Environmental factors are likely contributing factors in the development of Rheumatoid Arthritis (RA), an autoimmune disease, for which etiologic factors are still poorly known. Mineral oils are efficient adjuvants which increase immunological responses and are used in animal immunization and for induction of different experimental autoimmune diseases including arthritis. The relationship between environmental exposure to mineral oil and the risk of developing RA is the ...
Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Gardner, Jeffrey R.; LIVINGSTON, PHILIP O.; Ragupathi, Govind; Tan, Derek S.; Gin, David Y.
Immunoadjuvants are used to potentiate the activity of modern subunit vaccines that are based on molecular antigens. An emerging approach involves the combination of multiple adjuvants in a single formulation to achieve optimal vaccine efficacy. Herein, to investigate such potential synergies, we synthesized novel adjuvant conjugates based on the saponin natural product QS-21 and the aldehyde tucaresol via chemoselective acylation of an amine at the terminus of the acyl chain domain in QS sap...
While biomaterials provide a platform to control the delivery of vaccines, the recently discovered intrinsic inflammatory characteristics of many polymeric carriers can also complicate rational design because the carrier itself can alter the response to other vaccine components. To address this challenge, we recently developed immune-polyelectrolyte multilayer (iPEMs) capsules electrostatically assembled entirely from peptide antigen and molecular adjuvants. Here, we use iPEMs built from SIINFEKL model antigen and polyIC, a stimulatory toll-like receptor agonist, to investigate the impact of pH on iPEM assembly, the processing and interactions of each iPEM component with primary immune cells, and the role of these interactions during antigen-specific T cell responses in coculture and mice. We discovered that iPEM assembly is pH dependent with respect to both the antigen and adjuvant component. Controlling the pH also allows tuning of the relative loading of SIINFEKL and polyIC in iPEM capsules. During in vitro studies with primary dendritic cells (DCs), iPEM capsules ensure that greater than 95% of cells containing at least one signal (i.e., antigen, adjuvant) also contained the other signal. This codelivery leads to DC maturation and SIINFEKL presentation via the MHC-I antigen presentation pathway, resulting in antigen-specific T cell proliferation and pro-inflammatory cytokine secretion. In mice, iPEM capsules potently expand antigen-specific T cells compared with equivalent admixed formulations. Of note, these enhancements become more pronounced with successive booster injections, suggesting that iPEMs functionally improve memory recall response. Together our results reveal some of the features that can be tuned to modulate the properties of iPEM capsules, and how these modular vaccine structures can be used to enhance interactions with immune cells in vitro and in mice. PMID:27380137
Ouyang, Ke; Chen, Liqing; Sun, Hongxiang; Du, Jing; Shi, Minghua
In this study, the total saponins from the root of Platycodon grandiflorum (PGS(t)) was subjected to D101 macroreticular resin column chromatography to afford four fractions (PGS₃₀, PGS₅₀, PGS₇₅ and PGS₉₅). PGS(t) and its four fractions were evaluated and compared for the haemolytic activities and adjuvant potentials on the specific cellular and humoral immune responses of ICR mice against recombinant hepatitis B surface antigen (HBsAg). PGS(t), PGS₃₀, PGS₅₀, PGS₇₅, and PGS₇₅ showed a slight haemolytic effect, with their concentration inducing 50% of the maximum haemolysis (HD₅₀) being 16.13 ± 0.81, >200, 17.53 ± 0.24, 20.16 ± 0.76, 76.31 ± 2.20 μg/mL against 0.5% rabbit red blood cell, respectively. PGS(t), PGS₅₀, and PGS₇₅ significantly not only enhanced the Con A-, lipopolysaccharide-, and HBsAg-induced splenocyte proliferation, but promoted the killing activities of natural killer (NK) cells from splenocytes in HBsAg-immunized mice (P < 0.01 or P < 0.001). HBsAg-specific IgG, IgG1, IgG2a, and IgG2b antibody levels in serum were also significantly enhanced by PGS(t), PGS₅₀, and PGS₇₅ compared with HBsAg control group (P < 0.05, P < 0.01, or P < 0.001). Moreover, the adjuvant effects of PGS₅₀ and PGS₇₅ on the cellular immune responses and HBsAg-specific IgG2a and IgG2b antibody responses were more significant than those of Alum, PGS₃₀, and PGS₉₅. The results indicated that PGS₅₀ and PGS₇₅ could improve both cellular and humoral immune responses, and elicit a balanced Th1/Th2 response to HBsAg in mice, and that PGS₇₅ may be developed as an ideal candidate adjuvant for hepatitis B vaccine. PMID:21682667
Cruz, Maria de Fátima Simão Jucá; Pereira, Gabriela Moysés; Ribeiro, Marcela Gonçalves; da Silva, Ari Miranda; Tinoco, Luzineide Wanderley; da Silva, Bernadete Pereira; Parente, José Paz
As part of our search of bioactive saponins from Brazilian plants, phytochemical study of the seeds of Inga laurina led to the isolation of a new complex triterpenoid saponin, named ingasaponin. It is the first saponin isolated from a species of Inga genus. It was isolated by using chromatographic methods and its structural elucidation was performed using detailed analyses of (1)H and (13)C NMR spectra including 2D-NMR spectroscopic techniques and chemical conversions. Its structure was established as 21-[[(2E,6S)-6-[[6-deoxy-4-O-[(2E,6S)-6-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2,6-dimethyl-1-oxo-2,7-octadienyl]-[(β-D-glucopyranosyl)oxy]-2-(hydroxymethyl)-6-methyl-1-oxo-2,7-octadienyl]oxy]-16-hydroxy-3-[[O-β-D-xylopyranosyl-(1 → 2)-O-α-L-arabinopyranosyl-(1 → 6)-2-(acetylamino)-2-deoxy-β-D-glucopyranosyl]oxy]-(3β,16α,21β)-olean-12-en-28-oic acid O-α-L-arabinofuranosyl-(1 → 4)-O-[β-D-glucopyranosyl-(1 → 3)]-O-6-deoxy-α-L-mannopyranosyl-(1 → 2)-β-D-glucopyranosyl ester (1). The hemolytic potential of 1 was evaluated using in vitro assays, and its adjuvant activity on the cellular immune response against ovalbumin antigen was investigated using in vivo models. PMID:26717546
Temporal profile of magnetic resonance angiography and decreased ratio of regulatory T cells after immunological adjuvant administration to mice lacking RNF213, a susceptibility gene for moyamoya disease.
Kanoke, Atsushi; Fujimura, Miki; Niizuma, Kuniyasu; Fujimura, Taku; Kakizaki, Aya; Ito, Akira; Sakata, Hiroyuki; Sato-Maeda, Mika; Kure, Shigeo; Tominaga, Teiji
Moyamoya disease (MMD) is a chronic, occlusive cerebrovascular disease with an unknown etiology and is characterized by an abnormal vascular network at the base of the brain. Recent studies identified the RNF213 gene (RNF213) as an important susceptibility gene for MMD; however, the mechanisms underlying the RNF213 abnormality related to MMD have not yet been elucidated. We previously reported that Rnf213-deficient mice and Rnf213 p. R4828K knock-in mice did not spontaneously develop MMD, indicating the importance of secondary insults in addition to genetic factors in the pathogenesis of MMD. The most influential secondary insult is considered to be an immunological reaction because RNF213 is predominantly expressed in immunological tissues. Therefore, we herein attempted to evaluate the role of an immunological stimulation as a supplementary insult to the target disruption of RNF213 in the pathophysiology of MMD. Rnf213-deficient mice were treated with strong immunological adjuvants including muramyl dipeptide (MDP)-Lys (L18), and then underwent time-sequential magnetic resonance angiography (MRA) up to 40 weeks of age. The results obtained did not reveal any characteristic finding of MMD, and no significant difference was observed in MRA findings or the anatomy of the circle of Willis between Rnf213-deficient mice and wild-type mice after the administration of MDP-Lys (L18). The ratio of regulatory T cells after the administration of MDP-Lys (L18) was significantly decreased in Rnf213-deficient mice (p<0.01), suggesting the potential role of the RNF213 abnormality in the differentiation of regulatory T cells. Although the mechanisms underlying the development of MMD currently remain unclear, the RNF213 abnormality may compromise immunological self-tolerance, thereby contributing to the development of MMD. PMID:26972532
Francesca Sabbatini; Alessandra Bandera; Giulio Ferrario; Daria Trabattoni; Giulia Marchetti; Fabio Franzetti; Mario Clerici; Andrea Gori
BACKGROUND: Treatment of HIV-infected patients with interleukin-2 (IL-2) produces significant increases in CD4 T cell counts; however an associated qualitative improvement in cells function has yet to be conclusively demonstrated. By measuring mycobacterial killing activity, we evaluated IL-2-mediated functional immune enhancement ex vivo in immunological non-responders (INRs). METHODS AND FINDINGS: PBMC from 12 immunological non-responders (INRs) (CD4+
Veselský, Leopold; Dostál, Jaromír; Železná, Blanka; Jurčovicová, J.; Holáň, Vladimír; Zajícová, Alena; Jonáková, Věra
Elsevier. Roč. 87, 1-3 (2003), s. 119. ISSN 0165-2478. [European Immunology Congress /15./. 08.06.2003-12.06.2003, Rhodes Island] Institutional research plan: CEZ:AV0Z5052915; CEZ:AV0Z5045916 Keywords : rat Subject RIV: ED - Physiology
@@ To the Editor: A recent article entitled "HIV-1 DNA vaccine with adjuvant cytokines induces specific immune responses against HIV-1 infection in mice"was published in the Chinese Medical Journal.1 The authors descriptively analyzed the adjuvant potential of an interleukin-12 (IL-12), interleukin-18 (IL-18),regulated on activation of normal T-cell expressed and secreted factor (RANTES), macrophage inflammatory protein 1 alpha (MIP-1α) or stromal cell derived factor 1 (SDF-1) plasmid when coimmunized with an HIV Gag gene-based DNA vaccine. Consequently the authors believed that IL-12, IL-18, or SDF-1 plasmid DNA potentially serves as immune adjuvants in combination with therapeutic HIV-1 DNA vaccine. The RANTES,MIP-1α plasmid DNA potentially serves as immune adjuvants in combination with HIV-1 prophylactic vaccine. Although the experiment allows us to consider such a coinoculation strategy as one of the means against HIV-1 infection, some special attentions should be highlighted.
Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866
Aljurayyan, A N; Sharma, R; Upile, N; Beer, H; Vaughan, C; Xie, C; Achar, P; Ahmed, M S; McNamara, P S; Gordon, S B; Zhang, Q
T Follicular helper cells (TFH) are considered critical for B cell antibody response, and recent efforts have focused on promoting TFH in order to enhance vaccine efficacy. We studied the frequency and function of TFH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti-influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes TFH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant TFH, suggesting efficient priming of TFH during early childhood. Stimulation by LAIV induced a marked increase in TFH that correlated with a strong production of anti-hemagglutinin (HA) IgA/IgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in TFH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of TFH, and addition of plasmacytoid dendritic cell to TFH-B cell co-culture enhanced the TFH-mediated antibody production following CpG-DNA and sH1N1 antigen stimulation. Induction of TFH differentiation from naïve T cells was also shown following the stimulation. Our results support a critical role of TFH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote TFH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens. PMID:27247060
Environmental microbiology does not deal with all aspects of immunology or the immune responses per se, but instead adapts immunology-based research technologies or immunoassays for the study of microorganisms and chemical contaminants in association with the environment. The primary immunologic-bas...
Ragupathi, Govind; Damani, Payal; Deng, Kai; Adams, Michelle M.; Hang, Jianfeng; George, Constantine; LIVINGSTON, PHILIP O.; Gin, David Y.
The saponin fraction QS-21 from Quillaja saponaria has been demonstrated to be a potent immunological adjuvant when mixed with keyhole limpet hemocyanin conjugate vaccines, as well as with other classes of subunit antigen vaccines. QS-21 adjuvant is composed of two isomers that include the apiose and xylose forms in a ratio of 65:35, respectively. The chemical syntheses of these two isomers in pure form have recently been disclosed. Herein we describe detailed in vivo immunological evaluation...
Hansen, Jitka Stilund; Larsen, Søren Thor; Poulsen, Lars K.;
) or on lung function parameters. Thus, MP did not possess irritant or inflammatory properties, which may be a precursive stimulus for adjuvant effects. Second, mice were exposed to aerosols of MP, 6 or 323 mg/m3, for 1 h followed by a 20-min low-dose ovalbumin (OVA) inhalation. OVA only and OVA + Al......Anthopogenically introduced substances and pollutants are suspected to promote sensitization and development of allergic airway diseases, that is, acting as adjuvants. Lipophilicity may serve as an immunological warning signal, promoting adjuvant effects. Whether the lipophilicity of an inhaled...... compound induces immunomodulatory effects was investigated in a murine inhalation model with the highly lipophilic methyl palmitate (MP) as model substance. First, studies of acute effects following a 1-h exposure of up to 348 mg/m3 MP showed no effects on cell composition in bronchoalveolar lavage (BAL...
Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; LIVINGSTON, PHILIP O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.
Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability, and an enigmatic molecular mechanism of action. Herein, we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the enti...
Fox, Christopher B
The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characterization of adjuvant-antigen interactions, the rational formulation design of a CD8+ T cell-inducing adjuvant based on immunological principles, and the development and production of a rabies vaccine by a developing country manufacturer. Throughout the session, the practical importance of sound formulation and manufacturing design accompanied by analytical characterization was highlighted. PMID:23787558
Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio
As immunology continues to evolve, many educational methods have found difficulty in conveying the degree of complexity inherent in its basic principles. Today, the teaching-learning process in such areas has been improved with tools such as educational software. This article introduces "Virtual Immunology," a software program available…
Dace Skrastina; Ivars Petrovskis; Ilva Lieknina; Janis Bogans; Regina Renhofa; Velta Ose; Andris Dishlers; Yuri Dekhtyar; Paul Pumpens
Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisatio...
Takemi Otsuki; Fuminori Hyodoh; Ayako Ueki; Yasumitsu Nishimura; Megumi Maeda; Shuko Murakami; Hiroaki Hayashi; Yoshie Miura; Masayasu Kusaka; Takashi Nakano; Kazuya Fukuoka; Takumi Kishimoto
Silicosis patients (SILs) and patients who have been exposed to asbestos develop not only respiratory diseases but also certain immunological disorders. In particular, SIL sometimes complicates autoimmune diseases such as systemic scleroderma, rheumatoid arthritis (known as Caplan syndrome), and systemic lupus erythematoses. In addition, malignant complications such as lung cancer and malignant mesothelioma often occurr in patients exposed to asbestos, and may be involved in the reduction of tumor immunity. Although silica-induced disorders of autoimmunity have been explained as adjuvant-type effects of silica, more precise analyses are needed and should reflect the recent progress in immunomolecular findings. A brief summary of our investigations related to the immunological effects of silica/asbestos is presented. Recent advances in immunomolecular studies led to detailed analyses of the immunological effects of asbestos and silica. Both affect immuno-competent cells and these effects may be associated with the pathophysiological development of complications in silicosis and asbestos-exposed patients such as the occurrence of autoimmune disorders and malignant tumors, respectively. In addition,immunological analyses may lead to the development of new clinical tools for the modification of the pathophysiological aspects of diseases such as the regulation of autoimmunity or tumor immunity using cellmediated therapies, various cytokines, and molecule-targeting therapies. In particular, as the incidence of asbestosrelated malignancies is increasing and such malignancies have been a medical and social problem since the summer of 2005 in Japan, efforts should be focused on developing a cure for these diseases to eliminate nationwide anxiety.
Fernández-Tejada, Alberto; Chea, Eric K.; George, Constantine; Pillarsetty, Nagavarakishore; Gardner, Jeffrey R.; Livingston, Philip O.; Ragupathi, Govind; Lewis, Jason S.; Tan, Derek S.; Gin, David Y.
Adjuvants are materials added to vaccines to enhance the immunological response to an antigen. QS-21 is a natural product adjuvant under investigation in numerous vaccine clinical trials, but its use is constrained by scarcity, toxicity, instability and an enigmatic molecular mechanism of action. Herein we describe the development of a minimal QS-21 analogue that decouples adjuvant activity from toxicity and provides a powerful platform for mechanistic investigations. We found that the entire branched trisaccharide domain of QS-21 is dispensable for adjuvant activity and that the C4-aldehyde substituent, previously proposed to bind covalently to an unknown cellular target, is also not required. Biodistribution studies revealed that active adjuvants were retained preferentially at the injection site and the nearest draining lymph nodes compared with the attenuated variants. Overall, these studies have yielded critical insights into saponin structure-function relationships, provided practical synthetic access to non-toxic adjuvants, and established a platform for detailed mechanistic studies.
Garret, Simon; Walker, Joanne; Wilson, William; Aickelin, Uwe
Accurate immunological models offer the possibility of performing highthroughput experiments in silico that can predict, or at least suggest, in vivo phenomena. In this chapter, we compare various models of immunological memory. We first validate an experimental immunological simulator, developed by the authors, by simulating several theories of immunological memory with known results. We then use the same system to evaluate the predicted effects of a theory of immunological memory. The resulting model has not been explored before in artificial immune systems research, and we compare the simulated in silico output with in vivo measurements. Although the theory appears valid, we suggest that there are a common set of reasons why immunological memory models are a useful support tool; not conclusive in themselves.
Belozersky V. I.
Full Text Available A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of action on immune system and theirinteraction with antigens. They’re given examples of different adjuvants in licensed vaccines use.
Belozersky V. I; Zhdamarova L.A.; Yelyseyeva I. V; Babych Ye. M.; Isaenko Ye. Yu.; Kolpak S. A
A concept of adjuvants and their story of creation ischaracterized in the article. They’re presented thevarious types of non-specific stimulators of immunesysteme, thier excipients and classification. They’redescribed basic properties of adjuvant systems, their significant advantages and disadvantages. Particular attention is paid to the numerous antigen delivery systems, including alive vectors, nanoparticles, bacterial toxins, etc. They’re considered non-specific stimulators mechanisms of a...
This report summarizes the available information on the immunology of filariasis, and discusses immunodiagnosis and the immunological factors influencing the host—parasite relationship in lymphatic filariasis and onchocerciasis. Several areas that require further research are identified, particularly concerning the development of new serological techniques, and the fractionation of specific antigens. The problems associated with vaccine development are considered and the importance of finding...
Claman, Henry N.
Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)
MUSHA, Muhetaerjiang; Hirai, Shuichi; Naito, Munekazu; Terayama, Hayato; Qu, Ning; Hatayama, Naoyuki; Itoh, Masahiro
Abstract Experimental autoimmune orchitis (EAO) is a model of immunologic male infertility and pathologically characterized by lymphocytic inflammation, which causes breakdown of the testicular immune privilege with spermatogenic disturbance. Generally, murine EAO is induced by immunization with testicular homogenate (TH) from the testes of donor mice + complete Freund's adjuvant (CFA) + Bordetella pertussigens (BP), and it has been considered that treatment with these two adjuvants is requir...
Chen, K S; Johnson, D. W.; Muscoplat, C C
Potentiation of the antibody response to inactivated bovine viral diarrhea virus by immunological adjuvants was studied in guinea pigs and cattle. The inactivated bovine viral diarrhea virus alone was demonstrated to be a weak immunogen. Addition of either 2 mg per mL diethylaminoethyl-dextran or 5% alhydrogel to inactivated bovine viral diarrhea virus did not or only slightly stimulated the antibody response; the combined adjuvants induced a significantly higher titer. A higher concentration...
Siminovitch, K A
Among the biomedical sciences, immunology stands out as a discipline in which knowledge emanating from fundamental research has rapidly been transferred to the clinical paradigm, with consequent improvement in human health. Virtually all medical subspecialties have benefitted from diagnostic reagents and technologies provided by basic immunology. In terms of numbers of lives saved, immunologic-based therapeutic strategies, most notably vaccination, rank among the most effective measures ever achieved by medical intervention. Yet, despite immunology's profound impact on medicine and the longstanding recognition of many of the general principles and cellular components involved in immunity, until relatively recently, the operational workings of the immune system eluded precise definition. The abstract nature of the immune system rendered the field intangible or, at the very least, confusing, to the nonimmunologic medical community. However, in recent years, this situation has changed radically, as cell cloning, hybridoma, and recombinant DNA technologies have provided the means to delineate the precise immunologic cellular structures and interactions. The purpose of this review is to highlight a few of the most significant advances in immunology during the past decade, and to show how they have made possible the translation of abstract concepts of classical immunology into tangible, structural information. Striking gains in the understanding of antigen recognition, one of the most fundamental aspects of immunity, are described as an illustrative case. PMID:1640405
Skov, J.; Chettri, J. K.; Jaafar, R. M.;
Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were the...
Gogas, Helen; Abali, Huseyin; Ascierto, Paolo A; Demidov, Lev; Pehamberger, Hubert; Robert, Caroline; Schachter, Jacob; Eggermont, Alexander M M; Hauschild, Axel; Espinosa, Enrique
Metastatic melanoma has a poor prognosis; the median survival for patients with stage IV melanoma ranges from 8 to 18 months after diagnosis. Interferon-α provides significant improvement in disease-free survival at the cost of poor tolerability. Identifying patients who benefit the most may improve the cost:benefit ratio. In addition, no data exist for the role of adjuvant therapy in noncutaneous melanoma. Molecular profiles may help to identify patients who benefit the most from adjuvant interferon therapy. In this review, the American Joint Commission on Cancer 2009 staging criteria and emerging biomarker data to guide adjuvant treatment decisions will be discussed. Several criteria to guide selection of patients are discussed in detail. These include Breslow thickness, number of positive lymph nodes, whether or not the primary lesion has ulcerated, immunologic markers, and cytokine profiles. Substantial progress has been made in deciding which patients benefit from interferon-α adjuvant therapy. Interferon-α is the only agent currently approved for the adjuvant treatment of this deadly disease, despite its side effect profile. More effective drugs with better tolerability are needed. PMID:24176884
Immunology is the study of the structure and function of the immune system. The immune system consists of an earlier-stage innate immunity and a later-stage adaptive immunity. The task of the immune system is to efficiently respond to non-self antigens and the invasion of pathogens, thereby protecting the host's homeostasis. This review article discusses the structure and function of the epididymis, including the composition of the epithelial cells of the epididymis and their relationship to the immune system, through the assessment of alterations in the immune cells of the epididymis. The review also shows the anti-inflammatory properties of rat epididymal defensin and the description of the blood-epididymis barrier, immune barrier, epididymitis and pathological mechanisms of infertility in males. Taken together, we see that the epididymis possesses a close link with immunology. Finally, this review discusses the future of studies involving epididymal immunology.
