The Known Immunologically Active Components of Astragalus Account for Only a Small Proportion of the Immunological Adjuvant Activity When Combined with Conjugate Vaccines

PubMed Central

Hong, Feng; Xiao, Weilie; Ragupathi, Govind; Lau, Clara B. S.; Leung, Ping Chung; Yeung, K. Simon; George, Constantine; Cassileth, Barrie; Kennelly, Edward; Livingston, Philip O.

2013-01-01

The 95% ethanol extract of Astragalus has been demonstrated to have potent activity as an immunological adjuvant when administered with vaccines of various types. We endeavor here to identify the components of this extract that are responsible for this adjuvant activity. Mice were immunized with KLH conjugated to cancer carbohydrate antigens globo H and GD3 and cancer peptide antigen MUC1 combined with different Astragalus fractions or with commercially available Astragalus saponins and flavonoids. The antibody responses against cancer antigens and KLH were quantitated in ELISA assays, and toxicity was calculated by weight loss. Astragalosides II and IV were the most active components, but the toxicity of these two differed dramatically. Astragaloside II was the most toxic Astragalus component with 5–10% weight loss at a dose of 500 µg while astragaloside IV showed no weight loss at all at this dose, suggesting that astragaloside IV might be utilized as an immunological adjuvant in future studies. Several flavonoids also had significant adjuvant activity. However, when the activities of these known immunologically active components of Astragalus (and of endotoxin) are calculated based on the extent of their presence in the 95% ethanol extract, they provide only a small proportion of the immunological activity. This raises the possibility that additional uniquely active components of Astragalus may contribute to adjuvant activity, or that the adjuvant activity of Astragalus is greater than the activity of the sum of its parts. PMID:21128203

The immunological synapse

PubMed Central

Dustin, Michael L.

2015-01-01

The molecular interactions underlying regulation of the immune response take place in a nano-scale gap between T cells and antigen presenting cells, termed the immunological synapse. If these interactions are regulated appropriately, the host is defended against a wide range of pathogens and deranged host cells. If these interactions are dis-regulated, the host is susceptible to pathogens or tumor escape at one extreme and autoimmunity at the other. Treatments targeting the synapse have helped to establish immunotherapy as a mainstream element in cancer treatment. This Masters primer will cover the basics of the immunological synapse and some of the applications to tumor immunology. PMID:25367977

The Influence of MHC and Immunoglobulins A and E on Host Resistance to Gastrointestinal Nematodes in Sheep

PubMed Central

Lee, C. Y.; Munyard, K. A.; Gregg, K.; Wetherall, J. D.; Stear, M. J.; Groth, D. M.

2011-01-01

Gastrointestinal nematode parasites in farmed animals are of particular importance due to their effects on production. In Australia, it is estimated that the direct and indirect effects of parasite infestation cost the animal production industries hundreds of millions of dollars each year. The main factors considered by immunologists when studying gastrointestinal nematode infections are the effects the host's response has on the parasite, which immunological components are responsible for these effects, genetic factors involved in controlling immunological responses, and the interactions between these forming an interconnecting multilevel relationship. In this paper, we describe the roles of immunoglobulins, in particular IgA and IgE, and the major histocompatibility complex in resistance to gastrointestinal parasites in sheep. We also draw evidence from other animal models to support the involvement of these immune components. Finally, we examine how IgA and IgE exert their influence and how methods may be developed to manage susceptible animals. PMID:21584228

Resolving dynamics of cell signaling via real-time imaging of the immunological synapse.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stevens, Mark A.; Pfeiffer, Janet R.; Wilson, Bridget S.

2009-10-01

This highly interdisciplinary team has developed dual-color, total internal reflection microscopy (TIRF-M) methods that enable us to optically detect and track in real time protein migration and clustering at membrane interfaces. By coupling TIRF-M with advanced analysis techniques (image correlation spectroscopy, single particle tracking) we have captured subtle changes in membrane organization that characterize immune responses. We have used this approach to elucidate the initial stages of cell activation in the IgE signaling network of mast cells and the Toll-like receptor (TLR-4) response in macrophages stimulated by bacteria. To help interpret these measurements, we have undertaken a computational modeling effortmore » to connect the protein motion and lipid interactions. This work provides a deeper understanding of the initial stages of cellular response to external agents, including dynamics of interaction of key components in the signaling network at the 'immunological synapse,' the contact region of the cell and its adversary.« less

Oxytocin-secreting system: A major part of the neuroendocrine center regulating immunologic activity.

PubMed

Wang, Ping; Yang, Hai-Peng; Tian, Shujun; Wang, Liwei; Wang, Stephani C; Zhang, Fengmin; Wang, Yu-Feng

2015-12-15

Interactions between the nervous system and immune system have been studied extensively. However, the mechanisms underlying the neural regulation of immune activity, particularly the neuroendocrine regulation of immunologic functions, remain elusive. In this review, we provide a comprehensive examination of current evidence on interactions between the immune system and hypothalamic oxytocin-secreting system. We highlight the fact that oxytocin may have significant effects in the body, beyond its classical functions in lactation and parturition. Similar to the hypothalamo-pituitary-adrenal axis, the oxytocin-secreting system closely interacts with classical immune system, integrating both neurochemical and immunologic signals in the central nervous system and in turn affects immunologic defense, homeostasis, and surveillance. Lastly, this review explores therapeutic potentials of oxytocin in treating immunologic disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

Homeostatic Immunity and the Microbiota.

PubMed

Belkaid, Yasmine; Harrison, Oliver J

2017-04-18

The microbiota plays a fundamental role in the induction, education, and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system. Here we review the dominant cellular mediators of these interactions and discuss emerging themes associated with our current understanding of the homeostatic immunological dialogue between the host and its microbiota. Published by Elsevier Inc.

Homeostatic immunity and the microbiota

PubMed Central

Belkaid, Yasmine; Harrison, Oliver J.

2017-01-01

The microbiota plays a fundamental role in the induction, education and function of the host immune system. In return, the host immune system has evolved multiple means by which to maintain its symbiotic relationship with the microbiota. The maintenance of this dialogue allows the induction of protective responses to pathogens and the utilization of regulatory pathways involved in the sustained tolerance to innocuous antigens. The ability of microbes to set the immunological tone of tissues, both locally and systemically, requires tonic sensing of microbes and complex feedback loops between innate and adaptive components of the immune system. In this review, we will highlight the dominant cellular mediators of these interactions and discuss emerging themes associated with our current understanding of the homeostatic immunological dialogue between the host and its microbiota. PMID:28423337

Virtual immunology: software for teaching basic immunology.

PubMed

Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

2013-01-01

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 free of charge in Portuguese and English, which can be used by teachers and students in physiology, immunology, and cellular biology classes. We discuss the development of the initial two modules: "Organs and Lymphoid Tissues" and "Inflammation" and the use of interactive activities to provide microscopic and macroscopic understanding in immunology. Students, both graduate and undergraduate, were questioned along with university level professors about the quality of the software and intuitiveness of use, facility of navigation, and aesthetic organization using a Likert scale. An overwhelmingly satisfactory result was obtained with both students and immunology teachers. Programs such as "Virtual Immunology" are offering more interactive, multimedia approaches to complex scientific principles that increase student motivation, interest, and comprehension. © 2013 by The International Union of Biochemistry and Molecular Biology.

Pathogen evolution and the immunological niche

PubMed Central

Cobey, Sarah

2014-01-01

Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible–infected–recovered (SIR) model. However, there is growing evidence that the complexity of many host–pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. PMID:25040161

Analysis of Ethylene Receptor Interactions by Co-immunoprecipitation Assays.

PubMed

Gao, Zhiyong; Schaller, G Eric

2017-01-01

Ethylene receptors are predominantly localized to the endoplasmic reticulum (ER) membrane, and coordinate ethylene signal output through protein-protein interactions with each other and additional signaling components. Here, we describe a co-immunoprecipitation (Co-IP) assay based on the use of the Tandem Affinity Purification (TAP) tag to examine the interactions of ethylene receptors in plant extracts. Human IgG-agarose beads are used to pull down TAP-tagged versions of the protein of interest from detergent extracts of Arabidopsis membranes, and the precipitate then is analyzed immunologically for co-purification of the ethylene receptors. This method has been successfully used to examine interactions of the receptors with each other as well as with the Raf-like kinase CTR1.

A Perspective on the Role of Computational Models in Immunology.

PubMed

Chakraborty, Arup K

2017-04-26

This is an exciting time for immunology because the future promises to be replete with exciting new discoveries that can be translated to improve health and treat disease in novel ways. Immunologists are attempting to answer increasingly complex questions concerning phenomena that range from the genetic, molecular, and cellular scales to that of organs, whole animals or humans, and populations of humans and pathogens. An important goal is to understand how the many different components involved interact with each other within and across these scales for immune responses to emerge, and how aberrant regulation of these processes causes disease. To aid this quest, large amounts of data can be collected using high-throughput instrumentation. The nonlinear, cooperative, and stochastic character of the interactions between components of the immune system as well as the overwhelming amounts of data can make it difficult to intuit patterns in the data or a mechanistic understanding of the phenomena being studied. Computational models are increasingly important in confronting and overcoming these challenges. I first describe an iterative paradigm of research that integrates laboratory experiments, clinical data, computational inference, and mechanistic computational models. I then illustrate this paradigm with a few examples from the recent literature that make vivid the power of bringing together diverse types of computational models with experimental and clinical studies to fruitfully interrogate the immune system.

Non-specific adsorption of complement proteins affects complement activation pathways of gold nanomaterials.

PubMed

Quach, Quang Huy; Kah, James Chen Yong

2017-04-01

The complement system is a key humoral component of innate immunity, serving as the first line of defense against intruders, including foreign synthetic nanomaterials. Although gold nanomaterials (AuNMs) are widely used in nanomedicine, their immunological response is not well understood. Using AuNMs of three shapes commonly used in biomedical applications: spherical gold nanoparticles, gold nanostars and gold nanorods, we demonstrated that AuNMs activated whole complement system, leading to the formation of SC5b-9 complex. All three complement pathways were simultaneously activated by all the AuNMs. Recognition molecules of the complement system interacted with all AuNMs in vitro, except for l-ficolin, but the correlation between these interactions and corresponding complement pathway activation was only observed in the classical and alternative pathways. We also observed the mediating role of complement activation in cellular uptake of all AuNMs by human U937 promonocytic cells, which expresses complement receptors. Taken together, our results highlighted the potential immunological challenges for clinical applications of AuNMs that were often overlooked.

Pathogen evolution and the immunological niche.

PubMed

Cobey, Sarah

2014-07-01

Host immunity is a major driver of pathogen evolution and thus a major determinant of pathogen diversity. Explanations for pathogen diversity traditionally assume simple interactions between pathogens and the immune system, a view encapsulated by the susceptible-infected-recovered (SIR) model. However, there is growing evidence that the complexity of many host-pathogen interactions is dynamically important. This revised perspective requires broadening the definition of a pathogen's immunological phenotype, or what can be thought of as its immunological niche. After reviewing evidence that interactions between pathogens and host immunity drive much of pathogen evolution, I introduce the concept of a pathogen's immunological phenotype. Models that depart from the SIR paradigm demonstrate the utility of this perspective and show that it is particularly useful in understanding vaccine-induced evolution. This paper highlights questions in immunology, evolution, and ecology that must be answered to advance theories of pathogen diversity. © 2014 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

21 CFR 866.4100 - Complement reagent.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunology Laboratory Equipment and Reagents § 866.4100... a component part of serological test kits used in the diagnosis of disease. (b) Classification...

Diagnostic Testing and Interpretation of Tests for Autoimmunity

PubMed Central

Castro, Christine; Gourley, Mark

2010-01-01

Laboratory testing is of great value when evaluating a patient with a suspected autoimmune disease. The results can confirm a diagnosis, estimate disease severity, aid in assessing prognosis and are useful to follow disease activity. Components of the laboratory exam include complete blood count with differential, comprehensive metabolic panel, inflammatory markers, autoantibodies, and flow cytometry. This chapter discusses these components and includes a discussion about organ-specific immunologic diseases where immunological laboratory testing is employed. Comprehensive laboratory evaluation of a suspected autoimmune illness in conjunction with a thorough clinical evaluation provides a better understanding of a patient's immunologic disease. PMID:20061009

Affective immunology: where emotions and the immune response converge.

PubMed

D'Acquisto, Fulvio

2017-03-01

Affect and emotion are defined as "an essential part of the process of an organism's interaction with stimuli." Similar to affect, the immune response is the "tool" the body uses to interact with the external environment. Thanks to the emotional and immunological response, we learn to distinguish between what we like and what we do not like, to counteract a broad range of challenges, and to adjust to the environment we are living in. Recent compelling evidence has shown that the emotional and immunological systems share more than a similarity of functions. This review article will discuss the crosstalk between these two systems and the need for a new scientific area of research called affective immunology. Research in this field will allow a better understanding and appreciation of the immunological basis of mental disorders and the emotional side of immune diseases.

Polish Scientists in Fish Immunology: A Short History.

PubMed

Van Muiswinkel, Willem B; Pilarczyk, Andrzej

2015-11-11

This review describes the role played by Polish scientists in the field of fish immunology and vaccination starting around 1900. In the early days, most publications were dealing with a description of relevant cells and organs in fish. Functional studies (phagocytosis, antibody response) came later starting in the late 1930s. Detailed papers on fish vaccination were published from 1970 onwards. Another important development was the unraveling of neuro-endocrine-immune interactions in the 1970s until today. Around 1980, it became more and more clear how important immunomodulation (stimulation or suppression by environmental factors, food components, drugs) was for fish health. The most recent findings are focusing on the discovery of genetic factors, signaling molecules, and receptors, which play a crucial role in the immune response. It can be concluded, that Polish scientists made considerable contributions to our present understanding of fish immunity and to applications in aquaculture worldwide.

Polish Scientists in Fish Immunology: A Short History

PubMed Central

Van Muiswinkel, Willem B.; Pilarczyk, Andrzej

2015-01-01

This review describes the role played by Polish scientists in the field of fish immunology and vaccination starting around 1900. In the early days, most publications were dealing with a description of relevant cells and organs in fish. Functional studies (phagocytosis, antibody response) came later starting in the late 1930s. Detailed papers on fish vaccination were published from 1970 onwards. Another important development was the unraveling of neuro-endocrine-immune interactions in the 1970s until today. Around 1980, it became more and more clear how important immunomodulation (stimulation or suppression by environmental factors, food components, drugs) was for fish health. The most recent findings are focusing on the discovery of genetic factors, signaling molecules, and receptors, which play a crucial role in the immune response. It can be concluded, that Polish scientists made considerable contributions to our present understanding of fish immunity and to applications in aquaculture worldwide. PMID:26569323

Modeling-Enabled Systems Nutritional Immunology

PubMed Central

Verma, Meghna; Hontecillas, Raquel; Abedi, Vida; Leber, Andrew; Tubau-Juni, Nuria; Philipson, Casandra; Carbo, Adria; Bassaganya-Riera, Josep

2016-01-01

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

Cellular damage in bacterial meningitis: an interplay of bacterial and host driven toxicity.

PubMed

Weber, Joerg R; Tuomanen, Elaine I

2007-03-01

Bacterial meningitis is still an important infectious disease causing death and disability. Invasive bacterial infections of the CNS generate some of the most powerful inflammatory responses known in medicine. Although the components of bacterial cell surfaces are now chemically defined in exquisite detail and the interaction with several receptor pathways has been discovered, it is only very recently that studies combining these advanced biochemical and cell biological tools have been done. Additional to the immunological response direct bacterial toxicity has been identified as an important contributor to neuronal damage. A detailed understanding of the complex interaction of bacterial toxicity and host response may generate opportunities for innovative and specific neuroprotective therapies.

Coinfection with Hymenolepis nana, Hymenolepis diminuta, Giardia intestinalis, and Human Immunodeficiency Virus: A Case Report with Complex Immunologic Interactions.

PubMed

Pérez-Chacón, Gladymar; Pocaterra, Leonor A; Rojas, Elsy; Hernán, Aurora; Jiménez, Juan Carlos; Núñez, Luz

2017-05-01

AbstractWe describe the case of a 43-year-old human immunodeficiency virus-infected man receiving combined antiretroviral therapy and coinfected with Hymenolepis nana , Hymenolepis diminuta , and Giardia intestinalis , presenting as chronic diarrhea and critical weight loss. Immunological aspects of these interactions are reviewed.

Agent-based modeling of the immune system: NetLogo, a promising framework.

PubMed

Chiacchio, Ferdinando; Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

2014-01-01

Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms.

Random Evolution of Idiotypic Networks: Dynamics and Architecture

NASA Astrophysics Data System (ADS)

Brede, Markus; Behn, Ulrich

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

Case Report: Coinfection with Hymenolepis nana, Hymenolepis diminuta, Giardia intestinalis, and Human Immunodeficiency Virus: A Case Report with Complex Immunologic Interactions

PubMed Central

Pérez-Chacón, Gladymar; Pocaterra, Leonor A.; Rojas, Elsy; Hernán, Aurora; Jiménez, Juan Carlos; Núñez, Luz

2017-01-01

We describe the case of a 43-year-old human immunodeficiency virus–infected man receiving combined antiretroviral therapy and coinfected with Hymenolepis nana, Hymenolepis diminuta, and Giardia intestinalis, presenting as chronic diarrhea and critical weight loss. Immunological aspects of these interactions are reviewed. PMID:28219994

Beyond mice and men: Environmental change, immunity and infections in wild ungulates

PubMed Central

Jolles, Anna E.; Beechler, Brianna R.; Dolan, Brian P.

2014-01-01

In the face of rapid environmental change, anticipating shifts in microparasite and macroparasite dynamics, including emergence events, is an enormous challenge. We argue that immunological studies in natural populations are pivotal to meeting this challenge: Many components of environmental change – shifts in biotic assemblages, altered climate patterns, and reduced environmental predictability – may affect host immunity. We suggest that wild ungulates can serve as model systems aiding the discovery of immunological mechanisms that link environmental change with parasite transmission dynamics. Our review of eco-immunological studies in wild ungulates reveals progress in understanding how co-infections affect immunity and parasite transmission; and how environmental and genetic factors interact to shape immunity. Changes in bioavailability of micronutrients have been linked to immunity and health in wild ungulates. Although physiological stress in response to environmental change has been assessed, downstream effects on immunity have not been studied. Moreover, the taxonomic range of ungulates studied is limited to bovids (bighorn sheep, Soay sheep, chamois, musk oxen, bison, African buffalo) and a few cervids (red deer, black-tailed deer). We discuss areas where future studies in ungulates could lead to significant contributions in understanding patterns of immunity and infection in natural populations and across species. PMID:25354672

Improving cancer treatment with cyclotron produced radionuclides. Progress report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Improving cancer treatment with cyclotron produced radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, S.M.; Finn, R.D.

1992-08-04

Our goal is to improve the scientific basis for tumor diagnosis, treatment and treatment follow-up based on the use of cyclotron produced radiotracers in oncology. The grant includes 3 interactive components: Radiochemistry/Cyclotron; Pharmacology; and Immunology. The radiochemistry group seeks to develop innovative cyclotron targetry, radiopharmaceuticals, and radiolabeled antibodies, which are then used to assess important unanswered questions in tumor pharmacology and immunology. Examples include selected positron emitting radionuclides, such as Iodine-124, and Ga-66; I-124, I-123, I-131 labeled iododeoxyuridine, C-11 colchicine, and antimetabolites, like C-11 methotrexate; and radiolabeled antibodies, 3F8, M195, A33, and MRK16 for application in the pharmacology and immunologymore » projects. The pharmacology program studies tumor resistance to chemotherapy, particularly the phenomenon of multidrug resistance and the relationship between tumor uptake and retention and the tumor response for anti-metabolite drugs. The immunology program studies the physiology of antibody localization at the tissue level as the basis for novel approaches to improving tumor localization such as through the use of an artificial lymphatic system which mechanically reduces intratumoral pressures in tumors in vivo. Quantitative imaging approaches based on PET and SPECT in radioimmunotherapy are studied to give greater insight into the physiology of tumor localization and dosimetry.« less

Assessment of interactions of efavirenz solid drug nanoparticles with human immunological and haematological systems.

PubMed

Liptrott, Neill J; Giardiello, Marco; McDonald, Tom O; Rannard, Steve P; Owen, Andrew

2018-03-15

Recent work has developed solid drug nanoparticles (SDNs) of efavirenz that have been demonstrated, preclinically, improved oral bioavailability and the potential to enable up to a 50% dose reduction, and is currently being studied in a healthy volunteer clinical trial. Other SDN formulations are being studied for parenteral administration, either as intramuscular long-acting formulations, or for direct administration intravenously. The interaction of nanoparticles with the immunological and haematological systems can be a major barrier to successful translation but has been understudied for SDN formulations. Here we have conducted a preclinical evaluation of efavirenz SDN to assess their potential interaction with these systems. Platelet aggregation and activation, plasma coagulation, haemolysis, complement activation, T cell functionality and phenotype, monocyte derived macrophage functionality, and NK cell function were assessed in primary healthy volunteer samples treated with either aqueous efavirenz or efavirenz SDN. Efavirenz SDNs were shown not to interfere with any of the systems studied in terms of immunostimulation nor immunosuppression. Although efavirenz aqueous solution was shown to cause significant haemolysis ex vivo, efavirenz SDNs did not. No other interaction with haematological systems was observed. Efavirenz SDNs have been demonstrated to be immunologically and haematologically inert in the utilised assays. Taken collectively, along with the recent observation that lopinavir SDN formulations did not impact immunological responses, these data indicate that this type of nanoformulation does not elicit immunological consequences seen with other types of nanomaterial. The methodologies presented here provide a framework for pre-emptive preclinical characterisation of nanoparticle safety.

Rare antibodies from combinatorial libraries suggests an S.O.S. component of the human immunological repertoire.

PubMed

Lerner, Richard A

2011-04-01

Convergence of observations from different sources is the norm in science. However, when convergence occurs in man for antibodies it is remarkable because the repertoire of possible immunoglobulin products is very large and diverse. Thus, one would not expect to see the same antibody twice from divergent populations unless there is special significance as to why the immune response is constrained. Now, broadly neutralizing antibodies isolated from combinatorial libraries from three separate populations have been shown to all use the same (V(H) 1-69) germ line gene and interact with the influenza virus in very similar ways. Here we discuss the reasons for this convergence in terms of how the immunological repertoire responds to emergency situations where time is short as occurs, for example, in potentially lethal infections. It is suggested that there is a first responder or S.O.S. component of the antibody repertoire that evolved to initiate rapid defense against infectious agents. The discovery of the homologies between these commonly produced antibodies may have significance for the design of novel vaccines. Finally, these convergent results may give much insight into why antibodies encoded by the V(H) 1-69 germ line gene are highly over represented in B-cell lymphomas.

Immunologic Regulation in Pregnancy: From Mechanism to Therapeutic Strategy for Immunomodulation

PubMed Central

Chen, Shyi-Jou; Liu, Yung-Liang; Sytwu, Huey-Kang

2012-01-01

The immunologic interaction between the fetus and the mother is a paradoxical communication that is regulated by fetal antigen presentation and/or by recognition of and reaction to these antigens by the maternal immune system. There have been significant advances in understanding of abnormalities in the maternal-fetal immunologic relationship in the placental bed that can lead to pregnancy disorders. Moreover, immunologic recognition of pregnancy is vital for the maintenance of gestation, and inadequate recognition of fetal antigens may cause abortion. In this paper, we illustrate the complex immunologic aspects of human reproduction in terms of the role of human leukocyte antigen (HLA), immune cells, cytokines and chemokines, and the balance of immunity in pregnancy. In addition, we review the immunologic processes of human reproduction and the current immunologic therapeutic strategies for pathological disorders of pregnancy. PMID:22110530

Innate lymphoid cells and parasites: Ancient foes with shared history.

PubMed

Neill, D R; Fallon, P G

2018-02-01

This special issue of Parasite Immunology charts the rapid advances made in our understanding of the myriad interactions between innate lymphoid cells and parasites and how these interactions have shaped our evolutionary history. Here, we provide an overview of the issue and highlight key findings from studies in mice and man. © 2017 The Authors. Parasite Immunology Published by John Wiley & Sons Ltd.

An interactive web application for the dissemination of human systems immunology data.

PubMed

Speake, Cate; Presnell, Scott; Domico, Kelly; Zeitner, Brad; Bjork, Anna; Anderson, David; Mason, Michael J; Whalen, Elizabeth; Vargas, Olivia; Popov, Dimitry; Rinchai, Darawan; Jourde-Chiche, Noemie; Chiche, Laurent; Quinn, Charlie; Chaussabel, Damien

2015-06-19

Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

Multivariate analysis of cytokine profiles in pregnancy complications.

PubMed

Azizieh, Fawaz; Dingle, Kamaludin; Raghupathy, Raj; Johnson, Kjell; VanderPlas, Jacob; Ansari, Ali

2018-03-01

The immunoregulation to tolerate the semiallogeneic fetus during pregnancy includes a harmonious dynamic balance between anti- and pro-inflammatory cytokines. Several earlier studies reported significantly different levels and/or ratios of several cytokines in complicated pregnancy as compared to normal pregnancy. However, as cytokines operate in networks with potentially complex interactions, it is also interesting to compare groups with multi-cytokine data sets, with multivariate analysis. Such analysis will further examine how great the differences are, and which cytokines are more different than others. Various multivariate statistical tools, such as Cramer test, classification and regression trees, partial least squares regression figures, 2-dimensional Kolmogorov-Smirmov test, principal component analysis and gap statistic, were used to compare cytokine data of normal vs anomalous groups of different pregnancy complications. Multivariate analysis assisted in examining if the groups were different, how strongly they differed, in what ways they differed and further reported evidence for subgroups in 1 group (pregnancy-induced hypertension), possibly indicating multiple causes for the complication. This work contributes to a better understanding of cytokines interaction and may have important implications on targeting cytokine balance modulation or design of future medications or interventions that best direct management or prevention from an immunological approach. © 2018 The Authors. American Journal of Reproductive Immunology Published by John Wiley & Sons Ltd.

Role of Osmolytes in Regulating Immune System.

PubMed

Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

2016-01-01

The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

Immunologically mediated ocular disease in the horse.

PubMed

Hines, M T

1984-11-01

The continued study of immunology and its relationship to diseases of the eye will hopefully give some insight into the pathogenic mechanisms of certain ocular diseases of many species, including the horse. It may lead to a better understanding of equine recurrent uveitis, a disease that has remained an enigma for years and that now appears to be an immunologic hypersensitivity response to a number of varied antigens. The precise mechanism of the inflammation is still unclear, and the immunologic response may be variable or mixed depending upon the inciting antigen. Other ophthalmic diseases in the horse, such as conjunctivitis, chorioretinitis, and less well-defined entities such as superficial punctate keratitis, may also have an immunologic component in their pathogenesis. An appreciation of immunopathologic mechanisms may thus enhance the veterinarian's understanding of the pathophysiology and treatment of equine ocular disease.

UC DAVIS CENTER FOR CHILDREN’S ENVIRONMENTAL HEALTH

EPA Science Inventory

The goals of the CCEH in the next five years are to: (1) better understand the mechanisms by which environmental, immunologic, and molecular factors interact to influence the risk and severity of autism; (2) identify early immunologic, environmental, and genomic markers of sus...

Immunological responses induced by the combination of phototherapy and immunotherapy in the treatment of metastatic tumors

NASA Astrophysics Data System (ADS)

Chen, Wei R.; Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Liu, Hong

2008-02-01

Combination therapy using laser photothermal interaction and immunological stimulation has demonstrated its ability to induce immunological responses. Glycated chitosan (GC), an immunological stimulant, and imiquimod, a new type of immune response modifier (IRM), when used in conjunction with laser phototherapy, have shown to have a great immunological stimulation function. Specifically, imiquimod can help release cytokines from immunocompetent cells, stimulate TH1 lymphocyte responses (CD8+ T-cells), and recruit additional dendritic cells. To study the effects of immunoadjuvnats in combination of laser photo-irradiation, we treated animal tumors with laser-ICG-GC combination and late-stage melanoma patients with laser-ICG-imiquimod combination. At designated times, tumors, blood, and spleens in both treated and untreated animals were colleted for analysis. The major immunological indicators, such as IL-6, IL-12, IFN-gamma, CD4, and CD8 were analyzed. The same immunological analysis was also performed for melanoma patients treated by the laser-imiquimod combination.

Dysbiotic infection in the stomach.

PubMed

Iizasa, Hisashi; Ishihara, Shyunji; Richardo, Timmy; Kanehiro, Yuichi; Yoshiyama, Hironori

2015-10-28

Microbiota in human alimentary tract plays important roles for homeostatic maintenance of the body. Compositional difference of gut microbiota is tightly associated with susceptibility of many diseases, including inflammatory diseases, obesity, diabetes mellitus, cancer, and atherosclerosis. "Dysbiosis" refers to a state of imbalance among the colonies of microorganisms within the body, which brings abnormal increase of specific minor components and decrease in the normally dominant species. Since stomach secrets strong acid for its digestive role, this organ has long been thought a sterile organ. However, the discovery of Helicobacter pylori (H. pylori) has changed the concept. This bacterium has proven to cause gastritis, peptic ulcer, and gastric cancer. However, recent cross-sectional studies revealed that H. pylori carriers had a decreased risk of developing immunological diseases, such as asthma. H. pylori coinfection also suppresses inflammatory bowel diseases. This review describes human gastric microbiota by discussing its mutual interaction and pathogenic enrollment. Gastric "dysbiosis" may affect host inflammatory response and play important role for gastric pathogenesis. We will topically discuss enrollment of dysbiosis for genesis of gastric cancer as well as for disruption of immunological homeostasis affecting oncogenic resistance.

Postdoctoral Fellow | Center for Cancer Research

Cancer.gov

Highly motivated postdoctoral fellows sought to work on tumor immunology with a strong background in biology preferentially cellular immunology. The tumor immunology group in the laboratory is exploring mechanisms of improving vaccines and immunotherapy for cancer, especially by discovering new principles to enhance and steer T cell immune responses. The group is focusing on negative immunoregulatory mechanisms used for immune evasion by cancer cells. The postdoctoral fellow will work on a project to understand the negative regulatory mechanisms of tumor immunity especially the mechanisms initiated by NKT cells. Group members also have an opportunity to gain knowledge of HIV/mucosal immunology by interacting with the HIV research group in the lab.

