibodies showed a significant decrease in core-specific T-cell IFN-gamma (505+/- 46 vs. 803 +/- 66 ISC/10(6) cells, P < 0.001), IL-4 (2 +/- 108 vs. 641 +/- 131 ISC/10(6) cells, P < 0.001), and IL-10 (159 +/- 105 vs. 466 +/- 407 ISC/10(6) cells, P < 0.002) responses. In contrast, there was no significant difference in cell-mediated immune response (CMI) to PHA mitogen between these two groups. Therefore, we concluded T cells from persons with anti-Schistosoma have reduced IFN-gamma, IL-4, and IL-10 secreting HCV-specific T-cell responses. This may explain why Schistosoma coinfection increases persistence and severity of HCV infection. PMID:15987342

  3. Immune responses of two Mastomys sibling species to Yersinia pestis.

    PubMed Central

    Arntzen, L; Wadee, A A; Isaäcson, M

    1991-01-01

    This study assessed the in vitro cell-mediated immune responses of Mastomys natalensis, with a diploid chromosome number of 2n = 32, and Mastomys coucha, with a diploid chromosome number of 2n = 36, to Yersinia pestis. Splenic mononuclear (MN) cells of uninfected M. natalensis proliferated in response to crude fraction 1 of Y. pestis and two subfractions derived from fraction 1 in vitro. Proliferation was dose dependent and followed the time kinetics of other well-known mitogens. Further characterization of the two fractions revealed similar protein profiles in sodium dodecyl sulfide-polyacrylamide gel electrophoresis and indicated a heat-stable protein of 25 kDa responsible for the mitogenic activity. No such response was observed with MN cells from M. coucha. The unresponsiveness of M. coucha-derived MN cells appears to be related to an inability to respond to Y. pestis organisms. The results may help explain the relative resistance and susceptibility of M. natalensis and M. coucha to Y. pestis infection. Images PMID:2037358

  4. Immune response modulation by curcumin in a latex allergy model

    PubMed Central

    Kurup, Viswanath P; Barrios, Christy S; Raju, Raghavan; Johnson, Bryon D; Levy, Michael B; Fink, Jordan N

    2007-01-01

    Background There has been a worldwide increase in allergy and asthma over the last few decades, particularly in industrially developed nations. This resulted in a renewed interest to understand the pathogenesis of allergy in recent years. The progress made in the pathogenesis of allergic disease has led to the exploration of novel alternative therapies, which include herbal medicines as well. Curcumin, present in turmeric, a frequently used spice in Asia has been shown to have anti-allergic and inflammatory potential. Methods We used a murine model of latex allergy to investigate the role of curcumin as an immunomodulator. BALB/c mice were exposed to latex allergens and developed latex allergy with a Th2 type of immune response. These animals were treated with curcumin and the immunological and inflammatory responses were evaluated. Results Animals exposed to latex showed enhanced serum IgE, latex specific IgG1, IL-4, IL-5, IL-13, eosinophils and inflammation in the lungs. Intragastric treatment of latex-sensitized mice with curcumin demonstrated a diminished Th2 response with a concurrent reduction in lung inflammation. Eosinophilia in curcumin-treated mice was markedly reduced, co-stimulatory molecule expression (CD80, CD86, and OX40L) on antigen-presenting cells was decreased, and expression of MMP-9, OAT, and TSLP genes was also attenuated. Conclusion These results suggest that curcumin has potential therapeutic value for controlling allergic responses resulting from exposure to allergens. PMID:17254346

  5. Methylisothiazolinone: dermal and respiratory immune responses in mice.

    PubMed

    Devos, Fien C; Pollaris, Lore; Van Den Broucke, Sofie; Seys, Sven; Goossens, An; Nemery, Benoit; Hoet, Peter H M; Vanoirbeek, Jeroen A J

    2015-06-15

    Methylisothiazolinone (MI), a widely used chemical preservative in industrial and household products, and cosmetics, has been associated with allergic contact dermatitis. However, the asthmogenic capacity of MI is currently unknown. In this study, we investigated the capacity of MI to elicit asthma-like responses in a validated mouse model. On days 1 and 8, mice (C57Bl/6 and BALB/c) were dermally treated with MI or vehicle on each ear. On day 15, mice received a single intranasal challenge with MI or vehicle. Immediately after the challenge, the early ventilatory response was measured using a double chamber plethysmograph. One day later, airway hyperreactivity, pulmonary inflammation and immune-related parameters were assessed. Dermal treatment with MI in both C57Bl/6 and BALB/c mice induced increased T- and B-cell proliferation in the auricular lymph nodes, along with IFN-γ production and limited increases in total serum IgE, confirming dermal sensitization. An airway challenge with MI led to an early ventilatory response (decreased breathing frequency), indicative for acute sensory irritation. However, 24h later no allergic respiratory response (no airway hyperreactivity (AHR) nor pulmonary inflammation) was found in either mouse strains. Our study indicates that MI can be classified as a strong dermal sensitizer and irritant, but not an asthmogen after initial dermal sensitization, followed by an airway challenge. PMID:25907379

  6. Ethnic differences in immune responses to hepatitis B vaccine.

    PubMed

    Hsu, L C; Lin, S R; Hsu, H M; Chao, W H; Hsieh, J T; Wang, M C; Lu, C F; Chang, Y H; Ho, M S