Doria, Gino; Koch, Giorgio; Strom, Roberto
This volume collects the contributions presented at the "Working Conference on System Theory in Immunology", held in Rome, May 1978. The aim of the Conference was to bring together immunologists on one side and experts in system theory and applied mathematics on the other, in order to identify problems of common interest and to establish a network of joint effort toward their solution. The methodologies of system theory for processing experimental data and for describing dynamical phenomena could indeed contribute significantly to the under standing of basic immunological facts. Conversely, the complexity of experimental results and of interpretative models should stimulate mathematicians to formulate new problems and to design appropriate procedures of analysis. The multitude of scientific publications in theoretical biology, appeared in recent years, confirms this trend and calls for extensive interaction between mat- matics and immunology. The material of this volume is divided into five sections, along ...
Smith, D.J.; Forrest, S. [New Mexico Univ., Albuquerque, NM (United States). Dept. of Computer Science; Perelson, A.S. [Los Alamos National Lab., NM (United States)
The purpose of this paper is to show that immunological memory is an associative and robust memory that belongs to the class of sparse distributed memories. This class of memories derives its associative and robust nature by sparsely sampling the input space and distributing the data among many independent agents. Other members of this class include a model of the cerebellar cortex and Sparse Distributed Memory (SDM). First we present a simplified account of the immune response and immunological memory. Next we present SDM, and then we show the correlations between immunological memory and SDM. Finally, we show how associative recall in the immune response can be both beneficial and detrimental to the fitness of an individual.
İlknur Aydın; Behice Erci
Infertility has been serious problem for couples that want to have a child. It is estimated that %10-15 of marriages are involuntary childless; that is, there is the serious problem of infertility. In more than 40% of infertility couples that is the reason of their infertility was unknown. In those couples, probably immunological factors were found to be responsible for the infertility. In the article, it was aimed to review the immunologic causes of male and female infertility in the light o...
Full Text Available Infertility has been serious problem for couples that want to have a child. It is estimated that %10-15 of marriages are involuntary childless; that is, there is the serious problem of infertility. In more than 40% of infertility couples that is the reason of their infertility was unknown. In those couples, probably immunological factors were found to be responsible for the infertility. In the article, it was aimed to review the immunologic causes of male and female infertility in the light of the current scientific data.
Full Text Available Infertility has been serious problem for couples that want to have a child. It is estimated that %10-15 of marriages are involuntary childless; that is, there is the serious problem of infertility. In more than 40% of infertility couples that is the reason of their infertility was unknown. In those couples, probably immunological factors were found to be responsible for the infertility. In the article, it was aimed to review the immunologic causes of male and female infertility in the light of the current scientific data.
MOK, KENNETH; O'Farrelly, Cliona
Obesity is characterized by chronic inflammation associated with neutrophil and M1 macrophage infiltration into white adipose tissue. However, the mechanisms underlying this process remain largely unknown. Based on the ability of oil-based adjuvants to induce immune responses, we hypothesized that endogenous oils derived from necrotic adipocytes may function as an immunological "danger signal." Here we show that endogenous oils of human origin are potent adjuvants, enhancing antibody response...
Chinen, Javier; Shearer, William T.
Progress in immunology continues to grow exponentially every year. New applications of this knowledge are being developed for a broad range of clinical conditions. Conversely, the study of primary and secondary immunodeficiencies is helping to elucidate the intricate mechanisms of the immune system. We have selected a few of the most significant contributions to the fields of basic and clinical immunology published between October 2001 and October 2002. Our choice of topics in basic immunology included the description of T-bet as a determinant factor for T(H)1 differentiation, the role of the activation-induced cytosine deaminase gene in B-cell development, the characterization of CD4(+)CD25(+) regulatory T cells, and the use of dynamic imaging to study MHC class II transport and T-cell and dendritic cell membrane interactions. Articles related to clinical immunology that were selected for review include the description of immunodeficiency caused by caspase 8 deficiency; a case series report on X-linked agammaglobulinemia; the mechanism of action, efficacy, and complications of intravenous immunoglobulin; mechanisms of autoimmunity diseases; and advances in HIV pathogenesis and vaccine development. We also reviewed two articles that explore the possible alterations of the immune system caused by spaceflights, a new field with increasing importance as human space expeditions become a reality in the 21st century.
Klemmensen, Thomas; Pedersen, Lars Ostergaard; Geisler, Carsten
distinct 3-dimensional supramolecular structure at the T cell/APC interface has been suggested to be involved in the information transfer. Due to its functional analogy to the neuronal synapse, the structure has been termed the "immunological synapse" (IS). Here, we review molecular aspects concerning IS...
Dahlén, Gunnar; Fiehn, Nils-Erik; Olsen, Ingar
, dental assistants and trainees may find it a useful source of reference. The contents are based on general microbiology and immunology. Oral microbiology is given particular attention, with examples relevant to oral infectious diseases. Each chapter opens with a relatively short pre-reading section...
Dawson, Jeffrey R.; And Others
This monograph was designed for the high school biology curriculum. The first section reviews the major areas of importance in immunology. Section three contains six instructional activities for the high school classroom and the second section contains teacher's materials for those activities. The activities address for students some of the major…
Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)
The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins
Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)
HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.
Richard Kim; John Chabot; Muhammad Wasif Saif
Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO) Annual Meeting, the largest trial (Abstract #4006) evaluating adjuvant treatment of ampullary cancer was presented.
Full Text Available Ampullary cancer is an uncommon tumor and tends to have a better prognosis than pancreatic cancer. However, one half of patients will die from recurrent disease suggesting the need for effective adjuvant therapy. Currently, there is lack of randomized trials to guide the use of adjuvant therapy in ampullary cancer. At the 2011 American Society of Clinical Oncology (ASCO Annual Meeting, the largest trial (Abstract #4006 evaluating adjuvant treatment of ampullary cancer was presented.
Ursem, Carling; Van Loon, Katherine; Venook, Alan
In 2015, ramucirumab and TAS-102 became the 10th and 11th drugs approved by the Food and Drug administration for the treatment of patients with colorectal cancer, not counting leucovorin, and yet only 3 agents, 5-fluorouracil, capecitabine, and oxaliplatin, have proven benefit in adjuvant treatment. In fact, there have been no additions (and 1 subtraction levamisole) to our arsenal of therapies for patients with stages II and III colon cancer for more than a decade. How did we get here? Are we stuck? And how do we move forward? PMID:27341598
There is increasing interest in establishing diagnostic markers of immunological tolerance applicable to efforts to minimize drug immunosuppression in transplantation and chronic immunological diseases. It is hoped that an understanding of the diverse mechanisms that can contribute to tolerance will guide efforts to establish diagnostic tolerance biomarkers. Not only would these be valuable for management of autoimmune diseases, transplants and allergies, but they might also guide efforts to override tolerance processes in cancer and vaccine development. Where tolerance is generated by deletion or inactivation of antigen reactive lymphocytes, it is unlikely that any long-term-valid blood biomarkers might be found. Where tolerance is mediated by active regulatory mechanisms, indicators that can be usefully measured may emerge, but these would likely show significant heterogeneity reflecting the diversity of active tolerance processes operating in different individuals. Given this, the most useful "kits" might be those "smart" enough to detect this diversity of tolerance players. PMID:26036868
Babu, Subash; Nutman, Thomas B.
The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-stan...
Angela S Clem
From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s) by which immunizations stimulate(s) immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of bo...
Giacomucci, E; Bulletti, C; Polli, V; Prefetto, R A; Flamigni, C
Roughly 20% of all clinical pregnancies evolve into "spontaneous abortions". The causes of spontaneous abortion have been determined in under 60% of the total and comprise genetic, infectious, hormonal and immunological factors. In some cases the immune tolerance mechanism may be impaired and the foetus immunologically rejected (IMA, immunologically mediated abortion). The immunological mechanism implicated depends on the time in which pregnancy loss takes place. During preimplantation and up to the end of implantation (13th day) the cell-mediated immune mechanism (potential alloimmune etiologies) is responsible for early abortion. This mechanism involves immunocompetent decidual cells (eGL, endometrial granulated lymphocytes) already present during pre-decidualization (late luteal phase) and their production of soluble factors or cytokines. Once the implantation process is over, after blastocyst penetration of the stroma and the decidual reaction of uterine tissue, IMA could be caused by cell-mediated and humoral mechanism (anti-paternal cytotoxic antibodies or autoantibody etiology), by the production of paternal anti major histocompatibility complex antibodies, or even by an autoimmune disorder leading to the production of autoantibodies (antiphospholipid antibodies, antinuclear antibodies or polyclonal B cell activation). The diagnostic work-up adopted to select IMA patients is crucial and includes primary (karyotype of both partners, toxo-test, hysterosalpingography, endometrial biopsy, thyroid function tests, serum hprolactin, luteal phase dating) and secondary (full hemochromocytometric test, search for LE cells, lupus anticoagulant, anticardiolipin, antinuclear antibodies, Rheumatoid factor, blood complement VDRL) investigations. Therapeutical approaches vary. If autoimmune disorders are demonstrated therapies with different combinations of corticosteroids, aspirin and heparin or intravenous immunoglobulin are administered. Otherwise, therapy with paternal
In the present study, sciatic nerve tissues of the cat were emulsified with the complete Freund's adjuvant and injected into the foot-pads of the guinea pig. Frozen and frozen-irradiated feline sciatic nerve tissues were treated in the similar manner, and their encephalitogenicity was comparatively studied. Affected animals became skinny, weak in the hind limbs and sometimes solid their tails. Antigenic mixtures of the fresh peripheral nerves with adjuvant have sensitized 75% (15 out of 20) of guinea pigs, whereas none of the 41 animals manifested any sign of experimental allergic neuritis (EAN) after intradermal Frozen-preserved peripheral nerve-adjuvant mixtures gave rise to EAN in 29% (6 out of 21) of guinea pigs. The present results appear to show that the electron-beam irradiation might have modified the specific chemical structures of the myelin basic protein to completely suppress the encephalitogenicity of the peripheral nerve-tissues. High-voltage cathode irradiations would be capable of depressing the antigenicity of the transplantation immunology when the antigenic determinants have the chemical structures in common with the encephalitogenic antigens. Excessive amount of the irradiation used to result in severe tissue damages, therefore, an optimum dosis of electron-beams should be determined for each tissue destined for grafting. As the frozen peripheral nerve-adjuvant mixtures have been less encephalitogenic, freezing alone might well be considered partially to improve the acceptability of the grafts. Cryopreservation of the irradiated allografts would be worth further studying. (author)
In February 1985 a small international meeting of scientists took place at the recreation resort of the Polish Academy of Sci ences in Mogilany, near Cracow, Poland. The initiative for holding the workshop came from a working meeting on mathematical immunology and related topics at the International Institute for Applied Sys tems Analysis in Laxenburg, Austria, in November 1983. In addition to representatives of IIASA, delegates of the IIASA National Member Organizations (NMO) of Czechoslovakia, Italy, and the soviet Union took part in that working meeting. The participants came to the conclusion that IIASA could play an important role in facilitating the development of research in this field. The first step that they recommended to I IASA was to organize a workshop on mathematical immunology. The purpose of the workshop was to review the progress that has been made in applying mathematics to problems in immunology and to explore ways in which further progress might be achieved, especially by more efficie...
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 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 current study involved a determination of the effects of flight on Cosmos mission 2044 on leukocyte subset distribution and the sensitivity of bone marrow cells to colony stimulating factor-GM. A parallel study with antiorthostatic suspension was also carried out. The study involved repetition and expansion of studies carried out on Cosmos 1887.
SHI PING ZHAO; JIAN MIN LI; GUI XIANG FU; YONG ZHOU
The aim of this study was to explore the effect of Cornus officinalis glucosides (COG) on adjuvant-induced arthritis in rats and its mechanism. Seventy-two rats were divided into six groups of normal, model, Dexasone (0. 125 mg/kg), high-dose COG (240 mg/kg), mid-dose COG (120 mg/kg),and low-dose COG (60 mg/kg). Rat arthritis was induced by injection of Freund's complete adjuvant in the hind paws. All treatment started from the day the arthritis was induced. The edema degree of the adjuvant injection location was determined on days 1, 3, 5, 7, 9, 11, 13, 15, 17, 20, 23 and the opposite side was observed on days 11, 13, 15, 17, 20, 23 after the injection of adjuvant. All rats were sacrificed on day 24 after the injection of adjuvant for microscopic examination of the ankle, and for the study of the immunological molecular mechanism. The results showed that the COG significantly suppressed both the primary and secondary edema, improved pathological injuries of adjuvant arthritis (AA)rat ankles, significantly suppressed the proliferation of T lymphocytes and DTH reaction. It significantly suppressed IL-1, IL-6 and TNF-α production from peritoneal macrophages and PGE2 in plasma. In conclusion, the Cornus officinalis glucosides (COG) is able to prevent and cure the rat adjuvant-induced arthritis, and can suppress the production of pro-inflammatory cytokine IL-1, IL-6, TNF-α and PGE2.
The management of colon and rectal cancer has changed dramatically over the last 25 years. The use of adjuvant therapies has become standard practice in locally advanced (stage Ⅲ and selected stage Ⅱ) colorectal cancer. Improved surgical techniques, chemotherapeutics and radiotherapy are resulting in higher cure rates and the development of agents targeting proliferative and angiogenic pathways offer further promise. Here we explore risk factors for local and distant recurrence after resection of colon and rectal cancer, and the role of adjuvant treatments. Discussion will focus on the evidence base for adjuvant therapies utilised in colorectal cancer, and the treatment of sub-groups such as the elderly and stage Ⅱ disease. The role of adjuvant radiotherapy in rectal cancer in reduction of recurrence will be explored and the role and optimal methods for surveillance post-curative resection with or without adjuvant therapy will also be addressed.
Kimzey, S. L.
A coordinated series of experiments were conducted to evaluate immunologic and hemotologic system responses of Skylab crewmen to prolonged space flights. A reduced PHA responsiveness was observed on recovery, together with a reduced number of T-cells, with both values returning to normal 3 to 5 days postflight. Subnormal red cell count, hemoglobin concentration, and hematocrit values also returned gradually to preflight limits. Most pronounced changes were found in the shape of red blood cells during extended space missions with a rapid reversal of these changes upon reentry into a normal gravitational environment.
Chinese Society of Immunology (CSI) was founded in 1984. It has had over 5000 members, among whom 1000 are members of IUIS. There are six Chinese periodicals associated with the Society: Chinese Journal of Immunology, Immunological Journal, Current Immunology, Chinese Journal of Cellular and Molecular Immunology; Chinese Journal of
Chinese Socicty of Immunology (CSI) was founded in 1984. It has had over 5000 members, among whom 1000 are members of IUIS. There are six Chinese periodicals associated with the Society: Chinese Journal of Immunology,Immunological Journal,Current Immunology,Chinese Journal of Cellular and Molecular Immunology,Chinese Journal of
M. L. Chuhlovina
Full Text Available Reduced incidence of syphilis was reported in Russia over last years, along with increased prevalence of neurosyphilis. The issues of the mechanisms of the damage of nervous system and the immune response to syphilis are actual. Origin of syphilis antibodies from cerebrospinal fluid of patients with neurosyphilis is considered. The role of intrathecal immunoglobulin production and dysfunction of blood-brain barrier in patients infected with syphilis is of special importance. The aim of the research was to analyze the immunological aspects of neurosyphilis. Polymorphonuclear leukocytes have been shown to play an important role in infection with Treponema pallidium during clearance of the pathogenes. Potential virulence factors of Treponema pallidium have been discovered. It has been found that cell-mediated immune response is very important for defense against Treponema pallidium, while the key importance in bacterial clearance is put on Th1. Evidence has shown that the level of cytokines which are secreted by Th1 (IL-2, interferon gamma and tumor necrosis factor and Th2 (IL-6 and IL-10 — lymphocytes, correlates with syphilis progression. The role of IL-10 in immune response regulation in patients infected with syphilis has been examined: this cytokine can inhibit the activity of immunocompetent cells. Some data has been produced concerning intrathecal production of immunoglobulins in neurosyphilis patients’ cerebrospinal fluid. The research of immunological parameters and composition of liquor in the patients with syphilis has revealed, that lymphocytes of peripheral blood are sensitized to antigens of the brain. It indicates the violation of permeability of patients’ blood-brain barrier. Nervous system becomes involved into the pathological process during the first weeks or months after syphilis infection. Cerebrospinal fluid changes can be detected at seronegative stage of the primary infection. The most expressed changes were found in
Angela S Clem
Full Text Available From a literature review of the current literature, this article provides an introduction to vaccine immunology including a primer on the components of the immune system, passive vs. active immunization, the mechanism(s by which immunizations stimulate(s immunity, and the types of vaccines available. Both the innate and adaptive immune subsystems are necessary to provide an effective immune response to an immunization. Further, effective immunizations must induce long-term stimulation of both the humoral and cell-mediated arms of the adaptive system by the production of effector cells and memory cells. At least seven different types of vaccines are currently in use or in development that produce this effective immunity and have contributed greatly to the prevention of infectious disease around the world.
The relative molecular mass of Arbutin is small.Both fluorolabeling and radiolabeling may affect its properties and functions.Therefore, the immunoassay of Arbutin was studied.Arbutin was coupled to bovine serum albumin to get the Arbutin-BSA conjugate with high molar ratio of Arbutin to BSA.Two rabbits were injected with the conjugate to develop the anti-Arbutin serum.Ammonium sulfate precipitation and affinity chromatography were used to purify the antibody.Double agar diffusion test and enzyme-linked immunosorbent assay (ELISA) were adopted to identify the antibody titer.The results demonstrated that the purity and activity of the antibody are high.The method proposed is satisfactory for the immunological detection of Arbutin.
Crispe, Ian N
Hepatocytes are targeted for infection by a number of major human pathogens, including hepatitis B virus, hepatitis C virus, and malaria. However, hepatocytes are also immunological agents in their own right. In systemic immunity, they are central in the acute-phase response, which floods the circulation with defensive proteins during diverse stresses, including ischemia, physical trauma, and sepsis. Hepatocytes express a variety of innate immune receptors and, when challenged with pathogen- or damage-associated molecular patterns, can deliver cell-autonomous innate immune responses that may result in host defense or in immunopathology. Important human pathogens have evolved mechanisms to subvert these responses. Finally, hepatocytes talk directly to T cells, resulting in a bias toward immune tolerance. PMID:26685314
Gherardi, R K; Aouizerate, J; Cadusseau, J; Yara, S; Authier, F J
Aluminum oxyhydroxide (Alhydrogel(®)) is a nano-crystalline compound forming aggregates that has been introduced in vaccine for its immunologic adjuvant effect in 1926. It is the most commonly used adjuvant in human and veterinary vaccines but mechanisms by which it stimulates immune responses remain ill-defined. Although generally well tolerated on the short term, it has been suspected to occasionally cause delayed neurologic problems in susceptible individuals. In particular, the long-term persistence of aluminic granuloma also termed macrophagic myofasciitis is associated with chronic arthromyalgias and fatigue and cognitive dysfunction. Safety concerns largely depend on the long biopersistence time inherent to this adjuvant, which may be related to its quick withdrawal from the interstitial fluid by avid cellular uptake; and the capacity of adjuvant particles to migrate and slowly accumulate in lymphoid organs and the brain, a phenomenon documented in animal models and resulting from MCP1/CCL2-dependant translocation of adjuvant-loaded monocyte-lineage cells (Trojan horse phenomenon). These novel insights strongly suggest that serious re-evaluation of long-term aluminum adjuvant phamacokinetics and safety should be carried out. PMID:26948677
Innate immunity was for a long time considered to be non-specific because the major function of this system is to digest pathogens and present antigens to the cells involved in acquired immunity. However, recent studies have shown that innate immunity is not non-specific, but is instead sufficiently specific to discriminate self from pathogens through evolutionarily conserved receptors, designated Toll-like receptors (TLRs). Indeed, innate immunity has a crucial role in early host defence against invading pathogens. Furthermore, TLRs were found to act as adjuvant receptors that create a bridge between innate and adaptive immunity, and to have important roles in the induction of adaptive immunity. This paradigm shift is now changing our thinking on the pathogenesis and treatment of infectious, immune and allergic diseases, as well as cancers. Besides TLRs, recent findings have revealed the presence of a cytosolic detector system for invading pathogens. I will review the mechanisms of pathogen recognition by TLRs and cytoplasmic receptors, and then discuss the roles of these receptors in the development of adaptive immunity in response to viral infection. PMID:21893536
Yang Tao; Deqing Wang; Yuanliang Hu; Yee Huang; Yun Yu; Deyun Wang
The aim of this study was to investigate and assess the effects of propolis flavonoids liposome imposed on the immune system by comparing it to propolis flavonoids and blank liposome. In vitro, the effects of the above drugs on macrophages were assessed by measuring the phagocytic function and cytokine production. In vivo, the immunological adjuvant activity of propolis flavonoids liposome was compared with those of propolis flavonoids and blank liposome. The results showed that in vitro prop...
SHUI-HUA ZHANG; JIA-XU LIANG; SHU-YAN DAI; XIAO-LIN QIU; YAN-RONG YI; YUN PAN
Objective To elevate the immunological effect of subunit influenza vaccine in infants and aged people (over 60) using liposomal adjuvant in the context of its relatively low immunity and to investigate the relation between vaccine antigens and liposomal characteristics. Methods Several formulations of liposomal subunit influenza vaccine were prepared. Their relevant characteristics were investigated to optimize the preparation method. Antisera obtained from immunizinged mice were used to evaluate the antibody titers of various samples by HI and ELISA. Results Liposomal trivalent influenza vaccine prepared by film evaporation in combinedation with freeze-drying significantly increased its immunological effect in SPF Balb/c mice. Liposomal vaccine stimulated the antibody titer of H3N2, H1N1, and B much stronger than conventional influenza vaccine. As a result, liposomal vaccine (mean size: 4.5-5.5 μm, entrapment efficiency: 30%-40%) significantly increased the immunological effect of subunit influenza vaccine. Conclusion The immune effect of liposomal vaccine depends on different antigens, and enhanced immunity is not positively correlated with the mean size of liposome or its entrapped efficiency.