[Immune status in infantile autism. Correlation between the immune status, autistic symptoms and levels of serotonin].

PubMed

Ferrari, P; Marescot, M R; Moulias, R; Bursztejn, C; Deville Chabrolle, A; Thiollet, M; Lesourd, B; Braconnier, A; Dreux, C; Zarifian, E

1988-01-01

In sixteen autistic children high values of IgG and a high level of lymphocyte stimulation with PHA were observed. Principal component analysis showed: 1) a significant correlation between basic lymphocyte mitogenic activity and the clinical symptoms opposition and hyperactivity, 2) a significant correlation between high Ig levels, high PHA stimulation responses and the main autistic symptoms (withdrawal, inaffectivity, hypoactivity, mannerism, stereotypy and negatively echolalia), 3) a significant correlation with serotonin uptake by platelets and high immunological responses. Such correlations are strongly in favor of an immunologic component in autistic disease.

Roles of Trypanosoma cruzi calreticulin in parasite-host interactions and in tumor growth.

PubMed

Ramírez, Galia; Valck, Carolina; Aguilar, Lorena; Kemmerling, Ulrike; López-Muñoz, Rodrigo; Cabrera, Gonzalo; Morello, Antonio; Ferreira, Jorge; Maya, Juan Diego; Galanti, Norbel; Ferreira, Arturo

2012-10-01

In Latin America, there are about 10-12 million people infected with Trypanosoma cruzi, the agent of Chagas' disease, one of the most important neglected tropical parasitism. Identification of molecular targets, specific for the aggressor or host cells or both, may be useful in the development of pharmacological and/or immunological therapeutic tools. Classic efforts in Chagas' disease explore those strategies. Although the immune system frequently controls parasite aggressions, sterile immunity is seldom achieved and chronic interactions are thus established. However, laboratory-modified immunologic probes aimed at selected parasite targets, may be more effective than their unmodified counterparts. Calreticulin (CRT) from vertebrates is a calcium binding protein, present mainly in the endoplasmic reticulum (ER), where it directs the conformation of proteins and controls calcium levels. We have isolated, gene-cloned, expressed and characterized T. cruzi calreticulin (TcCRT). Upon infection, the parasite can translocate this molecule from the ER to the surface, where it inhibits both the classical and lectin complement pathways. Moreover, by virtue of its capacity to bind and inactivate first complement component C1, it promotes parasite infectivity. These two related properties reside in the central domain of this molecule. A different domain, amino terminal, binds to endothelial cells, thus inhibiting their angiogenic capacity. Since tumor growth depends, to a large extent on angiogenesis, their growth is also inhibited. Copyright © 2012 Elsevier Ltd. All rights reserved.

Immunological and functional comparison between Clostridium perfringens iota toxin, C. spiroforme toxin, and anthrax toxins.

PubMed

Perelle, S; Scalzo, S; Kochi, S; Mock, M; Popoff, M R

1997-01-01

Clostridium perfringens iota and C. spiroforme toxins consist of two separate proteins. One is the binding component and the other the enzymatic component. The two toxins secreted by Bacillus anthracis are composed of binary combinations of three proteins: protective antigen, lethal factor, and edema factor. As shown by Western blotting and ELISA, the binding component of anthrax toxin shares common epitopes with that of iota toxin and C. spiroforme toxin which are closely related immunologically. However, no functional complementation was observed between iota toxin and anthrax toxin components. The binding components can form toxins active on macrophages only in combination with their respective enzymatic components. Agents which prevent acidification of endosomes do not have the same effects on anthrax toxin activity as they do on iota and C. spiroforme toxins. Therefore, the mechanisms of entry into the cells are presumably different. Since the binding components of anthrax toxins and iota toxin share a conserved putative translocation domain, these binding components could have a common mode of insertion into the cell membranes.

Electrochemical analysis of gold-coated magnetic nanoparticles for detecting immunological interaction

NASA Astrophysics Data System (ADS)

Pham, Thao Thi-Hien; Sim, Sang Jun

2010-01-01

An electrochemical impedance immunosensor was developed for detecting the immunological interaction between human immunoglobulin (IgG) and protein A from Staphylococcus aureus based on the immobilization of human IgG on the surface of modified gold-coated magnetic nanoparticles. The nanoparticles with an Au shell and Fe oxide cores were functionalized by a self-assembled monolayer of 11-mercaptoundecanoic acid. The electrochemical analysis was conducted on the modified magnetic carbon paste electrodes with the nanoparticles. The magnetic nanoparticles were attached to the surface of the magnetic carbon paste electrodes via magnetic force. The cyclic voltammetry technique and electrochemical impedance spectroscopy measurements of the magnetic carbon paste electrodes coated with magnetic nanoparticles-human IgG complex showed changes in its alternating current (AC) response both after the modification of the surface of the electrode and the addition of protein A. The immunological interaction between human IgG on the surface of the modified magnetic carbon paste electrodes and protein A in the solution could be successfully monitored.

[Inflammasome and its role in immunological and inflammatory response at early stage of burns].

PubMed

Zhang, Fang; Li, Jiahui; Xia, Zhaofan

2014-06-01

Inflammasomes are large multi-protein complexes that serve as a platform for caspase-1 activation, and this process induces subsequent maturation and secretion of the proinflammatory cytokines IL-1β and IL-18, as well as pyroptosis. As an important component of the innate immune system, early activation of inflammasomes in a variety of immune cell subsets can mediate inflammatory response and immunological conditions after burn injury. Here, we review the current knowledge of inflammasomes and its role in immunological and inflammatory response at the early stage of burn injury.

Immunological Demyelination Triggers Macrophage/Microglial Cells Activation without Inducing Astrogliosis

PubMed Central

Sears-Kraxberger, Ilse; Keirstead, Hans S.

2013-01-01

The glial scar formed by reactive astrocytes and axon growth inhibitors associated with myelin play important roles in the failure of axonal regeneration following central nervous system (CNS) injury. Our laboratory has previously demonstrated that immunological demyelination of the CNS facilitates regeneration of severed axons following spinal cord injury. In the present study, we evaluate whether immunological demyelination is accompanied with astrogliosis. We compared the astrogliosis and macrophage/microglial cell responses 7 days after either immunological demyelination or a stab injury to the dorsal funiculus. Both lesions induced a strong activated macrophage/microglial cells response which was significantly higher within regions of immunological demyelination. However, immunological demyelination regions were not accompanied by astrogliosis compared to stab injury that induced astrogliosis which extended several millimeters above and below the lesions, evidenced by astroglial hypertrophy, formation of a glial scar, and upregulation of intermediate filaments glial fibrillary acidic protein (GFAP). Moreover, a stab or a hemisection lesion directly within immunological demyelination regions did not induced astrogliosis within the immunological demyelination region. These results suggest that immunological demyelination creates a unique environment in which astrocytes do not form a glial scar and provides a unique model to understand the putative interaction between astrocytes and activated macrophage/microglial cells. PMID:24319469

Immunological properties of Micrococcus lysodeikticus membranes.

PubMed

Fukui, Y; Nachbar, M S; Salton, M R

1971-01-01

Membranes of Micrococcus lysodeikticus possess antigens which are distinct from other cellular components such as cytoplasm, ribosomes, and cell walls. Only a few (two to three) components are found when dissociated membranes are examined by immunodiffusion and immunoelectrophoresis techniques. Membranes treated with 0.3% sodium dodecyl sulfate, 0.3% Triton X-100, trypsin, phospholipase A or C, or by sonic oscillation at pH 9.0, all showed the same pattern (three major bands) when examined against membrane antisera by immunoelectrophoresis. Immunological analysis of fractions isolated by sucrose gradient centrifugation or by polyacrylamide gel electrophoresis suggests that individual components cross-react. Antibodies to adenosine triphosphatase (EC 3.6.1.3) and fast-moving component are not removed by absorption with protoplasts. Removal of antibody to one of the membrane antigens by protoplast absorption indicated a surface location. Glutaraldehyde fixation of protoplasts resulted in the loss of membrane antigens detectable by immunodiffusion.

A current perspective on availability of tools, resources and networks for veterinary immunology.

PubMed

Entrican, Gary; Lunney, Joan K; Rutten, Victor P; Baldwin, Cynthia L

2009-03-15

There are many diseases of fish, livestock and companion animals that impact negatively on animal health, welfare and productivity and for which there are no effective vaccines. The development of new vaccines is reliant on the availability of well-characterised immunological tools and reagents to understand host-pathogen interactions and identify protective immune responses. Veterinary immunology has always lagged behind mouse and human immunology in terms of development and availability of tools and reagents. However, several initiatives are underway to address this. The Veterinary Immunology Committee (VIC) Toolkit was initiated 6 years ago at the sixth International Veterinary Immunology Symposium (IVIS) in Uppsala and in the intervening period there have been several notable developments that have advanced reagent development and information exchange. This review will discuss advances in veterinary reagent development, networks, databases and commercial availability with particular reference to the second VIC Toolkit workshop held at the eighth IVIS in Ouro Preto, Brazil on the 15th of August 2007.

Towards a General Theory of Immunity?

PubMed

Eberl, Gérard; Pradeu, Thomas

2018-04-01

Theories are indispensable to organize immunological data into coherent, explanatory, and predictive frameworks. We propose to combine different models to develop a unifying theory of immunity which situates immunology in the wider context of physiology. We believe that the immune system will be increasingly understood as a central component of a network of partner physiological systems that interconnect to maintain homeostasis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Actin Engine in Immunological Synapse

PubMed Central

Piragyte, Indre

2012-01-01

T cell activation and function require physical contact with antigen presenting cells at a specialized junctional structure known as the immunological synapse. Once formed, the immunological synapse leads to sustained T cell receptor-mediated signalling and stabilized adhesion. High resolution microscopy indeed had a great impact in understanding the function and dynamic structure of immunological synapse. Trends of recent research are now moving towards understanding the mechanical part of immune system, expanding our knowledge in mechanosensitivity, force generation, and biophysics of cell-cell interaction. Actin cytoskeleton plays inevitable role in adaptive immune system, allowing it to bear dynamic and precise characteristics at the same time. The regulation of mechanical engine seems very complicated and overlapping, but it enables cells to be very sensitive to external signals such as surface rigidity. In this review, we focus on actin regulators and how immune cells regulate dynamic actin rearrangement process to drive the formation of immunological synapse. PMID:22916042

Multiscale modelling in immunology: a review.

PubMed

Cappuccio, Antonio; Tieri, Paolo; Castiglione, Filippo

2016-05-01

One of the greatest challenges in biomedicine is to get a unified view of observations made from the molecular up to the organism scale. Towards this goal, multiscale models have been highly instrumental in contexts such as the cardiovascular field, angiogenesis, neurosciences and tumour biology. More recently, such models are becoming an increasingly important resource to address immunological questions as well. Systematic mining of the literature in multiscale modelling led us to identify three main fields of immunological applications: host-virus interactions, inflammatory diseases and their treatment and development of multiscale simulation platforms for immunological research and for educational purposes. Here, we review the current developments in these directions, which illustrate that multiscale models can consistently integrate immunological data generated at several scales, and can be used to describe and optimize therapeutic treatments of complex immune diseases. © The Author 2015. Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Immune-Neuroendocrine Interactions: Evolution, Ecology, and Susceptibility to Illness.

PubMed

Blom, Johanna M C; Ottaviani, Enzo

2017-11-16

The integration between immune and neuroendocrine systems is crucial for maintaining homeostasis from invertebrates to humans. In the first, the phagocytic cell, i.e., the immunocyte, is the main actor, while in the latter, the principle player is the lymphocyte. Immunocytes are characterized by the presence of pro-opiomelanocortin (POMC) peptides, CRH, and other molecules that display a significant similarity to their mammalian counterparts regarding their functions, as both are mainly involved in fundamental functions such as immune (chemotaxis, phagocytosis, cytotoxicity, etc.) and neuroendocrine (stress) responses. Furthermore, the immune-neuroendocrine system provides vital answers to ecological and immunological demands in terms of economy and efficiency. Finally, susceptibility to disease emerges as the result of a continuous dynamic interaction between the world within and the world outside. New fields such as ecological immunology study the susceptibility to pathogens in an evolutionary perspective while the field of neuro-endocrine-immunology studies the susceptibility from a more immediate perspective.

Network representations of immune system complexity

PubMed Central

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

2015-01-01

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

Identification of Major Signaling Pathways in Prion Disease Progression Using Network Analysis

PubMed Central

Newaz, Khalique; Sriram, K.; Bera, Debajyoti

2015-01-01

Prion diseases are transmissible neurodegenerative diseases that arise due to conformational change of normal, cellular prion protein (PrPC) to protease-resistant isofrom (rPrPSc). Deposition of misfolded PrpSc proteins leads to an alteration of many signaling pathways that includes immunological and apoptotic pathways. As a result, this culminates in the dysfunction and death of neuronal cells. Earlier works on transcriptomic studies have revealed some affected pathways, but it is not clear which is (are) the prime network pathway(s) that change during the disease progression and how these pathways are involved in crosstalks with each other from the time of incubation to clinical death. We perform network analysis on large-scale transcriptomic data of differentially expressed genes obtained from whole brain in six different mouse strain-prion strain combination models to determine the pathways involved in prion diseases, and to understand the role of crosstalks in disease propagation. We employ a notion of differential network centrality measures on protein interaction networks to identify the potential biological pathways involved. We also propose a crosstalk ranking method based on dynamic protein interaction networks to identify the core network elements involved in crosstalk with different pathways. We identify 148 DEGs (differentially expressed genes) potentially related to the prion disease progression. Functional association of the identified genes implicates a strong involvement of immunological pathways. We extract a bow-tie structure that is potentially dysregulated in prion disease. We also propose an ODE model for the bow-tie network. Predictions related to diseased condition suggests the downregulation of the core signaling elements (PI3Ks and AKTs) of the bow-tie network. In this work, we show using transcriptomic data that the neuronal dysfunction in prion disease is strongly related to the immunological pathways. We conclude that these immunological pathways occupy influential positions in the PFNs (protein functional networks) that are related to prion disease. Importantly, this functional network involvement is prevalent in all the five different mouse strain-prion strain combinations that we studied. We also conclude that the dysregulation of the core elements of the bow-tie structure, which belongs to PI3K-Akt signaling pathway, leads to dysregulation of the downstream components corresponding to other biological pathways. PMID:26646948

Exploiting fluorescence for multiplex immunoassays on protein microarrays

NASA Astrophysics Data System (ADS)

Herbáth, Melinda; Papp, Krisztián; Balogh, Andrea; Matkó, János; Prechl, József

2014-09-01

Protein microarray technology is becoming the method of choice for identifying protein interaction partners, detecting specific proteins, carbohydrates and lipids, or for characterizing protein interactions and serum antibodies in a massively parallel manner. Availability of the well-established instrumentation of DNA arrays and development of new fluorescent detection instruments promoted the spread of this technique. Fluorescent detection has the advantage of high sensitivity, specificity, simplicity and wide dynamic range required by most measurements. Fluorescence through specifically designed probes and an increasing variety of detection modes offers an excellent tool for such microarray platforms. Measuring for example the level of antibodies, their isotypes and/or antigen specificity simultaneously can offer more complex and comprehensive information about the investigated biological phenomenon, especially if we take into consideration that hundreds of samples can be measured in a single assay. Not only body fluids, but also cell lysates, extracted cellular components, and intact living cells can be analyzed on protein arrays for monitoring functional responses to printed samples on the surface. As a rapidly evolving area, protein microarray technology offers a great bulk of information and new depth of knowledge. These are the features that endow protein arrays with wide applicability and robust sample analyzing capability. On the whole, protein arrays are emerging new tools not just in proteomics, but glycomics, lipidomics, and are also important for immunological research. In this review we attempt to summarize the technical aspects of planar fluorescent microarray technology along with the description of its main immunological applications.

Immunological characteristics and response to lipopolysaccharide of mouse lines selectively bred with natural and acquired immunities.

PubMed

Narahara, Hiroki; Sakai, Eri; Katayama, Masafumi; Ohtomo, Yukiko; Yamamoto, Kanako; Takemoto, Miki; Aso, Hisashi; Ohwada, Shyuichi; Mohri, Yasuaki; Nishimori, Katsuhiko; Isogai, Emiko; Yamaguchi, Takahiro; Fukuda, Tomokazu

2012-05-01

Genetic improvement of resistance to infectious diseases is a challenging goal in animal breeding. Infection resistance involves multiple immunological characteristics, including natural and acquired immunity. In the present study, we developed an experimental model based on genetic selection, to improve immunological phenotypes. We selectively established three mouse lines based on phagocytic activity, antibody production and the combination of these two phenotypes. We analyzed the immunological characteristics of these lines using a lipopolysaccharide (LPS), which is one of the main components of Gram-negative bacteria. An intense immunological reaction was induced in each of the three mouse lines. Severe loss of body weight and liver damage were observed, and a high level of cytokine messenger RNA was detected in the liver tissue. The mouse line established using a combination of the two selection standards showed unique characteristics relative to the mouse lines selected on the basis of a single phenotype. Our results indicate that genetic selection and breeding is effective, even for immunological phenotypes with a relatively low heritability. Thus, it may be possible to improve resistance to infectious diseases by means of genetic selection. © 2011 The Authors. Animal Science Journal © 2011 Japanese Society of Animal Science.

A mechanistic insight into curcumin modulation of the IL-1β secretion and NLRP3 S-glutathionylation induced by needle-like cationic cellulose nanocrystals in myeloid cells.

PubMed

Guglielmo, Andrew; Sabra, Adham; Elbery, Mostafa; Cerveira, Milena M; Ghenov, Fernanda; Sunasee, Rajesh; Ckless, Karina

2017-08-25

Recently we have demonstrated that needle-like cationic cellulose nanocrystals (CNC-AEMA2) evoke immunological responses through NLRP3 inflammasome/IL-1β inflammatory pathway. In this study we demonstrated that curcumin, a naturally occurring polyphenolic compound isolated from Curcuma longa (Zingiberaceae), was able to suppress, at least in part, this immunological response, as observed by diminished IL-1β secretion in CNC-AEMA2-stimulated macrophages primed with LPS. Curcumin is a well-known antioxidant and anti-inflammatory natural compound and in addition to acting as "scavenger" of reactive oxygen species (ROS), it can also upregulates antioxidant enzymes. However, the mechanisms by which this natural compound exerts its protective activity is still under investigation. We hypothesize that curcumin may also affect S-glutathionylation of key proteins involved in the NLRP3 inflammasome/IL-1β pathway, and therefore impact their protein-protein interactions. The goal of this study was to investigate the effects of curcumin on the S-glutathionylation of NLRP3 induced by CNC-AEMA2 in LPS-primed mouse macrophages (J774A.1), as well as interactions among proteins of the NLRP3 inflammasome complex. Our main finding indicates that the addition of curcumin concomitantly with LPS caused the greatest decrease in NLRP3 S-glutathionylation and a respective increase in caspase-1 S-glutathionylation, which appears to favor protein-protein interactions in the NLRP3 complex. Taking together, our results suggest that, at least in part, the anti-inflammatory activity of curcumin is associated with changes in S-glutathionylation of key NLRP3 inflammasome components, and perhaps resulting in sustained complex assembly and suppression of IL-1β secretion. Copyright © 2017 Elsevier B.V. All rights reserved.

Reproductive immunology: a focus on the role of female sex hormones and other gender-related factors.

PubMed

Peeva, Elena

2011-02-01

Reproductive immunology has attracted the attention of researchers interested in fertility and pregnancy as well as those interested in immunity and autoimmunity. Over the past couple of decades, a wealth of data on the immune-reproductive interactions has been generated. This issue of the Journal will examine several topics including the role of immune factors in the induction of anti-Ro antibody-mediated autoimmunity in neonates and the immunological effects of gender and sex hormones. The possible implications of the research reviewed here for the development of novel therapeutic approaches are also addressed.

Therapeutic Role of Hematopoietic Stem Cells in Autism Spectrum Disorder-Related Inflammation

PubMed Central

Siniscalco, Dario; Bradstreet, James Jeffrey; Antonucci, Nicola

2013-01-01

Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neuro-developmental disorders with core symptoms of dysfunctions in social interactions and communication skills, restricted interests, repetitive – stereotypic verbal and non-verbal behaviors. Biomolecular evidence points to complex gene-environmental interactions in ASDs. Several biochemical processes are associated with ASDs: oxidative stress (including endoplasmic reticulum stress), decreased methylation capacity, limited production of glutathione; mitochondrial dysfunction, intestinal dysbiosis, increased toxic metal burden, and various immune abnormalities. The known immunological disorders include: T-lymphocyte populations and function, gene expression changes in monocytes, several autoimmune-related findings, high levels of N-acetylgalactosaminidase (which precludes macrophage activation), and primary immune deficiencies. These immunological observations may result in minicolumn structural changes in the brain, as well as, abnormal immune mediation of synaptic functions. Equally, these immune dysregulations serve as the rationale for immune-directed interventions such as hematopoietic stem cells (HSCs), which are pivotal in controlling chronic inflammation and in the restoration of immunological balance. These properties make them intriguing potential agents for ASD treatments. This prospective review will focus on the current state-of-the-art knowledge and challenges intrinsic in the application of HSCs for ASD-related immunological disorders. PMID:23772227

Importin Beta Plays an Essential Role in the Regulation of the LysRS-Ap4A Pathway in Immunologically Activated Mast Cells ▿

PubMed Central

Carmi-Levy, Irit; Motzik, Alex; Ofir-Birin, Yifat; Yagil, Zohar; Yang, Christopher Maolin; Kemeny, David Michael; Han, Jung Min; Kim, Sunghoon; Kay, Gillian; Nechushtan, Hovav; Suzuki, Ryo; Rivera, Juan; Razin, Ehud

2011-01-01

We recently reported that diadenosine tetraphosphate hydrolase (Ap4A hydrolase) plays a critical role in gene expression via regulation of intracellular Ap4A levels. This enzyme serves as a component of our newly described lysyl tRNA synthetase (LysRS)-Ap4A biochemical pathway that is triggered upon immunological challenge. Here we explored the mechanism of this enzyme's translocation into the nucleus and found its immunologically dependent association with importin beta. Silencing of importin beta prevented Ap4A hydrolase nuclear translocation and affected the local concentration of Ap4A, which led to an increase in microphthalmia transcription factor (MITF) transcriptional activity. Furthermore, immunological activation of mast cells resulted in dephosphorylation of Ap4A hydrolase, which changed the hydrolytic activity of the enzyme. PMID:21402779

Environmental Immunology: Lessons learned from exposure to a select panel of immunotoxicants

PubMed Central

Kreitinger, Joanna M.; Beamer, Celine A.; Shepherd, David M.

2016-01-01

Exposure to environmental contaminants can produce profound effects on the immune system. Many different classes of xenobiotics can significantly suppress or enhance immune responsiveness depending on the levels (i.e. dose) and context (i.e. timing, route) of exposure. While defining the effects that toxicants can have on the immune system is a valuable component to improving public health, environmental immunology has greatly enhanced our understanding of how the immune system functions and explore new immunotherapies. This Brief Review focuses on three different examples of how immunotoxicology has benefitted the field of immunology, presenting information on (A) the aryl hydrocarbon receptor (AhR) signaling pathway, (B) the immunomodulatory effects of nanomaterials, and (C) the impact of xenobiotic exposure on the developing immune system. Collectively, contributions from immunotoxicology have significantly enhanced public health and spurred seminal advances in both basic and applied immunology. PMID:27044635

Immunologic Approaches for the Treatment of Multiple Myeloma

PubMed Central

Rasche, Leo; Weinhold, Niels; Morgan, Gareth J; van Rhee, Frits; Davies, Faith E

2017-01-01

The FDA approval of two monoclonal antibodies in 2015 has heralded a new era of targeted immunotherapies for multiple myeloma (MM). In this review we discuss the recent approaches using different immunological components to treat MM. In particular, we review current monoclonal antibody based therapies, engineered T- and NK cell products, ‘off-target’ immunomodulation, and strategies utilizing allogeneic cell transplantation in MM. We discuss how an immunologic approach offers promise for the treatment of this genetically heterogeneous disease, and how patients with acquired drug resistance may particularly benefit from these therapies. We also describe some of the limitations of the current strategies and speculate on the future of personalized immunotherapies for MM. PMID:28431262

Birth of the science of immunology.

PubMed

Schmalstieg, Frank C; Goldman, Armond S

2010-05-01

The science of immunology emerged in the last of the 19th and the first of the 20th century. Substantial progress in physics, chemistry and microbiology was essential for its development. Indeed, microorganisms became one of the principal investigative tools of the major founders of that science - Louis Pasteur, Robert Koch, Ilya Ilich Metchnikoff, Paul Ehrlich and Jules Bordet. It is pertinent that these pioneering scientists were born when questioning and exploration were encouraged because of the legacies of the previous century of enlightenment. Mentors greatly aided their development. Their discoveries were shaped by their individual personalities. In turn they developed other contributors to the nascent field. Their discoveries included the types of leukocytes, the roles of neutrophils in inflammation and defence, cellular lysis due to complement, the principles of humoral and cellular immunology, passive and active immunization, tissue antigens, anaphylaxis, anaphylactoid reactions and autoimmunity. Their work formed the basis of modern immunology that developed many decades later. Immunology has enormously impacted our understanding of the pathogenesis, diagnosis and treatment of infections, immune-mediated disorders and inflammation. Burgeoning advances forecast further important clinical applications of immunology. Yet, their applications will be problematic because few physicians sufficiently understand the science. We propose that understanding modern immunology requires a grasp of how that science developed - who made the discoveries, how they were made, their successes and failures, their interactions and debates all reveal the foundation of modern immunology.

American College of Allergy, Asthma & Immunology Position Paper on the Use of Telemedicine for Allergists.

PubMed

Elliott, Tania; Shih, Jennifer; Dinakar, Chitra; Portnoy, Jay; Fineman, Stanley

2017-12-01

The integration of telecommunications and information systems in health care first began 4 decades ago with 500 patient consultations performed via interactive television. The use of telemedicine services and technology to deliver health care at a distance is increasing exponentially. Concomitant with this rapid expansion is the exciting ability to provide enhancements in quality and safety of care. Telemedicine enables increased access to care, improvement in health outcomes, reduction in medical costs, better resource use, expanded educational opportunities, and enhanced collaboration between patients and physicians. These potential benefits should be weighed against the risks and challenges of using telemedicine. The American College of Allergy, Asthma, and Immunology advocates for incorporation of meaningful and sustained use of telemedicine in allergy and immunology practice. This article serves to offer policy and position statements of the use of telemedicine pertinent to the allergy and immunology subspecialty. Copyright © 2017 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

How-to-do-it: Immunological Assays for the Classroom 1. Enzyme Linked Immunosorbent Assay (ELISA): A Laboratory Tool for Demonstration of Antibody-Antigen Interaction.

ERIC Educational Resources Information Center

Russo, A. J.; And Others

1984-01-01

Background information, list of required materials, and procedures are provided for an immunological assay which has been modified for use as a classroom/laboratory demonstration of antigen-antibody reaction. The assay is designed for a two and one-half hour laboratory period but may be modified for one hour laboratories. (JN)

Screening and Identification for Immunological Active Components from Andrographis Herba Using Macrophage Biospecific Extraction Coupled with UPLC/Q-TOF-MS.

PubMed

Wang, Yaqi; Jiao, Jiaojiao; Yang, Yuanzhen; Yang, Ming; Zheng, Qin

2018-04-30

The method of cell biospecific extraction coupled with UPLC/Q-TOF-MS has been developed as a tool for the screening and identification of potential immunological active components from Andrographis Herba (AH). In our study, a macrophage cell line (RAW264.7) was used to extract cell-combining compounds from the ethanol extract of AH. The cell binding system was then analyzed and identified by UPLC/Q-TOF-MS analysis. Finally, nine compounds, which could combine with macrophages, in an ethanol extract of AH were detected by comparing basic peak intensity (BPI) profiles of macrophages before and after treatment with AH. Then they were identified as Andrographidine E ( 1 ), Andrographidine D ( 2 ), Neoandrographolide ( 3 ), Dehydroandrographolide ( 4 ), 5, 7, 2′, 3′-tetramethoxyflavone ( 5 ), β-sitosterol ( 7 ), 5-hydroxy-7, 2′, 3′-trimethoxyflavone ( 8 ) and 5-hydroxy-7, 8, 2′, 3′-tetramethoxyflavone ( 9 ), which could classified into five flavonoids, three diterpene lactones, and one sterol. Their structures were recognized by their characteristic fragment ions and fragmentations pattern of diterpene lactones and flavonoids. Additionally, the activity of compounds 3 , 4 , and 7 was tested in vitro. Results showed that these three compounds could decrease the release of NO ( p < 0.01) in macrophages remarkably. Moreover, 3 , 4 , and 7 showed satisfactory dose-effect relationships and their IC 50 values were 9.03, 18.18, and 13.76 μg/mL, respectively. This study is the first reported work on the screening of immunological active components from AH. The potential immunological activity of flavonoids from AH has not been reported previously.