    1996-04-01

    A national vaccination program against hepatitis B virus (HBV) to immunize every newborn was initiated in Taiwan in 1986. A serologic survey of 1,812 fully vaccinated children residing in four aboriginal villages and four adjacent nonaboriginal Han Chinese rural villages was conducted in 1993. Children in three of the four aboriginal villages had significantly lower titers of antibody against hepatitis B surface antigen (anti-HBs) than did children in the nonaboriginal villages. Evaluation of cold chain operation for vaccine storage and transport suggested that cold chain failure was not responsible for the fact that children residing in the more remote aboriginal villages had lower mean titers of anti-HBs. However, children whose parents were both aborigines had lower anti-HBs mean titer than did children whose parents were both ethnic Han Chinese. Children of mixed parental origins had intermediate mean titer of anti-HBs. Serologic responses to Japanese encephalitis virus and diphtheria vaccines did not show such correlation with ethnic groups, indicating that the determinant for HBV hyporesponsiveness among the aboriginal children is distinct from that of other childhood vaccines. It was therefore concluded that host factors pertaining to ethnic origin might be responsible for the hyporesponsiveness to HBV vaccine in the aboriginal populations. This finding, if substantiated with further prospective studies, might provide possible means for more targeted trials to improve vaccine response and to reduce vaccine failure among these well-defined ethnic groups. PMID:8651234

  7. Characterization and role of the immune response during ligament healing

    NASA Astrophysics Data System (ADS)

    Chamberlain, Connie S.

    inflammation and stimulating remodeling. IL-4 dose- and time-dependently stimulated early ligament regeneration but was unable to maintain the response during later healing. In summary, this work demonstrated the association between the immune cells and ligament healing, indicating a potential for obtaining a more regenerative response by modulating the immune response in a time, dose, and spatial manner.

  8. Free radical functionalization of surfaces to prevent adverse responses to biomedical devices

    PubMed Central

    Bilek, Marcela M. M.; Bax, Daniel V.; Kondyurin, Alexey; Yin, Yongbai; Nosworthy, Neil J.; Fisher, Keith; Waterhouse, Anna; Weiss, Anthony S.; dos Remedios, Cristobal G.; McKenzie, David R.

    2011-01-01

    Immobilizing a protein, that is fully compatible with the patient, on the surface of a biomedical device should make it possible to avoid adverse responses such as inflammation, rejection, or excessive fibrosis. A surface that strongly binds and does not denature the compatible protein is required. Hydrophilic surfaces do not induce denaturation of immobilized protein but exhibit a low binding affinity for protein. Here, we describe an energetic ion-assisted plasma process that can make any surface hydrophilic and at the same time enable it to covalently immobilize functional biological molecules. We show that the modification creates free radicals that migrate to the surface from a reservoir beneath. When they reach the surface, the radicals form covalent bonds with biomolecules. The kinetics and number densities of protein molecules in solution and free radicals in the reservoir control the time required to form a full protein monolayer that is covalently bound. The shelf life of the covalent binding capability is governed by the initial density of free radicals and the depth of the reservoir. We show that the high reactivity of the radicals renders the binding universal across all biological macromolecules. Because the free radical reservoir can be created on any solid material, this approach can be used in medical applications ranging from cardiovascular stents to heart-lung machines. PMID:21844370

  9. Suppression of Hyperactive Immune Responses Protects against Nitrogen Mustard Injury

    PubMed Central

    Au, Liemin; Meisch, Jeffrey P; Das, Lopa M; Binko, Amy M; Boxer, Rebecca S; Wen, Amy M; Steinmetz, Nicole F; Lu, Kurt Q

    2015-01-01

    DNA alkylating agents like nitrogen mustard (NM) are easily absorbed through the skin and exposure to such agents manifest not only in direct cellular death but also in triggering inflammation. We show that toxicity resulting from topical mustard exposure is mediated in part by initiating exaggerated host innate immune responses. Using an experimental model of skin exposure to NM we observe activation of inflammatory dermal macrophages that exacerbate local tissue damage in an inducible nitric oxide synthase (iNOS)-dependent manner. Subsequently these activated dermal macrophages reappear in the bone marrow to aid in disruption of hematopoiesis and contribute ultimately to mortality in an experimental mouse model of topical NM exposure. Intervention with a single dose of 25-hydroxyvitamin D3 (25(OH)D) is capable of suppressing macrophage-mediated iNOS production resulting in mitigation of local skin destruction, enhanced tissue repair, protection from marrow depletion, and rescue from severe precipitous wasting. These protective effects are recapitulated experimentally using pharmacological inhibitors of iNOS or by compounds that locally deplete skin macrophages. Taken together, these data highlight a critical unappreciated role of the host innate immune system in exacerbating injury following exposure to NM and support the translation of 25(OH)D in the therapeutic use against these chemical agents. PMID:26288355

  10. Immune response in pemphigus and beyond: progresses and emerging concepts.

    PubMed

    Di Zenzo, Giovanni; Amber, Kyle T; Sayar, Beyza S; Müller, Eliane J; Borradori, Luca