Babu, Subash; Nutman, Thomas B.
The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen - specific Th2 response and an expansion of IL-10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen specific T cell hypo-responsiveness appears to be crucial for the maintenance of the sustained, long-standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4+ T cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T cell hypo-responsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general. PMID:24134686
The use of chemotherapy as an adjuvant to surgery and/or radiotherapy is well founded in experimental tumor systems and appears to be effective in patients in some circumstances. It is clear from both clinical and experimental studies that (1) the dose is important, (2) the earlier chemotherapy is started after primary therapy the better, and (3) combination chemotherapy may be more effective than single-agent treatment. The better the estimation of risk of recurrence, the better the assessment of the risk-benefit ratio with adjuvant therapy. Salvage therapy as well as relative risk of recurrence are considerations in the choice of patients to be treated. Finally, some evidence is presented to indicate that alkylating agents may not be necessary in combination regimens for adjuvant therapy if effective antimetabolite combinations are available
Chakra P Chaulagain
Full Text Available There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145 represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients’ survival. Another study by Fan et al. (Abstract #269 examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.
Skrastina, Dace; Petrovskis, Ivars; Lieknina, Ilva; Bogans, Janis; Renhofa, Regina; Ose, Velta; Dishlers, Andris; Dekhtyar, Yuri; Pumpens, Paul
Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm) with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs) formed by recombinant full-length Hepatitis B virus core (HBc) protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL) led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component. PMID:25436773
Jones, W R
Recent research on immunological infertility in men and women is reviewed and the possibilities for therapeutic success in this area are assessed. Surface antigens of the acrosome and main tail piece appear to provoke antibodies of special relevance to male and female infertility and are recognized by circulating sperm-immobilizing antibodies in women and by immobilizing and agglutinizing antibodies in men. Assessment methods have focused on the development of tests of local immunity to sperm. Antisperm antibodies have been tested via sperm microagglutination, the gelatin agglutination test, the sperm immobilization test, and immunofluorescence techniques. In addition, measurement has focused on antibodies in cervical mucus, antibodies in seminal plasma, and cell-mediated immunity. Methods involving both partners include postcoital test, the sperm-cervical mucus penetration test, and the sperm-cervical mucus contact test. There remains a need for the development of specific radioimmunoassys for the precise detection and quantitation of antibodies to sperm antigens, especially those of cell membrane origin. In males, autoimmunity to sperm antigens can be related to infertility by 2 main pathogenic mechanisms: 1) the adverse effects of antibodies directly on spermatozoa, and 2) the association with disordered spermatogenesis resulting in oligospermia and azoospermia. In women, the effector pathways of local immunization mediate both systemic and cell-mediated immune responses. Local antibodies can interfere with the reproductive process by arming macrophages and enhancing phagocytic clearance of spermatozoa from the genital tract, mediating cytotoxic effects on sperm, preventing sperm from adequately penetrating cervical mucus, intefering with sperm capacitation, and influencing sperm selection within the female genital tract. Between 5-10% of infertile men and women show evidence of anitbodies to sperm. Treatment has included occlusion therapy, intrauterine
Nagao, S.; Tanaka, A.
Muramyl dipeptide, N-acetylmuramyl-L-alanyl-D-isoglutamine, induced adjuvant arthritis in WKA rats when injected in a water-in-oil emulsion prepared with Freund incomplete adjuvant (Difco), but not when emulsified with Drackeol and Arlacel A.
The history, present status and future prospects of adjuvants application in herbicides were briefly reviewed. Adjuvants can be separated into two groups, activator adjuvants and utility adjuvants. The former directly enhances the efficacy of a herbicide through increasement of herbicide absorption, spreading, cuticular penetration, rainfastness and retention enhancement, and photodegradation of the herbicide can also be decreased. And the latter is utilized for improving application characteristics, behaviors and physical properties of herbicides and reducing or minimizing unwanted side effects on application.
Yong Xie; Nan-Jin Zhou; Yan-Feng Gong; Xiao-Jiang Zhou; Jiang Chen; Si-Juan Hu; Nong-Hua Lu; Xiao-Hua Hou
AIM: To study the immunological protective effect of H pylori vaccine with chitosan as an adjuvant and its mechanism.METHODS: Female BALB/c mice were randomly divided into seven groups and orally immunized respectively with PBS, chitosan solution, chitosan particles, H pylori antigen, H pylori antigen plus cholera toxin (CT), H pylori antigen plus chitosan solution, H pylori antigen plus chitosan particles once a week for four weeks. Four weeks after the last immunization, the mice were challenged twice by alive H pylori (1 × 109 CFU/mL) and sacrificed. Part of the gastric mucosa was embedded in paraffin, cut into sections and assayed with Giemsa staining. Part of the gastric mucosa was used to quantitatively culture H pylori. ELISA was used to detect cytokine level in gastric mucosa and anti- H pylori IgGl, IgG2a levels in serum.RESULTS: In the groups with chitosan as an adjuvant, immunological protection was achieved in 60% mice, which was significantly higher than in groups with H pylori antigen alone and without H pylori antigen (P ＜ 0.05 or 0.001). Before challenge, the level of IFN and IL-12 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in the control group and the group without adjuvant (P ＜ 0.05 or 0.005). After challenge, the level of IFN and IL-12 was significantly higher in the groups with adjuvant than in the groups without adjuvant and antigen (P ＜ 0.05 or 0.001). Before challenge, the level of IL-2 in gastric mucosa was not different among different groups. Afterchallenge the level of IL-2 was significantly higher in the groups with adjuvant than in the control group (P ＜ 0.05 or 0.001). Before challenge, the level of IL-10 in gastric mucosa was significantly higher in the groups with chitosan as an adjuvant than in other groups without adjuvant (P ＜ 0.05 or 0.01). After challenge, the level of IL-10 was not different among different groups. Before challenge, the level of IL-4 in gastric mucosa
Paula Ghaneh; John Slavin; Robert Sutton; Mark Hartley; John P Neoptolemos
The outlook for patients with pancreatic cancer has been grim. There have been major advances in the surgical treatment of pancreatic csncer, leading to a drsmatic reduction in post-operative mortality from the development of high volume specialized centres. This stimulated the study of adjuvant and neoadjuvant treatments in pancreatic cancer including chemoradiotherapy and chemotherapy. Initial protocols have been based on the original but rather small GITSG study first reported in 1985. There have been two large European trials totalling over 600 patients (EORTC and ESPAC-1) that do not support the use of chemoradiation as adjuvant therapy. A second major finding from the ESPAC-1 trial (541 patients randomized) was some but not conclusive evidence for a survival benefit associated with chemotherapy. A third major finding from the ESPAC-1 trial was that the quality of life was not affected by the use of adjuvant treatments compared to surgery alone.The ESPAC-3 trial aims to assess the definitive use of adjuvant chemotherapy in a randomized controlled trial of 990 patients.
Maria do Carmo Santos Araújo
Full Text Available Breast cancer is the most frequent neoplasm affecting women worldwide. Some of the recommended treatments involve chemotherapy whose toxic effects include leukopenia and neutropenia. This study assessed the effectiveness of Uncaria tomentosa (Ut in reducing the adverse effects of chemotherapy through a randomized clinical trial. Patients with Invasive Ductal Carcinoma—Stage II, who underwent a treatment regimen known as FAC (Fluorouracil, Doxorubicin, Cyclophosphamide, were divided into two groups: the UtCa received chemotherapy plus 300 mg dry Ut extract per day and the Ca group that only received chemotherapy and served as the control experiment. Blood samples were collected before each one of the six chemotherapy cycles and blood counts, immunological parameters, antioxidant enzymes, and oxidative stress were analyzed. Uncaria tomentosa reduced the neutropenia caused by chemotherapy and was also able to restore cellular DNA damage. We concluded that Ut is an effective adjuvant treatment for breast cancer.
Li, Qian; Liu, Qiang
Cancer immunology is the study of interaction between cancer cells and immune system by the application of immunology principle and theory. With the recent approval of several new drugs targeting immune checkpoints in cancer, cancer immunology has become a very attractive field of research and is thought to be the new hope to conquer cancer. This chapter introduces the aberrant expression and function of noncoding RNAs, mainly microRNAs and long noncoding RNAs, in tumor-infiltrating immune cells, and their significance in tumor immunity. It also illustrates how noncoding RNAs are shuttled between tumor cells and immune cells in tumor microenvironments via exosomes or other microvesicles to modulate tumor immunity. PMID:27376738
Pichichero, Michael E
Adjuvants have been common additions to vaccines to help facilitate vaccine delivery. With advancements in vaccine technology, several adjuvants which activate immune specific responses have emerged. Available data show these adjuvants elicit important immune responses in both healthy and immunocompromised populations, as well as the elderly. Guidelines for the use and licensure of vaccine adjuvants remain under discussion. However, there is a greater understanding of the innate and adaptive immune response, and the realization of the need for immune specific adjuvants appears to be growing. This is a focused review of four adjuvants currently in clinical trial development: ASO4, ASO2A, CPG 7907, and GM-CSF. The vaccines including these adjuvants are highly relevant today, and are expected to reduce the disease burden of cervical cancer, hepatitis B and malaria. PMID:18398303
Pamela T Wong
Full Text Available Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17 could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications.
Acquaviva, Joseph T.; Zhou, Feifan; Boarman, Ellen; Chen, Wei R.
While successes of different cancer therapies have been achieved in various degrees a systemic immune response is needed to effectively treat late-stage, metastatic cancers, and to establish long-term tumor resistance in the patients. A novel method for combating metastatic cancers has been developed using immunologically modified carbon nanotubes in conjunction with phototherapy. Glycated chitosan (GC) is a potent immunological adjuvant capable of increasing host immune responses, including antigen presentation by activation of dendritic cells (DCs) and causing T cell proliferation. GC is also an effective surfactant for nanomaterials. By combining single-walled carbon nanotubes (SWNTs) and GC, immunologically modified carbon nanotubes (SWNT-GC) were constructed. The SWNT-GC suspension retains the enhanced light absorption properties in the near infrared (NIR) region and the ability to enter cells, which are characteristic of SWNTs. The SWNT-GC also retains the immunological properties of GC. Cellular SWNT-GC treatments increased macrophage activity, DC activation and T cell proliferation. When cellular SWNT-GC was irradiated with a laser of an appropriate wavelength, these immune activities could be enhanced. The combination of laser irradiation and SWNT-GC induced cellular toxicity in targeted tumor cells, leading to a systemic antitumor response. Immunologically modified carbon nanotubes in conjunction with phototherapy is a novel and promising method to produce a systemic immune response for the treatment of metastatic cancers.
Chakra P Chaulagain; Muhammad Wasif Saif; Goodman, Martin D.; John Ng
There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposiu...
The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of CCL8.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...
Nossal, Gustav J. V.
The immune system can recognize and produce antibodies to virtually any molecule in the Universe. This enormous diversity arises from the ingenious reshuffling of DNA sequences encoding components of the immune system. Immunology is an example of a field completely transformed during the past 50 years by the discovery of the structure of DNA and the emergence of DNA technologies that followed.
The main general objective of this project was to define immunotherapy protocols based on the new concept of using IFN-a as and immune adjuvant, developing innovative methodologies suitable for predicting and monitoring the immunological and clinical responses. Specific aim of developing new micro arrays technologies particularly suitable for a molecular tracking and prediction of the response to IFN of cytokine-treated patients
... 42 Public Health 5 2010-10-01 2010-10-01 false Diagnostic immunology. 493.921 Section 493.921... Testing Proficiency Testing Programs by Specialty and Subspecialty § 493.921 Diagnostic immunology. The subspecialties under the specialty of immunology for which a program may offer proficiency testing are...
Sebastiano Buti; Melissa Bersanelli; Maddalena Donini; Andrea Ardizzoni
Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to d...
Full Text Available Background: Heat shock proteins (Hsps are evolutionary ancient and highly conserved molecular chaperons found in prokaryotes as well as eukaryotes. Hsp70 is a predominant member of Hsp family. Microbial Hsp70s (mHsp70s have acquired special significance in immunity since they have been shown to be potent activators of the innate immune system and generate specific immune responses against tumours and infectious agents. Objectives: The present study was aimed to clone express and purify recombinant Hsp70 from the Mycobacterium tuberculosis and characterise it immunologically. The study also aimed at determining the potential of recombinant M. tuberculosis heat shock protein (rMTB-Hsp70 as adjuvant or antigen carrier. Materials and Methods: Cloning of M. tuberculosis heat shock protein (MTB-Hsp70 amplicon was carried out using the pGEMT-Easy vector although for expression, pProExHTb prokaryotic expression vector was used. Purification of recombinant Hsp70 was carried out by nickel-nitrilotriacetic acid (Ni-NTA affinity chromatography. For immunological characterization and determining the adjuvant effect of MTB-Hsp70, BALB/c mice were used. The data obtained was statistically analysed. Results: Hsp70 gene was cloned, sequenced and the sequence data were submitted to National Center for Biotechnology Information (NCBI. Recombinant MTB-Hsp70 was successfully over-expressed using the prokaryotic expression system and purified to homogeneity. The protein was found to be immunodominant. Significant adjuvant effect was produced by the rMTB-Hsp70 when inoculated with recombinant outer membrane protein 31; however, effect was less than the conventionally used the Freund′s adjuvant. Conclusion: Protocol standardised can be followed for bulk production of rHsp70 in a cost-effective manner. Significant adjuvant effect was produced by rMTB-Hsp70; however, the effect was than Freund′s adjuvant. Further, studies need to be carried out to explore its
Full Text Available Perhaps the oldest empirical therapeutic modality in the history of medicine, photo(chemotherapy has well documented benefits but its mode of action is not fully elucidated. Today, thanks to advances in photoimmunology and molecular biology we are provided with important clues as to how photo(chemotherapy works. Initial research on UV light and skin cancer has brought about the groundbreaking discovery of the immunological effects UV. UVB is the UV light most frequently used for therapeutic purposes and its mechanisms of action are best demonstrated. UV light has several distinct effects on various components of the innate and acquired immune systems, especially T lymphocyte functions the common endpoint of which is immune supression. The antiproliferative and antifibrotic therapeutic effects of UVA and UVB have so far not been directly associated with immunological mechanisms.
Full Text Available Immunological responses of sheep against adult worm extract antigen of Fasciola gigantica were evaluated in an effort to identify the protein antigen for the candidate of vaccine. In this study the protein antigen from adult worms was extracted, and the extract antigen was then intramuscularly injected into 4 groups of 5 sheep. Two groups received one injection, these included one group injected only with extract antigen and the other group injected with extract antigen emulsified in Quil A adjuvant. The other two groups received two injections with a two week interval, these included one group injected only with extract antigen and the other group injected with extract antigen emulsified in Quil A adjuvant. Three weeks later all of the sheep were challenged with 300 metacercariae of F. gigantica. The antibody titer was monitored every two weeks by using ELISA and the protein profile from each group was compared by using western blotting. Fifteen weeks after challenged all of the sheep were killed and the liver flukes were collected from the liver and counted. The results showed that the antibody titer was higher in the group which received two injections, and the additional of Quil A adjuvant gave much better protection from the infection of F. gigantica (57% and could avoid the death of the sheep than twice injection of antigen without Quil A adjuvant (37%.
Heegaard, Peter M. H.; Fang, Yongxiang; Jungersen, Gregers
Adjuvants are crucial for efficacy of vaccines, especially subunit and recombinant vaccines. Rational vaccine design, including knowledge-based and molecularly defined adjuvants tailored for directing and potentiating specific types of host immune responses towards the antigens included in the va...
Under nutritional support, surgical and postoperative adjuvant therapy were performed in 27 patients with thoracic esophageal cancer. The patients were divided into 2 groups, that were patients with postoperative chemotherapy (group A; 13 cases) and patients with postoperative radiation therapy (group B; 14 cases). Nutritional and immunological parameters were measured and compared among each groups. Group B had received higher nutritional support than group A, especially during the period of postoperative therapy. In group B, nutritional and immunological parameters maintained normal level, except serum albumin levels, counts of peripheral lymphocytes and factor XIII. In spite of higher nutritional support, levels of Zn in group B kept low. As for arterio-venous difference of amino acids, the tendency of negative balance in group B was stronger than that in group A. Arginine concentration in venous plasma increased evidently in group B. (author)
Apostólico, Juliana de Souza
Vaccination is one of the most efficient strategies for the prevention of infectious diseases. Although safer, subunit vaccines are poorly immunogenic and for this reason the use of adjuvants is strongly recommended. Since their discovery in the beginning of the 20th century, adjuvants have been used to improve immune responses that ultimately lead to protection against disease. The choice of the adjuvant is of utmost importance as it can stimulate protective immunity. Their mechanisms of action have now been revealed. Our increasing understanding of the immune system, and of correlates of protection, is helping in the development of new vaccine formulations for global infections. Nevertheless, few adjuvants are licensed for human vaccines and several formulations are now being evaluated in clinical trials. In this review, we briefly describe the most well known adjuvants used in experimental and clinical settings based on their main mechanisms of action and also highlight the requirements for licensing new vaccine formulations.
3.1 Autoimmume disease 2006019 The study of inhibitory peptides on T cell activation in rheumatoid arthritis LI Xia(李霞) , Dept Rheumatol & Immunol, People’s Hosp, Peking Univ, Beijing 100044. Natl Med J China 2005;85(24) :1679 -1682. Objective:To study the inhibitory role of altered HA308 -317 peptides in T cell responses in patients with rheumatoid arthritis (RA). Methods :Peripheral blood mononuclear cells (PBMC) were obtained from 27 HLA -
5.1 Autoimmune disease2004189 Serum levels of matrix metallopro-teinases-9 in patients with systemic lupus erythemato-sus. YIN Wenhao (殷文浩), et al. Dept Dermatol 2nd Affili Hosp, Med Sch Zhejiang Univ, Hangzhou 310009. Chin J Dermatol 2004;37(2):77-79.Objective: To determine the serum levels of matrix
3.1 Autoimmune disease2004022 BL-2, IL-6 and their receptors in patients with systemic lupus erythematosus. QIAN Qihong (钱齐宏), et al. Dept Dermatol & Venereol, 1st Affili Hosp, Suzhou Univ, Suzhou 215006. Chin J Dermatol 2003; 36 (12): 696-698.
Full Text Available Rheumatoid arthritis (RA is the most common connective tissue disease of autoimmune origin. The disease is characterized by chronic inflammation leading to bone erosions and organ involvement. RA is a progressive disease. It affects the quality of life, leading to disability and death mainly due to premature cardiovascular disease. Early diagnosis and appropriate treatment are essential for prognosis and quality of life improvement. In 2010 the American College of Rheumatology (ACR and The European League Against Rheumatism (EULAR established new RA classification criteria. Besides clinical symptoms it includes two immunologic criteria: rheumatoid factor (RF and anti-citrullinated protein antibodies (anti-CCP antibodies. RF is the first well-known RA immunologic marker. It is observed in 80-85% of patients with RA. Elevated serum level of RF has been associated with increased disease activity, radiographic progression, and the presence of extraarticular manifestations. The sensitivity of RF is 50-90%, and specificity is 50-95%. Anti-CCP antibodies appear to be a more specific marker than RF. They are often present at the very beginning of the disease, or even years before the first symptoms. The prognostic value of anti-CCP antibodies is well established. High serum level of anti-CCP correlates with poor prognosis and early erosions of the joints. The sensitivity of anti-CCP2 is 48-80%, and specificity is 96-98%. New immunologic markers include anti-carbamylated protein antibodies (anti-CarP and antibodies against heterogeneous nuclear ribonucleoproteins (anti-hnRNP A2/B1, RA33. Scientists aim to identify a highly sensitive and specific biomarker of the disease that not only has diagnostic and prognostic value but also may predict the response to treatment.
Full Text Available Hair follicles are accepted as a component of skin in mammals. Considering the continuous contact with environment and microorganisms in the normal flora, it is crucial that various elements of immune system are necessary to reside within hair follicles. On the contrary, the protection of hair follicles from the intense anti-infective elements and autoimmunity is mandatory; hence some antigens are not expressed in hair follicle and construct an immune privileged area. In this review, immunologic functions of hair follicle and hair follicle immunology’s effect in pathogenesis of dermatological diseases are discussed in the light of recent studies.
Romain Kroum Gherardi
Full Text Available Aluminum oxyhydroxide (alum is a crystaline compound widely used as an immunologic adjuvant of vaccines. Concerns linked to the use of alum particles emerged following recognition of their causative role in the so-called macrophagic myofasciitis (MMF lesion detected in patients with myalgic encephalomyelitis/chronic fatigue/syndrome. MMF revealed an unexpectedly long-lasting biopersistence of alum within immune cells in presumably susceptible individuals, stressing the previous fundamental misconception of its biodisposition. We previously showed that poorly biodegradable aluminum-coated particles injected into muscle are promptly phagocytozed in muscle and the draining lymph nodes, and can disseminate within phagocytic cells throughout the body and slowly accumulate in brain. This strongly suggests that long-term adjuvant biopersistence within phagocytic cells is a prerequisite for slow brain translocation and delayed neurotoxicity. The understanding of basic mechanisms of particle biopersistence and brain translocation represents a major health challenge, since it could help to define susceptibility factors to develop chronic neurotoxic damage. Biopersistence of alum may be linked to its lysosome-destabilizing effect, which is likely due to direct crystal-induced rupture of phagolysosomal membranes. Macrophages that continuously perceive foreign particles in their cytosol will likely reiterate, with variable interindividual efficiency, a dedicated form of autophagy (xenophagy until they dispose of alien materials. Successful compartmentalization of particles within double membrane autophagosomes and subsequent fusion with repaired and re-acidified lysosomes will expose alum to lysosomal acidic pH, the sole factor that can solubilize alum particles. Brain translocation of alum particles is linked to a Trojan horse mechanism previously described for infectious particles (HIV, HCV, that obeys to CCL2 signaling the major inflammatory monocyte
Taylor, G. R.