AntiJen: a quantitative immunology database integrating functional, thermodynamic, kinetic, biophysical, and cellular data

PubMed Central

Toseland, Christopher P; Clayton, Debra J; McSparron, Helen; Hemsley, Shelley L; Blythe, Martin J; Paine, Kelly; Doytchinova, Irini A; Guan, Pingping; Hattotuwagama, Channa K; Flower, Darren R

2005-01-01

AntiJen is a database system focused on the integration of kinetic, thermodynamic, functional, and cellular data within the context of immunology and vaccinology. Compared to its progenitor JenPep, the interface has been completely rewritten and redesigned and now offers a wider variety of search methods, including a nucleotide and a peptide BLAST search. In terms of data archived, AntiJen has a richer and more complete breadth, depth, and scope, and this has seen the database increase to over 31,000 entries. AntiJen provides the most complete and up-to-date dataset of its kind. While AntiJen v2.0 retains a focus on both T cell and B cell epitopes, its greatest novelty is the archiving of continuous quantitative data on a variety of immunological molecular interactions. This includes thermodynamic and kinetic measures of peptide binding to TAP and the Major Histocompatibility Complex (MHC), peptide-MHC complexes binding to T cell receptors, antibodies binding to protein antigens and general immunological protein-protein interactions. The database also contains quantitative specificity data from position-specific peptide libraries and biophysical data, in the form of diffusion co-efficients and cell surface copy numbers, on MHCs and other immunological molecules. The uses of AntiJen include the design of vaccines and diagnostics, such as tetramers, and other laboratory reagents, as well as helping parameterize the bioinformatic or mathematical in silico modeling of the immune system. The database is accessible from the URL: . PMID:16305757

Immunological and Toxinological Responses to Jellyfish Stings

PubMed Central

Tibballs, James; Yanagihara, Angel A.; Turner, Helen C.; Winkel, Ken

2013-01-01

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

Immunology of breast milk.

PubMed

Palmeira, Patricia; Carneiro-Sampaio, Magda

2016-09-01

In the critical phase of immunological immaturity of the newborn, particularly for the immune system of mucous membranes, infants receive large amounts of bioactive components through colostrum and breast milk. Colostrum is the most potent natural immune booster known to science. Breastfeeding protects infants against infections mainly via secretory IgA (SIgA) antibodies, but also via other various bioactive factors. It is striking that the defense factors of human milk function without causing inflammation; some components are even anti-inflammatory. Protection against infections has been well evidenced during lactation against, e.g., acute and prolonged diarrhea, respiratory tract infections, including otitis media, urinary tract infection, neonatal septicemia, and necrotizing enterocolitis. The milk's immunity content changes over time. In the early stages of lactation, IgA, anti-inflammatory factors and, more likely, immunologically active cells provide additional support for the immature immune system of the neonate. After this period, breast milk continues to adapt extraordinarily to the infant's ontogeny and needs regarding immune protection and nutrition. The need to encourage breastfeeding is therefore justifiable, at least during the first 6 months of life, when the infant's secretory IgA production is insignificant.

Parental investment matters for maternal and offspring immune defense in the mouthbrooding cichlid Astatotilapia burtoni.

PubMed

Keller, Isabel S; Salzburger, Walter; Roth, Olivia

2017-12-20

Parental care, while increasing parental fitness through offspring survival, also bears cost to the care-giving parent. Consequentially, trade offs between parental care and other vitally important traits, such as the immune system seem evident. In co-occurring phases of parental care and immunological challenges negative consequences through a resource allocation trade off on both the parental and the offspring conditions can be predicted. While the immune system reflects parental stress conditions, parental immunological investments also boost offspring survival via the transfer of immunological substances (trans-generational immune priming). We investigated this relationship in the mouthbrooding East African cichlid Astotatilapia burtoni. Prior to mating, females were exposed to an immunological activation, while others remained immunologically naïve. Correspondingly, the immunological status of females was either examined directly after reproduction or after mouthbrooding had ceased. Offspring from both groups were exposed to immunological challenges to assess the extent of trans-generational immune priming. As proxy for immune status, cellular immunological activity and gene expression were determined. Both reproducing and mouthbrooding females allocate their resources towards reproduction. While upon reproduction the innate immune system was impeded, mouthbrooding females showed an attenuation of inflammatory components. Juveniles from immune challenged mouthbrooding females showed downregulation of immune and life history candidate genes, implying a limitation of trans-generational plasticity when parents experience stress during the costly reproductive phase. Our results provide evidence that both parental investment via mouthbrooding and the rise of the immunological activity upon an immune challenge are costly traits. If applied simultaneously, not only mothers seem to be impacted in their performance, but also offspring are impeded in their ability to react upon a potentially virulent pathogen exposure.

Immunity and fitness in a wild population of Eurasian kestrels Falco tinnunculus

NASA Astrophysics Data System (ADS)

Parejo, Deseada; Silva, Nadia

2009-10-01

The immune system of vertebrates consists of several components that partly interact and complement each other. Therefore, the assessment of the overall effectiveness of immune defence requires the simultaneous measurement of different immune components. In this study, we investigated intraspecific variability of innate [i.e. natural antibodies (NAb) and complement] and acquired (i.e. leucocyte profiles) immunity and its relationship with fitness correlates (i.e. blood parasite load and reproductive success in adults and body mass and survival until fledging in nestlings) in the Eurasian kestrel Falco tinnunculus. Immunity differed between nestlings and adults and also between adult males and females. Adult kestrels with higher levels of complement were less parasitised by Haemoproteus, and males with higher values of NAbs showed a higher reproductive success. In nestlings, the H/L ratio was negatively related to body mass. Survival until fledging was predicted by all measured immunological variables of nestlings as well as by their fathers' level of complement. This is the first time that innate immunity is linked to survival in a wild bird. Thus, intraspecific variation in different components of immunity predicts variation in fitness prospects in kestrels, which highlights the importance of measuring innate immune components together with components of the acquired immunity in studies assessing the effectiveness of the immune system in wild animals.

[Immunological background and pathomechanisms of food allergies].

PubMed

Schülke, Stefan; Scheurer, Stephan

2016-06-01

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.

Strategy for selecting nanotechnology carriers to overcome immunological and hematological toxicities challenging clinical translation of nucleic acid-based therapeutics.

PubMed

Dobrovolskaia, Marina A; McNeil, Scott E

2015-07-01

Clinical translation of nucleic acid-based therapeutics (NATs) is hampered by assorted challenges in immunotoxicity, hematotoxicity, pharmacokinetics, toxicology and formulation. Nanotechnology-based platforms are being considered to help address some of these challenges due to the nanoparticles' ability to change drug biodistribution, stability, circulation half-life, route of administration and dosage. Addressing toxicology and pharmacology concerns by various means including NATs reformulation using nanotechnology-based carriers has been reviewed before. However, little attention was given to the immunological and hematological issues associated with nanotechnology reformulation. This review focuses on application of nanotechnology carriers for delivery of various types of NATs, and how reformulation using nanoparticles affects immunological and hematological toxicities of this promising class of therapeutic agents. NATs share several immunological and hematological toxicities with common nanotechnology carriers. In order to avoid synergy or exaggeration of undesirable immunological and hematological effects of NATs by a nanocarrier, it is critical to consider the immunological compatibility of the nanotechnology platform and its components. Since receptors sensing nucleic acids are located essentially in all cellular compartments, a strategy for developing a nanoformulation with reduced immunotoxicity should first focus on precise delivery to the target site/cells and then on optimizing intracellular distribution.

Integrating Lung Physiology, Immunology, and Tuberculosis.

PubMed

Torrelles, Jordi B; Schlesinger, Larry S

2017-08-01

Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several 'interaction points' (IPs) which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence. Copyright © 2017 Elsevier Ltd. All rights reserved.

An immunological method for quantifying antibacterial activity in Salmo salar (Linnaeus, 1758) skin mucus.

PubMed

Narvaez, Edgar; Berendsen, Jorge; Guzmán, Fanny; Gallardo, José A; Mercado, Luis

2010-01-01

Antimicrobial peptides (AMPs) are a pivotal component of innate immunity in lower vertebrates. The aim of this study was to develop an immunological method for quantifying AMPs in Salmo salar skin mucus. A known antimicrobial peptide derived from histone H1 previously purified and described from S. salar skin mucus (SAMP H1) was chemically synthesized and used to obtain antibodies for the quantification of the molecule via ELISA. Using skin mucus samples, a correlation of bacterial growth inhibition versus SAMP H1 concentration (ELISA) was established. The results provide the first evidence for quantifying the presence of active AMPs in the skin mucus of S. salar through the use of an immunological method. Copyright 2009 Elsevier Ltd. All rights reserved.

In vivo imaging and tracking of host-microbiota interactions via metabolic labeling of gut anaerobic bacteria

PubMed Central

Geva-Zatorsky, Naama; Alvarez, David; Hudak, Jason E.; Reading, Nicola C.; Erturk-Hasdemir, Deniz; Dasgupta, Suryasarathi; von Andrian, Ulrich H.; Kasper, Dennis L.

2015-01-01

The intestine is densely populated by anaerobic commensal bacteria. These microorganisms shape immune system development, but our understanding of host–commensal interactions is hampered by a lack of tools for studying the anaerobic intestinal environment. We applied metabolic oligosaccharide engineering and bioorthogonal click-chemistry to label various commensal anaerobes, including Bacteroides fragilis, a common and immunologically important commensal. We studied the dissemination of B. fragilis following acute peritonitis, and characterized the interactions of the intact microbe and its polysaccharide components in myeloid and B cell lineages. The distribution and colonization of labeled B. fragilis along the intestine can be assessed, as well as niche competition following coadministration of multiple species of the microbiota. Nine additional anaerobic commensals (both gram-negative and gram-positive) from three phyla common in the gut—Bacteroidetes, Firmicutes, and Proteobacteria—and five families and one aerobic pathogen (Staphylococcus aureus) were also fluorescently labeled. This strategy permits visualization of the anaerobic microbial niche by various methods, including intravital two-photon microscopy and non-invasive whole-body imaging, and an approach to study microbial colonization and host–microbe interactions in real-time. PMID:26280120

The Coxiella Burnetii type IVB secretion system (T4BSS) component DotA is released/secreted during infection of host cells and during in vitro growth in a T4BSS-dependent manner.

PubMed

Luedtke, Brandon E; Mahapatra, Saugata; Lutter, Erika I; Shaw, Edward I

2017-06-01

Coxiella burnetii is a Gram-negative intracellular pathogen and is the causative agent of the zoonotic disease Q fever. To cause disease, C. burnetii requires a functional type IVB secretion system (T4BSS) to transfer effector proteins required for the establishment and maintenance of a membrane-bound parasitophorous vacuole (PV) and further modulation of host cell process. However, it is not clear how the T4BSS interacts with the PV membrane since neither a secretion pilus nor an extracellular pore forming apparatus has not been described. To address this, we used the acidified citrate cysteine medium (ACCM) along with cell culture infection and immunological techniques to identify the cellular and extracellular localization of T4BSS components. Interestingly, we found that DotA and IcmX were secreted/released in a T4BSS-dependent manner into the ACCM. Analysis of C. burnetii-infected cell lines revealed that DotA colocalized with the host cell marker CD63 (LAMP3) at the PV membrane. In the absence of bacterial protein synthesis, DotA also became depleted from the PV membrane. These data are the first to identify the release/secretion of C. burnetii T4BSS components during axenic growth and the interaction of a T4BSS component with the PV membrane during infection of host cells. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation.

PubMed

Yang, Seung Won; Jang, Yo Han; Kwon, Soon Bin; Lee, Yoon Jae; Chae, Wonil; Byun, Young Ho; Kim, Paul; Park, Chan; Lee, Young Jae; Kim, Choon Kang; Kim, Young Seok; Choi, Seong Il; Seong, Baik Lin

2018-05-01

A novel protein-folding function of RNA has been recognized, which can outperform previously known molecular chaperone proteins. The RNA as a molecular chaperone (chaperna) activity is intrinsic to some ribozymes and is operational during viral infections. Our purpose was to test whether influenza hemagglutinin (HA) can be assembled in a soluble, trimeric, and immunologically activating conformation by means of an RNA molecular chaperone (chaperna) activity. An RNA-interacting domain (RID) from the host being immunized was selected as a docking tag for RNA binding, which served as a transducer for the chaperna function for de novo folding and trimeric assembly of RID-HA1. Mutations that affect tRNA binding greatly increased the soluble aggregation defective in trimer assembly, suggesting that RNA interaction critically controls the kinetic network in the folding/assembly pathway. Immunization of mice resulted in strong hemagglutination inhibition and high titers of a neutralizing antibody, providing sterile protection against a lethal challenge and confirming the immunologically relevant HA conformation. The results may be translated into a rapid response to a new influenza pandemic. The harnessing of the novel chaperna described herein with immunologically tailored antigen-folding functions should serve as a robust prophylactic and diagnostic tool for viral infections.-Yang, S. W., Jang, Y. H., Kwon, S. B., Lee, Y. J., Chae, W., Byun, Y. H., Kim, P., Park, C., Lee, Y. J., Kim, C. K., Kim, Y. S., Choi, S. I., Seong, B. L. Harnessing an RNA-mediated chaperone for the assembly of influenza hemagglutinin in an immunologically relevant conformation.

Inflammation, Self-Regulation, and Health: An Immunologic Model of Self-Regulatory Failure.

PubMed

Shields, Grant S; Moons, Wesley G; Slavich, George M

2017-07-01

Self-regulation is a fundamental human process that refers to multiple complex methods by which individuals pursue goals in the face of distractions. Whereas superior self-regulation predicts better academic achievement, relationship quality, financial and career success, and lifespan health, poor self-regulation increases a person's risk for negative outcomes in each of these domains and can ultimately presage early mortality. Given its centrality to understanding the human condition, a large body of research has examined cognitive, emotional, and behavioral aspects of self-regulation. In contrast, relatively little attention has been paid to specific biologic processes that may underlie self-regulation. We address this latter issue in the present review by examining the growing body of research showing that components of the immune system involved in inflammation can alter neural, cognitive, and motivational processes that lead to impaired self-regulation and poor health. Based on these findings, we propose an integrated, multilevel model that describes how inflammation may cause widespread biobehavioral alterations that promote self-regulatory failure. This immunologic model of self-regulatory failure has implications for understanding how biological and behavioral factors interact to influence self-regulation. The model also suggests new ways of reducing disease risk and enhancing human potential by targeting inflammatory processes that affect self-regulation.

Assessment of microbiota:host interactions at the vaginal mucosa interface.

PubMed

Pruski, Pamela; Lewis, Holly V; Lee, Yun S; Marchesi, Julian R; Bennett, Phillip R; Takats, Zoltan; MacIntyre, David A

2018-04-27

There is increasing appreciation of the role that vaginal microbiota play in health and disease throughout a woman's lifespan. This has been driven partly by molecular techniques that enable detailed identification and characterisation of microbial community structures. However, these methods do not enable assessment of the biochemical and immunological interactions between host and vaginal microbiota involved in pathophysiology. This review examines our current knowledge of the relationships that exist between vaginal microbiota and the host at the level of the vaginal mucosal interface. We also consider methodological approaches to microbiomic, immunologic and metabolic profiling that permit assessment of these interactions. Integration of information derived from these platforms brings the potential for biomarker discovery, disease risk stratification and improved understanding of the mechanisms regulating vaginal microbial community dynamics in health and disease. Copyright © 2018 Elsevier Inc. All rights reserved.

B-cell acquisition of antigen: Sensing the surface.

PubMed

Knight, Andrew M

2015-06-01

B-cell antigen receptor (BCR) recognition and acquisition of antigen by B cells is the essential first step in the generation of effective antibody responses. As B-cell-mediated antigen presentation is also believed to play a significant role in the activation of CD4(+) Th-cell responses, considerable effort has focused on clarifying the nature of antigen/BCR interactions. Following earlier descriptions of interactions of soluble antigens with the BCR, it is now clear that B cells also recognize, physically extract and present antigens that are tethered to, or integral components of, the surfaces or extracellular matrix of other cells. In this issue of the European Journal of Immunology, Zeng et al. [Eur. J. Immunol. 2015. 45: XXXX-XXXX] examine how the physical property or "stiffness" of the surface displaying antigens to B cells influences the B-cell response. This commentary reports that antigen tethered on "less stiff" surfaces induces increased B-cell activation and antibody responses. I then infer how "sensing the surface" by B cells may represent a new component of the immune system's ability to detect "damage," and how this understanding may influence approaches to clinical therapies where immune activity is either unwanted or desired. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

[Immune response of Hansen's disease. Review].

PubMed

Rada, Elsa; Aranzazu, Nacarid; Convit, Jacinto

2009-12-01

Hansen's disease presents a wide spectrum of clinical and histopathological manifestations that reflect the nature of the immunological response of the host towards diverse Mycobacterium leprae components. The immunological system, composed by both innate and adaptive immunology, offers protection towards infections of various etiologies, among them bacterial. Bacteria, of course, have developed multiple strategies for evading host defenses, based on either very complex or simple mechanisms, but with a single purpose: to "resist" host attacks and to be able to survive. We have tried to summarize some recent studies in Hansen's disease, with more emphasis in the inmunology area. We think that in the future, all illnesses should also be very strongly related to other important aspects such as the social, environmental and economic, and whose development is not solved in a laboratory.

Pathophysiology and immunological profile of myasthenia gravis and its subgroups.

PubMed

Romi, Fredrik; Hong, Yu; Gilhus, Nils Erik

2017-12-01

Myasthenia gravis (MG) is an autoimmune antibody-mediated disease characterized by muscle weakness and fatigability. It is believed that the initial steps triggering humoral immunity in MG take place inside thymic tissue and thymoma. The immune response against one or several epitopes expressed on thymic tissue cells spills over to neuromuscular junction components sharing the same epitope causing humoral autoimmunity and antibody production. The main cause of MG is acetylcholine receptor antibodies. However, many other neuromuscular junction membrane protein targets, intracellular and extracellular proteins are suggested to participate in MG pathophysiology. MG should be divided into subgroups based on clinical presentation and immunology. This includes onset age, clinical characteristics, thymic pathology and antibody profile. The immunological profile of these subgroups is determined by the antibodies present. Copyright © 2017. Published by Elsevier Ltd.

ELECTROPHORETIC AND IMMUNOLOGICAL STUDIES OF SQUID AXOPLASM PROTEINS.

PubMed

HUNEEUS-COX, F

1964-03-06

By disc electrophoresis of the axoplasm of Dosidicus gigas, 14 protein bands have been resolved. Anti-bodies to the intra-axonal proteins and to squid blood proteins were produced in rabbits. By Ouchterlony's technique, six antigenic components can be demonstrated in axoplasm; the combined use of disc electrophoresis and immune diflusion in agar resolves seven antigenic components in axoplasm; none of these components is detectable in squid blood.

Single cell transcriptomics to explore the immune system in health and disease†

PubMed Central

Regev, Aviv; Teichmann, Sarah A.

2017-01-01

The immune system varies in cell types, states, and locations. The complex networks, interactions and responses of immune cells produce diverse cellular ecosystems composed of multiple cell types, accompanied by genetic diversity in antigen receptors. Within this ecosystem, innate and adaptive immune cells maintain and protect tissue function, integrity and homeostasis upon changes in functional demands and diverse insults. Characterizing this inherent complexity requires studies at single-cell resolution. Recent advances such as, massively-parallel single cell RNA-Seq and sophisticated computational methods are catalysing a revolution in our understanding of immunology. Here, we provide an overview of the state of single cell genomics methods and an outlook on the use of single-cell techniques to decipher the adaptive and innate components of immunity. PMID:28983043

Assembly and Immunological Processing of Polyelectrolyte Multilayers Composed of Antigens and Adjuvants.

PubMed

Chiu, Yu-Chieh; Gammon, Joshua M; Andorko, James I; Tostanoski, Lisa H; Jewell, Christopher M

2016-07-27

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.

The top ten clues to understand the origin of chronic lymphocytic leukemia (CLL).

PubMed

García-Muñoz, Ricardo; Feliu, Jesús; Llorente, Luis

2015-01-01

The fundamental task of the immune system is to protect the individual from infectious organisms without serious injury to self. The essence of acquired immunity is molecular self/non self discrimination. Chronic lymphocytic leukemia is characterized by a global failure of immune system that begins with the failure of immunological tolerance mechanisms (autoimmunity) and finish with the incapacity to response to non-self antigens (immunodeficiency). Immunological tolerance mechanisms are involved in chronic lymphocytic leukemia (CLL) development. During B cell development some self-reactive B cells acquire a special BCR that recognize their own BCR. This self-autoantibody-self BCR interaction promotes survival, differentiation and proliferation of self-reactive B cells. Continuous self-autoantibody-self BCR interaction cross-linking induces an increased rate of surface BCR elimination, CD5+ expression, receptor editing and anergy. Unfortunately, some times this mechanisms increase genomic instability and promote additional genetic damage that immortalize self-reactive B cells and convert them into CLL like clones with the capability of clonal evolution and transformed CLL B cells. This review summarizes the immunological effects of continuous self-autoantibody-self BCR interaction cross-linking in the surface of self-reactive B cells and their role in CLL development. Copyright © 2014 Elsevier Ltd. All rights reserved.

Computational and Experimental Validation of B and T-Cell Epitopes of the In Vivo Immune Response to a Novel Malarial Antigen

DTIC Science & Technology

2013-08-16

approach in the context of a novel, immunologically relevant antigen. The limited accuracy of the tested algorithms to predict the in vivo immune responses...overlapping peptides spanning the entire sequence are individually tested for antibody interacting residues. Conformational B cell epitopes, in contrast...a blind assessment of this approach in the context of a novel, immunologically relevant antigen. The limited accuracy of the tested algorithms to

Marital conflict in older adults: endocrinological and immunological correlates.

PubMed

Kiecolt-Glaser, J K; Glaser, R; Cacioppo, J T; MacCallum, R C; Snydersmith, M; Kim, C; Malarkey, W B

1997-01-01

To assess endocrinological and immunological correlates of marital conflict and marital satisfaction, 31 older couples (mean age 67 years) who had been married an average of 42 years were studied. Couples were admitted to the Clinical Research Center and a catheter was placed in each subject's arm. Blood was drawn on entry for immunological assays; for hormone analyses, five blood samples were drawn during a 30-minute conflict discussion and a 15-minute recovery session. The conflict session was recorded on videotapes that were later coded for problem-solving behaviors using the Marital Interaction Coding System (MICS). Among wives, escalation of negative behavior during conflict and marital satisfaction showed strong relationships to endocrine changes, accounting for 16% to 21% of the variance in the rates of change of cortisol, adrenocorticotropic hormone (ACTH), and norepinephrine (but not epinephrine). In contrast, husbands' endocrine data did not show significant relationships with negative behavior or marital quality. Both men and women who showed relatively poorer immunological responses across three functional assays (the blastogenic response to two T-cell mitogens and antibody titers to latent Epstein-Barr virus) displayed more negative behavior during conflict; they also characterized their usual marital disagreements as more negative than individuals who showed better immune responses across assays. Abrasive marital interactions may have physiological consequences even among older adults in long-term marriages.

Immunological differences in the global release of the major cat allergen Fel d 1 are influenced by sex and behaviour.

PubMed

Bienboire-Frosini, Cécile; Cozzi, Alessandro; Lafont-Lecuelle, Céline; Vervloet, Daniel; Ronin, Catherine; Pageat, Patrick

2012-07-01

The biological function of Fel d 1, the major cat allergen released in the environment, is still unclear despite studies suggesting a putative role in chemical communication. Structural and immunological polymorphisms of Fel d 1 have been described. This study examined how Fel d 1 immunological polymorphism may have a physiological origin by estimating a potential relationship with the sex of cats and cat-human interactions. Samples from bath washes of 21 cats were screened to study antibody binding to Fel d 1 using an ELISA. Personality and Tolerance Handling scores were used to assess the behaviour of the cats. In the washes, Fel d 1 concentrations were significantly lower in females than in males (P<0.05). Slopes from the ELISA dose-dependent curves varied among the cats: males secreted Fel d 1 variants with higher antibody recognition than females (P<0.01). Females that were aggressive and difficult to handle displayed a diminished slope value, and therefore a weaker Fel d 1 immunoreactivity in global washes, compared to females that were sociable (P=0.09) and easy to handle (P=0.07). This study shows a variable immunological polymorphism of Fel d 1 within a cat population, particularly between males and females, and this polymorphism appears to be related to cat-human interactions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Overview on experimental models of interactions between nanoparticles and the immune system.

PubMed

Najafi-Hajivar, Saeedeh; Zakeri-Milani, Parvin; Mohammadi, Hamed; Niazi, Mehri; Soleymani-Goloujeh, Mehdi; Baradaran, Behzad; Valizadeh, Hadi

2016-10-01

Nanotechnology increasingly plays a significant role in modern medicine development. The clear benefits of using nanomaterials in various biomedical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. Two decades of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and biosystem are remarkably complex. This complexity derives from NPs' ability to bind and interact with biological cells and change their surface characteristics. One area of interest involves the interactions between NPs and the immune component. Immune system's function in the maintenance of tissue homeostasis is to protect the host from unfamiliar agents. This is done through effective surveillance and elimination of foreign substances and abnormal self cells from the body. Research shows that nanomaterials can stimulate and/or suppress the immune responses, and that their compatibility with the immune system is largely determined by their surface properties. NP size, shape, composition, protein binding and administration routes seem to be the main factors that contribute to the interactions of NPs with the immune system. In the present article, we focus on the relationship between effective physiochemical properties of NPs and their immunogenic effects. In addition, we review more details about immunological responses of different types of NPs. Understanding the interactions of nanomaterials with the immune system is essential for the engineering of new NP-based systems for medical applications. Copyright © 2016. Published by Elsevier Masson SAS.

T cell costimulation by chemokine receptors.

PubMed

Molon, Barbara; Gri, Giorgia; Bettella, Monica; Gómez-Moutón, Concepción; Lanzavecchia, Antonio; Martínez-A, Carlos; Mañes, Santos; Viola, Antonella

2005-05-01

Signals mediated by chemokine receptors may compete with T cell receptor stop signals and determine the duration of T cell-antigen-presenting cell interactions. Here we show that during T cell stimulation by antigen-presenting cells, T cell chemokine receptors coupled to G(q) and/or G(11) protein were recruited to the immunological synapse by a G(i)-independent mechanism. When chemokine receptors were sequestered at the immunological synapse, T cells became insensitive to chemotactic gradients, formed more stable conjugates and finally responded with enhanced proliferation and cytokine production. We suggest that chemokine receptor trapping at the immunological synapse enhances T cell activation by improving T cell-antigen-presenting cell attraction and impeding the 'distraction' of successfully engaged T cells by other chemokine sources.

An experimental test of the effects of behavioral and immunological defenses against vectors: do they interact to protect birds from blood parasites?

PubMed Central

2014-01-01

Background Blood-feeding arthropods can harm their hosts in many ways, such as through direct tissue damage and anemia, but also by distracting hosts from foraging or watching for predators. Blood-borne pathogens transmitted by arthropods can further harm the host. Thus, effective behavioral and immunological defenses against blood-feeding arthropods may provide important fitness advantages to hosts if they reduce bites, and in systems involving pathogen transmission, if they lower pathogen transmission rate. Methods We tested whether Rock Pigeons (Columba livia) have effective behavioral and immunological defenses against a blood-feeding hippoboscid fly (Pseudolynchia canariensis) and, if so, whether the two defenses interact. The fly vectors the blood parasite Haemoproteus columbae; we further tested whether these defenses reduced the transmission success of blood parasites when birds were exposed to infected flies. We compared four experimental treatments in which hosts had available both purported defenses, only one of the defenses, or no defenses against the flies. Results We found that preening and immunological defenses were each effective in decreasing the survival and reproductive success of flies. However, the two defenses were additive, rather than one defense enhancing or decreasing the effectiveness of the other defense. Neither defense reduced the prevalence of H. columbae, nor the intensity of infection in birds exposed to infected flies. Conclusions Flies experience reduced fitness when maintained on hosts with immunological or preening defenses. This suggests that if vectors are given a choice among hosts, they may choose hosts that are less defended, which could impact pathogen transmission in a system where vectors can choose among hosts. PMID:24620737

[Immunologic parameters in pericholangitis and primary sclerosing cholangitis with and without ulcerative colitis].

PubMed

Hopf, U; Riecken, E O; Zeitz, M; Eckhardt, R; Lobeck, H; Malchus, R; Möller, B

1983-10-07

Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.

ImmPort, toward repurposing of open access immunological assay data for translational and clinical research.

PubMed

Bhattacharya, Sanchita; Dunn, Patrick; Thomas, Cristel G; Smith, Barry; Schaefer, Henry; Chen, Jieming; Hu, Zicheng; Zalocusky, Kelly A; Shankar, Ravi D; Shen-Orr, Shai S; Thomson, Elizabeth; Wiser, Jeffrey; Butte, Atul J

2018-02-27

Immunology researchers are beginning to explore the possibilities of reproducibility, reuse and secondary analyses of immunology data. Open-access datasets are being applied in the validation of the methods used in the original studies, leveraging studies for meta-analysis, or generating new hypotheses. To promote these goals, the ImmPort data repository was created for the broader research community to explore the wide spectrum of clinical and basic research data and associated findings. The ImmPort ecosystem consists of four components-Private Data, Shared Data, Data Analysis, and Resources-for data archiving, dissemination, analyses, and reuse. To date, more than 300 studies have been made freely available through the Shared Data portal (www.immport.org/immport-open), which allows research data to be repurposed to accelerate the translation of new insights into discoveries.

Mass spectrometry-based proteomic exploration of the human immune system: focus on the inflammasome, global protein secretion, and T cells.

PubMed

Nyman, Tuula A; Lorey, Martina B; Cypryk, Wojciech; Matikainen, Sampsa

2017-05-01

The immune system is our defense system against microbial infections and tissue injury, and understanding how it works in detail is essential for developing drugs for different diseases. Mass spectrometry-based proteomics can provide in-depth information on the molecular mechanisms involved in immune responses. Areas covered: Summarized are the key immunology findings obtained with MS-based proteomics in the past five years, with a focus on inflammasome activation, global protein secretion, mucosal immunology, immunopeptidome and T cells. Special focus is on extracellular vesicle-mediated protein secretion and its role in immune responses. Expert commentary: Proteomics is an essential part of modern omics-scale immunology research. To date, MS-based proteomics has been used in immunology to study protein expression levels, their subcellular localization, secretion, post-translational modifications, and interactions in immune cells upon activation by different stimuli. These studies have made major contributions to understanding the molecular mechanisms involved in innate and adaptive immune responses. New developments in proteomics offer constantly novel possibilities for exploring the immune system. Examples of these techniques include mass cytometry and different MS-based imaging approaches which can be widely used in immunology.