    2016-01-01

    Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are two severe autoimmune bullous diseases of the mucosae and/or skin associated with autoantibodies directed against desmoglein (Dsg) 3 and/or Dsg1. These two desmosomal cadherins, typifying stratified epithelia, are components of cell adhesion complexes called desmosomes and represent extra-desmosomal adhesion receptors. We herein review the advances in our understanding of the immune response underlying pemphigus, including human leucocyte antigen (HLA) class II-associated genetic susceptibility, characteristics of pathogenic anti-Dsg antibodies, antigenic mapping studies as well as findings about Dsg-specific B and T cells. The pathogenicity of anti-Dsg autoantibodies has been convincingly demonstrated. Disease activity and clinical phenotype correlate with anti-Dsg antibody titers and profile while passive transfer of anti-Dsg IgG from pemphigus patients' results in pemphigus-like lesions in neonatal and adult mice. Finally, adoptive transfer of splenocytes from Dsg3-knockout mice immunized with murine Dsg3 into immunodeficient mice phenotypically recapitulates PV. Although the exact pathogenic mechanisms leading to blister formation have not been fully elucidated, intracellular signaling following antibody binding has been found to be necessary for inducing cell-cell dissociation, at least for PV. These new insights not only highlight the key role of Dsgs in maintenance of tissue homeostasis but are expected to progressively change pemphigus management, paving the way for novel targeted immunologic and pharmacologic therapies. PMID:26597100

  11. Anaphylatoxins coordinate innate and adaptive immune responses in allergic asthma.

    PubMed

    Schmudde, Inken; Laumonnier, Yves; Köhl, Jörg

    2013-02-01

    Allergic asthma is a chronic disease of the airways in which maladaptive Th2 and Th17 immune responses drive airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation and mucus overproduction. Airway epithelial and pulmonary vascular endothelial cells in concert with different resident and monocyte-derived dendritic cells (DC) play critical roles in allergen sensing and consecutive activation of TH cells and their differentiation toward TH2 and TH17 effector or regulatory T cells (Treg). Further, myeloid-derived regulatory cells (MDRC) act on TH cells and either suppress or enhance their activation. The complement-derived anaphylatoxins (AT) C3a and C5a are generated during initial antigen encounter and regulate the development of maladaptive immunity at allergen sensitization. Here, we will review the complex role of ATs in activation and modulation of different DC populations, MDRCs and CD4⁺ TH cells. We will also discuss the potential impact of ATs on the regulation of the pulmonary stromal compartment as an important means to regulate DC functions. PMID:23694705

  12. How sex and age affect immune responses, susceptibility to infections, and response to vaccination

    PubMed Central

    Giefing-Kröll, Carmen; Berger, Peter; Lepperdinger, Günter; Grubeck-Loebenstein, Beatrix

    2015-01-01

    Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions. PMID:25720438

  13. Low Concentrations of Silver Nanoparticles in Biosolids Cause Adverse Ecosystem Responses under Realistic Field Scenario

    PubMed Central

    Colman, Benjamin P.; Arnaout, Christina L.; Anciaux, Sarah; Gunsch, Claudia K.; Hochella, Michael F.; Kim, Bojeong; Lowry, Gregory V.; McGill, Bonnie M.; Reinsch, Brian C.; Richardson, Curtis J.; Unrine, Jason M.; Wright, Justin P.; Yin, Liyan; Bernhardt, Emily S.

    2013-01-01

    A large fraction of engineered nanomaterials in consumer and commercial products will reach natural ecosystems. To date, research on the biological impacts of environmental nanomaterial exposures has largely focused on high-concentration exposures in mechanistic lab studies with single strains of model organisms. These results are difficult to extrapolate to ecosystems, where exposures will likely be at low-concentrations and which are inhabited by a diversity of organisms. Here we show adverse responses of plants and microorganisms in a replicated long-term terrestrial mesocosm field experiment following a single low dose of silver nanoparticles (0.14 mg Ag kg−1 soil) applied via a likely route of exposure, sewage biosolid application. While total aboveground plant biomass did not differ between treatments receiving biosolids, one plant species, Microstegium vimeneum, had 32 % less biomass in the Slurry+AgNP treatment relative to the Slurry only treatment. Microorganisms were also affected by AgNP treatment, which gave a significantly different community composition of bacteria in the Slurry+AgNPs as opposed to the Slurry treatment one day after addition as analyzed by T-RFLP analysis of 16S-rRNA genes. After eight days, N2O flux was 4.5 fold higher in the Slurry+AgNPs treatment than the Slurry treatment. After fifty days, community composition and N2O flux of the Slurry+AgNPs treatment converged with the Slurry. However, the soil microbial extracellular enzymes leucine amino peptidase and phosphatase had 52 and 27% lower activities, respectively, while microbial biomass was 35% lower than the Slurry. We also show that the magnitude of these responses was in all cases as large as or larger than the positive control, AgNO3, added at 4-fold the Ag concentration of the silver nanoparticles. PMID:23468930

  14. A role for plasma cell targeting agents in immune tolerance induction in autoimmune disease and antibody responses to therapeutic proteins.

    PubMed

    Rosenberg, A S; Pariser, A R; Diamond, B; Yao, L; Turka, L A; Lacana, E; Kishnani, P S

    2016-04-01

    Antibody responses to life saving therapeutic protein products, such as enzyme replacement therapies (ERT) in the setting of lysosomal storage diseases, have nullified product efficacy and caused clinical deterioration and death despite treatment with immune-suppressive therapies. Moreover, in some autoimmune diseases, pathology is mediated by a robust antibody response to endogenous proteins such as is the case in pulmonary alveolar proteinosis, mediated by antibodies to Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF). In this work, we make the case that in such settings, when the antibody response is high titered, sustained, and refractory to immune suppressive treatments, the antibody response is mediated by long-lived plasma cells which are relatively unperturbed by immune suppressants including rituximab. However, long-lived plasma cells can be targeted by proteasome inhibitors such as bortezomib. Recent reports of successful reversal of antibody responses with bortezomib in the settings of ERT and Thrombotic Thrombocytopenic Purpura (TTP) argue that the safety and efficacy of such plasma cell targeting agents should be evaluated in larger scale clinical trials to delineate the risks and benefits of such therapies in the settings of antibody-mediated adverse effects to therapeutic proteins and autoantibody mediated pathology. PMID:26928739