The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5040 Albumin immunological test system. (a) Identification. An albumin immunological test system is a device that consists...
Full Text Available Glucocorticoids (GCs, synthetic analogues of the natural steroid hormones, are well known for their antiinflammatory and immunosuppressive properties in the periphery. They are widely and successfully used in the treatment of autoimmune diseases, chronic inflammation, and transplant rejection. Nowadays, GCs are claimed to have a beneficial role being as adjunct therapy in various infections. Different studies have been conducted to investigate their use as adjuvant therapy for different bacterial infection. This review, therefore, summarizes various bacterial infections for which glucocorticoids are reported to be used as adjuvant therapy, strategies for administration of glucocorticoids, and challenges of using glucocorticoids as adjuvant therapy.
Full Text Available Advances in nanotechnology and nanomaterials have facilitated the development of silicon dioxide, or Silica, particles as a promising immunological adjuvant for the generation of novel prophylactic and therapeutic vaccines. In the present study, we have compared the adjuvanting potential of commercially available Silica nanoparticles (initial particles size of 10-20 nm with that of aluminium hydroxide, or Alum, as well as that of complete and incomplete Freund's adjuvants for the immunisation of BALB/c mice with virus-like particles (VLPs formed by recombinant full-length Hepatitis B virus core (HBc protein. The induction of B-cell and T-cell responses was studied after immunisation. Silica nanoparticles were able to adsorb maximally 40% of the added HBc, whereas the adsorption capacity of Alum exceeded 90% at the same VLPs/adjuvant ratio. Both Silica and Alum formed large complexes with HBc VLPs that sedimented rapidly after formulation, as detected by dynamic light scattering, spectrophotometry, and electron microscopy. Both Silica and Alum augmented the humoral response against HBc VLPs to the high anti-HBc level in the case of intraperitoneal immunisation, whereas in subcutaneous immunisation, the Silica-adjuvanted anti-HBc level even exceeded the level adjuvanted by Alum. The adjuvanting of HBc VLPs by Silica resulted in the same typical IgG2a/IgG1 ratios as in the case of the adjuvanting by Alum. The combination of Silica with monophosphoryl lipid A (MPL led to the same enhancement of the HBc-specific T-cell induction as in the case of the Alum and MPL combination. These findings demonstrate that Silica is not a weaker putative adjuvant than Alum for induction of B-cell and T-cell responses against recombinant HBc VLPs. This finding may have an essential impact on the development of the set of Silica-adjuvanted vaccines based on a long list of HBc-derived virus-like particles as the biological component.
This Introduction to the special issue of Veterinary Immunology and Immunopathology summarizes the Proceedings of the 9th International Veterinary Immunology Symposium (9th IVIS) held August, 2010, in Tokyo, Japan. Over 340 delegates from 30 countries discussed research progress analyzing the immune...
A summary of a meta-analysis of randomized trials of bisphosphonates as adjuvant therapy for women with early-stage breast cancer that shows the drugs can reduce the rate of disease recurrence in bone.
Full Text Available Johne's disease or paratuberculosis is one of the most economically important diseases of the livestock. Most of the economiclosses associated with paratuberculosis are related to decreased milk production, reduced fertility and higher rates of culling.Understanding the immunology of the disease is very important for better understanding of the interplay between the host andthe causative agent, Mycobacterium avium subsp. paratuberculosis (MAP. After uptake of MAPby macrophages residing inhost's intestinal tissue, two possible scenarios may emerge; MAP may be destroyed or may establish persistent infectionwithin the macrophages. If MAPpersists in the infected macrophage, it continuously modulates adaptive immune responsesof the animal. In this short review we describe the host-pathogen interactions in Johne's disease and highlights potentialprotective mechanisms in order for future design of more effective diagnostic method and vaccine.
Agarwala, S S; Kirkwood, J M
After decades of research, the adjuvant therapy of patients with melanoma has recently shown significant survival and relapse-free interval benefit for the intravenous and subcutaneous administration of maximally tolerable dosages of recombinant IFN alpha 2b in a trial conducted by the ECOG (E1684). Despite the toxicity of this therapy, retrospective analyses of its impact upon quality-of-life using Q-TWiST methods and cost-efficacy analyses all argue for the benefit and utility of this intervention, especially for node-positive patients with resectable melanoma at highest risk of relapse. A confirmatory trial has been completed and will mature in the spring of 1998. The impact of lower dosages of IFN, apparent transiently during and for a period of time following treatment has not been sustained with longer follow-up in a number of trials. Current approaches in Europe and North America focus upon refinement of dose and duration of treatment with IFN and their potential interactions with, and comparison with, active specific immunotherapy with vaccines. A recently emerging area of research is the patient with stage IIA melanoma and the potential role of an abbreviated high-dose regimen of IFN alpha in this patient subset. PMID:9759581
Kidney cancer represents 3 % of the tumors in adults. In the United States, the 45% is diagnosed in early stages. Its natural history is characterized for being absolutely unpredictable and probably related to hormonal, immunologic and unknown factors. There are patients in advanced stage with prolonged or low average survival and even with metastasis declination. These particularities along with the lack of prospective random studies make difficult to establish which is the roll of the adjuvant radiotherapy, being considered not standard since 1997
Mogens H. Claesson; Ayako W. Pedersen; Pia Kvistborg; Mai-Britt Zocca; Lotte Engell-Noerregaard; Anders Mellemgaard
Background: We evaluated the clinical and immunological effects of dendritic cell (DC) vaccination of patients with NSCLC. Autologous DCs were pulsed with a MAGE containing allogeneic melanoma cell lysate (MelCancerVac&174, Dandrit Biotech,Copenhagen,Denmark). Imiquimod cream, proleukin and celecoxib were used as adjuvants to the vaccines. The objective of the study was to evaluate specific T cell response in vitro by IFNg EliSpot. Secondary objectives were overall survival, response and qua...
Meng, Chunchun; Zhi, Xiao; Li, Chao; Li, Chuanfeng; Chen, Zongyan; Qiu, Xusheng; Ding, Chan; Ma, Lijun; Lu, Hongmin; Chen, Di; Liu, Guangqing; Cui, Daxiang
Current studies have revealed the immune effects of graphene oxide (GO) and have utilized them as vaccine carriers and adjuvants. However, GO easily induces strong oxidative stress and inflammatory reaction at the site of injection. It is very necessary to develop an alternative adjuvant based on graphene oxide derivatives for improving immune responses and decreasing side effects. Carnosine (Car) is an outstanding and safe antioxidant. Herein, the feasibility and efficiency of ultrasmall graphene oxide decorated with carnosine as an alternative immune adjuvant were explored. OVA@GO-Car was prepared by simply mixing ovalbumin (OVA, a model antigen) with ultrasmall GO covalently modified with carnosine (GO-Car). We investigated the immunological properties of the GO-Car adjuvant in model mice. Results show that OVA@GO-Car can promote robust and durable OVA-specific antibody response, increase lymphocyte proliferation efficiency, and enhance CD4(+) T and CD8(+) T cell activation. The presence of Car in GO also probably contributes to enhancing the antigen-specific adaptive immune response through modulating the expression of some cytokines, including IL-6, CXCL1, CCL2, and CSF3. In addition, the safety of GO-Car as an adjuvant was evaluated comprehensively. No symptoms such as allergic response, inflammatory redness swelling, raised surface temperatures, physiological anomalies of blood, and remarkable weight changes were observed. Besides, after modification with carnosine, histological damages caused by GO-Car in lung, muscle, kidney, and spleen became weaken significantly. This study sufficiently suggest that GO-Car as a safe adjuvant can effectively enhance humoral and innate immune responses against antigens in vivo. PMID:26766427
RAJPUT Zahid Iqbal; HU Song-hua; XIAO Chen-wen; ARIJO Abdullah G.
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.
Full Text Available Immunological adjuvants that induce T cell-mediate immunity (TCMI with the least side effects are needed for the development of human vaccines. Glycoinositolphospholipids (GIPL and CpGs oligodeoxynucleotides (CpG ODNs derived from the protozoa parasite Trypanosoma cruzi induce potent pro-inflammatory reaction through activation of Toll-Like Receptor (TLR4 and TLR9, respectively. Here, using mouse models, we tested the T. cruzi derived TLR agonists as immunological adjuvants in an antitumor vaccine. For comparison, we used well-established TLR agonists, such as the bacterial derived monophosphoryl lipid A (MPL, lipopeptide (Pam3Cys, and CpG ODN. All tested TLR agonists were comparable to induce antibody responses, whereas significant differences were noticed in their ability to elicit CD4(+ T and CD8(+ T cell responses. In particular, both GIPLs (GTH, and GY and CpG ODNs (B344, B297 and B128 derived from T. cruzi elicited interferon-gamma (IFN-γ production by CD4(+ T cells. On the other hand, the parasite derived CpG ODNs, but not GIPLs, elicited a potent IFN-γ response by CD8(+ T lymphocytes. The side effects were also evaluated by local pain (hypernociception. The intensity of hypernociception induced by vaccination was alleviated by administration of an analgesic drug without affecting protective immunity. Finally, the level of protective immunity against the NY-ESO-1 expressing melanoma was associated with the magnitude of both CD4(+ T and CD8(+ T cell responses elicited by a specific immunological adjuvant.
Full Text Available Spongiform encephalopathies, categorized as a subclass of neuro-degenerative diseases and commonly known as prion diseases, are a group of progressive conditions that affect the brain and nervous system of many animals, including humans. Prion diseases are common among cannibalistic communities; further research has revealed that the infected or malformed prion protein (named PrPsc spreads its virulence to the normal, healthy prion protein (named PrPc when people consume infected tissues. Knowing that a small interaction between normal and infected prion protein creates virulence, this relationship can be studied as a simple antigen-antibody interaction to understand the series of events that transform a normal prion protein into a virulent misfolded protein. Thoroughly modeled and validated structures of both PrPsc and PrPc can be effectively used to map the epitopes and thereby screen the antigen-antibody interaction using docking studies for a particular organism of concern. This simple immunological approach is used to understand the vital interaction between the normal and malformed proteins that is involved in the disease-spreading mechanism. Clarification of this mechanism could be used in various immune- and bioinformatics algorithms to map the interaction epitopes, furthering an understanding of these pathologies.
Buti, Sebastiano; Bersanelli, Melissa; Donini, Maddalena; Ardizzoni, Andrea
Renal cell carcinoma (RCC) is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC. PMID:25992216
Full Text Available Renal cell carcinoma (RCC is one of the ten most frequent solid tumors worldwide. Recent innovations in the treatment of metastatic disease have led to new therapeutic approaches being investigated in the adjuvant setting. Observation is the only current standard of care after radical nephrectomy, although there is evidence of efficacy of adjuvant use of vaccine among all the strategies used. This article aims to collect published experiences with systemic adjuvant approaches in RCC and to describe the results of past and ongoing phase III clinical trials in this field. We explored all the systemic treatments, including chemotherapy, immunotherapy and targeted drugs while alternative approaches have also been described. Appropriate selection of patients who would benefit from adjuvant therapies remains a crucial dilemma. Although the international guidelines do not actually recommend any adjuvant treatment after radical surgery for RCC, no conclusions have yet been drawn pending the results of the promising ongoing clinical trials with the target therapies. The significant changes that these new drugs have made on advanced disease outcome could represent the key to innovation in terms of preventing recurrence, delaying relapse and prolonging survival after radical surgery for RCC.
Moyer, Tyson J; Zmolek, Andrew C; Irvine, Darrell J
The need to optimize vaccine potency while minimizing toxicity in healthy recipients has motivated studies of the formulation of vaccines to control how, when, and where antigens and adjuvants encounter immune cells and other cells/tissues following administration. An effective subunit vaccine must traffic to lymph nodes (LNs), activate both the innate and adaptive arms of the immune system, and persist for a sufficient time to promote a mature immune response. Here, we review approaches to tailor these three aspects of vaccine function through optimized formulations. Traditional vaccine adjuvants activate innate immune cells, promote cell-mediated transport of antigen to lymphoid tissues, and promote antigen retention in LNs. Recent studies using nanoparticles and other lymphatic-targeting strategies suggest that direct targeting of antigens and adjuvant compounds to LNs can also enhance vaccine potency without sacrificing safety. The use of formulations to regulate biodistribution and promote antigen and inflammatory cue co-uptake in immune cells may be important for next-generation molecular adjuvants. Finally, strategies to program vaccine kinetics through novel formulation and delivery strategies provide another means to enhance immune responses independent of the choice of adjuvant. These technologies offer the prospect of enhanced efficacy while maintaining high safety profiles necessary for successful vaccines. PMID:26928033
Payne, Richard; McDonald, David; Byrne, Scott
Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.
-, č. 3 (2011), s. 1421-1431. ISSN 1945-0524 R&D Projects: GA AV ČR IAA500200917 Institutional research plan: CEZ:AV0Z50200510 Keywords : colorectal cancer * inflammation * tumor Subject RIV: EC - Immunology
Song, Jing; Huang, Yi-Fei; Zhang, Wen-Jing; Chen, Xiao-Fei; Guo, Yu-Mian
Many factors, such as environmental, microbial and endogenous stress, antigen localization, can trigger the immunological events that affect the ending of the diverse spectrum of ocular disorders. Significant advances in understanding of immunological and molecular mechanisms have been researched to improve the diagnosis and therapy for patients with ocular inflammatory diseases. Some kinds of ocular diseases are inadequately responsive to current medications; therefore, immunotherapy may be a potential choice as an alternative or adjunctive treatment, even in the prophylactic setting. This article first provides an overview of the immunological and molecular mechanisms concerning several typical and common ocular diseases; second, the functions of immunological roles in some of systemic autoimmunity will be discussed; third, we will provide a summary of the mechanisms that dictate immune cell trafficking to ocular local microenvironment in response to inflammation.
Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep
This review highlights the fundamental role of nutrition in the maintenance of health, the immune response, and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition, and the immune system interact to delineate health and disease. The review sets an unconventional path to apply complex science methodologies to nutritional immunology research, discovery, and development through “use cases” centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, which include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism. PMID:26909350
Full Text Available This review highlights the fundamental role of nutrition in the maintenance of health, the immune response and disease prevention. Emerging global mechanistic insights in the field of nutritional immunology cannot be gained through reductionist methods alone or by analyzing a single nutrient at a time. We propose to investigate nutritional immunology as a massively interacting system of interconnected multistage and multiscale networks that encompass hidden mechanisms by which nutrition, microbiome, metabolism, genetic predisposition and the immune system interact to delineate health and disease. The review sets an unconventional path to applying complex science methodologies to nutritional immunology research, discovery and development through ‘use cases’ centered around the impact of nutrition on the gut microbiome and immune responses. Our systems nutritional immunology analyses, that include modeling and informatics methodologies in combination with pre-clinical and clinical studies, have the potential to discover emerging systems-wide properties at the interface of the immune system, nutrition, microbiome, and metabolism.
Kaur, A; Rosenzweig, M; Johnson, R. P.
Infection with the human immunodeficiency virus results in profound perturbations in immunological memory, ultimately resulting in increased susceptibility to opportunistic infections and acquired immunodeficiency syndrome (AIDS). We have used rhesus macaques infected with the simian immunodeficiency virus (SIV) as a model to understand better the effects of AIDS virus infection on immunological memory. Acute infection with SIV resulted in significant deficits in CD4+ helper responses to cyto...
Dobrovolskaia, Marina A
The Handbook of Immunological Properties of Engineered Nanomaterials provides a comprehensive overview of the current literature, methodologies, and translational and regulatory considerations in the field of nanoimmunotoxicology. The main subject is the immunological properties of engineered nanomaterials. Focus areas include interactions between engineered nanomaterials and red blood cells, platelets, endothelial cells, professional phagocytes, T cells, B cells, dendritic cells, complement and coagulation systems, and plasma proteins, with discussions on nanoparticle sterility and sterilizat
Full Text Available Root resorption seems to be related to a complex combination of mechanical factors and biological activity, which comprehends the role of immunologic structures including specialized cells. The aim of this research was to explain the development of the process - from mineralization to the destruction of hard tissues - and the possible relationship between root resorption and immunology, along with discussing current concepts described in the literature.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fecal calprotectin immunological test system. 866.5180 Section 866.5180 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5180 Fecal calprotectin immunological...
Full Text Available Pemphigus vulgaris (PV is a life threatening autoimmune blistering disease of skin and mucous membranes. Advent of systemic steroids has greatly reduced the mortality rate. However, steroids and adjuvant immunosuppressive therapy are nowadays frequent contributory agents of morbidity and mortality of PV. Mycophenolate mofetil (MMF has been reported to be an effective adjuvant to systemic steroids. It helps in increasing the immunosuppressive effect and minimizing the toxicities by steroid sparing effect. However, its efficacy in refractory cases of PV is not well documented. The lowest possible dose with satisfactory therapeutic efficacy and least side effects is known. We used MMF 1 g/day and systemic steroids in 3 Indian patients with pemphigus vulgaris who were resistant to systemic steroid monotherapy or combination treatment with azathioprine. In our experience, MMF offers an effective adjuvant with minimal side-effects in the treatment of resistant PV.
Stroncek David F
Full Text Available Abstract The advent of high-throughput technology challenges the traditional histopathological classification of cancer, and proposes new taxonomies derived from global transcriptional patterns. Although most of these molecular re-classifications did not endure the test of time, they provided bulk of new information that can reframe our understanding of human cancer biology. Here, we focus on an immunologic interpretation of cancer that segregates oncogenic processes independent from their tissue derivation into at least two categories of which one bears the footprints of immune activation. Several observations describe a cancer phenotype where the expression of interferon stimulated genes and immune effector mechanisms reflect patterns commonly observed during the inflammatory response against pathogens, which leads to elimination of infected cells. As these signatures are observed in growing cancers, they are not sufficient to entirely clear the organism of neoplastic cells but they sustain, as in chronic infections, a self-perpetuating inflammatory process. Yet, several studies determined an association between this inflammatory status and a favorable natural history of the disease or a better responsiveness to cancer immune therapy. Moreover, these signatures overlap with those observed during immune-mediated cancer rejection and, more broadly, immune-mediated tissue-specific destruction in other immune pathologies. Thus, a discussion concerning this cancer phenotype is warranted as it remains unknown why it occurs in immune competent hosts. It also remains uncertain whether a genetically determined response of the host to its own cancer, the genetic makeup of the neoplastic process or a combination of both drives the inflammatory process. Here we reflect on commonalities and discrepancies among studies and on the genetic or somatic conditions that may cause this schism in cancer behavior.
Bui-Nguyen, B; Italiano, A; Delva, F; Toulmond, M
The main progress in the management of soft tissue sarcomas have been obtained in the field of local control. Although the main evolutive, vital, risk of these diseases is metastatic dissemination, efficacy of adjuvant chemotherapy remains a controversial issue. Thus, adjuvant chemotherapy cannot be considered as a standard for any situation. The last results of clinical trials, meta-analysis and population studies are presented and discussed in this article. New therapeutic strategies are to be developed to prevent metastases in soft tissue sarcomas. This needs a better understanding of the biology of those tumors, of metastases risk factors and of the determinants of systemic therapies efficacy in these tumors. PMID:20547481
... § 582.99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001(c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Adjuvants for pesticide chemicals. 582.99...
....99 Adjuvants for pesticide chemicals. Adjuvants, identified and used in accordance with 40 CFR 180.1001 (c) and (d), which are added to pesticide use dilutions by a grower or applicator prior to... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Adjuvants for pesticide chemicals. 182.99...
Numerous drift reduction adjuvants and spray deposition aids are available to applicators of crop production and protection chemicals. Performance of many of the newly introduced drift control adjuvants has not been well documented for aerial application. Five new drift control adjuvants were sele...
This is the Special Issue of Vet. Immunol. Immunopathol. that summarizes the 8th International Veterinary Immunology Symposium (8 th IVIS) held August 15th-19th, 2007, in Ouro Preto, Brazil. The 8 th IVIS highlighted the importance of veterinary immunology for animal health, vaccinology, reproducti...
Feinen, Brandon; Petrovsky, Nikolai; Verma, Anita; Tod J Merkel
Subunit vaccines against anthrax based on recombinant protective antigen (PA) potentially offer more consistent and less reactogenic anthrax vaccines but require adjuvants to achieve optimal immunogenicity. This study sought to determine in a murine model of pulmonary anthrax infection whether the polysaccharide adjuvant Advax or the innate immune adjuvant murabutide alone or together could enhance PA immunogenicity by comparison to an alum adjuvant. A single immunization with PA plus Advax a...
Miguel Angel MUÑOZ
Full Text Available clinicians and researchers due to its rapid progression and its evidences of genetic character. Different theories have tried to explain the individual differences in susceptibility, where genetic and immunological assays have assumed great importance. The purpose of this study was to review the literature in order to comprehend the genetic and immunological features of aggressive periodontitis. Literature review: Articles were examined, specifically the ones dealing with information regarding genetic and/or immunological studies of individuals related to their disease susceptibility. Conclusions: In the presence of dental biofilm, host susceptibility to aggressive periodontitis varies among regions, countries and races. Immune-inflammatory processes that seem to be modified in aggressive periodontitis patients may be transmitted vertically, explaining familial aggregation associated with this disease.