The immunological synapse: the gateway to the HIV reservoir

PubMed Central

Kulpa, Deanna A; Brehm, Jessica H; Fromentin, Rémi; Cooper, Anthony; Cooper, Colleen; Ahlers, Jeffrey; Chomont, Nicolas; Sékaly, Rafick-Pierre

2013-01-01

A major challenge in the development of a cure for human immunodeficiency virus (HIV) has been the incomplete understanding of the basic mechanisms underlying HIV persistence during antiretroviral therapy. It is now realized that the establishment of a latently infected reservoir refractory to immune system recognition has thus far hindered eradication efforts. Recent investigation into the innate immune response has shed light on signaling pathways downstream of the immunological synapse critical for T-cell activation and establishment of T-cell memory. This has led to the understanding that the cell-to-cell contacts observed in an immunological synapse that involve the CD4+ T cell and antigen-presenting cell or T-cell–T-cell interactions enhance efficient viral spread and facilitate the induction and maintenance of latency in HIV-infected memory T cells. This review focuses on recent work characterizing the immunological synapse and the signaling pathways involved in T-cell activation and gene regulation in the context of HIV persistence. PMID:23772628

The IBD interactome: an integrated view of aetiology, pathogenesis and therapy.

PubMed

de Souza, Heitor S P; Fiocchi, Claudio; Iliopoulos, Dimitrios

2017-12-01

Crohn's disease and ulcerative colitis are prototypical complex diseases characterized by chronic and heterogeneous manifestations, induced by interacting environmental, genomic, microbial and immunological factors. These interactions result in an overwhelming complexity that cannot be tackled by studying the totality of each pathological component (an '-ome') in isolation without consideration of the interaction among all relevant -omes that yield an overall 'network effect'. The outcome of this effect is the 'IBD interactome', defined as a disease network in which dysregulation of individual -omes causes intestinal inflammation mediated by dysfunctional molecular modules. To define the IBD interactome, new concepts and tools are needed to implement a systems approach; an unbiased data-driven integration strategy that reveals key players of the system, pinpoints the central drivers of inflammation and enables development of targeted therapies. Powerful bioinformatics tools able to query and integrate multiple -omes are available, enabling the integration of genomic, epigenomic, transcriptomic, proteomic, metabolomic and microbiome information to build a comprehensive molecular map of IBD. This approach will enable identification of IBD molecular subtypes, correlations with clinical phenotypes and elucidation of the central hubs of the IBD interactome that will aid discovery of compounds that can specifically target the hubs that control the disease.

Interaction Between Immune Cells and Bacteria Associated With Periodontitis

ClinicalTrials.gov

2017-07-22

Periodontal Diseases; Periodontitis; Aggressive Periodontitis; Immunologic Disease; Microbial Disease; Periodontal Pocket; Inflammation; Inflammation Gum; Dysbiosis; Rheumatoid Arthritis; Generalized Aggressive Periodontitis; Generalized Chronic Periodontitis; Chronic Periodontitis

Maternal immunomodulation of the offspring's immunological system.

PubMed

Campos, Sylvia M N; de Oliveira, Vivian L; Lessa, Leonardo; Vita, Melissa; Conceição, Marcia; Andrade, Luiz Antonio Botelho; Teixeira, Gerlinde Agate Platais Brasil

2014-11-01

The mother's and the offspring's immunological system are closely related thus one can influence the other. This hypothesis drove our aim to study the impact of the mother's immunological status over the immunological response of their offspring. For this, female mice tolerant or allergic to peanuts were exposed or not to a challenge diet containing peanuts during the gestation-lactation period (TEP/AEP; TNEP/ANEP, respectively). After weaning the offspring was submitted to the peanut allergy or peanut tolerization protocol and then challenged with a peanut diet. Our results showed that when the offspring is submitted to the allergy induction protocol, they behave differently depending on their mother's immunological status. Offspring born to TEP mothers produced the lowest antibody titters while those born to AEP mothers produced the highest antibody titters compared to mice born to TNEP and ANEP. On the other hand when the offspring was submitted to the tolerization protocol all groups presented low antibody titers with no significant difference between groups, independent of the mothers immunological status and/or contact with peanuts during the gestation-lactation period. The analysis of the histological profile of the offspring correlates well to the serological response. In other words, offspring born to TEP mothers and submitted to the allergy induction protocol presented a normal histological profile, while the offspring born to AEP mothers produced the worst gut inflammation. These results indicate that mothers, exposed to the antigen (by the oral route) during gestation, actively influence the immune response of their offspring. This work sheds some light on the importance of the immunomodulation induced by dietary antigens during gestation and their influence on the immunological response of their offspring. However, more work is needed to elucidate the molecular and cellular components of this regulatory phenomenon. Copyright © 2014 Elsevier GmbH. All rights reserved.

A correlative and quantitative imaging approach enabling characterization of primary cell-cell communication: Case of human CD4+ T cell-macrophage immunological synapses.

PubMed

Kasprowicz, Richard; Rand, Emma; O'Toole, Peter J; Signoret, Nathalie

2018-05-22

Cell-to-cell communication engages signaling and spatiotemporal reorganization events driven by highly context-dependent and dynamic intercellular interactions, which are difficult to capture within heterogeneous primary cell cultures. Here, we present a straightforward correlative imaging approach utilizing commonly available instrumentation to sample large numbers of cell-cell interaction events, allowing qualitative and quantitative characterization of rare functioning cell-conjugates based on calcium signals. We applied this approach to examine a previously uncharacterized immunological synapse, investigating autologous human blood CD4 + T cells and monocyte-derived macrophages (MDMs) forming functional conjugates in vitro. Populations of signaling conjugates were visualized, tracked and analyzed by combining live imaging, calcium recording and multivariate statistical analysis. Correlative immunofluorescence was added to quantify endogenous molecular recruitments at the cell-cell junction. By analyzing a large number of rare conjugates, we were able to define calcium signatures associated with different states of CD4 + T cell-MDM interactions. Quantitative image analysis of immunostained conjugates detected the propensity of endogenous T cell surface markers and intracellular organelles to polarize towards cell-cell junctions with high and sustained calcium signaling profiles, hence defining immunological synapses. Overall, we developed a broadly applicable approach enabling detailed single cell- and population-based investigations of rare cell-cell communication events with primary cells.

Clostridium spiroforme toxin is a binary toxin which ADP-ribosylates cellular actin.

PubMed

Popoff, M R; Boquet, P

1988-05-16

We have purified from Clostridium spiroforme strain 246 an heterogeneous population of proteins (Sa) ranging from 43 to 47 kilodaltons exhibiting ADP-ribosyl transferase activity as do C. botulinum C2 toxin component I or the ia chain of C. perfringens E iota toxin. C. spiriforme Sa had alone no activity upon injection in mice or inoculated to Vero cells. When spiroforme ADP ribosyl transferase were mixed with a trypsin activated protein (Sb) separated from C. spiroforme bacterial supernatant, a lethal effect in mice and cytotoxicity on Vero cells were recorded. The Sa cross-reacted immunologically with either the light chain of C. perfringens E iota toxin or the ADP-ribosyl transferase from C. difficile 196 strain. No immunological relatedness was observed between Sa and C2 toxin component I. C. spiroforme toxin is thus another binary toxin close to iota.

A radioimmunoassay for ependymins beta and gamma: two goldfish brain proteins involved in behavioral plasticity.

PubMed

Schmidt, R; Shashoua, V E

1981-04-01

A radioimmunoassay (RIA) using 125I-labeled antigen was developed for the quantitative determination of two goldfish brain proteins (ependymins beta and gamma). The proteins were isolated from the cerebrospinal fluid (CSF) and cells of the ependymal zone surrounding goldfish brain ventricles. The turnover rates of beta and gamma were previously shown to be specifically enhanced after the animals successfully acquired a new pattern of swimming behavior. Femtomole quantities of ependymin beta were measurable by the RIA. In applications of the assay, beta and gamma ependymins were found to have common immunological properties, since 125I-beta-antigen bound to antibody could be displaced by unlabeled ependymin gamma as well as ependymin beta but not by a variety of other proteins including several purified glycoproteins isolated from goldfish brain. The ependymins were shown to constitute 14% of the total protein content of the brain extracellular fluid and also to be present as a minor component of the serum proteins (0.3%). Ependymins beta and gamma have an immunological reactivity in these fractions that can be increased by a factor of 30 on heating. The data suggest that the antigenicity of the molecules is highly masked, and that it may require some unraveling of the quaternary structure of the proteins before maximal interaction with the antisera becomes possible.

Characterization of the host response to the myxosporean parasite, Ceratomyxa shasta (Noble), by histology, scanning electron microscopy, and immunological techniques

USGS Publications Warehouse

Bartholomew, J.L.; Smith, C.E.; Rohovec, J.S.; Fryer, J.L.

1989-01-01

The tissue response of Salmo gairdneri Richardson, against the myxosporean parasite. Ceratomyxa shasta (Noble), was investigated using histological techniques, scanning electron microscopy and immunological methods. The progress of infection in C. shasta-susceptible and resistant steelhead and rainbow trout was examined by standard histological techniques and by indirect fluorescent antibody methods using monoclonal antibodies directed against C. shasta antigens. Trophozoite stages were first observed in the posterior intestine and there was indication that resistance was due to the inability of the parasite to penetrate this tissue rather than to an inflammatory response. Examination of a severely infected intestine by scanning electron microscopy showed extensive destruction of the mucosal folds of the posterior intestine. Western blotting and indirect fluorescent antibody techniques were used to investigate the immunological component of the host response. No antibodies specific for C. shasta were detected by either method.

Bee Pollen Flavonoids as a Therapeutic Agent in Allergic and Immunological Disorders.

PubMed

Jannesar, Masoomeh; Sharif Shoushtari, Maryam; Majd, Ahmad; Pourpak, Zahra

2017-06-01

Bee pollen grains, as the male reproductive part of seed-bearing plants contain considerable concentrations of various phytochemicals and nutrients. Since antiquity, people throughout the world used pollens to cure colds, flu, ulcers, premature aging, anemia and colitis. It is now well-documented that some bee pollen secondary metabolites (e.g. flavonoid) may have positive health effects. In recent years, the flavonoids have attracted much interest because of their wide range of biological properties and their beneficial effects on human health. The current review, points out potential therapeutic effects of bee pollen flavonoids as one of the main bee pollen bioactive compounds in allergic and immunological diseases. Due to the fact that some types of flavonoid components in bee pollen have anti-allergic, anti-oxidant and anti-inflammatory properties, bee pollen flavonoids can be excellent candidates for future studies including phytotherapy, molecular pharmacology and substitutes for chemicals used in treating allergic and immunological disorders.

An Investigation of Immunological Tolerance Based on Chimaera Analysis

PubMed Central

Michie, Donald; Woodruff, M. F. A.; Zeiss, Irmgard M.

1961-01-01

Newborn mice of strain A were injected intravenously at birth with 9–15 million spleen cells from adult CBA donors. The recipients exhibited splenomegaly and other signs of graft-versus-host reaction during the first 3 weeks of life. Adult survivors were uniformly tolerant of CBA skin. They showed no sign of a continuing graft-versus-host reaction. The spleens of the treated mice were tested for the presence of immunologically competent donor and host cells by Simonsen's discriminant spleen assay. From the age of 7 days onwards the spleens were found to contain a small percentage of donor cells which were immunologically active against antigens of a third strain. In spleens from adult survivors activity, attributable to the host component, against third-party antigens was undiminished as compared with that of untreated A-strain mice. But activity against the CBA donor strain was absent. PMID:14473459

21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...

21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...

21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...

21 CFR 866.5240 - Complement components immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

.... 866.5240 Section 866.5240 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... complement components C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9, in serum, other body fluids, and tissues. Complement is a group of serum proteins which destroy infectious agents. Measurements of these...

The microbiota: an exercise immunology perspective.

PubMed

Bermon, Stéphane; Petriz, Bernardo; Kajėnienė, Alma; Prestes, Jonato; Castell, Lindy; Franco, Octavio L

2015-01-01

The gut microbiota consists of a cluster of microorganisms that produces several signaling molecules of a hormonal nature which are released into the blood stream and act at distal sites. There is a growing body of evidence indicating that microbiota may be modulated by several environmental conditions, including different exercise stimulus, as well some pathologies. Enriched bacterial diversity has also been associated with improved health status and alterations in immune system, making multiple connections between host and microbiota. Experimental evidence has shown that reduced levels and variations in the bacterial community are associated with health impairments, while increased microbiota diversity improves metabolic profile and immunological responses. So far, very few controlled studies have focused on the interactions between acute or chronic exercise and the gut microbiota. However, some preliminary experimental data obtained from animal studies or probiotics studies show some interesting results at the immune level, indicating that the microbiota also acts like an endocrine organ and is sensitive to the homeostatic and physiological changes associated with exercise. Thus, our review intends to shed some light on the interaction between gut microbiota, exercise and immunomodulation. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

Dim light at night: physiological effects and ecological consequences for infectious disease.

PubMed

Kernbach, Meredith E; Hall, Richard J; Burkett-Cadena, Nathan; Unnasch, Thomas R; Martin, Lynn B

2018-06-23

Light pollution has emerged as a pervasive component of land development over the past century. Several detrimental impacts of this anthropogenic influence have been identified in night shift workers, laboratory rodents, and a plethora of wildlife species. Circadian, or daily, patterns are interrupted by the presence of light at night and have the capacity to alter rhythmic physiological or behavioral characteristics. Indeed, biorhythm disruption can lead to metabolic, reproductive, and immunological dysfunction depending on the intensity, timing, duration and wavelength of light exposure. Light pollution, in many forms and by many pathways, is thus apt to affect the nature of host-pathogen interactions. However, no research has yet investigated this possibility. The goal of this manuscript is to outline how dim light at night (dLAN), a relevant and common form of light pollution, may affect disease dynamics by interrupting circadian rhythms and regulation of immune responses as well as opportunities for host-parasite interactions and subsequent transmission risk including spillover into humans. We close by proposing some promising interventions including alternative lighting methods or vector control efforts.

Antibody Profile of Colostrum and the Effect of Processing in Human Milk Banks: Implications in Immunoregulatory Properties.

PubMed

Rodríguez-Camejo, Claudio; Puyol, Arturo; Fazio, Laura; Rodríguez, Analía; Villamil, Emilia; Andina, Eliana; Cordobez, Vanira; Díaz, Hernán; Lemos, Mary; Siré, Gabriela; Carroscia, Lilián; Castro, Mara; Panizzolo, Luis; Hernández, Ana

2018-02-01

When feeding preterm infants, donor milk is preferred if the mother's own milk is unavailable. Pasteurization may have detrimental effects on bioactivity, but more information is needed about its effects on the immunological compounds. Research aim: This work has two main aims: evaluate the antibody profile of colostrum and study the quantitative variations in the antibodies' level and specific reactivity after undergoing Holder pasteurization. The authors focused on immunoregulatory components of colostrum (antidietary antibodies and TGF-β2) in the neonatal gut. This is a descriptive cross-sectional study of a convenience sample of 67 donated colostrum samples at different days after delivery, both raw and pasteurized. Antibody profiles were analyzed at different times during breastfeeding, and total and specific antibodies (IgM, IgA, and IgG subclasses) were compared with tetanus toxoid and ovalbumin using enzyme-linked immunosorbent assay. The processing effect on total and specific antibodies, as well as TGF-β2, was evaluated by paired analyses. No variations in immunological compounds were observed throughout the colostrum stage. The TGF-β2, antibodies' concentrations, and antibodies' specific reactivity after pasteurization did not vary significantly as days of lactation varied. Changes in antibody levels were dependent on isotype and IgG subclass, and IgG4 showed remarkable resistance to heating. Moreover, the effect of the pasteurization on specific reactivity was antigen dependent. The supply of relevant immunological components is stable throughout the colostrum stage. The effects of pasteurization on antibodies depend on isotype, subclass, and specificity. This information is relevant to improving the immunological quality of colostrum, especially for preterm newborns.

Tumor immunology.

PubMed

Mocellin, Simone; Lise, Mario; Nitti, Donato

2007-01-01

Advances in tumor immunology are supporting the clinical implementation of several immunological approaches to cancer in the clinical setting. However, the alternate success of current immunotherapeutic regimens underscores the fact that the molecular mechanisms underlying immune-mediated tumor rejection are still poorly understood. Given the complexity of the immune system network and the multidimensionality of tumor/host interactions, the comprehension of tumor immunology might greatly benefit from high-throughput microarray analysis, which can portrait the molecular kinetics of immune response on a genome-wide scale, thus accelerating the discovery pace and ultimately catalyzing the development of new hypotheses in cell biology. Although in its infancy, the implementation of microarray technology in tumor immunology studies has already provided investigators with novel data and intriguing new hypotheses on the molecular cascade leading to an effective immune response against cancer. Although the general principles of microarray-based gene profiling have rapidly spread in the scientific community, the need for mastering this technique to produce meaningful data and correctly interpret the enormous output of information generated by this technology is critical and represents a tremendous challenge for investigators, as outlined in the first section of this book. In the present Chapter, we report on some of the most significant results obtained with the application of DNA microarray in this oncology field.

Basic and clinical immunology

NASA Technical Reports Server (NTRS)

Chinen, Javier; Shearer, William T.

2003-01-01

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.

The longitudinal and interactive effects of HIV status, stimulant use, and host genotype upon neurocognitive functioning.

PubMed

Levine, Andrew J; Reynolds, Sandra; Cox, Christopher; Miller, Eric N; Sinsheimer, Janet S; Becker, James T; Martin, Eileen; Sacktor, Ned

2014-06-01

Both human immunodeficiency virus (HIV)-1 infection and illicit stimulant use can adversely impact neurocognitive functioning, and these effects can be additive. However, significant variability exists such that as-of-yet unidentified exogenous and endogenous factors affect one's risk for neurocognitive impairment. Literature on both HIV and stimulant use indicates that host genetic variants in immunologic and dopamine-related genes are one such factor. In this study, the individual and interactive effects of HIV status, stimulant use, and genotype upon neurocognitive functioning were examined longitudinally over a 10-year period. Nine hundred fifty-two Caucasian HIV+ and HIV- cases from the Multicenter AIDS Cohort Study were included. All cases had at least two comprehensive neurocognitive evaluations between 1985 and 1995. Pre-highly active antiretroviral therapy (HAART) data were examined in order to avoid the confounding effect of variable drug regimens. Linear mixed models were used, with neurocognitive domain scores as the outcome variables. No four-way interactions were found, indicating that HIV and stimulant use do not interact over time to affect neurocognitive functioning as a function of genotype. Multiple three-way interactions were found that involved genotype and HIV status. All immunologically related genes found to interact with HIV status affected neurocognitive functioning in the expected direction; however, only C-C chemokine ligand 2 (CCL2) and CCL3 affected HIV+ individuals specifically. Dopamine-related genetic variants generally affected HIV-negative individuals only. Neurocognitive functioning among HIV+ individuals who also used stimulants was not significantly different from those who did not use stimulants. The findings support the role of immunologically related genetic differences in CCL2 and CCL3 in neurocognitive functioning among HIV+ individuals; however, their impact is minor. Being consistent with findings from another cohort, dopamine (DA)-related genetic differences do not appear to impact the longitudinal neurocognitive functioning of HIV+ individuals.

Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.

PubMed

McKenney, Erin A; Williamson, Lauren; Yoder, Anne D; Rawls, John F; Bilbo, Staci D; Parker, William

2015-01-01

The microbiome is now widely recognized as being important in health and disease, and makes up a substantial subset of the biome within the ecosystem of the vertebrate body. At the same time, multicellular, eukaryotic organisms such as helminths are being recognized as an important component of the biome that shaped the evolution of our genes. The absence of these macroscopic organisms during the early development and life of humans in Western culture probably leads to a wide range of human immunological diseases. However, the interaction between the microbiome and macroscopic components of the biome remains poorly characterized. In this study, the microbiome of the cecum in rats colonized for 2 generations with the small intestinal helminth Hymenolepis diminuta was evaluated. The introduction of this benign helminth, which is of considerable therapeutic interest, led to several changes in the cecal microbiome. Most of the changes were within the Firmicutes phylum, involved about 20% of the total bacteria, and generally entailed a shift from Bacilli to Clostridia species in the presence of the helminth. The results point toward ecological relationships between various components of the biome, with the observed shifts in the microbiome suggesting potential mechanisms by which this helminth might exert therapeutic effects.

Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta

PubMed Central

McKenney, Erin A; Williamson, Lauren; Yoder, Anne D; Rawls, John F; Bilbo, Staci D; Parker, William

2015-01-01

The microbiome is now widely recognized as being important in health and disease, and makes up a substantial subset of the biome within the ecosystem of the vertebrate body. At the same time, multicellular, eukaryotic organisms such as helminths are being recognized as an important component of the biome that shaped the evolution of our genes. The absence of these macroscopic organisms during the early development and life of humans in Western culture probably leads to a wide range of human immunological diseases. However, the interaction between the microbiome and macroscopic components of the biome remains poorly characterized. In this study, the microbiome of the cecum in rats colonized for 2 generations with the small intestinal helminth Hymenolepis diminuta was evaluated. The introduction of this benign helminth, which is of considerable therapeutic interest, led to several changes in the cecal microbiome. Most of the changes were within the Firmicutes phylum, involved about 20% of the total bacteria, and generally entailed a shift from Bacilli to Clostridia species in the presence of the helminth. The results point toward ecological relationships between various components of the biome, with the observed shifts in the microbiome suggesting potential mechanisms by which this helminth might exert therapeutic effects. PMID:25942385

[Metaphors of immunology: war and peace].

PubMed

Löwy, I

1996-01-01

Immunology has always relied on metaphorical language. In its early beginnings, it varied between bellicose images and images that stressed the interaction of immunity mechanisms with the organism's physiological functions overall. In the late nineteenth century, white blood globules were not only compared to 'border police' assigned to rebuffing intruders -- an army formed to combat the invaders -- but were also described as a physiological mechanism for eliminating aged, dead cells, at times exterminators of foreign bodies. Antibodies were described as very powerful, deadly weapons but also as an integral part of mechanisms that allowed cells to assimilate food. This duality of images holds true today. The article analyzes the emergence and development of these images, relating them to the redefinition of immunology as a science of the self and non-self and dissecting them in light of recent events, such as the Aids epidemic.

Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings

PubMed Central

Ayres, Cory M.; Corcelli, Steven A.; Baker, Brian M.

2017-01-01

Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic “energy landscapes” of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology. PMID:28824655

Peptide and Peptide-Dependent Motions in MHC Proteins: Immunological Implications and Biophysical Underpinnings.

PubMed

Ayres, Cory M; Corcelli, Steven A; Baker, Brian M

2017-01-01

Structural biology of peptides presented by class I and class II MHC proteins has transformed immunology, impacting our understanding of fundamental immune mechanisms and allowing researchers to rationalize immunogenicity and design novel vaccines. However, proteins are not static structures as often inferred from crystallographic structures. Their components move and breathe individually and collectively over a range of timescales. Peptides bound within MHC peptide-binding grooves are no exception and their motions have been shown to impact recognition by T cell and other receptors in ways that influence function. Furthermore, peptides tune the motions of MHC proteins themselves, which impacts recognition of peptide/MHC complexes by other proteins. Here, we review the motional properties of peptides in MHC binding grooves and discuss how peptide properties can influence MHC motions. We briefly review theoretical concepts about protein motion and highlight key data that illustrate immunological consequences. We focus primarily on class I systems due to greater availability of data, but segue into class II systems as the concepts and consequences overlap. We suggest that characterization of the dynamic "energy landscapes" of peptide/MHC complexes and the resulting functional consequences is one of the next frontiers in structural immunology.

[Inflammatory bowel diseases: an immunological approach].

PubMed

Sepúlveda, Sofía E; Beltrán, Caroll J; Peralta, Alexis; Rivas, Paola; Rojas, Néstor; Figueroa, Carolina; Quera, Rodrigo; Hermoso, Marcela A

2008-03-01

Inflammatory bowel diseases (IBD) are inflammatory diseases with a multifactorial component that involve the intestinal tract. The two relevant IBD syndromes are Crohn's disease (CD) and ulcerative colitis (UC). One factor involved in IBD development is a genetic predisposition, associated to NOD2/CARD15 and Toll-like receptor 4 (TLR4) polymorphisms that might favor infectious enterocolitis that is possibly associated to the development of IBD. The identification of specific immunologic alterations in IBD and their relationship to the etiology of the disease is a relevant research topic. The role of intra and extracellular molecules, such as transcription factors and cytokines that are involved in the inflammatory response, needs to be understood. The relevance of immunologic molecules that might drive the immune response to a T helper (Th) 1, Th 2 or the recently described Th 17 phenotype, has been demonstrated in animal models and clinical studies with IBD patients. CD and UC predominantly behave with a Th 1 and Th 2 immune phenotype, respectively. Recently, an association between CD and Th 17 has been reported. The knowledge acquired from immunologic and molecular research will help to develop accurate diagnostic methods and efficient therapies.

Steric-electronic effects in malarial peptides inducing sterile immunity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moreno-Vranich, Armando; Patarroyo, Manuel E., E-mail: mepatarr@mail.com; Universidad Nacional de Colombia, Bogota

Highlights: Black-Right-Pointing-Pointer Is it evident that the residues position are relevant regarding of {phi} angular value. Black-Right-Pointing-Pointer The geometry considered for detailing the alterations undergone by HABPs. Black-Right-Pointing-Pointer The inter planar interactions ruled by clashes between the atoms making them up. -- Abstract: Conserved Plasmodium falciparum high activity binding peptides' (HABPs) most relevant proteins involved in malaria parasite invasion are immunologically silent; critical binding residues must therefore be specifically replaced to render them highly immunogenic and protection-inducing. Such changes have a tremendous impact on these peptides' steric-electronic effects, such as modifications to peptide length peptide bonds and electronic orbitals' disposition,more » to allow a better fit into immune system MHCII molecules and better interaction with the TCR which might account for the final immunological outcome.« less

Behavioural and immunological responses to an immune challenge in Octopus vulgaris.

PubMed

Locatello, Lisa; Fiorito, Graziano; Finos, Livio; Rasotto, Maria B

2013-10-02

Behavioural and immunological changes consequent to stress and infection are largely unexplored in cephalopods, despite the wide employment of species such as Octopus vulgaris in studies that require their manipulation and prolonged maintenance in captivity. Here we explore O. vulgaris behavioural and immunological (i.e. haemocyte number and serum lysozyme activity) responses to an in vivo immune challenge with Escherichia coli lipopolysaccharides (LPS). Behavioural changes of immune-treated and sham-injected animals were observed in both sight-allowed and isolated conditions, i.e. visually interacting or not with a conspecific. Immune stimulation primarily caused a significant increase in the number of circulating haemocytes 4h after the treatment, while serum lysozyme activity showed a less clear response. However, the effect of LPS on the circulating haemocytes begins to vanish 24h after injection. Our observations indicate a significant change in behaviour consequent to LPS administration, with treated octopuses exhibiting a decrease of general activity pattern when kept in the isolated condition. A similar decrease was not observed in the sight-allowed condition, where we noticed a specific significant reduction only in the time spent to visually interact with the conspecific. Overall, significant, but lower, behavioural and immunological effects of injection were detected also in sham-injected animals, suggesting a non-trivial susceptibility to manipulation and haemolymph sampling. Our results gain importance in light of changes of the regulations for the use of cephalopods in scientific procedures that call for the prompt development of guidelines, covering many aspects of cephalopod provision, maintenance and welfare. © 2013.

Characterization of the oropharynx: anatomy, histology, immunology, squamous cell carcinoma and surgical resection.

PubMed

Fossum, Croix C; Chintakuntlawar, Ashish V; Price, Daniel L; Garcia, Joaquin J

2017-06-01

Understanding the structure and function of the oropharynx is paramount for providing excellent patient care. In clinical oncology, the oropharynx is generally divided into four distinct components: (i) the base of the tongue; (ii) the soft palate; (iii) the palatine tonsillar fossa; and (iv) the pharyngeal wall. The oropharyngeal mucosa is distinct from other mucosal surfaces in the body, as it is composed of a reticulated epithelium with a discontinuous basement membrane, also known as lymphoepithelium. This review describes the anatomy, histology, immunology and surgical resection of the oropharynx as they relate to oncological care. © 2016 John Wiley & Sons Ltd.

Pyruvate dehydrogenase has a major role in mast cell function, and its activity is regulated by mitochondrial microphthalmia transcription factor.

PubMed

Sharkia, Israa; Hadad Erlich, Tal; Landolina, Nadine; Assayag, Miri; Motzik, Alex; Rachmin, Inbal; Kay, Gillian; Porat, Ziv; Tshori, Sagi; Berkman, Neville; Levi-Schaffer, Francesca; Razin, Ehud

2017-07-01

We have recently observed that oxidative phosphorylation-mediated ATP production is essential for mast cell function. Pyruvate dehydrogenase (PDH) is the main regulator of the Krebs cycle and is located upstream of the electron transport chain. However, the role of PDH in mast cell function has not been described. Microphthalmia transcription factor (MITF) regulates the development, number, and function of mast cells. Localization of MITF to the mitochondria and its interaction with mitochondrial proteins has not been explored. We sought to explore the role played by PDH in mast cell exocytosis and to determine whether MITF is localized in the mitochondria and involved in regulation of PDH activity. Experiments were performed in vitro by using human and mouse mast cells, as well as rat basophil leukemia cells, and in vivo in mice. The effect of PDH inhibition on mast cell function was examined. PDH interaction with MITF was measured before and after immunologic activation. Furthermore, mitochondrial localization of MITF and its effect on PDH activity were determined. PDH is essential for immunologically mediated degranulation of mast cells. After activation, PDH is serine dephosphorylated. In addition, for the first time, we show that MITF is partially located in the mitochondria and interacts with PDH. This interaction is dependent on the phosphorylation state of PDH. Furthermore, mitochondrial MITF regulates PDH activity. The association of mitochondrial MITF with PDH emerges as an important regulator of mast cell function. Our findings indicate that PDH could arise as a new target for the manipulation of allergic diseases. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Biophotonics sensor acclimatization to stem cells environment

NASA Astrophysics Data System (ADS)

Mohamad Shahimin, Mukhzeer

2017-11-01

The ability to discriminate, characterise and purify biological cells from heterogeneous population of cells is fundamental to numerous prognosis and diagnosis applications; often forming the basis for current and emerging clinical protocols in stem cell therapy. Current sorting approaches exploit differences in cell density, specific immunologic targets, or receptor-ligand interactions to isolate particular cells. Identification of novel properties by which different cell types may be discerned and of new ways for their selective manipulation are clearly fundamental components for improving sorting methodologies. Biophotonics sensor developed by our team are potentially capable of discriminating cells according to their refractive index (which is highly dependable on the organelles inside the cell), size (indicator to cell stage) and shape (in certain cases as an indicator to cell type). The sensor, which already discriminate particles efficiently, is modified to acclimatize into biological environment, especially for stem cell applications.