  15. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine

    PubMed Central

    Sirskyj, Danylo; Kumar, Ashok; Azizi, Ali

    2016-01-01

    Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID:27384558

  16. Mechanisms Underlying the Immune Response Generated by an Oral Vibrio cholerae Vaccine.

    PubMed

    Sirskyj, Danylo; Kumar, Ashok; Azizi, Ali

    2016-01-01

    Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling. The results demonstrate differential requirements for generation of immune responses. These results also suggest that TLR pathways may be modulators of the quality of immune response elicited by the Dukoral vaccine. Determining the critical signaling pathways involved in the induction of immune response to this vaccine would be beneficial, and could contribute to more precisely-designed versions of other oral vaccines in the future. PMID:27384558

  17. Tissue Specific Heterogeneity in Effector Immune Cell Response

    PubMed Central

    Tufail, Saba; Badrealam, Khan Farheen; Sherwani, Asif; Gupta, Umesh D.; Owais, Mohammad

    2013-01-01

    Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct “homing codes” (adhesion molecules and chemokine receptors) during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A) and sunlight (vitamin D3) prime dendritic cells, imprinting them to play centre stage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue-tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues along with giving an overview of tissue tropism in B cells. PMID:23986763

  18. Immune response to HHV-6 and implications for immunotherapy.

    PubMed

    Becerra, Aniuska; Gibson, Laura; Stern, Lawrence J; Calvo-Calle, J Mauricio

    2014-12-01

    Most adults remain chronically infected with HHV-6 after resolution of a primary infection in childhood, with the latent virus held in check by the immune system. Iatrogenic immunosuppression following solid organ transplantation (SOT) or hematopoetic stem cell transplantation (HSCT) can allow latent viruses to reactivate. HHV-6 reactivation has been associated with increased morbidity, graft rejection, and neurological complications post-transplantation. Recent work has identified HHV-6 antigens that are targeted by the CD4+ and CD8+ T cell response in chronically infected adults. T cell populations recognizing these targets can be expanded in vitro and are being developed for use in autologous immunotherapy to control post-transplantation HHV-6 reaction. PMID:25462448

  19. Modulation of humoral immune response through probiotic intake.

    PubMed

    Fang, H; Elina, T; Heikki, A; Seppo, S

    2000-09-01

    Thirty healthy volunteers were randomised into three different treatment groups and consumed Lactobacillus GG, Lactococcus lactis or placebo (ethyl cellulose) for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine was given to all subjects to mimic an enteropathogenic infection. All subjects responded well to the vaccine, but no significant differences were observed in numbers of IgA-, IgG- and IgM-secreting cells among the different groups. There was a trend towards a greater increase in specific IgA among the subjects receiving the vaccine in combination with Lactobacillus GG. Those receiving L. lactis with their vaccine evinced significantly higher CR3 receptor expression on neutrophils than those receiving either the placebo or Lactobacillus GG. These results indicate that probiotics may influence differently the immune response to oral S. typhi vaccine and that the immunomodulatory effect of probiotics is strain-dependent. PMID:10967260

  20. Innate immune response in the sea urchin Echinometra lucunter (Echinodermata).

    PubMed

    de Faria, Marcos Tucunduva; da Silva, José Roberto Machado Cunha

    2008-05-01

    Echinometra lucunter, (Pindá) is a sea urchin encountered in the Brazilian coast and exposed to high and low temperatures related to low and high tides. Despite their great distribution and importance, few studies have been done on the biological function of their coelomocytes. Thus, Echinometra lucunter perivisceral coelomocytes were characterized under optical and transmission electron microscopy. Phagocytic amoebocytes in the perivisceral coelom were labelled by injecting ferritin, and ferritin labelled phagocytic amoebocytes were found in the peristomial connective tissue after injecting India ink into the tissue, indicating the amoebocytes ability to respond to an inflammatory stimulus. Results showed that the phagocytic amoebocytes were the main inflammatory cells found in the innate immune response of E. lucunter. While other works have recorded these phenomena in sea urchins found in moderate and constant temperature, this study reports on these same phenomena in a tropical sea urchin under great variation of temperature, thus providing new data to inflammatory studies in invertebrate pathology. PMID:17988681

  1. Humoral immune responses to periodontal pathogens in the elderly

    PubMed Central

    Shet, Uttom; Oh, Hee-Kyun; Chung, Hyun-Ju; Kim, Young-Joon; Kim, Ok-Su; Lim, Hoi-Jeong; Shin, Min-Ho