Jin, Pengfei; Li, Jingxin; Zhou, Yang; Zhu, Fengcai
An immunological surrogate endpoints is a vaccine-induced immune response (either humoral or cellular immune) that predicts protection against clinical endpoints (infection or disease), and can be used to evaluate vaccine efficacy in clinical vaccine trials. Compared with field efficacy trials observing clinical endpoints, immunological vaccine trials could reduce the sample size or shorten the duration of a trial, which promote the license and development of new candidate vaccines. For these reasons, establishing immunological surrogate endpoints is one of 14 Grand Challenges of Global Health of the National Institutes of Health (NIH) and the Bill and Melinda Gates Foundation. From two parts of definition and statistical methods for evaluation of surrogate endpoints, this review provides a more comprehensive description. PMID:26887309
The immune system provides an ideal metaphor for anomaly detection in general and computer security in particular. Based on this idea, artificial immune systems have been used for a number of years for intrusion detection, unfortunately so far with little success. However, these previous systems were largely based on immunological theory from the 1970s and 1980s and over the last decade our understanding of immunological processes has vastly improved. In this paper we present two new immune inspired algorithms based on the latest immunological discoveries, such as the behaviour of Dendritic Cells. The resultant algorithms are applied to real world intrusion problems and show encouraging results. Overall, we believe there is a bright future for these next generation artificial immune algorithms.
O'Hagan, Derek T; Fox, Christopher B
Adjuvants are an essential component of modern vaccine development. Despite many decades of development, only a few types of adjuvants are currently included in vaccines approved for human use. In order to better understand the reasons that development of some adjuvants succeeded while many others failed, we discuss some of the common attributes of successful first generation adjuvants. Next, we evaluate current trends in the development of second generation adjuvants, including the potential advantages of rationally designed synthetic immune potentiators appropriately formulated. Finally, we discuss desirable attributes of next generation adjuvants. Throughout, we emphasize that the importance of formulation and analytical characterization in all aspects of vaccine adjuvant development is often underappreciated. We highlight the formulation factors that must be evaluated in order to optimize interactions between vaccine antigens, immune potentiators, and particulate formulations, and the resulting effects on safety, biological activity, manufacturability, and stability. PMID:26022561
LI HaoWen; LI dinZhi; ZHAO GuoPing; WANG Ying
This review updates the current status of immunology research under the influence of genomics, both conceptually and technologically. It particularly highlights the advantages of employing the high-throughput and large-scale technology, the large genomic database, and bioinformatic power in the immunology research. The fast development in the fields of basic immunology, clinical immunology (tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy. We also speculate the future research directions of immunology in the era of genomics and post-genomics.
This review updates the current status of immunology research under the influence of genomics,both conceptually and technologically.It particularly highlights the advantages of employing the high-throughput and large-scale technology,the large genomic database,and bioinformatic power in the immunology research.The fast development in the fields of basic immunology,clinical immunology(tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy.We also speculate the future research directions of immunology in the era of genomics and post-genomics.
Wang, Nathalie F; Kolte, Astrid M; Larsen, Elisabeth C;
Recurrent pregnancy loss, depending on the definition, affects 1% to 3% of women aiming to have a child. Little is known about the direct causes of recurrent pregnancy loss, and the condition is considered to have a multifactorial and complex pathogenesis. The aim of this review was to summarize ...... the evaluation and the management of the condition with specific emphasis on immunologic biomarkers identified as risk factors as well as current immunologic treatment options. The review also highlights and discusses areas in need of further research....
Schneider, David S
Speculative fiction examines the leading edge of science and can be used to introduce ideas into the classroom. For example, most students are already familiar with the fictional infectious diseases responsible for vampire and zombie outbreaks. The disease dynamics of these imaginary ailments follow the same rules we see for real diseases and can be used to remind students that they already understand the basic rules of disease ecology and immunology. By engaging writers of this sort of fiction in an effort to solve problems in immunology we may be able to perform a directed evolution experiment where we follow the evolution of plots rather than genetic traits. PMID:26968492
Perfil'ev, D F
Examination of blood serum and cellular elements of 45 patients with postoperative diffuse purulent peritonitis shows that in the majority of examined persons before and in the first days after the operation immunodepression exists. The dynamics of immunologic disturbances (antibody titers, phagocytosis, immunoglobulines, T- and B-lymphocytes) are sufficiently informative and as a rule, correlate with clinical course of peritonitis. Adequate reaction of the organism to infection resulted in a favourable outcome. Low values of immunologic indices in postoperative period necessitate the use of stimulant therapy in combined treatment of this complication. PMID:9916429
Immunological mediated hepatitis can be initiated by bacterial product; Lipopolysaccharide (LPS). The later is increased during severe infection, bacterial overgrowth or translocation. LPS stimulates Kupffer cells. Activation of the kupffer cells contributes to the onset of liver injuries by producing and releasing cytotoxic agents, inflammatory cytokines and reactive oxygen species. In the present study, L-carnitine, a natural antioxidant and immunoprotective agent, is used to protect against LPS-induced hepatitis. Liver content of glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO) and the DNA adduct 8-hydroxydeoxyguanosine (8-HDG) are estimated. Serum activity of liver enzymes ALT, AST, and Gamma-GT, in addition to IL2 level are also estimated. Moreover, liver histopathological changes are determined. Results revealed that LPS (5mg/kg once i.p) significantly increased 8-HDG, MDA, NO and depleted GSH in the liver of the treated rats. It also increased serum IL2 and activity of all the estimated liver enzyme markers indicating massive hepatic cellular damage as also shown as a necrotic damage in liver histological sections. LCR administered (500mg/kg) 3h before LPS protected against LPS-induced lethality by 100%. LCR also prevented the increase in liver content of 8-HDG, MDA and NO. It reduced the depleted GSH and prevented the necrotic damage in the liver tissue as shown by normalization of ALT, AST and Gamma-Gt as well as IL2 and a remarkable improvement in liver histology. These data suggest that LCr could be used as an adjuvant therapy in severely infected and specific patients to counteract LPS-induced liver hepatitis. (author)
胡永秀; 赵文明; 钱娴娟; 张力平
Objective To investigate the effects of oral administration of type Ⅱ collagen (CⅡ) on a djuvant arthritis (AA) in rats and its mechanisms, and to compare the effects of CⅡ with those of the Chinese traditional medicine Tripterygium Polyglycoside a dministered similarly.Methods Arthritis was induced in rats by immunization using Freund's complete adjuvant (FCA). After feeding rats either soluble CⅡ or Tripterygium Polyglycoside, chan ges in degree of articular swelling and articular histological findings were observed in AA rats. Some correlative immunological indexes were measured, includi ng delayed type hypersensitivity (DTH) reaction, anti-collagen and anti-Mycoba cterium tuberculosis (MT) antibody in serum, and levels of IFN-γ and TNF-α i n articular steep in rats.Results Oral administration of CⅡ was able to alleviate both distinctly articular and general symptoms in AA rats, suppress synovium hyperplasia and inflammatory cells infiltration in arthrosis capsule. The effects brought about by CⅡ were stronger than those by Tripterygium Polyglycoside. Oral administration of CⅡ inhibi ted antigen-specific immune response, such as DTH and antibody reaction to CⅡ . In addition, the expression of IFN-γ and TNF-α in joints were locally dow nregulated. Conclusions The therapeutic effect of oral administration of CⅡ is obvious on adjuvant art hritis in rats. Its remedial mechanisms are likely related to the downregulation of both IFN-γ and TNF-α, and the suppression of cell immunity.
Klykken, P C; White, K L
Studies have been conducted in mice (B6C3F1) and rats (Sprague Dawley, Fischer 344) to investigate the adjuvancy potential of silicone mammary gel and the low molecular weight silicone fluid, octamethylcyclotetrasiloxane (D4). Dependent on the experimental conditions employed, a divergent data profile emerges. If the antigen (bovine serum albumin, BSA) is emulsified with either the gel or the D4 prior to intramuscular immunization, an amplified anti-BSA IgG antibody response, as measured by multipoint ELISA methodology, is noted over the 8 week measurement period. In parallel studies, a variety of non-silicone personal care ingredients (lanolin, white mineral oil, isopropyl palmitate) were also capable of amplifying this humoral response relative to the non-adjuvant phosphate buffered saline control. These observations are consistent with the empirical knowledge that hydrophobic substances tend to augment immune responses. However, under conditions in which the antigen is not blended with the silicone prior to immunization, normal immune responses are noted. In short (10 day) and long (180 day) term gel implant studies, the optimal IgM and IgG antibody responses, as determined in the antibody forming cell assay, were equivalent between the gel implanted and control animals. Moreover, under similar exposure conditions, no adjuvancy was noted in the three Host Resistance models (B16F10 Melanoma, Listeria monocytogenes, and Streptococcus pneumoniae) tested. Antibody forming cell studies conducted after 28 days of oral or inhalation exposure to D4 have also yielded responses similar to the non-silicone exposed vehicle controls. Collectively, these data suggest that in the absence of premixing the antigen with the silicone test material, there does not appear to be any silicone induced adjuvant response. PMID:8565549
The present invention relates to an immunological method and, more particularly, a method for measuring cell-mediated immune reactivity (CMI) in mammals based on the production of IP-10.The invention further discloses an assay and a kit for measuring CMI to an antigen using whole blood or other...
Nair, Smita K.; Sampson, John H.; Mitchell, Duane A.
Human cytomegalovirus (CMV) is purportedly present in glioblastoma (GBM) while absent from the normal brain, making CMV antigens potentially ideal immunological anti-GBM targets. We recently demonstrated that patient-derived CMV pp65-specific T cells are capable of recognizing and killing autologous GBM tumor cells. This data supports CMV antigen-directed immunotherapies against GBM.
What’s so special about chickens? Firstly, chickens are not only an invaluable model for studying immunology, they also provide the world’s main source of meat and will be a key protein source needed to feed the growing human population into the future. Poultry meat production is highly efficient ...
The study of host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated by a number of factors, including the protracted nature of the disease and the stealthy nature of the pathogen. Improved tools for the measurement of immunologic responses in ruminant species, par...
Diverse genomics-based databases have been developed to facilitate research with human and rodent models. Current porcine gene databases, however, lack the nutritional and immunological orientation and robust annotation to design effective molecular tools to study relevant pig models. To address t...
Huiming Fan; Song Guo Zheng
@@ The 10th meeting of the Federation of Clinical Immunology Societies (FOCIS) was held in Boston during 23-27 June 2010. As usual, this conference hightights the greatest advancements in the field of clinical immunology over the previous year.
Gliomatosis cerebri (GC) is characterized by a diffuse infiltration of tumor cells throughout CNS, however, few details are available about the chemotherapeutic effect on GC. The aim of this study was to investigate its clinical course and to determine the efficacy of chemotherapy for GC. Between Jan. 1999 and Dec. 2004, 37 GC patients were diagnosed by biopsy and treated with radiotherapy in a single institution. To determine the efficacy of chemotherapy for GC, we retrospectively reviewed their clinical courses. The study cohort was divided into 2 groups, those with and without receiving post-radiotherapy adjuvant chemotherapy such as temozolomide or nitrosourea-based chemotherapy. Nineteen patients with adjuvant chemotherapy were assigned to the chemotreatment group and 18 with radiotherapy alone were assigned to the control group. Mean survival for chemotreatment group and control group were 24.2 and 13.1 months, respectively (p = 0.045). Time to progression for these groups were 16.0 and 6.0 months, respectively (p = 0.007). Overall review of the clinical course of patients with GC provided that early appearance of new contrast-enhancing lesions within 6 months from the initial diagnosis and higher histological grade were closely associated with poor survival (p < 0.001 and p = 0.008). Adjuvant chemotherapy following radiotherapy could prolong the survival in patients with GC. In addition, newly developed contrast-enhanced lesions on the follow-up MR images indicate the progression of GC
Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda
Pancreatic adenocarcinoma is one of the most aggressive human malignancies,ranking 4th among causes for cancer-related death in the Western world including the United States.Surgical resection offers the only chance of cure,but only 15 to 20 percent of cases are potentially resectable at presentation.Different studies demonstrate and confirm that advanced pancreatic cancer is among the most complex cancers to treat and that these tumors are relatively resistant to chemotherapy and radiotherapy.Currently there is no consensus around the world on what constitutes "standard"adjuvant therapy for pancreatic cancer.This controversy derives from several studies,each fraught with its own limitations.Standards of care also vary somewhat with regard to geography and economy,for instance chemo-radiotherapy followed by chemotherapy or vice versa is considered the optimal therapy in North America while chemotherapy alone is the current standard in Europe.Regardless of the efforts in adjuvant and neoadjuvant improved therapy,the major goal to combat pancreatic cancer is to find diagnostic markers,identifying the disease in a pre-metastatic stage and making a curative treatment accessible to more patients.In this review,authors examined the different therapy options for advanced pancreatic patients in recent years and the future directions in adjuvant and neoadjuvant treatments for these patients.
Ghendon, Y; Markushin, S; Akopova, I; Koptiaeva, I; Krivtsov, G
The use of inactivated poliomyelitis vaccine is very important for eradicating poliomyelitis. However, this vaccine is not available readily in underdeveloped countries due to the high cost. Adjuvants can improve the immunogenicity of a vaccine and reduce the antigen dose required for vaccination, thus lowering the cost of the vaccine. Chitosan glutamate solution and a chitosan sulfate micro/nanoparticle suspension were tested as adjuvants for Imovax-inactivated poliovaccine and for inactivated monovalent poliovirus type 1, 2, and 3 vaccines obtained by inactivation of the attenuated Sabin poliovirus strains. Inactivated vaccines admixed with either chitosan glutamate or chitosan sulfate micro/nanoparticles and administered to mice showed significantly enhanced immunogenicity to poliovirus type 1, 2, and 3 strains compared to the respective vaccines administered without chitosan. Chitosan preparations increased the immunogenicity of 1:2 and 1:4 diluted inactivated Sabin strain preparations in mice 8- to 16-fold, so that the neutralizing antibody titers after vaccination with adjuvanted diluted vaccine were equal to those obtained after vaccination with undiluted vaccine administered without chitosan. Neutralizing antibodies could be detected in sera of rats vaccinated with undiluted, 1:10, and 1:100 diluted Imovax vaccine admixed with chitosan sulfate micro/nanoparticles, although in the control group, vaccination only with the undiluted vaccine resulted in antibody production. These results show that the chitosan glutamate solution and chitosan sulfate micro/nanoparticle suspension can significantly improve the immunogenicity of various poliovaccines, and reduce the effective antigen dose. PMID:21412793
Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and
Wei-Feng Chen; Kuang-Yen Chou
@@ Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and provided insights into creating a better environment for contemporary human existence.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Infectious mononucleosis immunological test system....5640 Infectious mononucleosis immunological test system. (a) Identification. An infectious mononucleosis immunological test system is a device that consists of the reagents used to measure...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimitochondrial antibody immunological test... Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An antimitochondrial antibody immunological test system is a device that consists of the reagents used to measure...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin immunological test system. 866.5470... Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... hemoglobin (the oxygen-carrying pigment in red blood cells) in blood, urine, plasma, or other body...
... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: General immunology. 493.1208 Section 493....1208 Condition: General immunology. If the laboratory provides services in the subspecialty of General immunology, the laboratory must meet the requirements specified in §§ 493.1230 through 493.1256, and §§...
... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Diagnostic immunology. 493.833 Section..., Or Any Combination of These Tests § 493.833 Condition: Diagnostic immunology. The specialty of diagnostic immunology includes for purposes of proficiency testing the subspecialties of syphilis...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test... Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A hypersensitivity pneumonitis immunological test system is a device that consists of the reagents used to measure...
...-storing protein) in serum and other body fluids. Measurements of ferritin aid in the diagnosis of diseases... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340... Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a...
Kwadwo A Kusi
Full Text Available There is increasing interest in multi-allele vaccines to overcome strain-specificity against polymorphic vaccine targets such as Apical Membrane Antigen 1 (AMA1. These have been shown to induce broad inhibitory antibodies in vitro and formed the basis for the design of three Diversity-Covering (DiCo proteins with similar immunological effects. The antibodies produced are to epitopes that are shared between vaccine alleles and theoretically, increasing the number of component AMA1 alleles is expected to broaden the antibody response. A plateau effect could however impose a limit on the number of alleles needed to achieve the broadest specificity. Moreover, production cost and the vaccine formulation process would limit the number of component alleles. In this paper, we compare rabbit antibody responses elicited with multi-allele vaccines incorporating seven (three DiCos and four natural AMA1 alleles and three (DiCo mix antigens for gains in broadened specificity. We also investigate the effect of three adjuvant platforms on antigen specificity and antibody functionality. Our data confirms a broadened response after immunisation with DiCo mix in all three adjuvants. Higher antibody titres were elicited with either CoVaccine HT™ or Montanide ISA 51, resulting in similar in vitro inhibition (65-82% of five out of six culture-adapted P. falciparum strains. The antigen binding specificities of elicited antibodies were also similar and independent of the adjuvant used or the number of vaccine component alleles. Thus neither the four extra antigens nor adjuvant had any observable benefits with respect to specificity broadening, although adjuvant choice influenced the absolute antibody levels and thus the extent of parasite inhibition. Our data confirms the feasibility and potential of multi-allele PfAMA1 formulations, and highlights the need for adjuvants with improved antibody potentiation properties for AMA1-based vaccines.
Yendo, Anna Carolina A; de Costa, Fernanda; Cibulski, Samuel P; Teixeira, Thais F; Colling, Luana C; Mastrogiovanni, Mauricio; Soulé, Silvia; Roehe, Paulo M; Gosmann, Grace; Ferreira, Fernando A; Fett-Neto, Arthur G
Quillaja brasiliensis (Quillajaceae) is a saponin producing species native from southern Brazil and Uruguay. Its saponins are remarkably similar to those of Q. saponaria, which provides most of the saponins used as immunoadjuvants in vaccines. The immunostimulating capacities of aqueous extract (AE) and purified saponin fraction (QB-90) obtained from leaves of Q. brasiliensis were favorably comparable to those of a commercial saponin-based adjuvant preparation (Quil-A(®)) in experimental vaccines against bovine herpesvirus type 1 and 5, poliovirus and bovine viral diarrhea virus in mice model. Herein, the immunogenicity and protection efficacy of rabies vaccines adjuvanted with Q. brasiliensis AE and its saponin fractions were compared with vaccines adjuvanted with either commercial Quil-A or Alum. Mice were vaccinated with one or two doses (on days 0 and 14) of one of the different vaccines and serum levels of total IgG, IgG1 and IgG2a were quantified over time. A challenge experiment with a lethal dose of rabies virus was carried out with the formulations. Viral RNA detection in the brain of mice was performed by qPCR, and RNA copy-numbers were quantified using a standard curve of in vitro transcribed RNA. All Q. brasiliensis saponin-adjuvanted vaccines significantly enhanced levels of specific IgG isotypes when compared with the no adjuvant group (P≤0.05). Overall, one or two doses of saponin-based vaccine were efficient to protect against the lethal rabies exposure. Both AE and saponin fractions from Q. brasiliensis leaves proved potent immunological adjuvants in vaccines against a lethal challenge with a major livestock pathogen, hence confirming their value as competitive or complementary sustainable alternatives to saponins of Q. saponaria. PMID:27032516
Morse, Michael A.
Options for the adjuvant therapy of resected stage III colon cancer have expanded beyond the previously well-accepted standard of 5-fluorouracil (5-FU) combined with leucovorin. The Xeloda in Adjuvant Colon Cancer Therapy (X-ACT) study confirmed that capecitabine (Xeloda) is at least as effective and is less toxic than a bolus 5-FU and leucovorin regimen for patients with stage III colon cancer. This study, in addition to National Surgical Adjuvant Breast and Bowel Project (NSABP) C-06, which...
Shimizu, Chikako; Watanabe, Toru
Adjuvant systemic therapy has contributed to a significant improvement of disease-free and overall survival in addition to surgery and irradiation to the local disease. The adjuvant therapy to a patient is determined integrating the information on estimated risk of recurrence, benefit and harm of the therapy and the patient's value. In this review, the state of the art of adjuvant therapy is discussed from several aspects, such as interpretation and evaluation of risk, the best available evidences on adjuvant systemic therapy, the future direction of primary therapy for breast cancer, and patient-oriented decision making. PMID:12506467
Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
The goal of this proposal is to demonstrate that co-localization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of recombinant subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. NLPs are are biocompatible, high-density lipoprotein mimetics that are amenable to the incorporation of multiple, chemically-disparate adjuvant and antigen molecules. We hypothesize that the ability to co-localize optimized adjuvant formulations with subunit antigens within a single particle will enhance the stimulation and activation of key immune effector cells, increasing the protective efficacy of subunit antigen-based vaccines. While Burkholderia spp. and F. tularensis subunit antigens are the focus of this proposal, we anticipate that this approach is applicable to a wide range of DOD-relevant biothreat agents. The F344 rat aerosol challenge model for F. tularensis has been successfully established at Battelle under this contract, and Year 3 efficacy studies performed at Battelle demonstrated that an NLP vaccine formulation was able to enhance survival of female F344 rats relative to naïve animals. In addition, Year 3 focused on the incorporation of multiple Burkholderia antigens (both polysaccharides and proteins) onto adjuvanted NLPs, with immunological analysis poised to begin in the next quarter.
Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the third quarter of the third year, F344 rats vaccinated with adjuvanted NLP formulations were challenged with F. tularensis SCHU S4 at Battelle. Preliminary data indicate that up to 65% of females vaccinated intranasally with an NLP-based formulation survived this challenge, compared to only 20% survival of naïve animals. In addition, NLPs were successfully formulated with Burkholderia protein antigens. IACUC approval for immunological assessments in BALB/c mice was received and we anticipate that these assessments will begin by March 2015, pending ACURO approval.
Kontos, Stephan; Grimm, Alizee J.; Hubbell, Jeffrey A.
Unwanted immunity develops in response to many protein drugs, in autoimmunity, in allergy, and in transplantation. Approaches to induce immunological tolerance aim to either prevent these responses or reverse them after they have already taken place. We present here recent developments in approaches, based on engineered peptides, proteins and biomaterials, that harness mechanisms of peripheral tolerance both prophylactically and therapeutically to induce antigenspecific immunological tolerance. These mechanisms are based on responses of B and T lymphocytes to other cells in their immune environment that result in cellular deletion or ignorance to particular antigens, or in development of active immune regulatory responses. Several of these approaches are moving toward clinical development, and some are already in early stages of clinical testing.