Shigella flexneri 3a Outer Membrane Protein C Epitope Is Recognized by Human Umbilical Cord Sera and Associated with Protective Activity

PubMed Central

Jarząb, Anna; Witkowska, Danuta; Ziomek, Edmund; Dąbrowska, Anna; Szewczuk, Zbigniew; Gamian, Andrzej

2013-01-01

Shigella flexneri 3a is one of the five major strains of the Shigella genus responsible for dysentery, especially among children, in regions of high poverty and poor sanitation. The outer membrane proteins (OMP) of this bacterium elicit immunological responses and are considered a prime target for vaccine development. When injected into mice they elicit a protective immunological response against a lethal dose of the pathogen. The OMPs from S. flexneri 3a were isolated and resolved by two-dimension-SDS-PAGE. Two 38-kDa spots were of particular interest since in our earlier studies OMPs of such molecular mass were found to interact with umbilical cord sera. These two spots were identified as OmpC by ESI-MS/MS spectrometry. By DNA sequencing, the ompC gene from S. flexneri 3a was identical to ompC from S. flexneri 2a [Gene Bank: 24113600]. A 3D model of OmpC was built and used to predict B-cell type (discontinuous) antigenic epitopes. Six epitopes bearing the highest score were selected and the corresponding peptides were synthesized. Only the peptides representing loop V of OmpC reacted strongly with the umbilical cord serum immunoglobulins. To determine which amino acids are essential for the antigenic activity of the epitope, the loop V was scanned with a series of dodecapeptides. The peptide RYDERY was identified as a minimal sequence for the loop V epitope. Truncation at either the C- or N-terminus rendered this peptide inactive. Apart from C-terminal tyrosine, substitution of each of the remaining five amino acids with glycine, led to a precipitous loss of immunological activity. This peptide may serve as a ligand in affinity chromatography of OmpC-specific antibodies and as a component of a vaccine designed to boost human immune defenses against enterobacterial infections. PMID:23940590

Problem-Solving Test: Submitochondrial Localization of Proteins

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2011-01-01

Mitochondria are surrounded by two membranes (outer and inner mitochondrial membrane) that separate two mitochondrial compartments (intermembrane space and matrix). Hundreds of proteins are distributed among these submitochondrial components. A simple biochemical/immunological procedure is described in this test to determine the localization of…

Introduction to a Special Issue of the Journal of Immunological Methods: Building global resource programs to support HIV/AIDS clinical trial studies.

PubMed

Sanchez, Ana M; Denny, Thomas N; O'Gorman, Maurice

2014-07-01

This Special Issue of the Journal of Immunological Methods includes 16 manuscripts describing quality assurance activities related to virologic and immunologic monitoring of six global laboratory resource programs that support international HIV/AIDS clinical trial studies: Collaboration for AIDS Vaccine Discovery (CAVD); Center for HIV/AIDS Vaccine Immunology (CHAVI); External Quality Assurance Program Oversight Laboratory (EQAPOL); HIV Vaccine Trial Network (HVTN); International AIDS Vaccine Initiative (IAVI); and Immunology Quality Assessment (IQA). The reports from these programs address the many components required to develop comprehensive quality control activities and subsequent quality assurance programs for immune monitoring in global clinical trials including: all aspects of processing, storing, and quality assessment of PBMC preparations used ubiquitously in HIV clinical trials, the development and optimization of assays for CD8 HIV responses and HIV neutralization, a comprehensive global HIV virus repository, and reports on the development and execution of novel external proficiency testing programs for immunophenotyping, intracellular cytokine staining, ELISPOT and luminex based cytokine measurements. In addition, there are articles describing the implementation of Good Clinical Laboratory Practices (GCLP) in a large quality assurance laboratory, the development of statistical methods specific for external proficiency testing assessment, a discussion on the ability to set objective thresholds for measuring rare events by flow cytometry, and finally, a manuscript which addresses a framework for the structured reporting of T cell immune function based assays. It is anticipated that this series of manuscripts covering a wide range of quality assurance activities associated with the conduct of global clinical trials will provide a resource for individuals and programs involved in improving the harmonization, standardization, accuracy, and sensitivity of virologic and immunologic testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Titania nanotube arrays as interfaces for blood-contacting implantable devices: a study evaluating the nanotopography-associated activation and expression of blood plasma components.

PubMed

Smith, Barbara S; Popat, Ketul C

2012-08-01

The constant exposure of implantable biomaterials such as titanium and titanium alloys to blood-introducesserious and ongoing concerns regarding poor blood-material interactions. To date, all blood-contacting materials have been shown to initiate immunological events in the form of inflammation, thrombosis, fibrosis and infection; potentially leading to complete implant failure. Material surfaces that provide biomimetic cues such as nanoscale architectures have been shown to elicit improved cellular interaction; and thus, may provide possible solutions for enhancing blood-compatibility. However, limited information exists about the thrombogenicityof nanoscalesurface architectures. In this study, we have evaluated the efficacy of titania nanotube arrays as interfaces for blood contacting devices by investigating the thrombogenic effects using whole blood plasma. Thus, platelet/leukocyte adhesion, activation and interaction, morphology, complement activation, contact activation, platelet release reaction, fibrinogen expression and material cytotoxicity were evaluated to determine the in vitro thrombogenicity. The results presented here indicate a decrease in thrombogenic effects of titania nanotube arrays as compared to biomedical grade titanium after 2 hours of contact with whole blood plasma. This work shows the improved blood-compatibility of titania nanotube arrays, identifying this specific nanoarchitecture as a potentially optimal interface for promoting the long-term success of blood contacting biomaterials.

Immunologic contact urticaria--the human touch.

PubMed

Wang, Christina Y; Maibach, Howard I

2013-06-01

To review immunologic contact urticaria (ICU) in the occupational and environmental context, and describe its continued relevance in light of the ever-increasing onslaught of new chemicals and products, as well as new technology placing novel interactions, such as nanoparticles, within reach of the population at home and work. Publications were searched via PubMed, using key words: Occupational, immunologic, contact urticaria, nanoparticle. ICU remains an important diagnosis to make and treat because it has widespread health and social morbidity, including job and income loss, persistent life-long allergies, and progression from self-limiting skin eruptions to multi-systemic, sometimes life-threatening, illnesses. There is no short supply of known ICU causing allergens, but it is equally important to be ever vigilant in recognizing, and even adding to, items in the constantly expanding list of novel allergenic agents provided to us by the advances of modern chemistry and technology, and by the changing social structure and lifestyle dynamics.

Diversity in immunological synapse structure

PubMed Central

Thauland, Timothy J; Parker, David C

2010-01-01

Immunological synapses (ISs) are formed at the T cell–antigen-presenting cell (APC) interface during antigen recognition, and play a central role in T-cell activation and in the delivery of effector functions. ISs were originally described as a peripheral ring of adhesion molecules surrounding a central accumulation of T-cell receptor (TCR)–peptide major histocompatibility complex (pMHC) interactions. Although the structure of these ‘classical’ ISs has been the subject of intense study, non-classical ISs have also been observed under a variety of conditions. Multifocal ISs, characterized by adhesion molecules dispersed among numerous small accumulations of TCR–pMHC, and motile ‘immunological kinapses’ have both been described. In this review, we discuss the conditions under which non-classical ISs are formed. Specifically, we explore the profound effect that the phenotypes of both T cells and APCs have on IS structure. We also comment on the role that IS structure may play in T-cell function. PMID:21039474

[Archives of "comprehensive approach on asbestos-related diseases" supported by the "special coordination funds for promoting science and technology (H18-1-3-3-1)"-- overview of group research project, care and specimen registration, cellular characteristics of mesothelioma and immunological effects of asbestos].

PubMed

Otsuki, Takemi; Nakano, Takashi; Hasegawa, Seiki; Okada, Morihito; Tsujimura, Tohru; Sekido, Yoshitaka; Toyokuni, Shinya; Nishimoto, Hiroshi; Fukuoka, Kazuya; Tanaka, Fumihiro; Kumagai, Naoko; Maeda, Megumi; Nishimura, Yasumitsu

2011-05-01

The research project entitled "Comprehensive approach on asbestos-related diseases" supported by the "Special Coordination Funds for Promoting Science and Technology (H18-1-3-3-1)" began in 2006 and was completed at the end of the Japanese fiscal year of 2010. This project included four parts; (1) malignant mesothelioma (MM) cases and specimen registration, (2) development of procedures for the early diagnosis of MM, (3) commencement of clinical investigations including multimodal approaches, and (4) basic research comprising three components; (i) cellular and molecular characterization of mesothelioma cells, (ii) immunological effects of asbestos, and (iii) elucidation of asbestos-induced carcinogenesis using animal models. In this special issue of the Japanese Journal of Hygiene, we briefly introduce the achievements of our project. The second and third parts and the third component of the fourth part are described in other manuscripts written by Professors Fukuoka, Hasegawa, and Toyokuni. In this manuscript, we introduce a brief summary of the first part "MM cases and specimen registration", the first component of the fourth part "Cellular and molecular characterization of mesothelioma cells" and the second component of the fourth part "Immunological effects of asbestos". In addition, a previous special issue presented by the Study Group of Fibrous and Particulate Substances (SGFPS) (chaired by Professor Otsuki, Kawasaki Medical School, Japan) for the Japanese Society of Hygiene and published in Environmental Health and Preventive Medicine Volume 13, 2008, included reviews of the aforementioned first component of the fourth part of the project. Taken together, our project led medical investigations regarding asbestos and MM progress and contributed towards the care and examination of patients with asbestos-related diseases during these five years. Further investigations are required to facilitate the development of preventive measures and the cure of asbestos-related diseases, particularly in Japan, where asbestos-related diseases are predicted to increase in the next 10 to 20 years.

AntigenMap 3D: an online antigenic cartography resource.

PubMed

Barnett, J Lamar; Yang, Jialiang; Cai, Zhipeng; Zhang, Tong; Wan, Xiu-Feng

2012-05-01

Antigenic cartography is a useful technique to visualize and minimize errors in immunological data by projecting antigens to 2D or 3D cartography. However, a 2D cartography may not be sufficient to capture the antigenic relationship from high-dimensional immunological data. AntigenMap 3D presents an online, interactive, and robust 3D antigenic cartography construction and visualization resource. AntigenMap 3D can be applied to identify antigenic variants and vaccine strain candidates for pathogens with rapid antigenic variations, such as influenza A virus. http://sysbio.cvm.msstate.edu/AntigenMap3D

Mechanisms of Graft Rejection and Immune Regulation after Lung Transplant.

PubMed

Gauthier, Jason M; Li, Wenjun; Hsiao, Hsi-Min; Takahashi, Tsuyoshi; Arefanian, Saeed; Krupnick, Alexander S; Gelman, Andrew E; Kreisel, Daniel

2017-09-01

Outcomes after lung transplant lag behind those of other solid-organ transplants. A better understanding of the pathways that contribute to rejection and tolerance after lung transplant will be required to develop new therapeutic strategies that take into account the unique immunological features of lungs. Mechanistic immunological investigations in an orthotopic transplant model in the mouse have shed new light on immune responses after lung transplant. Here, we highlight that interactions between immune cells within pulmonary grafts shape their fate. These observations set lungs apart from other organs and help provide the conceptual framework for the development of lung-specific immunosuppression.

Testisimmune privilege - Assumptions versus facts

PubMed Central

Kaur, G.; Mital, P.; Dufour, J.M.

2013-01-01

The testis has long enjoyed a reputation as an immunologically privileged site based on its ability to protect auto-antigenic germ cells and provide an optimal environment for the extended survival of transplanted allo- or xeno-grafts. Exploration of the role of anatomical, physiological, immunological and cellular components in testis immune privilege revealed that the tolerogenic environment of the testis is a result of the immunomodulatory factors expressed or secreted by testicular cells (mainly Sertoli cells, peritubular myoid cells, Leydig cells, and resident macrophages). The blood-testis barrier/Sertoli cell barrier, is also important to seclude advanced germ cells but its requirement in testis immune privilege needs further investigation. Testicular immune privilege is not permanent, as an effective immune response can be mounted against transplanted tissue, and bacterial/viral infections in the testis can be effectively eliminated. Overall, the cellular components control the fate of the immune response and can shift the response from immunodestructive to immunoprotective, resulting in immune privilege. PMID:25309630

RImmPort: an R/Bioconductor package that enables ready-for-analysis immunology research data.

PubMed

Shankar, Ravi D; Bhattacharya, Sanchita; Jujjavarapu, Chethan; Andorf, Sandra; Wiser, Jeffery A; Butte, Atul J

2017-04-01

: Open access to raw clinical and molecular data related to immunological studies has created a tremendous opportunity for data-driven science. We have developed RImmPort that prepares NIAID-funded research study datasets in ImmPort (immport.org) for analysis in R. RImmPort comprises of three main components: (i) a specification of R classes that encapsulate study data, (ii) foundational methods to load data of a specific study and (iii) generic methods to slice and dice data across different dimensions in one or more studies. Furthermore, RImmPort supports open formalisms, such as CDISC standards on the open source bioinformatics platform Bioconductor, to ensure that ImmPort curated study datasets are seamlessly accessible and ready for analysis, thus enabling innovative bioinformatics research in immunology. RImmPort is available as part of Bioconductor (bioconductor.org/packages/RImmPort). rshankar@stanford.edu. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Cancer Biochemistry and Host-Tumor Interactions: A Decimal Classification, (Categories 51.6, 51.7, and 51.8).

ERIC Educational Resources Information Center

Schneider, John H.

This is a hierarchical decimal classification of information related to cancer biochemistry, to host-tumor interactions (including cancer immunology), and to occurrence of cancer in special types of animals and plants. It is a working draft of categories taken from an extensive classification of many fields of biomedical information. Because the…

Pax6 interacts with Iba1 and shows age-associated alterations in brain of aging mice.

PubMed

Maurya, Shashank Kumar; Mishra, Rajnikant

2017-07-01

The Pax6, a transcriptional regulator and multifunctional protein, has been found critical for neurogenesis, neuro-degeneration, mental retardation, neuroendocrine tumors, glioblastoma and astrocytomas. The age-associated alteration in the expression of Pax6 in neuron and glia has also been observed in the immunologically privileged brain. Therefore, it is presumed that Pax6 may modulate brain immunity by activation of microglia either directly interacting with genes or proteins of microglia or indirectly though inflammation associated with neurodegeneration. This report describes evaluation of expression, co-localization and interactions of Pax6 with Ionized binding protein1 (Iba1) in brain of aging mice by Immunohistochemistry, Chromatin Immuno-precipitation (ChIP) and Co-immunoprecipitation (Co-IP), respectively. The co-localization of Pax6 with Iba1 was observed in the cerebellum, cerebral cortex, hippocampus, midbrain and olfactory lobe. The Pax6 and Iba1 also interact physically. The age-dependent alteration in their expression and co-localization were also observed in mice. Results indicate Pax6-dependent activities of Iba1 in the remodelling of microglia during immunological surveillance of the brain. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects on intestinal microbiota and immune genes of Solea senegalensis after suspension of the administration of Shewanella putrefaciens Pdp11.

PubMed

Vidal, Sara; Tapia-Paniagua, Silvana Teresa; Moriñigo, Jesús Miguel; Lobo, Carmen; García de la Banda, Inés; Balebona, María Del Carmen; Moriñigo, Miguel Ángel

2016-11-01

The interaction host-intestinal microbiota is essential for the immunological homeostasis of the host. Probiotics, prebiotics and synbiotics are promising tools for the manipulation of the intestinal microbiota towards beneficial effects to the host. The objective of this study was to evaluate the modulation effect on the intestinal microbiota and the transcription of genes involved in the immune response in head kidney of Solea senegalensis after administration of diet supplemented with the prebiotic alginate and the probiotic Shewanella putrefaciens Pdp11 CECT 7627 (SpPdp11). The results showed higher adaptability to dietary changes in the intestinal microbiota of fish fed diet with alginate and SpPdp11 together compared to those fish that received an alginate-supplemented diet. The alginate-supplemented diet produced up-regulation of genes encoding proteins involved in immunological responses, such as complement, lysozyme G and transferrin, and oxidative stress, such as NADPH oxidase and glutation peroxidase. On the other hand, the administration of alginate combined with SpPdp11 resulted in a significant increase of the transcription of genes encoding for glutation peroxidase and HSP70, indicating a potential protective effect of SpPdp11 against oxidative stress. In addition, these effects were maintained after the suspension of the probiotic treatment. The relationship between the modulation of the intestinal microbiota and the expression of genes with protective effect against the oxidative stress was demonstrated by the Principal Components Analysis. Copyright © 2016 Elsevier Ltd. All rights reserved.

The immunological contribution of NF-κB within the tumor microenvironment: A potential protective role of zinc as an anti-tumor agent

PubMed Central

Bao, Bin; Thakur, Archana; Li, Yiwei; Ahmad, Aamir; Azmi, Asfar S.; Banerjee, Sanjeev; Kong, Dejuan; Ali, Shadan; Lum, Lawrence G.; Sarkar, Fazlul H.

2013-01-01

Over decades, cancer treatment has been mainly focused on targeting cancer cells and not much attention to host tumor microenvironment. Recent advances suggest that the tumor microenvironment requires in-depth investigation for understanding the interactions between tumor cell biology and immunobiology in order to optimize therapeutic approaches. Tumor microenvironment consists of cancer cells and tumor associated reactive fibroblasts, infiltrating non-cancer cells, secreted soluble factors or molecules, and non-cellular support materials. Tumor associated host immune cells such as Th1, Th2, Th17, regulatory cells, dendritic cells, macrophages, and myeloid-derived suppressor cells are major components of the tumor microenvironment. Accumulating evidence suggests that these tumor associated immune cells may play important roles in cancer development and progression. However, the exact functions of these cells in the tumor microenvironment are poorly understood. In the tumor microenvironment, NF-κB plays an important role in cancer development and progression because this is a major transcription factor which regulates immune functions within the tumor microenvironment. In this review, we will focus our discussion on the immunological contribution of NF-κB in tumor associated host immune cells within the tumor microenvironment. We will also discuss the potential protective role of zinc, a well-known immune response mediator, in the regulation of these immune cells and cancer cells in the tumor microenvironment especially because zinc could be useful for conditioning the tumor microenvironment toward innovative cancer therapy. PMID:22155217

Host-pathogen interactions between the human innate immune system and Candida albicans—understanding and modeling defense and evasion strategies

PubMed Central

Dühring, Sybille; Germerodt, Sebastian; Skerka, Christine; Zipfel, Peter F.; Dandekar, Thomas; Schuster, Stefan

2015-01-01

The diploid, polymorphic yeast Candida albicans is one of the most important human pathogenic fungi. C. albicans can grow, proliferate and coexist as a commensal on or within the human host for a long time. However, alterations in the host environment can render C. albicans virulent. In this review, we describe the immunological cross-talk between C. albicans and the human innate immune system. We give an overview in form of pairs of human defense strategies including immunological mechanisms as well as general stressors such as nutrient limitation, pH, fever etc. and the corresponding fungal response and evasion mechanisms. Furthermore, Computational Systems Biology approaches to model and investigate these complex interactions are highlighted with a special focus on game-theoretical methods and agent-based models. An outlook on interesting questions to be tackled by Systems Biology regarding entangled defense and evasion mechanisms is given. PMID:26175718

Dendritic cell control of tolerogenic responses

PubMed Central

Manicassamy, Santhakumar; Pulendran, Bali

2011-01-01

Summary One of the most fundamental problems in immunology is the seemingly schizophrenic ability of the immune system to launch robust immunity against pathogens, while acquiring and maintaining a state of tolerance to the body’s own tissues and the trillions of commensal microorganisms and food antigens that confront it every day. A fundamental role for the innate immune system, particularly dendritic cells (DCs), in orchestrating immunological tolerance has been appreciated, but emerging studies have highlighted the nature of the innate receptors and the signaling pathways that program DCs to a tolerogenic state. Furthermore, several studies have emphasized the major role played by cellular interactions, and the microenvironment in programming tolerogenic DCs. Here we review these studies and suggest that the innate control of tolerogenic responses can be viewed as different hierarchies of organization, in which DCs, their innate receptors and signaling networks, and their interactions with other cells and local microenvironments represent different levels of the hierarchy. PMID:21488899

Helminths and HIV infection: epidemiological observations on immunological hypotheses

PubMed Central

BROWN, M; MAWA, P A; KALEEBU, P; ELLIOTT, A M

2006-01-01

Parasitic helminths have co-evolved with the mammalian immune system. Current hypotheses suggest that immunological stimulation in the presence of helminths is balanced by immuno-regulation and by the broad spectrum of mechanisms possessed by helminths for countering the host immune response. The degree to which this balance is perfected, and the mechanisms by which this is achieved, vary between helminth species; we suggest that this is reflected not only in the degree of pathology induced by helminths but also in a variety of relationships with HIV infection and HIV disease. Available epidemiological data regarding interactions between helminths and HIV are largely observational; results are variable and generally inconclusive. Well designed, controlled intervention studies are required to provide definitive information on the species-specific nature of these interactions and on the advantages, disadvantages and optimal timing of de-worming in relation to HIV infection. PMID:17042933

Optical Microfibre Based Photonic Components and Their Applications in Label-Free Biosensing

PubMed Central

Wang, Pengfei; Bo, Lin; Semenova, Yuliya; Farrell, Gerald; Brambilla, Gilberto

2015-01-01

Optical microfibre photonic components offer a variety of enabling properties, including large evanescent fields, flexibility, configurability, high confinement, robustness and compactness. These unique features have been exploited in a range of applications such as telecommunication, sensing, optical manipulation and high Q resonators. Optical microfibre biosensors, as a class of fibre optic biosensors which rely on small geometries to expose the evanescent field to interact with samples, have been widely investigated. Due to their unique properties, such as fast response, functionalization, strong confinement, configurability, flexibility, compact size, low cost, robustness, ease of miniaturization, large evanescent field and label-free operation, optical microfibres based biosensors seem a promising alternative to traditional immunological methods for biomolecule measurements. Unlabeled DNA and protein targets can be detected by monitoring the changes of various optical transduction mechanisms, such as refractive index, absorption and surface plasmon resonance, since a target molecule is capable of binding to an immobilized optical microfibre. In this review, we critically summarize accomplishments of past optical microfibre label-free biosensors, identify areas for future research and provide a detailed account of the studies conducted to date for biomolecules detection using optical microfibres. PMID:26287252

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy.

PubMed

Chen, Jiahuan; Ganguly, Anutosh; Mucsi, Ashley D; Meng, Junchen; Yan, Jiacong; Detampel, Pascal; Munro, Fay; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W; Qi, Hai; Shi, Yan

2017-02-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell-DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1-dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin-cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1-dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell-mediated DC suppression in a contact-dependent manner. © 2017 Chen et al.

Strong adhesion by regulatory T cells induces dendritic cell cytoskeletal polarization and contact-dependent lethargy

PubMed Central

Mucsi, Ashley D.; Meng, Junchen; Yan, Jiacong; Zhang, Zongde; Wu, Mei; Hari, Aswin; Stenner, Melanie D.; Zheng, Wencheng; Kubes, Paul; Xia, Tie; Amrein, Matthias W.

2017-01-01

Dendritic cells are targeted by regulatory T (T reg) cells, in a manner that operates as an indirect mode of T cell suppression. In this study, using a combination of single-cell force spectroscopy and structured illumination microscopy, we analyze individual T reg cell–DC interaction events and show that T reg cells exhibit strong intrinsic adhesiveness to DCs. This increased DC adhesion reduces the ability of contacted DCs to engage other antigen-specific cells. We show that this unusually strong LFA-1–dependent adhesiveness of T reg cells is caused in part by their low calpain activities, which normally release integrin–cytoskeleton linkage, and thereby reduce adhesion. Super resolution imaging reveals that such T reg cell adhesion causes sequestration of Fascin-1, an actin-bundling protein essential for immunological synapse formation, and skews Fascin-1–dependent actin polarization in DCs toward the T reg cell adhesion zone. Although it is reversible upon T reg cell disengagement, this sequestration of essential cytoskeletal components causes a lethargic state of DCs, leading to reduced T cell priming. Our results reveal a dynamic cytoskeletal component underlying T reg cell–mediated DC suppression in a contact-dependent manner. PMID:28082358

Optical Microfibre Based Photonic Components and Their Applications in Label-Free Biosensing.

PubMed

Wang, Pengfei; Bo, Lin; Semenova, Yuliya; Farrell, Gerald; Brambilla, Gilberto

2015-07-22

Optical microfibre photonic components offer a variety of enabling properties, including large evanescent fields, flexibility, configurability, high confinement, robustness and compactness. These unique features have been exploited in a range of applications such as telecommunication, sensing, optical manipulation and high Q resonators. Optical microfibre biosensors, as a class of fibre optic biosensors which rely on small geometries to expose the evanescent field to interact with samples, have been widely investigated. Due to their unique properties, such as fast response, functionalization, strong confinement, configurability, flexibility, compact size, low cost, robustness, ease of miniaturization, large evanescent field and label-free operation, optical microfibres based biosensors seem a promising alternative to traditional immunological methods for biomolecule measurements. Unlabeled DNA and protein targets can be detected by monitoring the changes of various optical transduction mechanisms, such as refractive index, absorption and surface plasmon resonance, since a target molecule is capable of binding to an immobilized optical microfibre. In this review, we critically summarize accomplishments of past optical microfibre label-free biosensors, identify areas for future research and provide a detailed account of the studies conducted to date for biomolecules detection using optical microfibres.

Sickle cell protection from malaria.

PubMed

Eridani, Sandro

2011-10-19

A linkage between presence of Sickle Haemoglobin (HbS) and protection from malaria infection and clinical manifestations in certain areas was suspected from early observations and progressively elucidated by more recent studies. Research has confirmed the abovementioned connection, but also clarified how such protection may be abolished by coexistence of sickle cell trait (HbS trait) and alpha thalassemia, which may explain the relatively low incidence of HbS trait in the Mediterranean. The mechanisms of such protective effect are now being investigated: factors of genetic, molecular and immunological nature are prominent. As for genetic factors attention is given to the role of the red blood cell (RBC) membrane complement regulatory proteins as polymorphisms of these components seem to be associated with resistance to severe malaria; genetic ligands like the Duffy group blood antigen, necessary for erythrocytic invasion, and human protein CD36, a major receptor for P. falciparum-infected RBC's, are also under scrutiny: attention is focused also on plasmodium erythrocyte-binding antigens, which bind to RBC surface components. Genome-wide linkage and association studies are now carried out too, in order to identify genes associated with malaria resistance. Only a minor role is attributed to intravascular sickling, phagocytosis and haemolysis, while specific molecular mechanisms are the object of intensive research: among these a decisive role is played by a biochemical sequence, involving activation of haeme oxygenase (HMO-1), whose effect appears mediated by carbon monoxide (CO). A central role in protection from malaria is also played by immunological factors, which may stimulate antibody production to plasmodium antigens in the early years of life; the role of agents like pathogenic CD8 T-cells has been suggested while the effects of molecular actions on the immunity mechanism are presently investigated. It thus appears that protection from malaria can be explained by interaction of different factors: the elucidation of such mechanisms may prove valuable for the prevention and treatment strategy of a disease which still affects large parts of the world.

From Immunologically Archaic to Neoteric Glycovaccines

PubMed Central

Cavallari, Marco; De Libero, Gennaro

2017-01-01

Polysaccharides (PS) are present in the outermost surface of bacteria and readily come in contact with immune cells. They interact with specific antibodies, which in turn confer protection from infections. Vaccines with PS from pneumococci, meningococci, Haemophilus influenzae type b, and Salmonella typhi may be protective, although with the important constraint of failing to generate permanent immunological memory. This limitation has in part been circumvented by conjugating glycovaccines to proteins that stimulate T helper cells and facilitate the establishment of immunological memory. Currently, protection evoked by conjugated PS vaccines lasts for a few years. The same approach failed with PS from staphylococci, Streptococcus agalactiae, and Klebsiella. All those germs cause severe infections in humans and often develop resistance to antibiotic therapy. Thereby, prevention is of increasing importance to better control outbreaks. As only 23 of more than 90 pneumococcal serotypes and 4 of 13 clinically relevant Neisseria meningitidis serogroups are covered by available vaccines there is still tremendous clinical need for PS vaccines. This review focuses on glycovaccines and the immunological mechanisms for their success or failure. We discuss recent advances that may facilitate generation of high affinity anti-PS antibodies and confer specific immunity and long-lasting protection. PMID:28134792

Adipose tissue as an immunological organ

PubMed Central

Grant, Ryan W.; Dixit, Vishwa Deep

2014-01-01

Objective This review will focus on the immunological aspects of adipose tissue and its potential role in development of chronic inflammation that instigates obesity-associated co-morbidities. Design and Methods The review utilized PubMed searches of current literature to examine adipose tissue leukocytosis. Results The adipose tissue of obese subjects becomes inflamed and contributes to the development of insulin resistance, type 2 diabetes and metabolic syndrome. Numerous immune cells including B cells, T cells, macrophages and neutrophils have been identified in adipose tissue, and obesity influences both the quantity and the nature of immune cell subtypes which emerges as an active immunological organ capable of modifying whole body metabolism through paracrine and endocrine mechanisms. Conclusion Adipose tissue is a large immunologically active organ during obesity that displays hallmarks of both and innate and adaptive immune response. Despite the presence of hematopoietic lineage cells in adipose tissue, it is presently unclear whether the adipose compartment has a direct role in immune-surveillance or host defense. Understanding the interactions between leukocytes and adipocytes may reveal the clinically relevant pathways that control adipose tissue inflammation and is likely to reveal mechanism by which obesity contributes to increased susceptibility to both metabolic and certain infectious disease. PMID:25612251

Immunological Assays as an Opportunity of Assessment of Health Risks of Airborne Particle Mixture Including Nanoparticles

NASA Astrophysics Data System (ADS)

Brzicová, Táňa; Lochman, Ivo; Danihelka, Pavel; Lochmanová, Alexandra; Lach, Karel; Mička, Vladimír

2013-04-01

The aim of this pilot study was to evaluate perspectives of the assessment of nonspecific biological effects of airborne particulate matter including nanoparticles using appropriate immunological assays. We have selected various in vitro immunological assays to establish an array allowing us to monitor activation of the cell-mediated and humoral response of both the innate and adaptive immunity. To assess comprehensive interactions and effects, the assays were performed in whole blood cultures from healthy volunteers and we used an original airborne particle mixture from high pollution period in Ostrava region representing areas with one of the most polluted air in Europe. Even if certain effects were observed, the results of the immunological assays did not prove significant effects of airborne particles on immune cells' functions of healthy persons. However, obtained data do not exclude health risks of long-term exposure to airborne particles, especially in case of individuals with genetic predisposition to certain diseases or already existing disease. This study emphasizes the in vitro assessment of complex effects of airborne particles in conditions similar to actual ones in an organism exposed to particle mixture present in the polluted air.