    2015-01-01

    Purpose Elderly people are thought to be more susceptible to periodontal disease due to reduced immune function associated with aging. However, little information is available on the nature of immune responses against putative periodontal pathogens in geriatric patients. The purpose of this study was to evaluate the serum IgG antibody responses to six periodontal pathogens in geriatric subjects. Methods The study population consisted of 85 geriatric patients and was divided into three groups: 29 mild (MCP), 27 moderate (MoCP) and 29 severe (SCP) chronic periodontitis patients. Serum levels of IgG antibody to Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Prevotella intermedia were measured by enzyme-linked immunosorbent assay (ELISA) and compared among the groups. Results All three groups showed levels of serum IgG in response to P. gingivalis, A. actinomycetemcomitans, and P. intermedia that were three to four times higher than levels of IgG to T. forsythia, T. denticola, and F. nucleatum. There were no significant differences among all three groups in IgG response to P. gingivalis (P=0.065), T. forsythia (P=0.057), T. denticola (P=0.1), and P. intermedia (P=0.167), although the IgG levels tended to be higher in patients with SCP than in those with MCP or MoCP (with the exception of those for P. intermedia). In contrast, there were significant differences among the groups in IgG levels in response to F. nucleatum (P=0.001) and A. actinomycetemcomitans (P=0.003). IgG levels to A. actinomycetemcomitans were higher in patients with MCP than in those with MoCP or SCP. Conclusions When IgG levels were compared among three periodontal disease groups, only IgG levels to F. nucleatum significantly increased with the severity of disease. On the contrary, IgG levels to A. actinomycetemcomitans decreased significantly in patients with SCP compared to those with MCP. There were no

  2. Development and characterization of an innovative heparin coating to stabilize and protect liposomes against adverse immune reactions.

    PubMed

    Duehrkop, Claudia; Leneweit, Gero; Heyder, Christoph; Fromell, Karin; Edwards, Katarina; Ekdahl, Kristina N; Nilsson, Bo

    2016-05-01

    Liposomes have been recognized as excellent drug delivery systems, but when they come in direct contact with different blood components they may trigger an immediate activation of the innate immune system. The aim of the present study was to produce long-circulating, blood-compatible liposomes by developing a construct of liposomes covered by a novel unique heparin complex (CHC; 70 heparin molecules per complex) to avoid recognition by the innate immune system. Unilamellar, cationic liposomes were produced by hand extrusion through a 100-nm polycarbonate membrane. Coating of liposomes with the macromolecular CHC was accomplished by electrostatic interactions. Dynamic light scattering as well as QCM-D measurements were used to verify the electrostatic deposition of the negatively charged CHC to cationic liposomes. The CHC-coated liposomes did not aggregate when in contact with lepirudin anti-coagulated plasma. Unlike previous attempts to coat liposomes with heparin, this technique produced freely moveable heparin strands sticking out from the liposome surface, which exposed AT binding sites reflecting the anticoagulant potentials of the liposomes. In experiments using lepirudin-anticoagulated plasma, CHC-coated liposomes, in contrast to non-coated control liposomes, did not activate the complement system, as evidenced by low C3a and sC5b-9 generation and reduced leakage from the liposomes. In conclusion, we show that liposomes can be successfully coated with the biopolymer CHC, resulting in biocompatible and stable liposomes that have significant application potential. PMID:26897551

  3. Adverse cardiometabolic response to aerobic exercise training: Should this be a concern?

    PubMed Central

    Leifer, Eric S.; Church, Timothy S.; Earnest, Conrad P.; Fleg, Jerome L.; Hakkinen, Keijo; Karavirta, Laura; Kraus, William E.; Mikus, Catherine; Resnick, Benjamin

    2016-01-01

    .36) for SBP. Conclusion Compared to control subjects, exercise subjects were not at an increased risk for meeting the AC thresholds for SBP, FI, TG, or HDL-C and significantly fewer exercise subjects met AC thresholds for FI, and HDL. Exercise subjects also had significantly more favorable mean changes in FI, TG, and HDL-C than control subjects. These findings do not support the concept that aerobic exercise training increases the risk of adverse changes in CV risk factors. and that, with respect to group responses PMID:26258860

  4. Protective efficacy and immune responses by homologous prime-booster immunizations of a novel inactivated Salmonella Gallinarum vaccine candidate

    PubMed Central

    2016-01-01

    Purpose Salmonella enterica serovar Gallinarum (SG) ghost vaccine candidate was recently constructed. In this study, we evaluated various prime-boost vaccination strategies using the candidate strain to optimize immunity and protection efficacy against fowl typhoid. Materials and Methods The chickens were divided into five groups designated as group A (non-immunized control), group B (orally primed and boosted), group C (primed orally and boosted intramuscularly), group D (primed and boosted intramuscularly), and group E (primed intramuscularly and boosted orally). The chickens were primed with the SG ghost at 7 days of age and were subsequently boosted at the fifth week of age. Post-immunization, the plasma IgG and intestinal secretory IgA (sIgA) levels, and the SG antigen-specific lymphocyte stimulation were monitored at weekly interval and the birds were subsequently challenged with a virulent SG strain at the third week post-second immunization. Results Chickens in group D showed an optimized protection with significantly increased plasma IgG, sIgA, and lymphocyte stimulation response compared to all groups. The presence of CD4+ and CD8+ T cells and monocyte/macrophage (M/M) in the spleen, and splenic expression of cytokines such as interferon γ (IFN-γ) and interleukin 6 (IL-6) in the immunized chickens were investigated. The prime immunization induced significantly higher splenic M/M population and mRNA levels of IFN-γ whereas the booster showed increases of splenic CD4+ and CD8+ T-cell population and IL-6 cytokine in mRNA levels. Conclusion Our results indicate that the prime immunization with the SG ghost vaccine induced Th1 type immune response and the booster elicited both Th1- and Th2-related immune responses. PMID:27489805