Messaoudi, Ilhem; Basler, Christopher F
Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. PMID:26163194
Schülke, Stefan; Scheurer, Stephan
Recent advances in immunology have greatly improved our understanding of the pathomechanisms of food allergies. Food allergies are caused and maintained by complex interactions of the innate and adaptive immune system involving antigen-presenting cells (APC), T cells, group 2 innate lymphoid cells (ILC2), epithelial cells (EC) and effectors cells. Additionally, epigenetic factors, the intestinal microbiome and nutritional factors modulating the gastrointestinal lymphatic tissue probably have a significant impact on allergy development. However, why certain individuals develop tolerance while others mount allergic responses, the factors defining the allergenicity of food proteins, as well as the immunological mechanisms triggering allergy development have yet to be analyzed in detail. PMID:27177897
Fox, Christopher B.
The Modern Vaccines/Adjuvants Formulation meeting aims to fill a critical gap in current vaccine development efforts by bringing together formulation scientists and immunologists to emphasize the importance of rational formulation design in order to optimize vaccine and adjuvant bioactivity, safety, and manufacturability. Session 6 on Vaccine and Adjuvant Formulation and Production provided three examples of this theme, with speakers emphasizing the need for extensive physicochemical characte...
Michael J. McCluskie; Weeratna, Risini D.; Evans, Dana M.; Shawn Makinen; Debbie Drane; Heather L. Davis
For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG), and ISCOMATRIX adjuvant (ISCOMATRIX), composed of saponin, phospholipid, and cholesterol, which possesses both immunostim...
O. V. Berdugina
Abstract. We have performed clinical and immunological investigation in the patients with trauma of face bones before and after stable mandibular ostheosynthesis. Blood samples for analysis were taken upon admission of the patient to clinics, and following treatment (3, 10, and 1-2 months). The patients with initially retarded bone consolidation exhibited low levels of monocytes and lactoferrine before surgical treatment. It was shown that the consecutive stages of bone regeneration (inflamma...
Raymond T. Damian
Full Text Available The complex immunological relationships between schistosomes and their vertebrate hosts are considered to be conveniently divisible into four distinct, though interrelated categories: the parasite's vulnerability to, its evasion of, and its exploitation of the host's immune response, and its stimulation of the host's immune response to produce immunopathology. Some significant recent advances in the first three categories are discussed, as well as their relationships to the fourth category of immunopathology.
Niedergang, Florence; Di Bartolo, Vincenzo; Alcover, Andrés
The generation of phagocytic cups and immunological synapses are crucial events of the innate and adaptive immune responses, respectively. They are triggered by distinct immune receptors and performed by different cell types. However, growing experimental evidence shows that a very close series of molecular and cellular events control these two processes. Thus, the tight and dynamic interplay between receptor signaling, actin and microtubule cytoskeleton, and targeted vesicle traffic are all ...
Kisalay Ghosh; Gautam Banerjee; Asok Kumar Ghosal; Jayoti Nandi
Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and ph...
Fern??ndez-P??rez, Antonio Manuel; Peralta-Ram??rez, Mar??a Isabel; Moreno-Lorenzo, Carmen; Pilat, Andrzej; Arroyo-Morales, Manuel; Villaverde-Guti??rrez, Carmen
Objectives: The objective was to determine the effect of myofascial techniques on the modulation of immunological variables. Design: Thirty-nine healthy male volunteers were randomly assigned to an experimental or control group. Interventions: The experimental group underwent three manual therapy modalities: suboccipital muscle release, so-called fourth intracranial ventricle compression, and deep cervical fascia release. The control group remained in a resting position for the sa...
Pregnancy is interesting from an immunological point of view. The maternal immune system has to tolerate the fetus and at the same time also protect against infection. The placenta is not a completely tight barrier: in fact, cells can pass through in both directions. Allergy often starts early in life and intrauterine factors have been proposed to play a role in development of allergy. The overall aim of this thesis was to study the innate response to infection and the p...
In order to know the effects of ultra-violet radiations on the integrity of their immunological system, a hematologic and immunological study was carried out in 30 clinically healthy children aged between 10 and 15; 15 of each sex, who come from a region in Bielorussia that was affected by the Chernobyl nuclear accident, and who received medical and recreational services at the 'Jose Marti' Pioneers'City, located Tarara Beach (Havana, Cuba) from July 9,1990 to August 27,1990. Data from the initial evaluations upon their arrival in Cuba were compared whit the final results before their return to Bielorussia, in the following variables: haemoglobin, leucocytes, platelets, absolute counts of lymphocytes and neutrophylous polymorphonuclears, levels of sericeus of Igs G, A, M, and E sericas and (CH50), as well as the presence of circulating immuno complexes; besides spot-forming cellular clusters (spontaneous, active, and medial by the receptor Fc in neutrophylous) and the cells identified with monoclonal antibodies against CD2, CD3, CD8 and CD4/CD8 quotient. Cutaneous response to antigen and lymphoblastic transformation in the presence of PHA and PwN were also assessed. Results of this research allow to infer that the adequate and monitored position against ultra-violet rays from the solar radiation in children exposed to low doses of ionizing irradiation does not deteriorate the human immunological system, and do favor its regulation and normal performance
Voena, Claudia; Chiarle, Roberto
After decades of setbacks, cancer immunology is living its Golden Age. Recent advances in cancer immunology have provided new therapeutic approaches to treat cancer. The objective clinical response observed in patients treated with antibodies that block the immune checkpoints, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell-death protein 1 (PD-1)/programmed cell-death 1 ligand 1 (PD-L1) pathways, has led to their FDA approval for the treatment of melanoma in 2011 and in 2014, respectively. The anti-PD-1 antibody nivolumab has received the FDA-approval in March 2015 for squamous lung cancer treatment. In addition, antibodies targeting PD-1 or PD-L1 have demonstrated their efficacy and safety in additional tumors, including non-small cell lung carcinoma (NSCLC), renal cell carcinoma (RCC), bladder cancer, and Hodgkin's lymphoma. Almost at the same time, the field of adoptive cell transfer has exploded. The chimeric antigen receptor (CAR) T technology has provided strong evidence of efficacy in the treatment of B cell malignancies, and different T cell based treatments are currently under investigation for different types of tumors. In this review we will discuss the latest advances in cancer immunology and immunotherapy as well as new treatments now under development in the clinic and potential strategies that have shown promising results in preclinical models. PMID:27011048
Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)
Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.
Fischer, N. O. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
The goal of this proposal is to demonstrate that colocalization of protein subunit antigens and adjuvants on nanolipoprotein particles (NLPs) can increase the protective efficacy of subunit antigens from Burkholderia spp. and Francisella tularensis against an aerosol challenge. In the second quarter of the third year, LLNL finalized all immunological assessments of NLP vaccine formulations in the F344 model. Battelle has immunized rats with three unique NLP formulations by either intramuscular or intranasal administration. All inoculations have been completed, and protective efficacy against an aerosolized challenge will begin at the end of October, 2014.
Casali, Paolo G
Adjuvant chemotherapy is not standard treatment in soft tissue sarcoma (STS). However, when the risk of relapse is high, it is an option for shared decision making with the patient in conditions of uncertainty. This is because available evidence is conflicting, even if several randomized clinical trials have been performed for 4 decades and also have been pooled into meta-analyses. Indeed, available meta-analyses point to a benefit in the 5% to 10% range in terms of survival and distant relapse rate. Some local benefit also was suggested by some trials. Placing chemotherapy in the preoperative setting may help gain a local advantage in terms of the quality of surgical margins or decreased sequelae. This may be done within a personalized approach according to the clinical presentation. Attempts to personalize treatment on the basis of the variegated pathology and molecular biology of STS subgroups are ongoing as well, according to what is done in the medical treatment of advanced STS. Thus, decision making for adjuvant and neoadjuvant indications deserves personalization in clinical research and in clinical practice, taking profit from all multidisciplinary clinical skills available at a sarcoma reference center, though with a degree of subjectivity because of the limitations of available evidence. PMID:25993233
Fry, Tricia; Van Dalen, Kaci; Hurley, Jerome; Nash, Paul
RABORAL V-RG(®)a is a recombinant vaccine used in oral rabies vaccination (ORV) programs for wildlife in the United States. Vaccination rates for raccoons are substantially lower than vaccination rates for gray foxes and coyotes. Research suggests that the low viscosity of the oral vaccine may preclude animals from receiving an effective dose when biting into the vaccine bait delivery system. We evaluated the possibility of using two benign compounds, chitosan and N,N,N-trimethylated chitosan (TMC), to increase the viscosity of the vaccine and potentially act as adjuvants to improve the immune response in raccoons (Procyon lotor). Forty mildly sedated raccoons were orally vaccinated via needleless syringe with either RABORAL V-RG (n = 12), chitosan+RABORAL V-RG (n = 12), TMC+ RABORAL V-RG (n = 12), or no vaccine (n = 4), on day 0 and again on day 90. We collected sera every 2-4 wk for 4 mo and evaluated rabies virus-neutralizing antibodies (rVNA). Raccoons were considered responders if rVNA titers were ≥ 0.1 IU/mL. Eleven of 12 raccoons vaccinated with TMC+RABORAL V-RG responded after one dose of vaccine, as did eight of 12 vaccinated with RABORAL V-RG, and three of 12 vaccinated with chitosan+ RABORAL V-RG. Our results suggest that the inclusion of an adjuvant, such as TMC, could increase vaccine efficacy to aid in controlling rabies virus spread in wildlife reservoirs. PMID:23060506
Paul H. Sugarbaker
Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.
Mallmann, Peter; Mallmann, Christoph
Neoadjuvant chemotherapy is indicated in patients who can tolerate the side effects of a chemotherapy and with preoperative presentation of one of the following clinical risk situations: bulky disease with a maximal tumor diameter of > 4 cm, suspicious lymph nodes in magnetic resonance imaging (MRI), computed tomography (CT) scan or endosonography, histopathologically confirmed lymph node metastasis, or histopathologically documented risk factors such as G3 and L1V1. A neoadjuvant chemotherapy followed by surgery should be performed with cisplatin at a dosage of > 25 mg/m2 per week and an application interval of < 14 days. The previously published data suggests an improved rate of complete resection and reduced incidences of positive lymph nodes and parametric infiltration. Accordingly, the percentage of patients in need for adjuvant radiochemotherapy after operation can be significantly reduced. Some studies demonstrated a prolongation of progression-free and overall survival. Following the previously published studies, adjuvant chemotherapy after operation or after radiochemotherapy has no significant effect on the overall survival and, following the current guidelines, should be avoided. PMID:27614740
CHENG Zi-qiang; ZHAO Zhen-hua; RI Mudema
Oil emulsion inactivated vaccine was prepared by susceptible embryos, with different strains of AEV. Four groups of normal chickens of 2 - 7 days of age were given injections for immunization, respectively. Another group was used as control. This study was expected to evaluate the immunological effect and discuss the immunological mechanism by means of five different experiments, i.e. the agar-gel precipitin test,the isolation of lymphokine, the isolation, purification and analysis of blood serum IgG, embryo-susceptibility test, and clinical and pathological examination. The results of these experiments indicated that oil emulsion inactivated vaccine is safe and effective. The chickens were normal when inoculated with AE strong virus after immunity at 4 and 37 weeks. Immunological mechanism is that the humoral immunity played an important role and celluar immunity exists, but it is not important in the process of the resistance to AEV.
Samantha Sayers; Guerlain Ulysse; Zuoshuang Xiang; Yongqun He
Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bi...
Pasquale, Alberta Di; Preiss, Scott; Silva, Fernanda Tavares Da; Garçon, Nathalie
The concept of stimulating the body's immune response is the basis underlying vaccination. Vaccines act by initiating the innate immune response and activating antigen presenting cells (APCs), thereby inducing a protective adaptive immune response to a pathogen antigen. Adjuvants are substances added to vaccines to enhance the immunogenicity of highly purified antigens that have insufficient immunostimulatory capabilities, and have been used in human vaccines for more than 90 years. While early adjuvants (aluminum, oil-in-water emulsions) were used empirically, rapidly increasing knowledge on how the immune system interacts with pathogens means that there is increased understanding of the role of adjuvants and how the formulation of modern vaccines can be better tailored towards the desired clinical benefit. Continuing safety evaluation of licensed vaccines containing adjuvants/adjuvant systems suggests that their individual benefit-risk profile remains favorable. Adjuvants contribute to the initiation of the innate immune response induced by antigens; exemplified by inflammatory responses at the injection site, with mostly localized and short-lived effects. Activated effectors (such as APCs) then move to draining lymph nodes where they direct the type, magnitude and quality of the adaptive immune response. Thus, the right match of antigens and adjuvants can potentiate downstream adaptive immune responses, enabling the development of new efficacious vaccines. Many infectious diseases of worldwide significance are not currently preventable by vaccination. Adjuvants are the most advanced new technology in the search for new vaccines against challenging pathogens and for vulnerable populations that respond poorly to traditional vaccines. PMID:26343190
Four drift adjuvants, Array, In-Place, Vector and Control, were tested and physical properties and spray spectrum parameters measured. Array had the highest conductivity, indicating a good potential for the electrostatic charging, and the highest shear viscosity. All adjuvants had very similar neut...
Hamborg, Mette; Jorgensen, Lene; Bojsen, Anders Riber; Christensen, Dennis; Foged, Camilla
Understanding the nature of adjuvant-antigen interactions is important for the future design of efficient and safe subunit vaccines, but remains an analytical challenge. We studied the interactions between three model protein antigens and the clinically tested cationic liposomal adjuvant composed...
Ana Claudia Marinho da Silva
Full Text Available In the last half of the century, a large amount of substances has been used as immune adjuvant. The immune adjuvant effect of olive, soybean and corn oils in Swiss mice immunized with ovalbumin (OVA plus aluminum hydroxide or emulsified in Marcol, soybean, olive or corn oils was evaluated through the OVA-specific antibodies determined by ELISA and Passive Cutaneous Anaphylaxis. In this work the comparison of the intensity of the immune response was established by the Bayesian analysis. The adjuvant effect of the vegetable oils was shown to be more effective than aluminium hydroxide. Regarding to OVA-specific IgE synthesis, olive oil had the slowest adjuvant effect of the three vegetable oils. Accordingly, olive oil was the most convenient among the vegetable oils to be used as immune adjuvant, since it stimulated a higher production of OVA-specific Ig and lower levels of anti-OVA IgE.
Rimaniol, Anne-Cécile; Gras, Gabriel; Clayette, Pascal
Intramuscular administration of aluminum-adjuvanted vaccines induces an infiltration of aluminum-containing macrophages between muscle fibers. In vitro stimulation of human monocyte-derived macrophages with aluminum hydroxide (AlOOH) induces similar intracellular crystalline inclusions as well as phenotypical and functional modifications. We compared in this study the ability of other adjuvants to exert similar changes in macrophages in vitro. All mineral salts, i.e. aluminic (AlOOH, AlPO(4)) and non-aluminic mineral adjuvants (CaPO(4), FePO(4)) but not emulsion were able to increase macrophages capacity to potentiate autologous memory T lymphocyte proliferation, while only aluminic adjuvants induced CD83 expression and increased CD86 on macrophages. All together, this suggests that aluminic and non-aluminic adjuvants exerted their immunoactivities by distinct mechanisms on macrophages. PMID:17689842
Gupta, Ankur; Das, Soumen; Schanen, Brian; Seal, Sudipta
Adjuvants have been used in vaccines for over 70 years to promote long-lived and sterilizing immunity. Since then, various adjuvant systems were developed by combining nanotechnology with natural and/or synthetic immunomodulatory molecules. These systems are biocompatible, immunogenic, and possess higher antigen carrying capacity. This article showcases advancements made in the adjuvant systems formulations, their synthesis routes, and the improvement of these adjuvants have brought in response to combat against ongoing global health threats such as malaria, hepatitis C, universal influenza, and human immunodeficiency virus. This review also highlights the interaction of adjuvants with the delivery of antigens to cells and unfolds mechanism of actions. In addition, this review discusses the physicochemical factors responsible for the efficient interaction of nanoadjuvants with antigen receptors to develop more effective, less reactogenic, and multifunctional systems for the next generation vaccines. PMID:26053286
Full Text Available Vaccine adjuvants are compounds that enhance host immune responses to co-administered antigens in vaccines. Vaxjo is a web-based central database and analysis system that curates, stores, and analyzes vaccine adjuvants and their usages in vaccine development. Basic information of a vaccine adjuvant stored in Vaxjo includes adjuvant name, components, structure, appearance, storage, preparation, function, safety, and vaccines that use this adjuvant. Reliable references are curated and cited. Bioinformatics scripts are developed and used to link vaccine adjuvants to different adjuvanted vaccines stored in the general VIOLIN vaccine database. Presently, 103 vaccine adjuvants have been curated in Vaxjo. Among these adjuvants, 98 have been used in 384 vaccines stored in VIOLIN against over 81 pathogens, cancers, or allergies. All these vaccine adjuvants are categorized and analyzed based on adjuvant types, pathogens used, and vaccine types. As a use case study of vaccine adjuvants in infectious disease vaccines, the adjuvants used in Brucella vaccines are specifically analyzed. A user-friendly web query and visualization interface is developed for interactive vaccine adjuvant search. To support data exchange, the information of vaccine adjuvants is stored in the Vaccine Ontology (VO in the Web Ontology Language (OWL format.
Full Text Available Signaling networks are key elements in all major aspects of cellular life, playing a major role in inter- and intracellular communications. They are involved in diverse processes such as cell-cycle progression, cellular metabolism, cell-cell communication and appropriate response to the cellular environment. The latter comprises a whole range of networks that are involved in regulation of cell development, differentiation, proliferation, apoptosis, and immunologic responses. The key mechanism involves the transduction of extracellular signals across the cell sur-face to different effectors in the cytosol and the nucleus. Dysregulation of these pathways is often associated with immunology disorders and malignant diseases such as cancer. One of the most common mechanisms of activation and/or inactivation of signaling transduction pathways is phosphorylation and de-phosphorylation at serine, threonine and tyrosine residues. Phosphoproteomics is playing an important role in our understanding of how phosphorylation participates in translating distinct signals into the normal and or abnormal physiological responses, and has shifted research towards screening for potential therapies for diseases and in-depth analysis of phosphoproteomes. Given the importance of phosphoproteomics in translational research we aim at outlining phosphoproteomic approaches based on mass spectrometry (MS. This review focuses on (1b the role of phospho signaling in immunology, (2a current phosphopeptide enrichment methods based on IMAC and titanium dioxide, (2b phosphopeptide analysis by MS, and (2c issues concerned with interpretation of phospho spectra by database dependent search. Finally, quantitative methods used in phosphoproteomics such as Stable Isotope labeling with Amino acid in cell Culture (SILAC, isobaric Tag for Relative and Absolute Quantitation (iTRAQ and Absolute Quantification (AQUA is discussed in section 3.
Zinkernagel, Rolf M.
Simplified and generalizable rules of immune responses against infections or vaccines have been summarized into 20 statements previously (Scand. J. Immunol. 60 (2004) 9-13) and are restated in a slightly different form here. The key terms of immunology (e.g. specificity, tolerance and memory) are explained in terms of their co-evolutionary importance in the equilibrium between infectious agents and diseases with higher vertebrate hosts. Specificity is best defined by protective antibodies or protective activated T cells; e.g. serotype specific neutralizing antibodies against polio viruses represent the discriminatory power of an immune response very well indeed. Tolerance is reviewed in terms of reactivity rather than self-nonself discrimination. Immune respones are deleted against antigens expressed at sufficient levels within the lymphoheamopoetic system, but may well exist at both, the T and the B cell level against antigens strictly outside of secondary lymphatic organs. In this respect the immune system behaves identically against virus infections and against self antigens. Persistent virus infections delete responsive T cells, once eliminated immune T cell responses wane, if a virus keeps outside of secondary lymphatic tissues no immune response is induced. Immunological memory is usually defined as earlier and greater responses but this does not correlate with protective immunity stringently. It is summarized here that pre-existing titers of protective neutralizing antibodies or pre-existence of activated T cells are the correlates of protection acute cytopathic lethal infections and toxins or against intracellular parasites. It is concluded that many discrepancies and uncertainties in immunological research derive from model situations and experimental results that are correctly measured but cannot be related to co-evolutionary contexts, i.e. survival.
Full Text Available Drug hypersensitivity is an unpredictable, immunologically mediated adverse reaction, clustered in a genetically predisposed individual. The role of "hapten concept" in immune sensitization has recently been contested by the "pharmacological interaction" hypothesis. After completion of the "human genome project" and with the availability of high-resolution genotyping, genetic susceptibility to hypersensitivity for certain drugs has been proved beyond doubt though the trend is ethnicity and phenotype dependent. Application of this newly acquired knowledge may reduce or abolish the morbidity and mortality associated with cutaneous drug hypersensitivity.
Antibody targeted radiotherapy brings an important new treatment modality to Radiation oncology clinic. Radiation dose to tumor and normal tissues are determined by a complex interplay of antibody, antigen, tumor, radionuclide, and host-related factors. A basic understanding of these immunologic and physiologic factors is important to optimally utilize this therapy in the clinic. Preclinical and clinical studies need to be continued to broaden our understanding and to develop new strategies to further improve the efficacy of this promising form of targeted therapy
Mohler, R.R.; Asachenkov, A.L.
In 1988 the new IIASA project on System Immunology was inaugurated. The new activity focuses theoretical and experimental research in immunology and system mathematics to experimental planning and prediction for relevant disease applications and systematic understanding of immunology. IIASA analysis and simulation should lead to an effective plan of successive experiments to identify and to quantify particularly sensitive parameters in this most complex system of information processing, decis...
Nielsen, Hans Jørgen; Christensen, Ib Jarle; Moesgaard, F;
BACKGROUND: Results from short-term studies of histamine type 2 (H2) receptor antagonists on survival of patients with solid tumours are debatable. In this study the efficacy of the H2-receptor antagonist ranitidine on long-term survival of patients with colorectal cancer was evaluated. METHODS...... by oral ranitidine 150 mg or placebo twice daily for 5 years. Adjuvant cytotoxic or radiation therapy was not given. An observer-blinded interim analysis performed after 40 months showed that there was no effect of ranitidine on overall survival, and the study was discontinued in accordance with the...... postoperative infectious complications (n = 170; HR 0.6 (95 per cent c.i. 0.4 to 0.9), P = 0.01). In multivariate analysis of patients who had a curative resection, including Dukes' stage, age, gender, tumour location, blood transfusion, postoperative infectious complications and treatment, ranitidine still had...