Immunological research in clinical psychiatry: report on the consensus debate during the 7th Expert Meeting on Psychiatry and Immunology.

PubMed

Arolt, V; Rothermundt, M; Peters, M; Leonard, B

2002-01-01

There is convincing evidence that cytokines are involved in the physiology and pathophysiology of brain function and interact with different neurotransmitter and neuroendocrine pathways. The possible involvement of the immune system in the neurobiological mechanisms that underlie psychiatric disorders has attracted increasing attention in recent years. Thus in the last decade, numerous clinical studies have demonstrated dysregulated immune functions in patients with psychiatric disorders. Such findings formed the basis of the 7th Expert Meeting on Psychiatry and Immunology in Muenster, Germany, where a consensus symposium was held to consider the strengths and weaknesses of current research in psychoneuroimmunology. Following a general overview of the field, the following topics were discussed: (1) methodological problems in laboratory procedures and recruitment of clinical samples; (2) the importance of pre-clinical research and animal models in psychiatric research; (3) the problem of statistical vs biological relevance. It was concluded that, despite a fruitful proliferation of research activities throughout the last decade, the continuous elaboration of methodological standards including the implementation of hypothesis-driven research represents a task that is likely to prove crucial for the future development of immunology research in clinical psychiatry.

[Immunological aspects of ulcerative colitis. Treatment with disodium cromoglycate].

PubMed

Cavallini, L; Marchi, S; Spisni, L; Li Calzi, M

1980-01-01

The various components of the normal intestinal immunological system have been examined, i.e. immunocompetent cells (isolated and in clusters) and humoral factors. The modifications observed in this system during ulcerous colitis are then analysed, mention being made of the various pathogenetic interpretations that have been put forward to explain this condition. The pharmacology and action mechanism of DSCG are then examined. This drug has been in use for some years in the treatment of a number of extraintestinal and immuno-allergic based conditions and, recently, of some enteropathis attributed to food allergies. The reported results of using DSCG in ulcerous colitis are then reviewed. They would appear to be fairly encouraging.

Cutaneous immunology: basics and new concepts.

PubMed

Yazdi, Amir S; Röcken, Martin; Ghoreschi, Kamran

2016-01-01

As one of the largest organs, the skin forms a mechanical and immunological barrier to the environment. The skin immune system harbors cells of the innate immune system and cells of the adaptive immune system. Signals of the innate immune system typically initiate skin immune responses, while cells and cytokines of the adaptive immune system perpetuate the inflammation. Skin immune responses ensure effective host defense against pathogens but can also cause inflammatory skin diseases. An extensive crosstalk between the different cell types of the immune system, tissue cells, and pathogens is responsible for the complexity of skin immune reactions. Here we summarize the major cellular and molecular components of the innate and adaptive skin immune system.

HIV Molecular Immunology 2015

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yusim, Karina; Korber, Bette Tina; Brander, Christian

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 bindingmore » 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 are provided. Alignments of CTL, helper T-cell, and antibody epitopes are available through the search interface on our web site at http:// www.hiv.lanl.gov/content/immunology.« less

The Treatment of Cancer through Hypnosis.

ERIC Educational Resources Information Center

Goldberg, Bruce

1985-01-01

This report traces the immunological components of the cancer process and illustrates how vital a role is played by stress. The work of the Simontons is used to discuss the relationship between stress, the immune system and cancer. Hypnotic visualization techniques and their effects on the immune system are also reviewed. (Author)

Food-producing animals and their health in relation to human health

USDA-ARS?s Scientific Manuscript database

The fields of immunology, microbiology, and nutrition converge in an astonishing way. Dietary ingredients have a profound effect on the composition of the gut microflora, which in turn, regulates the physiology of metazoans. As such, nutritional components of the diet are of critical importance not ...

International Consensus (ICON): allergic reactions to vaccines.

PubMed

Dreskin, Stephen C; Halsey, Neal A; Kelso, John M; Wood, Robert A; Hummell, Donna S; Edwards, Kathryn M; Caubet, Jean-Christoph; Engler, Renata J M; Gold, Michael S; Ponvert, Claude; Demoly, Pascal; Sanchez-Borges, Mario; Muraro, Antonella; Li, James T; Rottem, Menachem; Rosenwasser, Lanny J

2016-01-01

Routine immunization, one of the most effective public health interventions, has effectively reduced death and morbidity due to a variety of infectious diseases. However, allergic reactions to vaccines occur very rarely and can be life threatening. Given the large numbers of vaccines administered worldwide, there is a need for an international consensus regarding the evaluation and management of allergic reactions to vaccines. Following a review of the literature, and with the active participation of representatives from the World Allergy Organization (WAO), the European Academy of Allergy and Clinical Immunology (EAACI), the American Academy of Allergy, Asthma, and Immunology (AAAAI), and the American College of Allergy, Asthma, and Immunology (ACAAI), the final committee was formed with the purpose of having members who represented a wide-range of countries, had previously worked on vaccine safety, and included both allergist/immunologists as well as vaccinologists. Consensus was reached on a variety of topics, including: definition of immediate allergic reactions, including anaphylaxis, approaches to distinguish association from causality, approaches to patients with a history of an allergic reaction to a previous vaccine, and approaches to patients with a history of an allergic reaction to components of vaccines. This document provides comprehensive and internationally accepted guidelines and access to on-line documents to help practitioners around the world identify allergic reactions following immunization. It also provides a framework for the evaluation and further management of patients who present either following an allergic reaction to a vaccine or with a history of allergy to a component of vaccines.

Host Competence: An Organismal Trait to Integrate Immunology and Epidemiology.

PubMed

Martin, Lynn B; Burgan, S C; Adelman, James S; Gervasi, Stephanie S

2016-12-01

The new fields of ecological immunology and disease ecology have begun to merge, and the classic fields of immunology and epidemiology are beginning to blend with them. This merger is occurring because the integrative study of host-parasite interactions is providing insights into disease in ways that traditional methods have not. With the advent of new tools, mathematical and technological, we could be on the verge of developing a unified theory of infectious disease, one that supersedes the barriers of jargon and tradition. Here we argue that a cornerstone of any such synthesis will be host competence, the propensity of an individual host to generate new infections in other susceptible hosts. In the last few years, the emergence of systems immunology has led to novel insight into how hosts control or eliminate pathogens. Most such efforts have stopped short of considering transmission and the requisite behaviors of infected individuals that mediate it, and few have explicitly incorporated ecological and evolutionary principles. Ultimately though, we expect that the use of a systems immunology perspective will help link suborganismal processes (i.e., health of hosts and selection on genes) to superorganismal outcomes (i.e., community-level disease dynamics and host-parasite coevolution). Recently, physiological regulatory networks (PRNs) were cast as whole-organism regulatory systems that mediate homeostasis and hence link suborganismal processes with the fitness of individuals. Here, we use the PRN construct to develop a roadmap for studying host competence, taking guidance from systems immunology and evolutionary ecology research. We argue that PRN variation underlies heterogeneity in individual host competence and hence host-parasite dynamics. © The Author 2016. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

HIV Molecular Immunology 2014

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yusim, Karina; Korber, Bette Tina Marie; Barouch, Dan

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 themore » 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.« less

Involvement of Pacific oyster CgPGRP-S1S in bacterial recognition, agglutination and granulocyte degranulation.

PubMed

Iizuka, Masao; Nagasaki, Toshihiro; Takahashi, Keisuke G; Osada, Makoto; Itoh, Naoki

2014-03-01

Peptidoglycan recognition protein (PGRP) recognizes invading bacteria through their peptidoglycans (PGN), a component of the bacterial cell wall. Insect PGRPs contribute to effective immune systems as inducers of other host defense responses, while this function has not been reported from PGRP of bivalves. In this study, recombinant CgPGRP-S1S (rCgPGRP-S1S), produced in the mantle and the gill, was synthesized and used to elucidate the immunological function of CgPGRP-S1S. rCgPGRP-S1S bound specifically to DAP-type PGN and to Escherichia coli cells, but not to other DAP-type PGN-containing bacterial species, Vibrio anguillarum, or Bacillus subtilis. Antibacterial activity was not detected, but E. coli cells were agglutinated. Moreover, in addition to these direct interactions with bacterial cells, rCgPGRP-S1S induced secretion of granular contents by hemocyte degranulation. Taken together, these results suggest for the first time that a PGRP of bivalves is, just as in insects, involved in host defense, not only by direct interaction with bacteria, but also by triggering other defense pathways. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using Polymeric Materials to Control Stem Cell Behavior for Tissue Regeneration

PubMed Central

Zhang, Nianli; Kohn, David H.

2017-01-01

Patients with organ failure often suffer from increased morbidity and decreased quality of life. Current strategies of treating organ failure have limitations, including shortage of donor organs, low efficiency of grafts, and immunological problems. Tissue engineering emerged about two decades ago as a strategy to restore organ function with a living, functional engineered substitute. However, the ability to engineer a functional organ substitute is limited by a limited understanding of the interactions between materials and cells that are required to yield functional tissue equivalents. Polymeric materials are one of the most promising classes of materials for use in tissue engineering due to their biodegradability, flexibility in processing and property design, and the potential to use polymer properties to control cell function. Stem cells offer potential in tissue engineering because of their unique capacity to self renew and differentiate into neurogenic, osteogenic, chondrogenic, myogenic lineages under appropriate stimuli from extracellular components. This review examines recent advances in stem cell-polymer interactions for tissue regeneration, specifically highlighting control of polymer properties to direct adhesion, proliferation, and differentiation of stem cells, and how biomaterials can be designed to provide some of the stimuli to cells that the natural extracellular matrix does. PMID:22457178

Structural Studies of Complex Carbohydrates of Plant Cell Walls

DOE Office of Scientific and Technical Information (OSTI.GOV)

Darvill, Alan; Hahn, Michael G.; O'Neill, Malcolm A.

Most of the solar energy captured by land plants is converted into the polysaccharides (cellulose, hemicellulose, and pectin) that are the predominant components of the cell wall. These walls, which account for the bulk of plant biomass, have numerous roles in the growth and development of plants. Moreover, these walls have a major impact on human life as they are a renewable source of biomass, a source of diverse commercially useful polymers, a major component of wood, and a source of nutrition for humans and livestock. Thus, understanding the molecular mechanisms that lead to wall assembly and how cell wallsmore » and their component polysaccharides contribute to plant growth and development is essential to improve and extend the productivity and value of plant materials. The proposed research will develop and apply advanced analytical and immunological techniques to study specific changes in the structures and interactions of the hemicellulosic and pectic polysaccharides that occur during differentiation and in response to genetic modification and chemical treatments that affect wall biosynthesis. These new techniques will make it possible to accurately characterize minute amounts of cell wall polysaccharides so that subtle changes in structure that occur in individual cell types can be identified and correlated to the physiological or developmental state of the plant. Successful implementation of this research will reveal fundamental relationships between polysaccharide structure, cell wall architecture, and cell wall functions.« less

Spaceflight and immune responses of Rhesus monkeys

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald

1994-01-01

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

100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology.

PubMed

Pomés, Anna; Chruszcz, Maksymilian; Gustchina, Alla; Minor, Wladek; Mueller, Geoffrey A; Pedersen, Lars C; Wlodawer, Alexander; Chapman, Martin D

2015-07-01

Current knowledge of molecules involved in immunology and allergic disease results from the significant contributions of x-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and x-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact 3-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind LPSs can also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. In turn, this surface determines antibody specificity and cross-reactivity, which are important factors for the selection of allergen panels used for molecular diagnosis and the interpretation of clinical symptoms. This review celebrates the contributions of x-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Characterisation of the immune compounds in koala milk using a combined transcriptomic and proteomic approach

PubMed Central

Morris, Katrina M.; O’Meally, Denis; Zaw, Thiri; Song, Xiaomin; Gillett, Amber; Molloy, Mark P.; Polkinghorne, Adam; Belov, Katherine

2016-01-01

Production of milk is a key characteristic of mammals, but the features of lactation vary greatly between monotreme, marsupial and eutherian mammals. Marsupials have a short gestation followed by a long lactation period, and milk constituents vary greatly across lactation. Marsupials are born immunologically naïve and rely on their mother’s milk for immunological protection. Koalas (Phascolarctos cinereus) are an iconic Australian species that are increasingly threatened by disease. Here we use a mammary transcriptome, two milk proteomes and the koala genome to comprehensively characterise the protein components of koala milk across lactation, with a focus on immune constituents. The most abundant proteins were well-characterised milk proteins, including β-lactoglobulin and lactotransferrin. In the mammary transcriptome, 851 immune transcripts were expressed, including immunoglobulins and complement components. We identified many abundant antimicrobial peptides, as well as novel proteins with potential antimicrobial roles. We discovered that marsupial VELP is an ortholog of eutherian Glycam1, and likely has an antimicrobial function in milk. We also identified highly-abundant koala endogenous-retrovirus sequences, identifying a potential transmission route from mother to young. Characterising the immune components of milk is key to understanding protection of marsupial young, and the novel immune compounds identified may have applications in clinical research. PMID:27713568

Immunology of BVDV vaccines

USDA-ARS?s Scientific Manuscript database

The use of vaccination to control bovine viral diarrhea virus (BVDV) infections presents exceptional challenges due to the nature of the virus, the unique interaction of the virus with the immune system, and its ability to establish persistent infections. The lack of proof reading function during th...

Common antigenic determinants of haemoglobin as basis of immunological cross-reactivity between chironomid species (Diptera, Chironomidae): studies with human and animal sera.

PubMed Central

Baur, X; Dewair, M; Haegele, K; Prelicz, H; Scholl, A; Tichy, H

1983-01-01

Chironomids, of which approximately 10,000 species exist, are reported to cause severe immediate type allergic diseases in man. In the present study, immunological cross-reactivity between 14 chironomid species from different continents was proven by RAST inhibition, double immunodiffusion and a new allergoprint technique, based upon PAGE separation of insect crude extracts. Using isolated chironomid haemoglobins and sera of sensitized persons, as well as rabbit antibodies against larval crude extract or against the haemoglobin fraction of Chironomus thummi, it could be proven that cross-reactivity derives at least predominantly from haemoglobin components with common antigenic determinants in the different species. Images Fig. 2 Fig. 7 Fig. 8 Fig. 9 PMID:6197219

CRISPR-Cas adaptation: insights into the mechanism of action.

PubMed

Amitai, Gil; Sorek, Rotem

2016-02-01

Since the first demonstration that CRISPR-Cas systems provide bacteria and archaea with adaptive immunity against phages and plasmids, numerous studies have yielded key insights into the molecular mechanisms governing how these systems attack and degrade foreign DNA. However, the molecular mechanisms underlying the adaptation stage, in which new immunological memory is formed, have until recently represented a major unresolved question. In this Progress article, we discuss recent discoveries that have shown both how foreign DNA is identified by the CRISPR-Cas adaptation machinery and the molecular basis for its integration into the chromosome to form an immunological memory. Furthermore, we describe the roles of each of the specific CRISPR-Cas components that are involved in memory formation, and consider current models for their evolutionary origin.

THE EFFICACY OF THREE MEDICINAL PLANTS: GARLIC, GINGER AND MIRAZID AND A CHEMICAL DRUG METRONIDAZOLE AGAINST CRYPTOSPORIDIUM PARVUM. I-IMMUNOLOGICAL RESPONSE.

PubMed

Abouel-Nour, Mohamed F; EL-Shewehy, Dina Magdy M; Hamada, Shadia F; Morsy, Tosson A

2015-12-01

Cryptosporidisis parvum is a zoonotic protozoan parasite infects intestinal epithelial cells causing a major health problem for man and animals. Experimentally the immunologic mediated elimination of C. parvum requires CD4+ T cells and IFN-gamma. But, the innate immune responses also have a significant protective role in both man and animals. the mucosal immune response to C. parvum in C57BL/6 neonatal and GKO mice shows a concomitant Thl and Th2 cytokine mRNA expression, with a crucial role for IFN-gamma in the resolution of the infection. NK cells and IFN-gamma have been shown to be important components in immunity in T and B cell-deficient mice, but IFN-gamma-dependent resistance is demonstrated in alymphocytic mice. Epithelial cells may play a vital role in immunity as once infected these cells have increased expression of inflammatory chemokines and cytokines and demonstrate anti-infection killing mechanisms. C. parvum immunological response was used to evaluate the efficacy of anti-cryptosporidisis agents of Garlic, Ginger, Mirazid and Metronidazole in experimentally infected mice.

SLAT promotes TCR-mediated, Rap1-dependent LFA-1 activation and adhesion through interaction of its PH domain with Rap1

PubMed Central

Côte, Marjorie; Fos, Camille; Canonigo-Balancio, Ann J.; Ley, Klaus; Bécart, Stéphane; Altman, Amnon

2015-01-01

ABSTRACT SLAT (also known as DEF6) promotes T cell activation and differentiation by regulating NFAT-Ca2+ signaling. However, its role in TCR-mediated inside-out signaling, which induces integrin activation and T cell adhesion, a central process in T cell immunity and inflammation, has not been explored. Here, we show that SLAT is crucial for TCR-induced adhesion to ICAM-1 and affinity maturation of LFA-1 in CD4+ T cells. Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4+ T cell adhesion. Finally, we established that a constitutively active form of Rap1, which is present at the plasma membrane, rescues the defective LFA-1 activation and ICAM-1 adhesion in SLAT-deficient (Def6−/−) T cells. These findings ascribe a new function to SLAT, and identify Rap1 as a target of SLAT function in TCR-mediated inside-out signaling. PMID:26483383

SLAT promotes TCR-mediated, Rap1-dependent LFA-1 activation and adhesion through interaction of its PH domain with Rap1.

PubMed

Côte, Marjorie; Fos, Camille; Canonigo-Balancio, Ann J; Ley, Klaus; Bécart, Stéphane; Altman, Amnon

2015-12-01

SLAT (also known as DEF6) promotes T cell activation and differentiation by regulating NFAT-Ca(2+) signaling. However, its role in TCR-mediated inside-out signaling, which induces integrin activation and T cell adhesion, a central process in T cell immunity and inflammation, has not been explored. Here, we show that SLAT is crucial for TCR-induced adhesion to ICAM-1 and affinity maturation of LFA-1 in CD4(+) T cells. Mechanistic studies revealed that SLAT interacts, through its PH domain, with a key component of inside-out signaling, namely the active form of the small GTPase Rap1 (which has two isoforms, Rap1A and Rap1B). This interaction has been further shown to facilitate the interdependent recruitment of Rap1 and SLAT to the T cell immunological synapse upon TCR engagement. Furthermore, a SLAT mutant lacking its PH domain drastically inhibited LFA-1 activation and CD4(+) T cell adhesion. Finally, we established that a constitutively active form of Rap1, which is present at the plasma membrane, rescues the defective LFA-1 activation and ICAM-1 adhesion in SLAT-deficient (Def6(-/-)) T cells. These findings ascribe a new function to SLAT, and identify Rap1 as a target of SLAT function in TCR-mediated inside-out signaling. © 2015. Published by The Company of Biologists Ltd.

Immunological dysfunction in periparturient cows: Evidence, causes and ramifications

USDA-ARS?s Scientific Manuscript database

With a $35.7 billion Gross Domestic Value for milk produced in the U.S. during 2007, the dairy industry was the single largest component of the 2007 U.S. animal agriculture economic engine. The value of milk produced in 2007 represented 30.2% of the total value of animal agriculture production; thi...

Online Series presents Cancer Prevention Through Immunomodulation. Does Diet Play a Role? | Division of Cancer Prevention

Cancer.gov

Scientists are increasingly harnessing the power of the immune system to prevent cancer. Nutrition provides an opportunity for a generalized immune activation and reduction of cancer risk in certain populations. Research on several foods and bioactive food components as immunologic modulators is showing promising results. |

Endosafe(R)-Portable Test System (PTS)

NASA Technical Reports Server (NTRS)

Maule, Jake; Wainwright, Norm; Burbank, Dan

2005-01-01

The Portable Test System (PTS) is a hand-held device for monitoring the presence of potentially hazardous bacteria in the environment. It uses an immunological method derived from the horseshoe crab (Limulus polyphemus) to detect bacterial cell membranes and other molecular components of a cell. Further modifications of the PTS will allow detection of individual hazardous species of bacteria. This study was a follow-up of previous PTS and other immunological tests performed on the KC-135 during 2002-2003 (Maule et al., 2003, J. Gravit. Physiol.) and in the underwater habitat Aquarius during NEEMO 5 (Maule et al., 2005, Appl. Environ. Microbiol in prep.). The experiments described here were part of a final testing phase prior to use of the PTS on the International Space Station (ISS), scheduled for launch on 12A.1 on February 9th 2006. The specific aspects of PTS operation studied were those involving a fluid component: pumping, mixing, incubations and pipetting into the instrument. The PTS uses a stepper motor to move fluid along small channels, which may be affected by reduced gravity.

In vitro and in vivo antitumor effects of 50 to 100-KDa components from B16 melanoma culture supernatant.

PubMed

Qin, Ying-Song; Zhang, X U; Zhang, Xiang-Yu

2015-07-01

The development of immunological therapies for melanoma has been of considerable concern in recent years. Whole tumor cell lysates have been used to develop antitumor vaccines, but the effective components of the lysates have not been identified. In the present study, protein elements were purified from the B16 supernatant to analyze the in vitro chemotaxis towards mouse spleen lymphocytes using a Boyden chamber. Prior to establishing a B16 melanoma model, C57BL/6 mice were vaccinated with these proteins, and melanoma growth, tumor appearance time and behavioral changes were observed. Next, the cytotoxicity and subsets of the tumor infiltrating lymphocytes, and the histological characteristics of the melanoma were analyzed. The isolated purified fragments of B16 melanoma culture supernatant had strong antitumor effects. The possible antitumor mechanism was delineated, and was identified to possibly be through the activation of cluster of differentiation 8-positive T cells and the promotion of B16 cell differentiation. These methods will provide a novel insight into understanding antitumor immunological mechanisms and provide a potential avenue for immunotherapy.

Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model

PubMed Central

Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W.; Kasper, Dennis L.

1998-01-01

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules. PMID:9573085

Immunology of Gut Mucosal Vaccines

PubMed Central

Pasetti, Marcela F.; Simon, Jakub K.; Sztein, Marcelo B.; Levine, Myron M.

2011-01-01

Summary Understanding the mechanisms underlying the induction of immunity in the gastrointestinal mucosa following oral immunization and the cross-talk between mucosal and systemic immunity should expedite the development of vaccines to diminish the global burden caused by enteric pathogens. Identifying an immunological correlate of protection in the course of field trials of efficacy, animal models (when available), or human challenge studies is also invaluable. In industrialized country populations, live attenuated vaccines (e.g. polio, typhoid, and rotavirus) mimic natural infection and generate robust protective immune responses. In contrast, a major challenge is to understand and overcome the barriers responsible for the diminished immunogenicity and efficacy of the same enteric vaccines in underprivileged populations in developing countries. Success in developing vaccines against some enteric pathogens has heretofore been elusive (e.g. Shigella). Different types of oral vaccines can selectively or inclusively elicit mucosal secretory immunoglobulin A and serum immunoglobulin G antibodies and a variety of cell-mediated immune responses. Areas of research that require acceleration include interaction between the gut innate immune system and the stimulation of adaptive immunity, development of safe yet effective mucosal adjuvants, better understanding of homing to the mucosa of immunologically relevant cells, and elicitation of mucosal immunologic memory. This review dissects the immune responses elicited in humans by enteric vaccines. PMID:21198669

Clustering of immunological, metabolic and genetic features in latent autoimmune diabetes in adults: evidence from principal component analysis.

PubMed

Pes, Giovanni Mario; Delitala, Alessandro Palmerio; Errigo, Alessandra; Delitala, Giuseppe; Dore, Maria Pina

2016-06-01

Latent autoimmune diabetes in adults (LADA) which accounts for more than 10 % of all cases of diabetes is characterized by onset after age 30, absence of ketoacidosis, insulin independence for at least 6 months, and presence of circulating islet-cell antibodies. Its marked heterogeneity in clinical features and immunological markers suggests the existence of multiple mechanisms underlying its pathogenesis. The principal component (PC) analysis is a statistical approach used for finding patterns in data of high dimension. In this study the PC analysis was applied to a set of variables from a cohort of Sardinian LADA patients to identify a smaller number of latent patterns. A list of 11 variables including clinical (gender, BMI, lipid profile, systolic and diastolic blood pressure and insulin-free time period), immunological (anti-GAD65, anti-IA-2 and anti-TPO antibody titers) and genetic features (predisposing gene variants previously identified as risk factors for autoimmune diabetes) retrieved from clinical records of 238 LADA patients referred to the Internal Medicine Unit of University of Sassari, Italy, were analyzed by PC analysis. The predictive value of each PC on the further development of insulin dependence was evaluated using Kaplan-Meier curves. Overall 4 clusters were identified by PC analysis. In component PC-1, the dominant variables were: BMI, triglycerides, systolic and diastolic blood pressure and duration of insulin-free time period; in PC-2: genetic variables such as Class II HLA, CTLA-4 as well as anti-GAD65, anti-IA-2 and anti-TPO antibody titers, and the insulin-free time period predominated; in PC-3: gender and triglycerides; and in PC-4: total cholesterol. These components explained 18, 15, 12, and 12 %, respectively, of the total variance in the LADA cohort. The predictive power of insulin dependence of the four components was different. PC-2 (characterized mostly by high antibody titers and presence of predisposing genetic markers) showed a faster beta-cells failure and PC-3 (characterized mostly by gender and high triglycerides) and PC-4 (high cholesterol) showed a slower beta-cells failure. PC-1 (including dislipidemia and other metabolic dysfunctions), showed a mild beta-cells failure. In conclusion variable clustering might be consistent with different pathogenic pathways and/or distinct immune mechanisms in LADA and could potentially help physicians improve the clinical management of these patients.

Purified Timothy grass pollen major allergen Phl p 1 may contribute to the modulation of allergic responses through a pleiotropic induction of cytokines and chemokines from airway epithelial cells.

PubMed

Röschmann, K I L; van Kuijen, A-M; Luiten, S; Jonker, M J; Breit, T M; Fokkens, W J; Petersen, A; van Drunen, C M

2012-03-01

By definition, allergens are proteins with the ability to elicit powerful T helper lymphocyte type 2 (Th2) responses, culminating in immunoglobulin (Ig)E antibody production. Why specific proteins cause aberrant immune responses has remained largely unanswered. Recent data suggest that there may be several molecular paths that may affect allergenicity of proteins. The focus of this study is the response of airway epithelium to a major allergen from Phleum pratense Phl p 1. Instead of focusing on a few genes and proteins that might be affected by the major allergen, our aim was to obtain a broader view on the immune stimulatory capacity of Phl p 1. We therefore performed detailed analysis on mRNA and protein level by using a microarray approach to define Phl p 1-induced gene expression. We found that this allergen induces modulation and release of a broad range of mediators, indicating it to be a powerful trigger of the immune system. We were able to show that genes belonging to the GO cluster 'cell communication' were among the most prominent functional groups, which is also reflected in cytokines and chemokines building centres in a computational model of direct gene interaction. Further detailed comparison of grass pollen extract (GPE)- and Phl p 1-induced gene expression might be beneficial with regard to the application of single components within diagnosis and immunotherapy. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

Maternal weight and excessive weight gain during pregnancy modify the immunomodulatory potential of breast milk.

PubMed

Collado, Maria Carmen; Laitinen, Kirsi; Salminen, Seppo; Isolauri, Erika

2012-07-01

Breast milk is an optimal source of nutrition for infants. It contains bioactive components including bacteria that support the microbial colonization and immune system development of the infant. The determinants of human milk composition remain poorly understood, although maternal nutritional and immunological status as well as lifestyle and dietary habits seem to have an impact. The subjects selected were women from a prospective follow-up study categorized by BMI. Milk samples were taken after delivery and at 1 and 6 mo later for analysis of composition in regard to transforming growth factor (TGF)-β2, soluble CD14 (sCD14), cytokines, and microbiota. TGF-β2 and sCD14 levels in the breast milk of overweight mothers tended to be lower than the levels in that of normal-weight mothers. Also, higher levels of Staphylococcus group bacteria and lower levels of Bifidobacterium group bacteria were detected in overweight mothers as compared with normal-weight ones. The prevalence of Akkermansia muciniphila-type bacteria was also higher in overweight mothers, and the numbers of these bacteria were related to the interleukin (IL)-6 concentration in the colostrum, which was in turn related to lower counts of Bifidobacterium group bacteria in the breast milk of overweight women. Complex interactions of cytokines and microbiota in breast milk guide the microbiological, immunological, and metabolic programming of infant health. Our data may indicate the presence of an additional mechanism that may explain the heightened risk of obesity for infants of overweight and excessive weight gain mothers.