  5. Tamibarotene modulates the local immune response in experimental periodontitis.

    PubMed

    Jin, Ying; Wang, Linyuan; Liu, Dixin; Lin, Xiaoping

    2014-12-01

    Tamibarotene (Am80), a synthetic retinoic acid receptor (RAR), is an agonist with high specificity for RARα and RARβ. Retinoid agonists have been shown to inhibit Th17 cell polarization and to enhance forkhead box P3 (Foxp3) expression during the course of inflammatory diseases. The aim of this study was to evaluate the previously unrecognized role of Am80 in regulating the immune responses of periodontitis within the oral microenvironment. The experimental model of periodontitis in mice was induced by oral infection with Porphyromonas gingivalis (P. gingivalis) W83. Our results indicated that Am80 effectively suppressed alveolar bone resorption induced by P. gingivalis W83 and decreased the number of osteoclasts. We clarified that these effects were closely associated with the reduced percentage of CD4(+) retinoid-related orphan receptor (ROR)γt(+) cells and increased the percentage of CD4(+) Foxp3(+) cells in the gingival tissues, cervical lymph nodes (CLNs), and spleen. Furthermore, in P. gingivalis-infected mice, Am80 down-regulated mRNA expression levels of interleukin-17A (IL-17A), receptor activator of nuclear factor-kappa beta ligand (RANKL), monocyte chemotactic protein-1 (MCP-1), IL-6, and IL-1β. Simultaneously, Am80 up-regulated expression levels of IL-10 and transforming growth factor-β1 (TGF-β1) in gingival tissues and the CLNs. Our results suggest that Am80 could protect against periodontal bone resorption, primarily through the modulation of immune responses in the oral microenvironment, and demonstrate the potential of Am80 as a novel clinical strategy for preventing periodontitis. PMID:25448496

  6. GITR Activation Positively Regulates Immune Responses against Toxoplasma gondii

    PubMed Central

    Costa, Frederico R. C.; Mota, Caroline M.; Santiago, Fernanda M.; Silva, Murilo V.; Ferreira, Marcela D.; Fonseca, Denise M.; Silva, João S.; Mineo, José R.; Mineo, Tiago W. P.

    2016-01-01

    Toxoplasma gondii is a widespread parasite responsible for causing clinical diseases especially in pregnant and immunosuppressed individuals. Glucocorticoid-induced TNF receptor (GITR), which is also known as TNFRS18 and belongs to the TNF receptor superfamily, is found to be expressed in various cell types of the immune system and provides an important costimulatory signal for T cells and myeloid cells. However, the precise role of this receptor in the context of T. gondii infection remains elusive. Therefore, the current study investigated the role of GITR activation in the immunoregulation mechanisms induced during the experimental infection of mice with T. gondii. Our data show that T. gondii infection slightly upregulates GITR expression in Treg cells and B cells, but the most robust increment in expression was observed in macrophages and dendritic cells. Interestingly, mice infected and treated with an agonistic antibody anti-GITR (DTA-1) presented a robust increase in pro-inflammatory cytokine production at preferential sites of parasite replication, which was associated with the decrease in latent brain parasitism of mice under treatment with DTA-1. Several in vivo and in vitro analysis were performed to identify the cellular mechanisms involved in GITR activation upon infection, however no clear alterations were detected in the phenotype/function of macrophages, Tregs and B cells under treatment with DTA-1. Therefore, GITR appears as a potential target for intervention during infection by the parasite Toxoplasma gondii, even though further studies are still necessary to better characterize the immune response triggered by GITR activation during T. gondii infection. PMID:27027302

  7. Escherichia coli heme oxygenase modulates host innate immune responses

    PubMed Central

    Maharshak, Nitsan; Ryu, Hyungjin Sally; Fan, Ting-Jia; Onyiah, Joseph C.; Schulz, Stephanie; Otterbein, Sherrie L.; Wong, Ron; Hansen, Jonathan; Otterbein, Leo E; Carroll, Ian; Plevy, Scott E.

    2015-01-01

    Induction of mammalian heme oxygenase-1 and exposure of animals to carbon monoxide ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an heme oxygenase-like enzyme, chuS, and metabolize heme into iron, biliverdin and carbon monoxide. Given the abundance of enteric bacteria residing in the intestinal lumen, we hypothesized that commensal intestinal bacteria may be a significant source of carbon monoxide, with the consequence that enteric bacteria expressing chuS and other heme oxygenase -like molecules suppress inflammatory immune responses through release of carbon monoxide. Carbon monoxide exposed mice have altered enteric bacterial composition and increased E. coli 16S and chuS DNA by real-time PCR. Moreover, severity of experimental colitis correlates with increased E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow derived macrophages results in decreased IL-12 p40 and increased IL-10 secretion compared to wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have increased levels of hepatic carbon monoxide and decreased serum IL-12 p40 compared to mice infected with chuS-deficient E. coli. Thus, carbon monoxide alters the composition of the commensal intestinal microbiota and expands E. coli populations harboring the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial heme oxygenase -like molecules and bacterial-derived carbon monoxide may represent novel targets for therapeutic intervention in inflammatory conditions. PMID:26146866

  8. Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans.