The conservative treatment of early breast cancer always requires irradiation of residual mammary tissue. The preliminary results obtained in 45 early breast cancer patients, who received quadrantectomy plus axillary dissection, followed by radiation of residual breast are reported. Radiation was performed by the two opposed field technique. In some cases the residual breast tissue was compressed using a special accessory provided with the Theratron 780. In addition to the tumor dose of 50 GY, 10 GY boots was added to the surgical scar using 7 MeV electrons. The 6 patients with positive axillary nodes received 6 courses of adjuvant chemotherapy (CMF) after radiotherapy. All patients are currently alive and free of disease. The 64% (29 patients) were followed up for at least 5 years, and 36% (16 patients) for at least 3 years. Only 2 cases of local recurrence were encountered (4,4%). The esthetic result was satisfactory in all cases. No side effects due to treatment were noted
Ranran Zhang; Dongchu Ma; Xiaodong Xie; Wanqing Xie Co-first author; Tao Han; Yongye Liu; Zhaozhe Liu; Fang Guo; Yaling Han; Zhenyu Ding; Yinghui Sun
Objective The aim of the present study was to investigate the ef ect of dendritic cel (DC)/cytokine-in-duced kil er cel (CIK) immunobiological cancer therapy in patients with triple-negative breast cancer (TNBC) who underwent adjuvant chemotherapy. Methods From January 2010 to October 2013, 120 patients with postoperative TNBC were recruited and included in the study. Patients were enrol ed in one of two groups according to whether they accepted DC/CIK immunobiological cancer therapy during adjuvant chemotherapy; the patients in the DC/CIK group underwent adjuvant chemotherapy combined with DC/CIK immunobiological cancer therapy, and the control group underwent adjuvant chemotherapy alone. When six cycles of adjuvant chemotherapy and six cycles of DC/CIK immunobiological cancer therapy had been completed, dif erences between the two groups with regard to quality of life (QoL), immunological indicators (CD3, CD4, CD8, and NK cel levels), disease-free survival (DFS), and side ef ects of chemotherapy and DC/CIK treatment were evaluated. Results In the DC/CIK group, the proportion of NK cel s and CD3+ and CD4+ T-cel subgroups significantly increased, and the proportion of CD8+ cel s decreased when they were compared before and after DC/CIK therapy (P Conclusion The DC/CIK treatment had potential benefits for patients with TNBC compared with the con-trol group, and was not associated with any obvious side ef ects. Therefore, DC/CIK therapy is a safe and ef ective method for the treatment of TNBC.
Neto, J C Rosa; Lira, F S; de Mello, M T; Santos, Ronaldo Vagner T
Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. The effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. In this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation. PMID:20976509
Lackie, A M
Transplantation of allogeneic and xenogeneic cuticle onto the American cockroach, Periplaneta americana, was carried out in order to compare the specificity of immune recognition of these 'skin grafts' with that of implanted tissues. In order to facilitate interpretation of results, the technique of transplanting cuticle from nymphal donors onto nymphal recipients was adopted - if donor subcuticular epidermis is not recognised as 'foreign', it will grow, fuse with the recipient's epidermal sheet and will be stimulated by the recipient's hormonal signals to produce new cuticle of donor type at the next moult. Neither allogeneic cuticle nor xenogeneic cuticle from Blatta orientalis were recognised as foreign by the immune system of P. americana - dark patches of Blatta-type cuticle were produced at the graft site post-moult. Conversely, xenogeneic cuticle of Blaberus craniifer was not visible post-moult. These results corroborate those from implantation studies, that allogeneic tissues from P. americana and xenogeneic tissues from B. orientalis are immunologically compatible with P. americana, whereas xenogeneic tissue from Blaberus craniifer is incompatible. Whether this incompatibility is immunological or 'positional' has not yet been determined; the observation that xenografts from Nauphoeta cinerea do not reappear on P. americana post-moult, whereas 50% of N. cinerea implants are not recognised as 'foreign', suggests that 'positional incompatibility' (i.e. the signals responsible for formation of cuticular pattern are incorrect for the donor epidermis) may also play an important part in the rejection of N. cinerea cuticular grafts. PMID:6341106
Tan, Zi Yan; Bealgey, Kenneth W; Fang, Yong; Gong, Yang Ming; Bao, Shisan
Increasing evidence has revealed the importance of IL-23, which closely resembles IL-12 both structurally and immunologically, in linking innate and adaptive immunity. IL-23, produced by activated type 1 macrophages and dendritic cells (DC), possesses unique roles in the differentiation and expansion of memory T cells. IL-23 has been associated with several inflammatory diseases such as rheumatoid arthritis, inflammatory bowel disease (IBD) and Helicobacter pylori associated gastritis, mainly due to its capacity to induce a strong Th1 type immune response. IL-23 is also associated with Th17 responses and the cytokine produced by the antigen presenting cells (APC), i.e. IL-12 vs IL-23 determines in part if a response is Th1 or Th17. Recent studies have also associated chronic inflammatory diseases such as IBD, psoriasis and myocardial infarction with polymorphisms of the IL-23 receptor complex. The current review focuses on the immunological role of IL-23 and possible therapeutic avenues for inflammatory diseases. PMID:18725317
Liimatainen, Suvi; Lehtimäki, Kai; Kai, Lehtimäki; Palmio, Johanna; Johanna, Palmio; Alapirtti, Tiina; Tiina, Alapirtti; Peltola, Jukka; Jukka, Peltola
The temporal lobes are affected in many different neurological disorders, such as neurodegenerative diseases, viral and immunological encephalitides, and epilepsy. Both experimental and clinical evidence suggests a different inflammatory response to seizures in patients with temporal lobe epilepsy (TLE) in comparison to those with extra-TLE (XTLE). Proinflammatory cytokines and several autoantibodies have been shown to be associated with TLE compared to other epilepsy types suggesting the specific role and structure of the temporal lobe. Abundant experience suggests that activation of both innate and adaptive immunity is associated with epilepsy, particularly refractory focal epilepsy. Limbic encephalitis often triggers temporal lobe seizures, and a proportion of these disorders are immune-mediated. Histological evidence shows activation of specific inflammatory pathways in resected temporal lobes of epileptic patients, and certain epileptic disorders have shown increased incidence in patients with autoimmune diseases. Rapid activation of proinflammatory cytokines is observed after single seizures, but there is also evidence of chronic overproduction of cytokines and other inflammatory mediators in patients with TLE, suggesting a neuromodulatory role of inflammation in epilepsy. In this review we summarize current data on the presence and the role of immunological factors in temporal lobe seizures, and their possible involvement in epileptogenesis. PMID:23998423
Tibballs, James; Yanagihara, Angel A.; Turner, Helen C.; Winkel, Ken
Just over a century ago, animal responses to injections of jellyfish extracts unveiled the phenomenon of anaphylaxis. Yet, until very recently, understanding of jellyfish sting toxicity has remained limited. Upon contact, jellyfish stinging cells discharge complex venoms, through thousands of barbed tubules, into the skin resulting in painful and, potentially, lethal envenomations. This review examines the immunological and toxinological responses to stings by prominent species of jellyfish including Physalia sp. (Portuguese Man-o-War, Blue-bottle), Cubozoan jellyfish including Chironex fleckeri, several Carybdeids including Carybdea arborifera and Alatina moseri, Linuche unguiculta (Thimble jellyfish), a jellyfish responsible for Irukandji syndrome (Carukia barnesi) and Pelagia noctiluca. Jellyfish venoms are composed of potent proteinaceous porins (cellular membrane pore-forming toxins), neurotoxic peptides, bioactive lipids and other small molecules whilst the tubules contain ancient collagens and chitins. We postulate that immunologically, both tubular structural and functional biopolymers as well as venom components can initiate innate, adaptive, as well as immediate and delayed hypersensitivity reactions that may be amenable to topical anti-inflammatory-immunomodifier therapy. The current challenge for immunotoxinologists is to deconstruct the actions of venom components to target therapeutic modalities for sting treatment. PMID:21824077
Purpose: Local recurrence is a significant problem following primary surgery for advanced vulva carcinoma. The objectives of this study were to evaluate the impact of adjuvant vulvar radiation on local control in high risk patients and the impact of local recurrence on overall survival. Methods and Materials: From 1980-1994, 62 patients with invasive vulva carcinoma and either positive or close (less 8 mm) margins of excision were retrospectively studied. Thirty-one patients were treated with adjuvant radiation therapy to the vulva and 31 patients were observed after surgery. Kaplan-Meier estimates and the Cox proportional hazard regression model were used to evaluate the effect of adjuvant radiation therapy on local recurrence and overall survival. Independent prognostic factors for local recurrence and survival were also assessed. Results: Local recurrence occurred in 58% of observed patients and 16% in patients treated with adjuvant radiation therapy. Adjuvant radiation therapy significantly reduced local recurrence rates in both the close margin and positive margin groups (p = 0.036, p = 0.0048). On both univariate and multivariate analysis adjuvant radiation and margins of excision were significant prognostic predictors for local control. Significant determinants of actuarial survival included International Federation of Gynecologists and Obstetricians (FIGO) stage, percentage of pathologically positive inguinal nodes and margins of excision. The positive margin observed group had a significantly poorer actuarial 5 year survival than the other groups (p = 0.0016) and adjuvant radiation significantly improved survival for this group. The 2 year actuarial survival after developing local recurrence was 25%. Local recurrence was a significant predictor for death from vulva carcinoma (risk ratio 3.54). Conclusion: Local recurrence is a common occurrence in high risk patients. In this study adjuvant radiation therapy significantly reduced local recurrence rates and
Full Text Available Substantial controversy remains regarding the optimal adjuvant treatment for patients with resectable pancreatic adenocarcinoma. Despite improvements in radiation techniques, systemic therapies, and incorporation of targeted agents, the 5-year survival rates for early stage patients remains less than 25% and the optimal adjuvant treatment approach remains unclear. Here we summarize the data presented at the 2012 American Society of Clinical Oncology (ASCO Gastrointestinal Cancers Symposium regarding controversial issues surrounding the role, timing, and selection of patients for adjuvant chemoradiation strategies following curative resection for pancreatic adenocarcinoma. (Abstracts #301, #333, and #206.
Conrad, Melanie L; Renz, Harald; Blaser, Kurt
Allergy is the consequence of an inappropriate inflammatory immune response generated against harmless environmental antigens. In allergic disorders such as asthma and rhinitis, the Th2 mediated phenotype is a result of loss of peripheral tolerance mechanisms. In cases such as these, approaches such as immunotherapy attempt to treat the underlying cause of allergic disease by restoring tolerance. Immunotherapy initiates many complex mechanisms within the immune system that result in initiation of innate immunity, activation of both cellular and humoral B cell immunity, as well as triggering T regulatory subsets which are major players in the establishment of peripheral tolerance. Though studies clearly demonstrate immunotherapy to be efficacious, research to improve this treatment is ongoing. Investigation of allergenicity versus immunogenicity, native versus modified allergens, and the use of adjuvant and modality of dosing are all current strategies for immunotherapy advancement that will be reviewed in this article. PMID:21598104
Michael J. McCluskie
Full Text Available For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN containing immunostimulatory CpG motifs (CpG, and ISCOMATRIX adjuvant (ISCOMATRIX, composed of saponin, phospholipid, and cholesterol, which possesses both immunostimulatory and delivery properties. While both individual adjuvants have been shown effective in numerous preclinical and clinical studies, it is likely that for optimal adjuvant activity a combined adjuvant approach will be necessary. Herein, using three different antigens, namely, hepatitis B surface antigen (HBsAg, ovalbumin (OVA, and influenza A haemagglutinin antigen (HA, we show in mice that some adjuvant effects of CpG and ISCOMATRIX are further enhanced if they are used in combination. In particular, with all three antigens, IFN-γ levels were greatly increased with the CpG/ISCOMATRIX combination. The ability of the CpG/ISCOMATRIX combination to induce antitumor responses when administered with OVA following administration to mice of a highly metastatic OVA-secreting tumor cell line (B16-OVA melanoma was also demonstrated. Thus the CpG/ISCOMATRIX combination may prove to be a valuable tool in the development of novel or improved vaccines.
these CMF regimens has not been compared within the context of a randomised trial. Shifting from the 77B's classic CMF regimen to the 82B four-weekly IV regimen or the 89B three-weekly IV regimen was associated with a 30% increased risk of a DFS event in a multivariate analysis of a population-based cohort study. Furthermore, the four-weekly regimen used in 82B was associated with a 40% increase in mortality. The strengths of the design include identical selection criteria, uniform and prospective registration of treatment, tumour and patient characteristics. Caution is still required due to the non-experimental design of the comparison. Another finding was a substantial difference in the risk of amenorrhoea; and while 15% of patients aged 40 or younger in 77B had regular menses throughout chemotherapy, the corresponding percentage was 37 in 82B and 47 in 89B. The DBCG in collaboration with a Swedish and a Dutch centre participating in the DBCG trial 89B compared CMF with ovarian ablation in premenopausal high-risk breast cancer patients with ER-positive tumours. No significant differences were found in DFS or OS in the preplanned analysis, suggesting that the benefits of CMF may, at least in part, be explained by ovarian suppression in premenopausal patients with ER-positive tumours. However, these results are not clinically useful by themselves as other chemotherapy regimens have been more efficacious, and knowledge is still lacking regarding the benefits from adding ovarian suppression to chemotherapy plus tamoxifen. The results from the DBCG 77B and 82C are in accordance with other large adjuvant trials and the EBCTCG meta-analyses. The benefits obtained with any individual anticancer drug are largely determined by the cancer (somatic) genome; and by being a molecular target of anthracyclines, TOP2A aberrations could obviously be associated with cancer drug benefits. In the DBCG 89D, a significant heterogeneity was observed between a beneficial effect on DFS and OS
Robinson, L; Knight-Jones, T J D; Charleston, B; Rodriguez, L L; Gay, C G; Sumption, K J; Vosloo, W
This study assessed gaps and priorities for FMDV (foot-and-mouth disease virus) research in the field of immunology. The study took the form of a literature review (2011-15) combined with research updates collected in 2014 from 33 institutes from across the world. Findings were used to identify priority areas for future FMD research. Improved understanding of FMDV immunology facilitates the development of vaccines, adjuvants and diagnostic tests, and will allow better assessment and prediction of vaccine potency and match, with reduced use of animals, particularly large animals, in experimental studies. Continued characterization of the immune systems of several FMD host species has underpinned substantial advances in knowledge of their interaction with FMDV. Recent studies have shed light on the mechanisms underlying formation of the bovine B- and T-cell response; there is also a greater understanding of the significance of non-neutralizing antibodies during FMDV infection and the interactions of antibody-bound virus with immune cells. This knowledge is directly relevant to vaccine development, as well as understanding protection and cross-protection. Despite ongoing research, significant knowledge gaps remain in the areas of neonatal and mucosal immunity. The impact of maternally derived antibody upon the neonate's ability to respond to FMD vaccination has received some attention, but few firm conclusions can be drawn at this stage, and little is known of the cellular response of young animals in general. The mucosal immune system of FMDV-susceptible species requires continued characterization, especially if the potential of mucosal vaccine-delivery systems is to be realized for FMD immunization. PMID:27320167
Randomized controlled trial to evaluate the effects of progressive resistance training compared to progressive muscle relaxation in breast cancer patients undergoing adjuvant radiotherapy: the BEST study
Cancer-related fatigue (CRF) is one of the most common and distressing side effects of cancer and its treatment. During and after radiotherapy breast cancer patients often suffer from CRF which frequently impairs quality of life (QoL). Despite the high prevalence of CRF in breast cancer patients and the severe impact on the physical and emotional well-being, effective treatment methods are scarce. Physical activity for breast cancer patients has been reported to decrease fatigue, to improve emotional well-being and to increase physical strength. The pathophysiological and molecular mechanisms of CRF and the molecular-biologic changes induced by exercise, however, are poorly understood. In the BEST trial we aim to assess the effects of resistance training on fatigue, QoL and physical fitness as well as on molecular, immunological and inflammatory changes in breast cancer patients during adjuvant radiotherapy. The BEST study is a prospective randomized, controlled intervention trial investigating the effects of a 12-week supervised progressive resistance training compared to a 12-week supervised muscle relaxation training in 160 patients with breast cancer undergoing adjuvant radiotherapy. To determine the effect of exercise itself beyond potential psychosocial group effects, patients in the control group perform a group-based progressive muscle relaxation training. Main inclusion criterion is histologically confirmed breast cancer stage I-III after lumpectomy or mastectomy with indication for adjuvant radiotherapy. Main exclusion criteria are acute infectious diseases, severe neurological, musculosceletal or cardiorespiratory disorders. The primary endpoint is cancer-related fatigue; secondary endpoints include immunological and inflammatory parameters analyzed in peripheral blood, saliva and urine. In addition, QoL, depression, physical performance and cognitive capacity will be assessed. The BEST study is the first randomized controlled trial comparing progressive
The immune system is known to be highly susceptible to various physical, chemical, and biological insults. The studies on the immediate and long-term effects of radiation on immune system of mice indicated very clearly that there was a dose-dependent reduction in the number of T and B cells, depression of antibody and cytotoxic T cell responses as well as proliferative responses of spleen cells to T and B cell mitogens shortly after irradiation, but they all recovered to the control level within a few months. Immunosuppression observed shortly after irradiation had little influence on the development of radiogenic tumors. The effects of radiation on the incidence of Friend leukemia virus (FLV)-induced leukemias are examined by using young adult B6C3F1 male mice which are normally resistant to FLV-induced leukemogenesis. There was a clear threshold dose of 2 Gy below which the development of FLV induced leukemias was not observed but after exposure to >3 Gy high incidence of leukemias was observed. Fractionated, weekly exposure of young C57BL strain mice to 1.6 Gy of X-rays for four successive weeks causes most of the exposed mice to develop thymic lymphomas between 3 and 10 months. However, when the exposed mice are grafted with bone marrow cells from normal donors, the development of thymic lymphomas on the exposed mice is greatly inhibited. There was a clear dose response relationship between the number of bone marrow cells injected and the inhibition of the development of thymic lymphomas. It now appears clear that T cell-mediated immunological surveillance against newly arising neoplasms conceived by Thomas and Burnet does not hold true anymore in the original form, although virus-infected host cells and other host cells expressing altered-self' markers on their cell surfaces are constantly monitored by the immunological surveillance mechanism. A surveillance function against newly arising neoplasms may be a property of surrounding normal tissue cells rather
... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement components immunological test system....5240 Complement components immunological test system. (a) Identification. A complement...
Jeppesen, Dorthe Lisbeth
thymus relevant to its function and could measurement of the thymus be a useful immunological diagnostic tool in the investigation of thymic function in humans with a depressed immune system? Conclusion: Studies using the size of the thymus as an immunological diagnostic tool should be encouraged....
Psycho-oncology and psycho-neuro-immunology are both powerful new disciplines. Although a lot of literature exists in both of these fields the evidence is often controversial. This paper gives a brief perspective on the origins of psycho-neuro-immunology and discusses how our current understanding of this subject can be translated into clinical practice in an Indian setting.
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antiparietal antibody immunological test system....5110 Antiparietal antibody immunological test system. (a) Identification. An antiparietal antibody... the specific antibody for gastric parietal cells in serum and other body fluids. Gastric...
... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system....5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular...
The Third Veterinary Immunology Committee (VIC) Toolkit Workshop took place at the Ninth International Veterinary Immunology Symposium (IVIS) in Tokyo, Japan on August 18, 2020. The Workshop built on previous Toolkit Workshops and covered various aspects of reagent development, commercialisation an...
... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; General immunology. 493.837 Section 493.837 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... These Tests § 493.837 Standard; General immunology. (a) Failure to attain a score of at least 80...
Debess, Jeanne; Riis, Jens Østergaard; Engebjerg, Malene Cramer;
start of adjuvant treatment and after 6 months by neuropsychological tests and questionnaires to evaluate cognitive function, quality of life and psychological distress. Neuropsychological tests did not reveal any differences in cognitive function between breast cancer patients after chemotherapy and......The purpose of this study was to examine cognitive function in patients with early breast cancer before and after adjuvant chemotherapy or 6 months of tamoxifen. We performed a population-based study in the county of North Jutland, Denmark, including 120 women aged <60 years who received adjuvant...... chemotherapy with seven cycles of cyclophosphamide, epirubicin and fluoruracil or adjuvant tamoxifen for 6 months for early breast cancer from 2004 to 2006. They were compared with an aged-matched group of 208 women without previous cancer selected randomly from the same population. Data were collected before...
Zhou, Huaiyu; Min, Juan; Zhao, Qunli; Gu, Qinmin; Cong, Hua; Li, Ying; He, Shenyi
Previous immunological studies from our laboratory have demonstrated the potential role of Toxoplasma gondii antigens SAG1 and GRA2 as vaccine candidates. To further evaluate the vaccine's effects, a series of recombinant DNA vaccines pVAX1-SAG1, pVAX1-GRA2 and pVAX1-SAG1-GRA2, termed pSAG1, pGRA2 and pSAG1-GRA2, respectively, were constructed. A plasmid pVAX1-S/PreS2, termed pSPreS2 encoding hepatitis B virus (HBV) surface antigen (HBsAg) S and PreS2 as a novel genetic adjuvant, was also constructed. The expression abilities of those DNA plasmids were examined in HFF cells by Western blotting. Then BALB/c mice were intramuscularly immunized with DNA plasmids and followed by challenging with the highly virulent T. gondii RH strain. The results demonstrated that the recombinant DNA vaccine pSAG1-GRA2 was capable of eliciting high levels of antibodies, a Th1 type of immune response with significant production of IFN-γ and low levels of IL-4 or IL-10 in BALB/c mice, and partial protection against the acute phase of toxoplasmosis as compared to pSAG1, pGRA2 and controls. In addition, the adjuvant pSPreS2 formulated with DNA vaccine induced a Th1 type of immune response and therefore might be a novel genetic adjuvant to DNA vaccine for further investigation. PMID:22240340
Rose, Noel R.; Bogazzi, Pierluigi E.