Tenure Eligible/Tenure Track Investigator | Center for Cancer Research

Cancer.gov

The HIV and AIDS Malignancy Branch (HAMB), Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), is a national leader in research in the cancers associated with HIV/AIDS, in the development of therapies for HIV infection, and in oncogenic viruses.  We are seeking a tenure-eligible or tenure-track investigator in the field of HIV–related malignancies or viral oncogenesis.  It is anticipated that the investigator will establish an independent translational research program targeted to the study of the treatment, pathogenesis, and/or prevention of viral-induced or other HIV-associated tumors. The program can be primarily clinical, laboratory-based, or a combination of the two, and can also include animal model studies.  There is the potential to interface with a strong existing clinical research program. Potential areas of focus may include, but are not limited to, therapies for HIV malignancies, including novel immunologic approaches; viral oncogenesis; pathogenesis of HIV-associated malignancies; and virus host interactions, including immunologic interactions. 

Space Flight Immunodeficiency

NASA Technical Reports Server (NTRS)

Shearer, William T.

1999-01-01

The National Aeronautics and Space Administration (NASA) has had sufficient concern for the well-being of astronauts traveling in space to create the National Space Biomedical Research Institute (NSBRI), which is investigating several areas of biomedical research including those of immunology. As part of the Immunology, Infection, and Hematology Team, the co-investigators of the Space Flight Immunodeficiency Project began their research projects on April 1, 1998 and are now just into the second year of work. Two areas of research have been targeted: 1) specific immune (especially antibody) responses and 2) non-specific inflammation and adhesion. More precise knowledge of these two areas of research will help elucidate the potential harmful effects of space travel on the immune system, possibly sufficient to create a secondary state of immunodeficiency in astronauts. The results of these experiments are likely to lead to the delineation of functional alterations in antigen presentation, specific immune memory, cytokine regulation of immune responses, cell to cell interactions, and cell to endothelium interactions.

PEGylated graphene oxide elicits strong immunological responses despite surface passivation

NASA Astrophysics Data System (ADS)

Luo, Nana; Weber, Jeffrey K.; Wang, Shuang; Luan, Binquan; Yue, Hua; Xi, Xiaobo; Du, Jing; Yang, Zaixing; Wei, Wei; Zhou, Ruhong; Ma, Guanghui

2017-02-01

Engineered nanomaterials promise to transform medicine at the bio-nano interface. However, it is important to elucidate how synthetic nanomaterials interact with critical biological systems before such products can be safely utilized in humans. Past evidence suggests that polyethylene glycol-functionalized (PEGylated) nanomaterials are largely biocompatible and elicit less dramatic immune responses than their pristine counterparts. We here report results that contradict these findings. We find that PEGylated graphene oxide nanosheets (nGO-PEGs) stimulate potent cytokine responses in peritoneal macrophages, despite not being internalized. Atomistic molecular dynamics simulations support a mechanism by which nGO-PEGs preferentially adsorb onto and/or partially insert into cell membranes, thereby amplifying interactions with stimulatory surface receptors. Further experiments demonstrate that nGO-PEG indeed provokes cytokine secretion by enhancing integrin β8-related signalling pathways. The present results inform that surface passivation does not always prevent immunological reactions to 2D nanomaterials but also suggest applications for PEGylated nanomaterials wherein immune stimulation is desired.

Intercorrelation between Immunological Biomarkers and Job Stress Indicators among Female Nurses: A 9-Month Longitudinal Study

PubMed Central

Yoon, Hyung-Suk; Lee, Kyoung-Mu; Kang, Daehee

2014-01-01

Some immunological biomarkers have been reported to be associated with job-related stress. This study was conducted to explore the intercorrelation between the psychosocial components of job stress and various immunological biomarkers among female nurses. To assess monthly and weekly job stress, 41 nurses have repeatedly completed questionnaires such as the National Institute for Occupational Safety and Health General Job Stress Questionnaire, the profile of mood states short version and the Center for Epidemiologic Studies-Depression scale. Using flow cytometry and radioimmunoassay, the number of white blood cells, lymphocytic proliferation to mitogens, and toxoid were measured. Moreover, levels of hydrocortisol, interleukin-β, interferon-γ, and tumor necrosis factor-α and salivary immunoglobulin A were evaluated by enzyme-linked immunosorbent assay. When the Pearson correlation coefficients between job stress and immunological biomarkers were estimated after adjusting for age and smoking status, “Clashes: conflict at work” was significantly related to the number of CD4 cells (r = 0.36, p-value <0.05), CD4 to CD8 ratio (0.35; <0.05), response to concanavalin A (0.42; <0.05), and phytohemagglutinin (0.35; <0.05). Additionally, the level of hydrocortisol was significantly related to seven psychosocial measures; i.e., role conflict (−0.47; <0.01), role ambiguity (−0.39; <0.05), clashes at work (−0.38; <0.05), control and influence at work (0.53; <0.01), task control (0.55; <0.001), resources at work (0.35; <0.05), and skill underutilization (0.43; <0.05). The results indicate that (1) the psychosocial job stress is associated with the levels of some immunological biomarkers in nurses; and in particular, (2) hydrocortisol shows a remarkable relationship with diverse job stress indicators. PMID:25353011

Intercorrelation between Immunological Biomarkers and Job Stress Indicators among Female Nurses: A 9-Month Longitudinal Study.

PubMed

Yoon, Hyung-Suk; Lee, Kyoung-Mu; Kang, Daehee

2014-01-01

Some immunological biomarkers have been reported to be associated with job-related stress. This study was conducted to explore the intercorrelation between the psychosocial components of job stress and various immunological biomarkers among female nurses. To assess monthly and weekly job stress, 41 nurses have repeatedly completed questionnaires such as the National Institute for Occupational Safety and Health General Job Stress Questionnaire, the profile of mood states short version and the Center for Epidemiologic Studies-Depression scale. Using flow cytometry and radioimmunoassay, the number of white blood cells, lymphocytic proliferation to mitogens, and toxoid were measured. Moreover, levels of hydrocortisol, interleukin-β, interferon-γ, and tumor necrosis factor-α and salivary immunoglobulin A were evaluated by enzyme-linked immunosorbent assay. When the Pearson correlation coefficients between job stress and immunological biomarkers were estimated after adjusting for age and smoking status, "Clashes: conflict at work" was significantly related to the number of CD4 cells (r = 0.36, p-value <0.05), CD4 to CD8 ratio (0.35; <0.05), response to concanavalin A (0.42; <0.05), and phytohemagglutinin (0.35; <0.05). Additionally, the level of hydrocortisol was significantly related to seven psychosocial measures; i.e., role conflict (-0.47; <0.01), role ambiguity (-0.39; <0.05), clashes at work (-0.38; <0.05), control and influence at work (0.53; <0.01), task control (0.55; <0.001), resources at work (0.35; <0.05), and skill underutilization (0.43; <0.05). The results indicate that (1) the psychosocial job stress is associated with the levels of some immunological biomarkers in nurses; and in particular, (2) hydrocortisol shows a remarkable relationship with diverse job stress indicators.

CD28-CD80 interactions control regulatory T cell motility and immunological synapse formation1,2

PubMed Central

Thauland, Timothy J.; Koguchi, Yoshinobu; Dustin, Michael L.; Parker, David C.

2014-01-01

Regulatory T cells (Tregs) are essential for tolerance to self and environmental antigens, acting in part by downmodulating costimulatory molecules on the surface of dendritic cells (DCs) and altering naïve CD4 T cell-DC interactions. Here, we show that Tregs form stable conjugates with DCs before, but not after, they decrease surface expression of the costimulatory molecule CD80 on the DCs. We use supported planar bilayers to show that Tregs dramatically slow down, but maintain a highly polarized and motile phenotype after recognizing antigen in the absence of costimulation. These motile cells are characterized by distinct accumulations of LFA-1-ICAM-1 in the lamella and TCR-MHC in the uropod, consistent with a motile immunological synapse or ‘kinapse’. However, in the presence of high, but not low, concentrations of CD80, Tregs form stationary, symmetrical synapses. Using blocking antibodies, we show that, while CTLA-4 is required for CD80 downmodulation, CD28-CD80 interactions are critical for modulating Treg motility in the presence of antigen. Together, these results support the hypothesis that Tregs are tuned to alter their motility depending on costimulatory signals. PMID:25355918

[Hematological and immunological parameters during Ebola virus passages in guinea-pigs].

PubMed

Dadaeva, A A; Sizikova, L P; Subbotina, E L; Chepurnov, A A

2006-01-01

The trend in hematological and immunological parameters during Ebola virus passages in guinea-pigs indicated that pathophysiological changes occurred just during the second passage and further became stronger. The increase of some parameters and their correlation with the occurrence of fatal outcomes allowed the authors to reveal the most significant changes as increased juvenile platelets, whole blood virus appearance, higher echinocytes, a rise in the pro mil of blast cells and megakaryocytes in the bone marrow, and decreased neutrophilic phagocytic activity. Viral acquisition of the properties of lethality to guinea-pigs depends on the fine mechanisms responsible for viral interaction with host cells, which may lead to viral genetic changes during passages.

Sarcoid-like lesions in Paracoccidioidomycosis: immunological factors*

PubMed Central

de Medeiros, Vanessa Lucília Silveira; Arruda, Lúcia

2013-01-01

The clinical presentation of paracoccidioidomycosis is spectral. Spontaneous cure, state of latency or active disease with different levels of severity can occur after the hematogenous dissemination. The morphology and number of skin lesions will depend on the interaction of host immunity, which is specific and individual, and fungus virulence. Some individuals have natural good immunity, which added to the low virulence of the fungus maintain the presence of well-marked granulomas with no microorganism and negative serology for a long time, making the diagnosis a challenge. Factors inherent to the fungus, however, may modulate the immune response and modify the clinical picture over the time. We present a sarcoidosis-like clinical presentation and discuss the immunological factors involved. PMID:23539015

'The Right Time and the Right Place': An Interview with Jacques Miller.

PubMed

Anderson, Warwick

2016-01-01

Professor Jacques F.P. Miller spoke about his career in immunology with Warwick Anderson on 3 February 2014. Born in Nice, France, Miller attended high school and medical school in Sydney, Australia. As a Ph.D. student and postgraduate researcher in London, Miller discovered the immunological function of the thymus gland. Spending the rest of his career at the Walter and Eliza Hall Institute for Medical Research in Melbourne, Miller conducted pioneering research in lymphocyte population dynamics and the mechanisms of the human immune response. With Graham Mitchell, he demonstrated that mammalian lymphocytes can be divided into what became known as T cells and B cells, which interact to produce antibodies.

Potential directions for chicken immunology research.

PubMed

Stewart, Cameron R; Keyburn, Anthony L; Deffrasnes, Celine; Tompkins, S Mark

2013-11-01

The importance of poultry, particularly chicken, as a food source continues to increase globally. Moreover, zoonotic infectious diseases such as avian influenza virus not only continue to impact poultry production, but also pose an increasing threat to public health. This review discusses the importance of poultry in both agricultural and public health arenas. Recent developments in avian immunology are described, with an emphasis on host-pathogen interactions and noting differences from mammalian systems. Next generation technologies including functional genomics and targeted gene disruption (e.g. zinc finger nucleases and meganucleases) are discussed as new approaches for not only understanding immune responses in poultry, but also as novel disease intervention strategies. Copyright © 2013. Published by Elsevier Ltd.

Periodontology: past, present, perspectives.

PubMed

Slots, Jørgen

2013-06-01

Periodontitis is an infectious disease that affects the tooth-supporting tissues and exhibits a wide range of clinical, microbiological and immunological manifestations. The disease is associated with and is probably caused by a multifaceted dynamic interaction of specific infectious agents, host immune responses, harmful environmental exposure and genetic susceptibility factors. This volume of Periodontology 2000 covers key subdisciplines of periodontology, ranging from etiopathogeny to therapy, with emphasis on diagnosis, classification, epidemiology, risk factors, microbiology, immunology, systemic complications, anti-infective therapy, reparative treatment, self-care and affordability issues. Learned and unlearned concepts of periodontitis over the past 50 years have shaped our current understanding of the etiology of the disease and of clinical practice. © 2013 John Wiley & Sons A/S.

Phagocytosis: history's lessons.

PubMed

Garg, Manish; Chandawarkar, Rajiv Y

2013-01-01

The assimilation of lessons from the past is an essential component of education for scientists of tomorrow. These lessons are not easy to find. History books on science are few and usually highly dramatized and biographies of scientists tend to exaggerate the pomp of scientific discovery. Both underplay the hard and laborious work that is integral to any scientific pursuit. Here we illustrate one such example. A century ago, the Nobel Prize in Medicine was awarded to two scientists: Ilya Metchnikoff, a Russian zoologist, for the discovery ofphagocytosis-a cell-mediated ingestion ofmicrobes; and Paul Ehrlich, a distinguished physician-scientist, for discovering a highly antigen-specific serum-derived antibody-based immune defense. These two diametrically opposing views of the host-pathogen interaction set the stage for a strife that led to seminal advancements in immunology. Mirrored in this journey are important lessons for scientists today--ubiquitously as applicable to modern scientific life as they were a century ago. This commentaryhighlights these lessons--a fitting centenary to a well-deserved recognition.

Inborn Errors of Human JAKs and STATs

PubMed Central

Casanova, Jean-Laurent; Holland, Steven M.; Notarangelo, Luigi D.

2012-01-01

Inborn errors of the genes encoding two of the four human JAKs (JAK3 and TYK2) and three of the six human STATs (STAT1, STAT3, and STAT5B) have been described. We review the disorders arising from mutations in these five genes, highlighting the way in which the molecular and cellular pathogenesis of these conditions has been clarified by the discovery of inborn errors of cytokines, hormones, and their receptors, including those interacting with JAKs and STATs. The phenotypic similarities between mice and humans lacking individual JAK-STAT components suggest that the functions of JAKs and STATs are largely conserved in mammals. However, a wide array of phenotypic differences has emerged between mice and humans carrying bi-allelic null alleles of JAK3, TYK2, STAT1, or STAT5B. Moreover, the high level of allelic heterogeneity at the human JAK3, STAT1, and STAT3 loci has revealed highly diverse immunological and clinical phenotypes, which had not been anticipated. PMID:22520845

Inborn errors of human JAKs and STATs.

PubMed

Casanova, Jean-Laurent; Holland, Steven M; Notarangelo, Luigi D

2012-04-20

Inborn errors of the genes encoding two of the four human JAKs (JAK3 and TYK2) and three of the six human STATs (STAT1, STAT3, and STAT5B) have been described. We review the disorders arising from mutations in these five genes, highlighting the way in which the molecular and cellular pathogenesis of these conditions has been clarified by the discovery of inborn errors of cytokines, hormones, and their receptors, including those interacting with JAKs and STATs. The phenotypic similarities between mice and humans lacking individual JAK-STAT components suggest that the functions of JAKs and STATs are largely conserved in mammals. However, a wide array of phenotypic differences has emerged between mice and humans carrying biallelic null alleles of JAK3, TYK2, STAT1, or STAT5B. Moreover, the high degree of allelic heterogeneity at the human JAK3, TYK2, STAT1, and STAT3 loci has revealed highly diverse immunological and clinical phenotypes, which had not been anticipated. Copyright © 2012 Elsevier Inc. All rights reserved.

Cross-Reactivity of Polyclonal Antibodies against Canavalia ensiformis (Jack Bean) Urease and Helicobacter pylori Urease Subunit A Fragments.

PubMed

Kaminski, Zbigniew Jerzy; Relich, Inga; Konieczna, Iwona; Kaca, Wieslaw; Kolesinska, Beata

2018-01-01

Overlapping decapeptide fragments of H. pylori urease subunit A (UreA) were synthesized and tested with polyclonal antibodies against Canavalia ensiformis (Jack bean) urease. The linear epitopes of UreA identified using the dot blot method were then examined using epitope mapping. For this purpose, series of overlapping fragments of UreA, frameshifted ± four amino acid residues were synthesized. Most of the UreA epitopes which reacted with the Jack bean urease polyclonal antibodies had been recognized in previous studies by monoclonal antibodies against H. pylori urease. Fragments 11 - 24, 21 - 33, and 31 - 42 were able to interact with the Jack bean urease antibodies, giving stable immunological complexes. However, the lack of recognition by these antibodies of all the components in the peptide map strongly suggests that a non-continuous (nonlinear) epitope is located on the N-terminal domain of UreA. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Immunological Tolerance, Pregnancy, and Preeclampsia: The Roles of Semen Microbes and the Father†

PubMed Central

Kenny, Louise C.; Kell, Douglas B.

2018-01-01

Although it is widely considered, in many cases, to involve two separable stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of preeclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its etiology. However, apart from recognizing, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focused on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focusing on the immunological tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the father’s semen assists this immunological tolerance. As well as these benefits, however, semen is not sterile, microbial tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus (and maybe the placenta) with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of PE. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination. PMID:29354635

Introduction of a Framework for Dynamic Knowledge Representation of the Control Structure of Transplant Immunology: Employing the Power of Abstraction with a Solid Organ Transplant Agent-Based Model

PubMed Central

An, Gary

2015-01-01

Agent-based modeling has been used to characterize the nested control loops and non-linear dynamics associated with inflammatory and immune responses, particularly as a means of visualizing putative mechanistic hypotheses. This process is termed dynamic knowledge representation and serves a critical role in facilitating the ability to test and potentially falsify hypotheses in the current data- and hypothesis-rich biomedical research environment. Importantly, dynamic computational modeling aids in identifying useful abstractions, a fundamental scientific principle that pervades the physical sciences. Recognizing the critical scientific role of abstraction provides an intellectual and methodological counterweight to the tendency in biology to emphasize comprehensive description as the primary manifestation of biological knowledge. Transplant immunology represents yet another example of the challenge of identifying sufficient understanding of the inflammatory/immune response in order to develop and refine clinically effective interventions. Advances in immunosuppressive therapies have greatly improved solid organ transplant (SOT) outcomes, most notably by reducing and treating acute rejection. The end goal of these transplant immune strategies is to facilitate effective control of the balance between regulatory T cells and the effector/cytotoxic T-cell populations in order to generate, and ideally maintain, a tolerant phenotype. Characterizing the dynamics of immune cell populations and the interactive feedback loops that lead to graft rejection or tolerance is extremely challenging, but is necessary if rational modulation to induce transplant tolerance is to be accomplished. Herein is presented the solid organ agent-based model (SOTABM) as an initial example of an agent-based model (ABM) that abstractly reproduces the cellular and molecular components of the immune response to SOT. Despite its abstract nature, the SOTABM is able to qualitatively reproduce acute rejection and the suppression of acute rejection by immunosuppression to generate transplant tolerance. The SOTABM is intended as an initial example of how ABMs can be used to dynamically represent mechanistic knowledge concerning transplant immunology in a scalable and expandable form and can thus potentially serve as useful adjuncts to the investigation and development of control strategies to induce transplant tolerance. PMID:26594211

Introduction of a Framework for Dynamic Knowledge Representation of the Control Structure of Transplant Immunology: Employing the Power of Abstraction with a Solid Organ Transplant Agent-Based Model.

PubMed

An, Gary

2015-01-01

Agent-based modeling has been used to characterize the nested control loops and non-linear dynamics associated with inflammatory and immune responses, particularly as a means of visualizing putative mechanistic hypotheses. This process is termed dynamic knowledge representation and serves a critical role in facilitating the ability to test and potentially falsify hypotheses in the current data- and hypothesis-rich biomedical research environment. Importantly, dynamic computational modeling aids in identifying useful abstractions, a fundamental scientific principle that pervades the physical sciences. Recognizing the critical scientific role of abstraction provides an intellectual and methodological counterweight to the tendency in biology to emphasize comprehensive description as the primary manifestation of biological knowledge. Transplant immunology represents yet another example of the challenge of identifying sufficient understanding of the inflammatory/immune response in order to develop and refine clinically effective interventions. Advances in immunosuppressive therapies have greatly improved solid organ transplant (SOT) outcomes, most notably by reducing and treating acute rejection. The end goal of these transplant immune strategies is to facilitate effective control of the balance between regulatory T cells and the effector/cytotoxic T-cell populations in order to generate, and ideally maintain, a tolerant phenotype. Characterizing the dynamics of immune cell populations and the interactive feedback loops that lead to graft rejection or tolerance is extremely challenging, but is necessary if rational modulation to induce transplant tolerance is to be accomplished. Herein is presented the solid organ agent-based model (SOTABM) as an initial example of an agent-based model (ABM) that abstractly reproduces the cellular and molecular components of the immune response to SOT. Despite its abstract nature, the SOTABM is able to qualitatively reproduce acute rejection and the suppression of acute rejection by immunosuppression to generate transplant tolerance. The SOTABM is intended as an initial example of how ABMs can be used to dynamically represent mechanistic knowledge concerning transplant immunology in a scalable and expandable form and can thus potentially serve as useful adjuncts to the investigation and development of control strategies to induce transplant tolerance.

Annual Research Report, 1 October 1977-30 September 1978.

DTIC Science & Technology

1978-09-30

and other lipid components. Collaboratihe studies with the National Cancer Institute and other medical centers include research on the immunological...copolymer, or glucan were administered intraperitoneally within 2 hours after sublethal X irradiation (600 rads), the adjuvant- induced cytotoxic...concentrations of inducer. When BCG, pyran, or glucan was administered intraperitoneally concurrently with subcutaneous cyclophosphamide, only the ability

Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the be...

Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects

PubMed Central

Prokopyuk, Volodymyr; Pogozhykh, Denys

2018-01-01

Placental structures, capable to persist in a genetically foreign organism, are a natural model of allogeneic engraftment carrying a number of distinctive properties. In this review, the main features of the placenta and its derivatives such as structure, cellular composition, immunological and endocrine aspects, and the ability to invasion and deportation are discussed. These features are considered from a perspective that determines the placental material as a unique source for regenerative cell therapies and a lesson for immunological tolerance. A historical overview of clinical applications of placental extracts, cells, and tissue components is described. Empirically accumulated data are summarized and compared with modern research. Furthermore, we define scopes and outlooks of application of placental cells and tissues in the rapidly progressing field of regenerative medicine. PMID:29535770

Slp1 and Slp2-a Localize to the Plasma Membrane of CTL and Contribute to Secretion from the Immunological Synapse

PubMed Central

Holt, Oliver; Kanno, Eiko; Bossi, Giovanna; Booth, Sarah; Daniele, Tiziana; Santoro, Alessandra; Arico, Maurizio; Saegusa, Chika; Fukuda, Mitsunori; Griffiths, Gillian M

2008-01-01

Rab27a is required for polarized secretion of lysosomes from cytotoxic T lymphocytes (CTLs) at the immunological synapse. A series of Rab27a-interacting proteins have been identified; however, only Munc13-4 has been found to be expressed in CTL. In this study, we screened for expression of the synaptotagmin-like proteins (Slps): Slp1/JFC1, Slp2-a/exophilin4, Slp3-a, Slp4/granuphilin, Slp5 and rabphilin in CTL. We found that both Slp1 and Slp2-a are expressed in CTL. Isoforms of Slp2-a in CTL showed variation of the linker region but conserved the C2A and C2B and Slp homology (SHD) domains. Both Slp1 and Slp2-a interact with Rab27a in CTL, and Slp2-a, but not Slp1, is rapidly degraded when Rab27a is absent. Slp2-a contains PEST-like sequences within its linker region, which render it susceptible to degradation. Both Slp1 and Slp2-a localize predominantly to the plasma membrane of both human and mouse CTLs, and we show that Slp2-a can focus tightly at the immunological synapse formed with a target cell. Individual knockouts of either Slp2-a or Slp1 fail to impair CTL-mediated killing of targets; however, overexpression of a dominant-negative construct consisting of the SHD of Slp2-a, which is 56% identical to that of Slp1, reduces target cell death, suggesting that both Slp1 and Slp2-a contribute to secretory lysosome exocytosis from CTL. These results suggest that both Slp1 and Slp2-a may form part of a docking complex, capturing secretory lysosomes at the immunological synapse. PMID:18266782

Immunity and Nutrition.

ERIC Educational Resources Information Center

Dupin, Henri; Guerin, Nicole

1990-01-01

The three articles in this issue of a periodical focussed on various aspects of the life and health of children in the tropics concern: (1) immune defenses; (2) interactions between nutrition disorders and infection; and (3) immunity and vaccination. The science of immunology has progressed rapidly in recent years. A brief review of present…

Droplet digital PCR quantifies host inflammatory transcripts in feces reliably and reproducibly

USDA-ARS?s Scientific Manuscript database

The gut is the most extensive, interactive, and complex interface between the human host and the environment and therefore a critical site of immunological activity. Non-invasive methods to assess the host response in this organ are currently lacking. Feces are the available analyte which have been ...

Helogmosomoides polygyrus infection can inhibit colitis through direct interaction with innate immunity

USDA-ARS?s Scientific Manuscript database

Less developed countries have a low incidence of immunological diseases like inflammatory bowel disease (IBD), perhaps prevented by the high prevalence of helminth infections in their populations. In the Rag IL10-/- T cell transfer model of colitis, Heligmosomoides polygyrus (Hp), an intestinal hel...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5210 Ceruloplasmin immunolog-ical test system. (a) Identification. A ceruloplasmin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210...

Allergic colitis in infants related to cow's milk: clinical characteristics, pathologic changes, and immunologic findings.

PubMed

Yu, Man-Chun; Tsai, Chia-Lun; Yang, Yao-Jong; Yang, Sing-San; Wang, Li-Hui; Lee, Chung-Ta; Jan, Ren-Long; Wang, Jiu-Yao

2013-02-01

Allergic colitis (AC) is an inflammatory condition characterized by eosinophils infiltrating the colonic wall. It can be a benign and/or severe illness among gastrointestinal diseases in infants. We report five infants who, since January 2009, in whom AC under fibrotic endoscopic examinations has been diagnosed. The criterion for histopathologic diagnosis of AC in this study was five or more eosinophils per high-power field. Patients' clinical symptoms, pathologic findings, and immunologic studies, such as specific antibodies against component of cow's milk protein, were compared with those of allergic children without AC and those of nonatopic control children. Histopathologic examinations of biopsy specimens revealed acute inflammation with characteristic eosinophilic infiltration of lamina propria (5-15 eosinophils per high-power field) in all five patients. They all had strongly positive skin prick tests against milk protein, which were not correlated with in vitro allergen-specific immunoglobulin (Ig) E levels. In contrast, there were significantly higher levels of IgE antibodies, and lower specific IgG4 and IgA levels to components and whole milk proteins in AC, as compared to control children without AC. Endoscopic biopsy specimens of intestine confirm the diagnosis of AC. However, allergen skin prick test and IgE antibody to milk protein components also provide helpful diagnostic tools for this rare disease in children. Copyright © 2012. Published by Elsevier B.V.

21 CFR 866.5160 - Beta-globulin immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5160 Beta-globulin immunolog-ical test system. (a) Identification. A beta-globulin immunological test system is a... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-globulin immunolog-ical test system. 866.5160...

Immunological Approaches to Biomass Characterization and Utilization

PubMed Central

Pattathil, Sivakumar; Avci, Utku; Zhang, Tiantian; Cardenas, Claudia L.; Hahn, Michael G.

2015-01-01

Plant biomass is the major renewable feedstock resource for sustainable generation of alternative transportation fuels to replace fossil carbon-derived fuels. Lignocellulosic cell walls are the principal component of plant biomass. Hence, a detailed understanding of plant cell wall structure and biosynthesis is an important aspect of bioenergy research. Cell walls are dynamic in their composition and structure, varying considerably among different organs, cells, and developmental stages of plants. Hence, tools are needed that are highly efficient and broadly applicable at various levels of plant biomass-based bioenergy research. The use of plant cell wall glycan-directed probes has seen increasing use over the past decade as an excellent approach for the detailed characterization of cell walls. Large collections of such probes directed against most major cell wall glycans are currently available worldwide. The largest and most diverse set of such probes consists of cell wall glycan-directed monoclonal antibodies (McAbs). These McAbs can be used as immunological probes to comprehensively monitor the overall presence, extractability, and distribution patterns among cell types of most major cell wall glycan epitopes using two mutually complementary immunological approaches, glycome profiling (an in vitro platform) and immunolocalization (an in situ platform). Significant progress has been made recently in the overall understanding of plant biomass structure, composition, and modifications with the application of these immunological approaches. This review focuses on such advances made in plant biomass analyses across diverse areas of bioenergy research. PMID:26579515

Effects of Hemagglutination Activity in the Serum of a Deep-Sea Vent Endemic Crab, Shinkaia Crosnieri, on Non-Symbiotic and Symbiotic Bacteria

PubMed Central

Fujiyoshi, So; Tateno, Hiroaki; Watsuji, Tomoo; Yamaguchi, Hideyuki; Fukushima, Daisuke; Mino, Sayaka; Sugimura, Makoto; Sawabe, Tomoo; Takai, Ken; Sawayama, Shigeki; Nakagawa, Satoshi

2015-01-01

In deep-sea hydrothermal environments, most invertebrates associate with dense populations of symbiotic microorganisms in order to obtain nutrition. The molecular interactions between deep-sea animals and environmental microbes, including their symbionts, have not yet been elucidated in detail. Hemagglutinins/lectins, which are carbohydrate-binding proteins, have recently been reported to play important roles in a wide array of biological processes, including the recognition and control of non-self materials. We herein assessed hemagglutination activity in the serum of a deep-sea vent endemic crab, Shinkaia crosnieri, which harbors chemosynthetic epibionts on its plumose setae. Horse and rabbit erythrocytes were agglutinated using this serum (opt. pH 7.5 and opt. temperature 15°C). Agglutinating activity was inhibited by eight kinds of sugars and several divalent cations, did not require any divalent metal ions, and remained detectable even after heating the serum at 100°C for 30 min. By using fluorescently labeled serum, we demonstrated that deep-sea crab serum components bound to the epibionts even in the presence of sugars. This study represents the first immunological assessment of a deep-sea vent endemic crab and demonstrated the possibility of a non-lectin-mediated symbiont-host interaction. PMID:26212518

Single-molecule analysis of the major glycopolymers of pathogenic and non-pathogenic yeast cells

NASA Astrophysics Data System (ADS)

El-Kirat-Chatel, Sofiane; Beaussart, Audrey; Alsteens, David; Sarazin, Aurore; Jouault, Thierry; Dufrêne, Yves F.