    PubMed

    Domer, J E; Hector, R F

    1987-05-01

    Immune consequences of gastrointestinal colonization of CD-1 and CBA/J mice with Candida albicans in the presence or absence of continuous antibiotic treatment with penicillin-tetracycline or trimethoprimsulfamethoxazole were investigated. Intubation with C. albicans in the absence of antibiotics resulted in the induction of low but detectable delayed-type hypersensitivity (DTH), demonstrable by footpad testing with a C. albicans wall glycoprotein (GP), and in the stimulation of a moderate level of protective immunity, demonstrable by intravenous (i.v.) challenge. DTH to a membrane extract, BEX, could not be detected in such animals. However, animals colonized in the presence of antibiotics and then inoculated cutaneously prior to being tested for DTH or protective immunity developed significantly enhanced levels of DTH to GP and BEX and were protected to an even greater extent than animals colonized in the absence of antibiotics who were not inoculated cutaneously. The priming effect of colonization, particularly with respect to the antigen GP, was also obvious from an enzyme-linked immunosorbent assay for GP-specific antibody with sera of mice surviving the i.v. challenge, in that GP-specific antibody was present in the highest titers in colonized animals that had been inoculated cutaneously prior to i.v. challenge. While the antibiotics promoted higher levels of colonization, as evidenced by stomach and fecal cultures of intubated mice, antibiotic administration was not necessary for the induction of C. albicans-specific responses. Moreover, contrary to reports in the literature, antibiotic administration had no adverse effect on the immune responses measured. Females were innately more resistant than males to i.v. challenge with C. albicans, but each sex was capable of developing protective immunity of equal intensity in response to colonization or immunization by cutaneous challenge. PMID:3300536

  9. Enhanced immune responses in mice treated with penicillin-tetracycline or trimethoprim-sulfamethoxazole when colonized intragastrically with Candida albicans.

    PubMed Central

    Domer, J E; Hector, R F

    1987-01-01

    Immune consequences of gastrointestinal colonization of CD-1 and CBA/J mice with Candida albicans in the presence or absence of continuous antibiotic treatment with penicillin-tetracycline or trimethoprimsulfamethoxazole were investigated. Intubation with C. albicans in the absence of antibiotics resulted in the induction of low but detectable delayed-type hypersensitivity (DTH), demonstrable by footpad testing with a C. albicans wall glycoprotein (GP), and in the stimulation of a moderate level of protective immunity, demonstrable by intravenous (i.v.) challenge. DTH to a membrane extract, BEX, could not be detected in such animals. However, animals colonized in the presence of antibiotics and then inoculated cutaneously prior to being tested for DTH or protective immunity developed significantly enhanced levels of DTH to GP and BEX and were protected to an even greater extent than animals colonized in the absence of antibiotics who were not inoculated cutaneously. The priming effect of colonization, particularly with respect to the antigen GP, was also obvious from an enzyme-linked immunosorbent assay for GP-specific antibody with sera of mice surviving the i.v. challenge, in that GP-specific antibody was present in the highest titers in colonized animals that had been inoculated cutaneously prior to i.v. challenge. While the antibiotics promoted higher levels of colonization, as evidenced by stomach and fecal cultures of intubated mice, antibiotic administration was not necessary for the induction of C. albicans-specific responses. Moreover, contrary to reports in the literature, antibiotic administration had no adverse effect on the immune responses measured. Females were innately more resistant than males to i.v. challenge with C. albicans, but each sex was capable of developing protective immunity of equal intensity in response to colonization or immunization by cutaneous challenge. PMID:3300536

  10. Immune Response in Microgravity: Genetic Basis and Countermeasure Development Implications

    NASA Technical Reports Server (NTRS)

    Risin, Diana; Ward, Nancy E.; Risin, Semyon A.; Pellis, Neal R.

    2006-01-01

    Impairment of the immunity in astronauts and cosmonauts even in shortterm flights is a recognized risk. Longterm orbital space missions and anticipated interplanetary flights increase the concern for more pronounced effects on the immune system with potential clinical consequences. Studies in true and modeled microgravity (MG) have demonstrated that MG directly affects numerous lymphocyte functions. The purpose of this study was to screen for genes involved in lymphocytes response to modeled microgravity (MMG) that could explain the functional and structural changes observed earlier. The microgravity-induced changes in gene expression were analyzed by microarray DNA chip technology. CD3and IL2activated Tcells were cultured in 1g (static) and modeled microgravity (NASA Rotating Wall Vessel bioreactor) conditions for 24 hours. Total RNA was extracted using the RNeasy isolation kit (Qiagen, Valencia, CA). Microarray experiments were performed utilizing Affymetrix Gene Chips (U133A), allowing testing for 18,400 human genes. To decrease the biological variation and aid in detecting microgravity-associated changes, experiments were performed in triplicate using cells obtained from three different donors. Exposure to modeled microgravity resulted in alteration of 89 genes, 10 of which were upregulated and 79 down-regulated. Altered genes were categorized by their function, structural role and by association with metabolic and regulatory pathways. A large proportion was found to be involved in fundamental cellular processes: signal transduction, DNA repair, apoptosis, and multiple metabolic pathways. There was a group of genes directly related to immune and inflammatory responses (IL7R, granulysin, proteasome activator subunit 2, peroxiredoxin 4, HLADRA, lymphocyte antigen 75, IL18R and DOCK2 genes). Among these genes only one (IL7R) was upregulated, the rest were downregulated. The upregulation of the IL7 receptor gene was confirmed by RT PCR. Three genes with altered

  11. Strain-Related Differences in the Immune Response: Relevance to Human Stroke.

    PubMed

    Becker, Kyra J

    2016-08-01

    There are significant differences in the immune response and in the susceptibility to autoimmune diseases among rodent strains. It would thus be expected that the contribution of the immune response to cerebral ischemic injury would also differ among rodent strains. More importantly, there are significant differences between the immune responses of rodents and humans. All of these factors are likely to impact the successful translation of immunomodulatory therapies from experimental rodent models to patients with stroke. PMID:26860504