The Center for Immunology at the University of Buffalo provides a viable resource for educating medical students in immunology until a department of immunology can be developed within the medical school. (HS)
Peltier Morgan R
Full Text Available Abstract During pregnancy there is an alteration in maternal immunity within the uterus where innate, proinflammatory immune responses are tightly regulated to prevent immunological rejection of the fetal allograft. Disruption of the delicate balance of cytokines by bacteria or other factors increases the production of proinflammatory cytokines at the maternal-fetal interface and activates the parturition mechanism prematurely. Despite years of searching, there is still no broadly effective strategy for preventing preterm labor and most therapies are directed at inhibiting myometrial contractions and improving neonatal outcome. Recent studies with progestins and interleukin-10 (IL-10, however, are showing promise in randomized clinical trials and animal studies. Furthermore, the identification of the Toll-like receptors as upstream mediators of inflammation may offer alternative therapeutic targets for preventing this common pregnancy complication.
Magnusson Carl GM
Full Text Available Abstract Disturbances in the immune system has been described in Turner syndrome, with an association to low levels of IgG and IgM and decreased levels of T- and B-lymphocytes. Also different autoimmune diseases have been connected to Turner syndrome (45, X, thyroiditis being the most common. Besides the typical features of Turner syndrome (short stature, failure to enter puberty spontaneously and infertility due to ovarian insufficiency ear problems are common (recurrent otitis media and progressive sensorineural hearing disorder. Levels of IgG, IgA, IgM, IgD and the four IgG subclasses as well as T- and B-lymphocyte subpopulations were investigated in 15 girls with Turners syndrome to examine whether an immunodeficiency may be the cause of their high incidence of otitis media. No major immunological deficiency was found that could explain the increased incidence of otitis media in the young Turner girls.
Risør, Louise Madeleine; Bendtsen, Flemming; Møller, Søren
Acute kidney injury (AKI) is one of the most severe complications of cirrhosis and is associated with significant morbidity and mortality. Liver fibrosis and liver insufficiency, portal hypertension, systemic vasodilation, and a subsequent hyperdynamic circulation undermine the renal and cardiac...... function, making cirrhotic patients more susceptible to hemodynamic incidents. In addition, the immune system is impaired in cirrhosis, leading to an exaggerated production of vasoactive mediators, and the adrenal cortisol response is insufficient, which causes further impairment of the vascular tonus...... dysfunction, but is not responsive to volume expansion. Recent research indicates that development of hepatic nephropathy represents a continuous spectrum of functional and structural dysfunction and may be precipitated by the inherent immunologic, adrenal, and hemodynamic incompetence in cirrhosis. New...
Zakrzewski, Johannes L; van den Brink, Marcel R M; Hubbell, Jeffrey A
Regenerative therapies that use allogeneic cells are likely to encounter immunological barriers similar to those that occur with transplantation of solid organs and allogeneic hematopoietic stem cells (HSCs). Decades of experience in clinical transplantation hold valuable lessons for regenerative medicine, offering approaches for developing tolerance-induction treatments relevant to cell therapies. Outside the field of solid-organ and allogeneic HSC transplantation, new strategies are emerging for controlling the immune response, such as methods based on biomaterials or mimicry of antigen-specific peripheral tolerance. Novel biomaterials can alter the behavior of cells in tissue-engineered constructs and can blunt host immune responses to cells and biomaterial scaffolds. Approaches to suppress autoreactive immune cells may also be useful in regenerative medicine. The most innovative solutions will be developed through closer collaboration among stem cell biologists, transplantation immunologists and materials scientists. PMID:25093888
He, Peng; Zou, Yening; Hu, Zhongyu
In the past few decades, hundreds of materials have been tried as adjuvant; however, only aluminum-based adjuvants continue to be used widely in the world. Aluminum hydroxide, aluminum phosphate and alum constitute the main forms of aluminum used as adjuvants. Among these, aluminum hydroxide is the most commonly used chemical as adjuvant. In spite of its wide spread use, surprisingly, the mechanism of how aluminum hydroxide-based adjuvants exert their beneficial effects is still not fully und...
Ji-Won, Shin; Jai-Young, Park; Hee-Soo,Park
Objective: To investigate effects of Cervi Cornu on Adjuvant Athritis in rats, the edema inhibit rate, the anaJgesic effects, the number of WBC, RA facter, Platelet, the quantity of CRP, total protein, albumin and globuline in the blood serum were measured in the arthritis part. Results: The results obtained as fonows ; 1. After arthritis of Sprague dawley(SD) rats was induced by injecting Freund's complete adjuvant for 2 weeks, any treatment was not for Control group, acupunctured for Tr...
Dong, Chunhui; Chen, Ling
Second malignant neoplasms (SMNs) are potentially life-threatening late sequelae of the adjuvant therapy for breast cancer (BC). The increased risk of SMNs is associated with adjuvant chemotherapy (development of secondary acute myeloid leukemia and myelodysplastic syndrome) and hormonal therapy (risk of uterine cancer secondary to tamoxifen treatment). Previous studies have demonstrated an increased risk of SMNs associated with alkylating agents, topoisomerase-II inhibitors, granulocyte-stim...
Timothy J Ciarlo
Full Text Available BACKGROUND: Spray adjuvants are often applied to crops in conjunction with agricultural pesticides in order to boost the efficacy of the active ingredient(s. The adjuvants themselves are largely assumed to be biologically inert and are therefore subject to minimal scrutiny and toxicological testing by regulatory agencies. Honey bees are exposed to a wide array of pesticides as they conduct normal foraging operations, meaning that they are likely exposed to spray adjuvants as well. It was previously unknown whether these agrochemicals have any deleterious effects on honey bee behavior. METHODOLOGY/PRINCIPAL FINDINGS: An improved, automated version of the proboscis extension reflex (PER assay with a high degree of trial-to-trial reproducibility was used to measure the olfactory learning ability of honey bees treated orally with sublethal doses of the most widely used spray adjuvants on almonds in the Central Valley of California. Three different adjuvant classes (nonionic surfactants, crop oil concentrates, and organosilicone surfactants were investigated in this study. Learning was impaired after ingestion of 20 µg organosilicone surfactant, indicating harmful effects on honey bees caused by agrochemicals previously believed to be innocuous. Organosilicones were more active than the nonionic adjuvants, while the crop oil concentrates were inactive. Ingestion was required for the tested adjuvant to have an effect on learning, as exposure via antennal contact only induced no level of impairment. CONCLUSIONS/SIGNIFICANCE: A decrease in percent conditioned response after ingestion of organosilicone surfactants has been demonstrated here for the first time. Olfactory learning is important for foraging honey bees because it allows them to exploit the most productive floral resources in an area at any given time. Impairment of this learning ability may have serious implications for foraging efficiency at the colony level, as well as potentially many
Verma, S.; Madarnas, Y.; Sehdev, S.; Martin, G; Bajcar, J.
Improvements in adjuvant systemic therapy and detection of early disease have resulted in a decline of breast cancer death rates across all patient age groups in Canada. Non-adherence to adjuvant hormonal therapy in the setting of early breast cancer may significantly affect patient outcome. Factors associated with medication adherence are complex and may be patient-related, therapy-related, and health care provider–related. To date, there is a gap in the literature concerning a comprehensive...
Ingvarsson, Pall Thor; Yang, Mingshi; Mulvad, Helle;
The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB).......The purpose of this study was to identify and optimize spray drying parameters of importance for the design of an inhalable powder formulation of a cationic liposomal adjuvant composed of dimethyldioctadecylammonium (DDA) bromide and trehalose-6,6'-dibehenate (TDB)....
EnaWang; MonicaCPanelli; VladiaMonsurró; FrancescoMMarincola
Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven approach. This conclusion is derived from our recognition that too many hypotheses or, in other words, no solid single hypothesis exist, based on experimental results, to further drive experimentation in human subjects. Functional genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven method. We believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each other. Indeed, immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of inflammation. It is reasonable to question what induces inflammation at the tumor site. We hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate theirmicroenvironment through cell-to-cell interactions or the secretion of soluble factors. Thus, in analogy the observation of immune cells within tumors parallels the presence of paramedics, police and firemen at thescene of an accident, which is reactive to and not causative of the occurrence. In this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the subject. Cellular & Molecular Immunology.
Lavelle Timothy J
Full Text Available Abstract Background The immune contribution to cancer progression is complex and difficult to characterize. For example in tumors, immune gene expression is detected from the combination of normal, tumor and immune cells in the tumor microenvironment. Profiling the immune component of tumors may facilitate the characterization of the poorly understood roles immunity plays in cancer progression. However, the current approaches to analyze the immune component of a tumor rely on incomplete identification of immune factors. Methods To facilitate a more comprehensive approach, we created a ranked immunological relevance score for all human genes, developed using a novel strategy that combines text mining and information theory. We used this score to assign an immunological grade to gene expression profiles, and thereby quantify the immunological component of tumors. This immunological relevance score was benchmarked against existing manually curated immune resources as well as high-throughput studies. To further characterize immunological relevance for genes, the relevance score was charted against both the human interactome and cancer information, forming an expanded interactome landscape of tumor immunity. We applied this approach to expression profiles in melanomas, thus identifying and grading their immunological components, followed by identification of their associated protein interactions. Results The power of this strategy was demonstrated by the observation of early activation of the adaptive immune response and the diversity of the immune component during melanoma progression. Furthermore, the genome-wide immunological relevance score classified melanoma patient groups, whose immunological grade correlated with clinical features, such as immune phenotypes and survival. Conclusions The assignment of a ranked immunological relevance score to all human genes extends the content of existing immune gene resources and enriches our understanding
Ippolito, Jill A.; Curtis, Brenda J.; Choudhry, Mashkoor A.; Kovacs, Elizabeth J.
On October 27, 2012, the 17th annual Alcohol and Immunology Research Interest Group (AIRIG) meeting was held at the Grand Wailea Hotel in Maui, Hawaii as a satellite meeting to the 2012 Society of Leukocyte Biology conference. This year’s meeting focused on the influence of alcohol on signal transduction pathways in various disease and injury models. Three plenary sessions were held where invited speakers shared their research on alcohol-mediated alterations of cell signaling components, immu...
Purpose: To determine the effects of adjuvant radiotherapy and chemotherapy for carcinoma of the ampulla of Vater. Methods and Materials: We retrospectively reviewed the records of 125 patients who underwent definitive surgery for carcinomas involving the ampulla of Vater between April 1977 and February 2005 and who survived more than 50 days after surgery. Twenty-nine of the patients also received adjuvant radiotherapy (median dose, 50.4 Gy in 28 fractions) with concurrent 5-fluorouracil chemotherapy. Adverse prognostic factors were investigated, and overall survival (OS) and local and distant failure were estimated. Results: Adverse prognostic factors for decreased OS by univariate analysis included lymph node (LN) involvement, locally advanced tumors (T3/T4), and poor histologic grade. By multivariate analysis, positive LN status (p = 0.02) alone was associated with decreased OS. The addition of adjuvant radiotherapy and chemotherapy improved OS for patients with positive LN (p = 0.01). Median survival for positive LN patients receiving adjuvant therapy was 3.4 years, vs. 1.6 years for those with surgery alone. Conclusions: The addition of adjuvant radiotherapy and 5-fluorouracil chemotherapy may improve OS in patients with LN involvement. The effect of adjuvant therapy on outcomes for patients with poor histologic grade or T3/T4 tumors without LN involvement could not be assessed
Xia, Yufei; Fan, Qingze; Hao, Dongxia; Wu, Jie; Ma, Guanghui; Su, Zhiguo
Mucosal vaccination, which is shown to elicit systemic and mucosal immune responses, serves as a non-invasive and convenient alternative to parenteral administration, with stronger capability in combatting diseases at the site of entry. The exploration of potent mucosal adjuvants is emerging as a significant area, based on the continued necessity to amplify the immune responses to a wide array of antigens that are poorly immunogenic at the mucosal sites. As one of the inspirations from the ocean, chitosan-based mucosal adjuvants have been developed with unique advantages, such as, ability of mucosal adhesion, distinct trait of opening the junctions to allow the paracellular transport of antigen, good tolerability and biocompatibility, which guaranteed the great potential in capitalizing on their application in human clinical trials. In this review, the state of art of chitosan and its derivatives as mucosal adjuvants, including thermo-sensitive chitosan system as mucosal adjuvant that were newly developed by author's group, was described, as well as the clinical application perspective. After a brief introduction of mucosal adjuvants, chitosan and its derivatives as robust immune potentiator were discussed in detail and depth, in regard to the metabolism, safety profile, mode of actions and preclinical and clinical applications, which may shed light on the massive clinical application of chitosan as mucosal adjuvant. PMID:26271831
Dudek, Katarzyna; Bednarek, Dariusz; Ayling, Roger D; Kycko, Anna; Szacawa, Ewelina; Karpińska, Teresa A
Mycoplasma bovis is a major pathogen affecting cattle causing bronchopneumonia, mastitis, and other disorders. Only autogenous vaccines made specifically for individual farms are available in parts of Europe and the United States. A novel experimental vaccine composed of a field M. bovis isolate combined with saponin and Emulsigen(®) adjuvants was evaluated. Eighteen 3-4 week old calves were placed in three equal groups: vaccinated (Vac), positive control (PC) and negative control (NC). The Vac calves were subcutaneously injected with 8ml of the vaccine; the PC and NC calves received phosphate buffered saline (PBS). Three weeks later the Vac and PC calves were challenged with a virulent M. bovis strain, the NC group received PBS. Throughout the study clinical observations, microbiology and immunological tests were carried out. Three weeks post challenge two calves from each group were euthanased for necropsy and histopathological examination. The vaccine effectively stimulated the humoral immune response, with high titres of anti-M. bovis specific antibodies and total Ig concentration. This vaccine also intensified the IgA response. A clinically protective effect of the vaccine was demonstrated as it also reduced the gross pathological lung lesions and nasal shedding of M. bovis. PMID:27156637
Full Text Available The present study aimed at assessing the effects of methionine and arginine on the immune response of broiler chickens submitted to immunological stimuli. Three methionine concentrations (0.31, 0.51, and 0.66% from 1 to 21 days of age; 0.29, 0.49, and 0.64% from 22 to 42 days of age and 2 arginine concentrations (1.33 and 1.83%; 1.14 and 1.64% for the same life periods were tested. Birds were divided into two groups for immunological stimuli (3x2x2 arrangement. Vaccines against Marek's disease, fowl pox, infectious bronchitis, Freund's Complete Adjuvant, Sheep red blood cells (SRBC, and avian tuberculin were administered to one group as immunological stimuli; the other group did not receive any stimulus. The experiment was carried out with 432 one-day-old male Ross broilers, distributed into 12 treatments with 6 replicates of 6 birds each. Performance data were weekly collected. Anti-SRBC antibodies were collected by hemagglutination test and cell immune response (CIR was measured by tubercularization reaction in one wattle 24 hours after administration of the second tuberculin injection at 42 days of age. The weight difference between the two wattles of each bird (one injected with tuberculin and the other not was the measure of CIR. Arginine levels did not influence either bird performance or immune response. Methionine concentrations higher or lower than usually adopted in broiler production (0.51 and 0.49% equally failed to influence the birds' immune humoral response, but the best CIR was observed at the intermediate methionine level. Vaccines administered on the first day of age impaired bird performance up to the 21st day of age.
Huub F. J. Savelkoul
Full Text Available The existence of pathogens that escape recognition by specific vaccines, the need to improve existing vaccines and the increased availability of therapeutic (non-infectious disease vaccines necessitate the rational development of novel vaccine concepts based on the induction of protective cell-mediated immune responses. For naive T-cell activation, several signals resulting from innate and adaptive interactions need to be integrated, and adjuvants may interfere with some or all of these signals. Adjuvants, for example, are used to promote the immunogenicity of antigens in vaccines, by inducing a pro-inflammatory environment that enables the recruitment and promotion of the infiltration of phagocytic cells, particularly antigen-presenting cells (APC, to the injection site. Adjuvants can enhance antigen presentation, induce cytokine expression, activate APC and modulate more downstream adaptive immune reactions (vaccine delivery systems, facilitating immune Signal 1. In addition, adjuvants can act as immunopotentiators (facilitating Signals 2 and 3 exhibiting immune stimulatory effects during antigen presentation by inducing the expression of co-stimulatory molecules on APC. Together, these signals determine the strength of activation of specific T-cells, thereby also influencing the quality of the downstream T helper cytokine profiles and the differentiation of antigen-specific T helper populations (Signal 3. New adjuvants should also target specific (innate immune cells in order to facilitate proper activation of downstream adaptive immune responses and homing (Signal 4. It is desirable that these adjuvants should be able to exert such responses in the context of mucosal administered vaccines. This review focuses on the understanding of the potential working mechanisms of the most well-known classes of adjuvants to be used effectively in vaccines.
Hyperthermia is another important method in the treatment of tumors, secondary to surgery, radiotherapy, chemotherapy and biotherapy. It has been demonstrated the efifcacy and versatility of hyperthermia in a lot of randomized trials across various primary cancers. Both heat shock proteins (HSPs) and dendritic cells (DCs) are greatly affected by hyperthermia and closely related to the tumor immunology. Nowadays, tumor hyperthermia and tumor immunology have been attached much attention in the field of translational medicine. In this article, the action mechanism and immunological effects of hyperthermia, activation of HSPs and DCs as well as HSP- and DC-based cancer vaccine were reviewed from the perspective of translational medicine.
Davenport, V; Morris, J F; Chu, A C
Several studies have suggested a lack of correlation between sunscreen sun protection factor and protection of the skin immune system, potentially allowing greater damage to the skin by removing the natural protective erythemal response to sun exposure. Despite this, routine testing of immune protection afforded by sunscreens is not performed by industry. Current laboratory methods for investigating the efficacy of sunscreen protection of epidermal immune function use the induction of contact hypersensitivity or epidermal cell alloantigen presentation. Animal models, cell culture systems, and in vivo human studies are commonly employed, but all these systems have significant drawbacks for use in routine testing. The purpose of this study was to develop an in vitro system for testing the immunologic protection afforded by sunscreens in human skin. Five test sunscreens plus a vehicle control were tested in a "blind" fashion for their in vitro level of immune protection. Creams were applied in a standard manner to human whole skin explants and were irradiated over a range of physiologic doses using an Oriel solar simulator. A mixed epidermal lymphocyte reaction was used to quantify epidermal alloantigen-presenting capacity, in the presence or absence of test cream, for five explants. Results consistently demonstrated that all the test sunscreens protected beyond their designated sun protection factors, whereas the vehicle conferred no protection. The explant-mixed epidermal lymphocyte reaction system gave consistent, reproducible results and may prove useful for the allocation of an immune protection factor to all sunscreens. PMID:9182811
O. V. Berdugina
Full Text Available Abstract. We have performed clinical and immunological investigation in the patients with trauma of face bones before and after stable mandibular ostheosynthesis. Blood samples for analysis were taken upon admission of the patient to clinics, and following treatment (3, 10, and 1-2 months. The patients with initially retarded bone consolidation exhibited low levels of monocytes and lactoferrine before surgical treatment. It was shown that the consecutive stages of bone regeneration (inflammation, osteoblastic proliferation, collagenogenesis, and ossification are accompanied by certain changes in immune parameters. In particular, we observed increased levels of IgМ, TNF, and activation of leucopoiesis after treatment. The results obtained allow us of discriminating some natural reactions of immune system in cases of normal and retarded bone consolidation. For each of these criteria, diagnostic sensitivity and informativity of tests are calculated, thus providing an opportunity to predict retarded consolidation in surgical treatment of the face bones. (Med. Immunol., 2007, vol. 10, N 4-5, pp 371-388.
Shephard, Roy J
Interest in the influence of exercise upon the human white cell population dates back more than a 100 years. Thus, when introducing the third meeting of the International Society of Exercise Immunology in Brussels, Dr. Bente Klarlund-Pedersen noted that Schulte had already described an exercise-induced leukocytosis as early as 1893. However, for much of the following century interest remained strictly clinical, with physicians assessing the possible changes in vulnerability to bacterial and viral diseases that were induced by various forms of physical activity. In the absence of specific remedies, bed rest was a common medical recommendation for infectious disease, and if the patient recovered from the immediate infection there was often a substantial residual loss of physical condition. Army hospitals in particular were thus anxious to know whether recovery would be compromised if physical activity were to be encouraged during convalescence. Prominent concerns of this era were the influence of exercise upon anterior poliomyelitis and viral hepatitis. The paralysis resulting from the anterior poliomyelitis virus was generally localized to body parts that had been active, and it seemed most likely to develop in those who continued to engage in vigorous exercise in the face of early symptoms (46, 57, 119, 120). Data on viral hepatitis also suggested a need for rest in the acute phase of the disease (1, 65, 115, 128), although most authors concluded that in this condition exercise could be resumed during convalescence, provided that the patient was no longer severely jaundiced (5, 32, 136). PMID:20839500
Full Text Available This preliminary investigation compares peripheral blood cell counts including red blood cells (RBCs, white blood cells (WBCs, neutrophils, peripheral blood lymphocytes (PBLs, CD4+, CD8+ and CD16+ lymphocytes, CD4+/CD8+ ratio, hematocrit, humoral parameters including serum interferon-γ and interleukin-6, salivary secretory immunoglobulin A (IgA. Psychological measures including the State–Trait Anxiety Inventory (STAI questionnaire and the Self-rating Depression Scale (SDS between recipients (n = 11 of carrier oil massage and aromatherapy massage, which includes sweet almond oil, lavender oil, cypress oil and sweet marjoram oil. Though both STAI and SDS showed a significant reduction (P 0.05 increase in PBLs, possibly due to an increase in CD8+ and CD16+ lymphocytes, which had significantly increased post-treatment (P < 0.01. Consequently, the CD4+/CD8+ ratio decreased significantly (P < 0.01. The paucity of such differences after carrier oil massage suggests that aromatherapy massage could be beneficial in disease states that require augmentation of CD8+ lymphocytes. While this study identifies the immunological benefits of aromatherapy massage, there is a need to validate the findings prospectively in a larger cohort of patients.