  12. Cellular immune responses in cattle experimentally infected with Neospora caninum.

    PubMed

    Lundén, A; Marks, J; Maley, S W; Innes, E A

    1998-11-01

    Neospora caninum has recently been identified as an important cause of infectious abortion in cattle. The parasite is closely related to Toxoplasma gondii, but the two species are antigenically distinct. To examine cell proliferative responses and the induction of IFN-gamma in experimentally infected cattle, four 2-4 months old calves were subcutaneously inoculated with N. caninum tachyzoites. Peripheral blood mononuclear cells were collected regularly and stimulated in vitro with a crude lysate of N. caninum or T. gondii tachyzoites. Significant proliferative responses to N. caninum antigen were recorded in all calves from days 4-6 postinoculation. This response was accompanied by production of high levels of IFN-gamma. Although the calves remained seronegative to T. gondii, while seroconverting to N. caninum, stimulation with T. gondii lysate resulted in cell proliferation of a similar magnitude as that obtained using the N. caninum lysate. However, the T. gondii lysate appeared less effective than the N. caninum lysate to stimulate IFN-gamma production. Cells taken from uninfected control animals did not show any significant proliferation to either N. caninum or T. gondii antigen and no IFN-gamma was produced. These results suggest that the two parasites may possess cross-reacting T-cell epitopes, but that the T cells specific for N. caninum may have a different functional capacity. This highlights the need to investigate the antigen specificity and cytokine profile of T cells from infected animals to help understand their role in immunity to N. caninum. PMID:9988308

  13. Pleomorphic forms of Borrelia burgdorferi induce distinct immune responses.

    PubMed

    Meriläinen, Leena; Brander, Heini; Herranen, Anni; Schwarzbach, Armin; Gilbert, Leona

    2016-01-01

    Borrelia burgdorferi is the causative agent of tick-borne Lyme disease. As a response to environmental stress B. burgdorferi can change its morphology to a round body form. The role of B. burgdorferi pleomorphic forms in Lyme disease pathogenesis has long been debated and unclear. Here, we demonstrated that round bodies were processed differently in differentiated macrophages, consequently inducing distinct immune responses compared to spirochetes in vitro. Colocalization analysis indicated that the F-actin participates in internalization of both forms. However, round bodies end up less in macrophage lysosomes than spirochetes suggesting that there are differences in processing of these forms in phagocytic cells. Furthermore, round bodies stimulated distinct cytokine and chemokine production in these cells. We confirmed that spirochetes and round bodies present different protein profiles and antigenicity. In a Western blot analysis Lyme disease patients had more intense responses to round bodies when compared to spirochetes. These results suggest that round bodies have a role in Lyme disease pathogenesis. PMID:27139815

  14. Increased Immune Response Variability during Simultaneous Viral Coinfection Leads to Unpredictability in CD8 T Cell Immunity and Pathogenesis

    PubMed Central

    Kenney, Laurie L.; Cornberg, Markus; Chen, Alex T.; Emonet, Sebastien; de la Torre, Juan Carlos

    2015-01-01

    ABSTRACT T cell memory is usually studied in the context of infection with a single pathogen in naive mice, but how memory develops during a coinfection with two pathogens, as frequently occurs in nature or after vaccination, is far less studied. Here, we questioned how the competition between immune responses to two viruses in the same naive host would influence the development of CD8 T cell memory and subsequent disease outcome upon challenge. Using two different models of coinfection, including the well-studied lymphocytic choriomeningitis (LCMV) and Pichinde (PICV) viruses, several differences were observed within the CD8 T cell responses to either virus. Compared to single-virus infection, coinfection resulted in substantial variation among mice in the size of epitope-specific T cell responses to each virus. Some mice had an overall reduced number of virus-specific cells to either one of the viruses, and other mice developed an immunodominant response to a normally subdominant, cross-reactive epitope (nucleoprotein residues 205 to 212, or NP205). These changes led to decreased protective immunity and enhanced pathology in some mice upon challenge with either of the original coinfecting viruses. In mice with PICV-dominant responses, during a high-dose challenge with LCMV clone 13, increased immunopathology was associated with a reduced number of LCMV-specific effector memory CD8 T cells. In mice with dominant cross-reactive memory responses, during challenge with PICV increased immunopathology was directly associated with these cross-reactive NP205-specific CD8 memory cells. In conclusion, the inherent competition between two simultaneous immune responses results in significant alterations in T cell immunity and subsequent disease outcome upon reexposure. IMPORTANCE Combination vaccines and simultaneous administration of vaccines are necessary to accommodate required immunizations and maintain vaccination rates. Antibody responses generally correlate with

  15. Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells.

    PubMed

    Currier, Jenna M; Cheng, Wan-Yun; Menendez, Daniel; Conolly, Rory; Chorley, Brian N

    2016-01-01

    Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2-10 μM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p < 0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the

  16. Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells

    PubMed Central

    Currier, Jenna M.; Cheng, Wan-Yun; Menendez, Daniel; Conolly, Rory; Chorley, Brian N.

    2016-01-01

    Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 2–10 μM Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p < 0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the

  17. Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood.

    PubMed

    Buchmann, Arlette F; Holz, Nathalie; Boecker, Regina; Blomeyer, Dorothea; Rietschel, Marcella; Witt, Stephanie H; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Brandeis, Daniel; Zimmermann, Ulrich S; Laucht, Manfred

    2014-06-01

    Recent research suggests an important role of FKBP5, a glucocorticoid