2013-05-01

Most microbes are coated with carbohydrates that show remarkable structural variability and play a crucial role in mediating microbial-host interactions. Understanding the functions of cell wall glycoconjugates requires detailed knowledge of their molecular organization, diversity and heterogeneity. Here we use atomic force microscopy (AFM) with tips bearing specific probes (lectins, antibodies) to analyze the major glycopolymers of pathogenic and non-pathogenic yeast cells at molecular resolution. We show that non-ubiquitous β-1,2-mannans are largely exposed on the surface of native cells from pathogenic Candida albicans and C. glabrata, the former species displaying the highest glycopolymer density and extensions. We also find that chitin, a major component of the inner layer of the yeast cell wall, is much more abundant in C. albicans. These differences in molecular properties, further supported by flow cytometry measurements, may play an important role in strengthening cell wall mechanics and immune interactions. This study demonstrates that single-molecule AFM, combined with immunological and fluorescence methods, is a powerful platform in fungal glycobiology for probing the density, distribution and extension of specific cell wall glycoconjugates. In nanomedicine, we anticipate that this new form of AFM-based nanoglycobiology will contribute to the development of sugar-based drugs, immunotherapeutics, vaccines and diagnostics.

Biomolecular aspects of depression: A retrospective analysis.

PubMed

Peacock, Brandon N; Scheiderer, David J; Kellermann, Gottfried H

2017-02-01

The effects of psychological stress, oxidative stress, and chronic low grade inflammation on the neuro-immune connection have been implicated in the pathogenesis of depression. Thus, in the recent past, there has been a growing effort in determining the mechanism of this pathogenesis. While attempting to map out, this mechanism researchers and clinicians have searched for clinically relevant biomarkers for use in the diagnosis and for the assessment of those suffering from depression. In this study, we have performed a retrospective analysis of biomarkers with clinically relevant potentials, including peripheral catecholamines, chemokines, cytokines, and neurotransmitters. The retrospective analysis was performed on data collected over a six-year period of time (July 2009 to July 2015), gathered from patients (N=1399; Mage=42, SD=13; 71% female, 29% male) who submitted samples with complaints of feeling hopeless, worthless, isolated, alone, general sadness, overwhelmed, and/or a lack of interest in things they once enjoyed. The data collected consisted of quantitative values of urinary catecholamines and neurotransmitters (peripheral dopamine, epinephrine, histamine, kynurenic acid, norepinephrine, β-PEA, and serotonin), salivary hormones (peripheral cortisol and melatonin), and peripheral blood mononuclear cell secreted cytokines and chemokines (Interleukins 1β, 6, 8, 10, MCP-1, GCSF, and TNFα). Statistical and clinical significance was assessed by comparison with a control group (N=2395; Mage=42, SD=13; 70% female, 30% male), calculating the percent mean difference, p value, and effect size (Cohen's ɗ) for each parameter between groups. The findings of this study suggested that, in a model of general depression, there is a dysregulation in the enzymatic production and degradation of catecholamines, neurotransmitters, hormones, and immunological proteins. A cycle of interaction was found between all of these biomolecules, where an increase or decrease in one marker could result in a stimulatory or inhibitory effect on others. The mechanism of this was proposed to occur through the interaction of psychological stress, inflammation, and oxidative stress pathways. All of these biomolecules were found to be significantly altered in the general depression group and are key components of the interaction between the neurological and immunological systems. This study serves to further elucidate the role of biomolecules in the regulation of affective disorders, such as depression. Resulting in providing a network of clinically relevant biomarkers to objectively assess and monitor general depression. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

An immunological approach to quantifying the saprotrophic growth dynamics of Trichoderma species during antagonistic interactions with Rhizoctonia solani in a soil-less mix.

PubMed

Thornton, Christopher R

2004-04-01

Studies of the saprotrophic growth dynamics of Trichoderma species and their fungal hosts during antagonistic interactions are severely hampered by the absence of methods that allow the unambiguous identification and quantification of individual genera in complex environments such as soil or compost containing mixed populations of fungi. Furthermore, methods are required that allow discrimination between active hyphal growth and other components of fungal biomass such as quiescent spores that are produced in large numbers by Trichoderma species. This study details the use of monoclonal antibodies to quantify the saprotrophic growth dynamics of the soil-borne plant pathogen Rhizoctonia solani and biological control strains of Trichoderma asperellum and Trichoderma harzianum during antagonistic interactions in peat-based microcosms. Quantification was based on the immunological detection of constitutive, extracellular antigens that are secreted from the growing tip of Rhizoctonia and Trichoderma mycelium and, in the case of Trichoderma harzianum, from quiescent phialoconidia also. The Trichoderma-specific monoclonal antibody (MF2) binds to a protein epitope of the enzyme glucoamylase, which was shown by immunofluorescence and immunogold electron gold microscopy studies of Trichoderma virens in vitro to be produced at the origin of germ tube emergence in phialoconidia and from the growing tip of germ tubes. In addition, a non-destructive immunoblotting technique showed that the enzyme was secreted during active growth of Trichoderma asperellum mycelium in peat. The Rhizoctonia solani-specific monoclonal antibody (EH2) similarly binds to a protein epitope of a glycoprotein that is secreted during active mycelial growth. Extracts derived from lyophilized mycelium were used as a quantifiable and repeatable source of antigens for construction of calibration curves. These curves were used to convert the absorbance values obtained in ELISA tests of peat extracts to biomass equivalents, which allowed comparisons of the saprotrophic growth dynamics of the pathogen and antagonists to be made in single or mixed species microcosms. Trichoderma species were able to compete successfully with R. solani for nutrients and to prevent saprotrophic growth of the pathogen. Specificity of the Trichoderma quantitative assay was tested in non-sterile soil-based microcosms artificially inoculated with T. asperellum. The assay was highly specific and only detected T. asperellum population dynamics. No cross-reactivity was found with extracts from soil samples containing contaminant fungi.

The regulations and role of circadian clock and melatonin in uterine receptivity and pregnancy-An immunological perspective.

PubMed

Man, Gene Chi Wai; Zhang, Tao; Chen, Xiaoyan; Wang, Jianzhang; Wu, Fangrong; Liu, Yingyu; Wang, Chi Chiu; Cheong, Ying; Li, Tin Chiu

2017-08-01

During normal pregnancy, the mechanism by which the fetus escapes immunological rejection by the maternal womb remains elusive. Given the biological complexities, the immunological mechanism is unlikely to be simply an allograft response in acceptance or rejection of the early pregnancy. Circadian clock responsible for the mammalian circadian rhythm is an endogenously generated rhythm associated with almost all physiological processes including reproduction. There is now growing evidence to suggest that the circadian clocks are intricately linked to the immune system and pregnancy. When perturbed, the role of immune cells can be affected on maintaining the enriched vascular system needed for placentation. This alteration can be triggered by the irregular production of maternal and placental melatonin. Hence, the role of circadian rhythm modulators such as melatonin offers intriguing opportunities for therapy. In this review, we evaluate the complex interaction between the circadian clock and melatonin within the immune system and their roles in the circadian regulation and maintenance of normal pregnancy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Ezrin tunes T-cell activation by controlling Dlg1 and microtubule positioning at the immunological synapse

PubMed Central

Lasserre, Rémi; Charrin, Stéphanie; Cuche, Céline; Danckaert, Anne; Thoulouze, Maria-Isabel; de Chaumont, Fabrice; Duong, Tarn; Perrault, Nathalie; Varin-Blank, Nadine; Olivo-Marin, Jean-Christophe; Etienne-Manneville, Sandrine; Arpin, Monique; Di Bartolo, Vincenzo; Alcover, Andrés

2010-01-01

T-cell receptor (TCR) signalling is triggered and tuned at immunological synapses by the generation of signalling complexes that associate into dynamic microclusters. Microcluster movement is necessary to tune TCR signalling, but the molecular mechanism involved remains poorly known. We show here that the membrane-microfilament linker ezrin has an important function in microcluster dynamics and in TCR signalling through its ability to set the microtubule network organization at the immunological synapse. Importantly, ezrin and microtubules are important to down-regulate signalling events leading to Erk1/2 activation. In addition, ezrin is required for appropriate NF-AT activation through p38 MAP kinase. Our data strongly support the notion that ezrin regulates immune synapse architecture and T-cell activation through its interaction with the scaffold protein Dlg1. These results uncover a crucial function for ezrin, Dlg1 and microtubules in the organization of the immune synapse and TCR signal down-regulation. Moreover, they underscore the importance of ezrin and Dlg1 in the regulation of NF-AT activation through p38. PMID:20551903

The Structural Immunology of Antibody Protection against West Nile Virus

PubMed Central

Diamond, Michael S.; Pierson, Theodore C.; Fremont, Daved H.

2009-01-01

Summary Recent investigations of the interaction between the West Nile virus (WNV) envelope protein (E) and monoclonal antibodies (mAbs) have elucidated fundamental insights into the molecular mechanisms of neutralization. Structural studies have defined an epitope on the lateral ridge of domain III (DIII-lr) of the WNV E protein that is recognized by antibodies with the strongest neutralizing activity in vitro and in vivo. Antibodies that bind this epitope are highly potent because they efficiently block at a post-entry step of viral infection with relatively low virion occupancy requirements. In this review, we will discuss the structural, molecular, and immunologic basis for antibody-mediated protection against WNV, and its implications for novel therapeutic or vaccine strategies. PMID:18837784

Effects of microgravity on the immune system

NASA Technical Reports Server (NTRS)

Sonnenfeld, Gerald; Taylor, Gerald R.

1991-01-01

Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

Is appendectomy a causative factor in ulcerative colitis?

PubMed

Russel, M G; Stockbrügger, R W

1998-06-01

There are strong indicators that the aetiology of inflammatory bowel disease should be regarded as multifactorial, involving an interaction between genetic and environmental factors which give rise to an inadequate immunological response. During the past decade at least seven case-control studies have shown an inverse association between appendectomy and ulcerative colitis. Conclusions have been that either ulcerative colitis protects against appendicitis, or appendectomy protects against ulcerative colitis. The immunological function of the appendix is not well known, but experimental studies suggest that the appendix is possibly an important site for priming of the cells involved in the development of inflammatory bowel disease. Experimental and prospective cohort studies are needed to provide more insight in a possible relation between ulcerative colitis and the appendix.

Advances in basic and clinical immunology in 2006.

PubMed

Chinen, Javier; Shearer, William T

2007-08-01

This article reviews the progress in the field of basic and clinical immunology in 2006, focusing on the articles published in the Journal. The role of Toll-like receptors in the immune response was explored in detail in several articles. The knowledge gained in these investigations is being used to develop strategies that enhance the immunogenicity of vaccines to prevent infectious diseases and to have an immunomodulatory effect on allergic diseases. Other components of the innate immunity reported on were the recognition of allergens with lipid-derived motifs by CD1d-restricted T cells and the role of dendritic cells in the development of an allergic response. More than 120 primary immunodeficiencies were defined at a molecular level, and biological agents such as TNF-alpha antagonists and IFN-alpha were shown to have therapeutic use. New anti-HIV drugs that block cell entry were proven to be effective, thus offering alternative therapies to respond to the development of multidrug-resistant HIV strains. The modern understanding of immunologic concepts is helping to elucidate the mechanisms of defense against viruses, bacteria, and parasites; as a result, strategies to improve management and prevention continue to emerge.

Integration of Immunity with Physical and Cognitive Function in Definitions of Successful Aging

PubMed Central

Griffin, Patricia; Michel, Joshua J.; Huysman, Kristy; Logar, Alison J.; Vallejo, Abbe N.

2012-01-01

Studies comparing chronologically “young” versus “old” humans document age-related decline of classical immunological functions. However, older adults aged ≥65 years have very heterogeneous health phenotypes. A significant number of them are functionally independent and are surviving well into their 8th–11th decade life, observations indicating that aging or old age is not synonymous with immune incompetence. While there are dramatic age-related changes in the immune system, not all of these changes may be considered detrimental. Here, we review evidences for novel immunologic processes that become elaborated with advancing age that complement preserved classical immune functions and promote immune homeostasis later in life. We propose that elaboration such of late life immunologic properties is indicative of beneficial immune remodeling that is an integral component of successful aging, an emerging physiologic construct associated with similar age-related physiologic adaptations underlying maintenance of physical and cognitive function. We suggest that a systems approach integrating immune, physical, and cognitive functions, rather than a strict immunodeficiency-minded approach, will be key towards innovations in clinical interventions to better promote protective immunity and functional independence among the elderly. PMID:22500270

Perspectives on Immunoglobulins in Colostrum and Milk

PubMed Central

Hurley, Walter L.; Theil, Peter K.

2011-01-01

Immunoglobulins form an important component of the immunological activity found in milk and colostrum. They are central to the immunological link that occurs when the mother transfers passive immunity to the offspring. The mechanism of transfer varies among mammalian species. Cattle provide a readily available immune rich colostrum and milk in large quantities, making those secretions important potential sources of immune products that may benefit humans. Immune milk is a term used to describe a range of products of the bovine mammary gland that have been tested against several human diseases. The use of colostrum or milk as a source of immunoglobulins, whether intended for the neonate of the species producing the secretion or for a different species, can be viewed in the context of the types of immunoglobulins in the secretion, the mechanisms by which the immunoglobulins are secreted, and the mechanisms by which the neonate or adult consuming the milk then gains immunological benefit. The stability of immunoglobulins as they undergo processing in the milk, or undergo digestion in the intestine, is an additional consideration for evaluating the value of milk immunoglobulins. This review summarizes the fundamental knowledge of immunoglobulins found in colostrum, milk, and immune milk. PMID:22254105

An immunologically relevant rodent model demonstrates safety of therapy using a tumour-specific IgE.

PubMed

Josephs, Debra H; Nakamura, Mano; Bax, Heather J; Dodev, Tihomir S; Muirhead, Gareth; Saul, Louise; Karagiannis, Panagiotis; Ilieva, Kristina M; Crescioli, Silvia; Gazinska, Patrycja; Woodman, Natalie; Lomardelli, Cristina; Kareemaghay, Sedigeh; Selkirk, Christopher; Lentfer, Heike; Barton, Claire; Canevari, Silvana; Figini, Mariangela; Downes, Noel; Dombrowicz, David; Corrigan, Christopher J; Nestle, Frank O; Jones, Paul S; Gould, Hannah J; Blower, Philip J; Tsoka, Sophia; Spicer, James F; Karagiannis, Sophia N

2018-04-13

Designing biologically informative models for assessing the safety of novel agents, especially for cancer immunotherapy, carries substantial challenges. The choice of an in vivo system for studies on IgE antibodies represents a major impediment to their clinical translation, especially with respect to class-specific immunological functions and safety. Fcε receptor expression and structure are different in humans and mice, so that the murine system is not informative when studying human IgE biology. By contrast, FcεRI expression and cellular distribution in rats mirrors that of humans. We are developing MOv18 IgE, a human chimeric antibody recognizing the tumour-associated antigen folate receptor alpha. We created an immunologically congruent surrogate rat model likely to recapitulate human IgE-FcεR interactions, and engineered a surrogate rat IgE equivalent to MOv18. Employing this model, we examined in vivo safety and efficacy of anti-tumour IgE antibodies. In immunocompetent rats, rodent IgE restricted growth of syngeneic tumours in the absence of clinical, histopathological or metabolic signs associated with obvious toxicity. No physiological or immunological evidence of a 'cytokine-storm' or allergic response was seen, even at 50 mg/kg weekly doses. IgE treatment was associated with elevated serum concentrations of TNFα, a mediator previously linked with IgE-mediated anti-tumour and anti-parasitic functions, alongside evidence of substantially elevated tumoural immune cell infiltration and immunological pathway activation in tumour-bearing lungs. Our findings indicate safety of MOv18 IgE, in conjunction with efficacy and immune activation, supporting the translation of this therapeutic approach to the clinical arena. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

mTOR plays an important role in cow's milk allergy-associated behavioral and immunological deficits.

PubMed

Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; van der Horst, Hilma; Reinders, Margot T M; Broersen, Laus M; Willemsen, Linette E M; Kas, Martien J H; Garssen, Johan; Kraneveld, Aletta D

2015-10-01

Autism spectrum disorder (ASD) is multifactorial, with both genetic as well as environmental factors working in concert to develop the autistic phenotype. Immunological disturbances in autistic individuals have been reported and a role for food allergy has been suggested in ASD. Single gene mutations in mammalian target of rapamycin (mTOR) signaling pathway are associated with the development of ASD and enhanced mTOR signaling plays a central role in directing immune responses towards allergy as well. Therefore, the mTOR pathway may be a pivotal link between the immune disturbances and behavioral deficits observed in ASD. In this study it was investigated whether the mTOR pathway plays a role in food allergy-induced behavioral and immunological deficits. Mice were orally sensitized and challenged with whey protein. Meanwhile, cow's milk allergic (CMA) mice received daily treatment of rapamycin. The validity of the CMA model was confirmed by showing increased allergic immune responses. CMA mice showed reduced social interaction and increased repetitive self-grooming behavior. Enhanced mTORC1 activity was found in the brain and ileum of CMA mice. Inhibition of mTORC1 activity by rapamycin improved the behavioral and immunological deficits of CMA mice. This effect was associated with increase of Treg associated transcription factors in the ileum of CMA mice. These findings indicate that mTOR activation may be central to both the intestinal, immunological, and psychiatric ASD-like symptoms seen in CMA mice. It remains to be investigated whether mTOR can be seen as a therapeutic target in cow's milk allergic children suffering from ASD-like symptoms. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Importance of Human Milk for Immunity in Preterm Infants.

PubMed

Lewis, Erin D; Richard, Caroline; Larsen, Bodil M; Field, Catherine J

2017-03-01

The immune system of preterm infants is immature, placing them at increased risk for serious immune-related complications. Human milk provides a variety of immune protective and immune maturation factors that are beneficial to the preterm infant's poorly developed immune system. The most studied immune components in human milk include antimicrobial proteins, maternal leukocytes, immunoglobulins, cytokines and chemokines, oligosaccharides, gangliosides, nucleotides, and long-chain polyunsaturated fatty acids. There is growing evidence that these components contribute to the lower incidence of immune-related conditions in the preterm infant. Therefore, provision of these components in human milk, donor milk, or formula may provide immunologic benefits. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of inflammatory factors by double-stranded RNA receptors in breast cancer cells.

PubMed

Venkatesh, Amritha; Nandigam, Harika; Muccioli, Maria; Singh, Manindra; Loftus, Tiffany; Lewis, Deana; Pate, Michelle; Benencia, Fabian

Malignant cells are not the only components of a tumor mass since other cells (e.g., fibroblasts, infiltrating leukocytes and endothelial cells) are also part of it. In combination with the extracellular matrix, all these cells constitute the tumor microenvironment. In the last decade the role of the tumor microenvironment in cancer progression has gained increased attention and prompted efforts directed to abrogate its deleterious effects on anti-cancer therapies. The immune system can detect and attack tumor cells, and tumor-infiltrating lymphocytes (particularly CD8 T cells) have been associated with improved survival or better response to therapies in colorectal, melanoma, breast, prostate and ovarian cancer patients among others. Contrariwise, tumor-associated myeloid cells (myeloid-derived suppressor cells [MDSCs], dendritic cells [DCs], macrophages) or lymphoid cells such as regulatory T cells can stimulate tumor growth via inhibition of immune responses against the tumor or by participating in tumor neoangiogenesis. Herewith we analyzed the chemokine profile of mouse breast tumors regarding their capacity to generate factors capable of attracting and sequestering DCs to their midst. Chemoattractants from tumors were investigated by molecular biology and immunological techniques and tumor infiltrating DCs were investigated for matched chemokine receptors. In addition, we investigated the inflammatory response of breast cancer cells, a major component of the tumor microenvironment, to double-stranded RNA stimulation. By using molecular biology techniques such as qualitative and quantitative PCR, PCR arrays, and immunological techniques (ELISA, cytokine immunoarrays) we examined the effects of dsRNA treatment on the cytokine secretion profiles of mouse and human breast cancer cells and non-transformed cells. We were able to determine that tumors generate chemokines that are able to interact with receptors present on the surface of tumor infiltrating DCs. We observed that PRR signaling is able to modify the production of chemokines by breast tumor cells and normal breast cells, thereby constituting a possible player in shaping the profile of the leukocyte population in the TME. Copyright © 2017 Elsevier GmbH. All rights reserved.

Inflammatory bowel disease: pathogenesis.

PubMed

Zhang, Yi-Zhen; Li, Yong-Yu

2014-01-07

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. It has been a worldwide health-care problem with a continually increasing incidence. It is thought that IBD results from an aberrant and continuing immune response to the microbes in the gut, catalyzed by the genetic susceptibility of the individual. Although the etiology of IBD remains largely unknown, it involves a complex interaction between the genetic, environmental or microbial factors and the immune responses. Of the four components of IBD pathogenesis, most rapid progress has been made in the genetic study of gut inflammation. The latest internationally collaborative studies have ascertained 163 susceptibility gene loci for IBD. The genes implicated in childhood-onset and adult-onset IBD overlap, suggesting similar genetic predispositions. However, the fact that genetic factors account for only a portion of overall disease variance indicates that microbial and environmental factors may interact with genetic elements in the pathogenesis of IBD. Meanwhile, the adaptive immune response has been classically considered to play a major role in the pathogenesis of IBD, as new studies in immunology and genetics have clarified that the innate immune response maintains the same importance in inducing gut inflammation. Recent progress in understanding IBD pathogenesis sheds lights on relevant disease mechanisms, including the innate and adaptive immunity, and the interactions between genetic factors and microbial and environmental cues. In this review, we provide an update on the major advances that have occurred in above areas.

The Microbiome in Infectious Disease and Inflammation

PubMed Central

Honda, Kenya; Littman, Dan R.

2015-01-01

The mammalian alimentary tract harbors hundreds of species of commensal microorganisms (microbiota) that intimately interact with the host and provide it with genetic, metabolic, and immunological attributes. Recent reports have indicated that the microbiota composition and its collective genomes (microbiome) are major factors in predetermining the type and robustness of mucosal immune responses. In this review, we discuss the recent advances in our understanding of host-microbiota interactions and their effect on the health and disease susceptibility of the host. PMID:22224764

A Brief Journey through the Immune System

PubMed Central

Yatim, Karim M.

2015-01-01

This review serves as an introduction to an Immunology Series for the Nephrologist published in CJASN. It provides a brief overview of the immune system, how it works, and why it matters to kidneys. This review describes in broad terms the main divisions of the immune system (innate and adaptive), their cellular and tissue components, and the ways by which they function and are regulated. The story is told through the prism of evolution in order to relay to the reader why the immune system does what it does and why imperfections in the system can lead to renal disease. Detailed descriptions of cell types, molecules, and other immunologic curiosities are avoided as much as possible in an effort to not detract from the importance of the broader concepts that define the immune system and its relationship to the kidney. PMID:25845377

Immunology and Immunotherapy of Head and Neck Cancer

PubMed Central

Ferris, Robert L.

2015-01-01

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented. PMID:26351330

Current problems in applied mathematics and mathematical modeling

NASA Astrophysics Data System (ADS)

Alekseev, A. S.

Papers are presented on mathematical modeling noting applications to such fields as geophysics, chemistry, atmospheric optics, and immunology. Attention is also given to models of ocean current fluxes, atmospheric and marine interactions, and atmospheric pollution. The articles include studies of catalytic reactors, models of global climate phenomena, and computer-assisted atmospheric models.

Convergent immunological solutions to Argentine hemorrhagic fever virus neutralization.

PubMed

Zeltina, Antra; Krumm, Stefanie A; Sahin, Mehmet; Struwe, Weston B; Harlos, Karl; Nunberg, Jack H; Crispin, Max; Pinschewer, Daniel D; Doores, Katie J; Bowden, Thomas A

2017-07-03

Transmission of hemorrhagic fever New World arenaviruses from their rodent reservoirs to human populations poses substantial public health and economic dangers. These zoonotic events are enabled by the specific interaction between the New World arenaviral attachment glycoprotein, GP1, and cell surface human transferrin receptor (hTfR1). Here, we present the structural basis for how a mouse-derived neutralizing antibody (nAb), OD01, disrupts this interaction by targeting the receptor-binding surface of the GP1 glycoprotein from Junín virus (JUNV), a hemorrhagic fever arenavirus endemic in central Argentina. Comparison of our structure with that of a previously reported nAb complex (JUNV GP1-GD01) reveals largely overlapping epitopes but highly distinct antibody-binding modes. Despite differences in GP1 recognition, we find that both antibodies present a key tyrosine residue, albeit on different chains, that inserts into a central pocket on JUNV GP1 and effectively mimics the contacts made by the host TfR1. These data provide a molecular-level description of how antibodies derived from different germline origins arrive at equivalent immunological solutions to virus neutralization.

Contribution of vascular cell-derived cytokines to innate and inflammatory pathways in atherogenesis

PubMed Central

Loppnow, Harald; Buerke, Michael; Werdan, Karl; Rose-John, Stefan

2011-01-01

Abstract Inflammation is a central element of atherogenesis. Innate pathways contribute to vascular inflammation. However, the initial molecular process(es) starting atherogenesis remain elusive. The various risk factors, represented by particular compounds (activators), may cause altered cellular functions in the endothelium (e.g. vascular endothelial cell activation or -dysfunction), in invading cells (e.g. inflammatory mediator production) or in local vessel wall cells (e.g. inflammatory mediators, migration), thereby triggering the innate inflammatory process. The cellular components of innate immunology include granulocytes, natural killer cells and monocytes. Among the molecular innate constituents are innate molecules, such as the toll-like receptors or innate cytokines. Interleukin-1 (IL-1) and IL-6 are among the innate cytokines. Cytokines are potent activators of a great number of cellular functions relevant to maintain or commove homeostasis of the vessel wall. Within the vessel wall, vascular smooth muscle cells (SMCs) can significantly contribute to the cytokine-dependent inflammatory network by: (i) production of cytokines, (ii) response to cytokines and (iii) cytokine-mediated interaction with invading leucocytes. The cytokines IL-1 and IL-6 are involved in SMC-leucocyte interaction. The IL-6 effects are proposed to be mediated by trans-signalling. Dysregulated cellular functions resulting from dysregulated cytokine production may be the cause of cell accumulation, subsequent low-density lipoprotein accumulation and deposition of extracellular matrix (ECM). The deposition of ECM, increased accumulation of leucocytes and altered levels of inflammatory mediators may constitute an ‘innate-immunovascular-memory’ resulting in an ever-growing response to anew invasion. Thus, SMC-fostered inflammation, promoted by invading innate cells, may be a potent component for development and acceleration of atherosclerosis. PMID:21199323

Keystone predation and molecules of keystone significance

PubMed Central

Zimmer, Richard K.; Ferrier, Graham A.; Kim, Steven J.; Ogorzalek Loo, Rachel R.; Zimmer, Cheryl Ann; Loo, Joseph A.

2017-01-01

Keystone species structure ecological communities and are major determinants of biodiversity. A synthesis of research on keystone species is nonetheless missing a critical component – the sensory mechanisms for behavioral interactions that determine population- and community-wide attributes. Here, we establish the chemosensory basis for keystone predation by sea stars (Pisaster ochraceus) on mussels. This consumer-resource interaction is prototypic of top-down driven trophic cascades. Each mussel species (Mytilus californianus and M. galloprovincialis) secretes a glycoprotein orthologue (29.6 and 28.1 kDa, respectively) that acts, singularly, to evoke the sea star predatory response. The orthologues (named ‘KEYSTONEin’) are localized in the epidermis, extrapallial fluid, and organic shell coating (periostracum) of live, intact mussels. Thus, KEYSTONEin contacts chemosensory receptors on tube feet as sea stars crawl over rocky surfaces in search of prey. The complete nucleotide sequences reveal that KEYSTONEin shares 87 % (M. californianus) or 98 % (M. galloprovincialis) homology with a calcium-binding protein in the shell matrix of a closely related congener, M. edulis. All three molecules cluster tightly within the Complement Component 1 Domain Containing (C1qDC) protein family; each exhibits a large globular domain, low complexity region(s), coiled coil, and at least four of five histidine-aspartic acid tandem motifs. Collective results support the hypothesis that KEYSTONEin evolved ancestrally in immunological, and later, in biomineralization roles. More recently, the substance has become exploited by sea stars as a contact cue for prey recognition. As the first identified compound to evoke keystone predation, KEYSTONEin provides valuable sensory information, promotes biodiversity, and shapes community structure and function. Without this molecule, there would be no predation by sea stars on mussels. PMID:28376248

Modelling biological behaviours with the unified modelling language: an immunological case study and critique.

PubMed

Read, Mark; Andrews, Paul S; Timmis, Jon; Kumar, Vipin

2014-10-06

We present a framework to assist the diagrammatic modelling of complex biological systems using the unified modelling language (UML). The framework comprises three levels of modelling, ranging in scope from the dynamics of individual model entities to system-level emergent properties. By way of an immunological case study of the mouse disease experimental autoimmune encephalomyelitis, we show how the framework can be used to produce models that capture and communicate the biological system, detailing how biological entities, interactions and behaviours lead to higher-level emergent properties observed in the real world. We demonstrate how the UML can be successfully applied within our framework, and provide a critique of UML's ability to capture concepts fundamental to immunology and biology more generally. We show how specialized, well-explained diagrams with less formal semantics can be used where no suitable UML formalism exists. We highlight UML's lack of expressive ability concerning cyclic feedbacks in cellular networks, and the compounding concurrency arising from huge numbers of stochastic, interacting agents. To compensate for this, we propose several additional relationships for expressing these concepts in UML's activity diagram. We also demonstrate the ambiguous nature of class diagrams when applied to complex biology, and question their utility in modelling such dynamic systems. Models created through our framework are non-executable, and expressly free of simulation implementation concerns. They are a valuable complement and precursor to simulation specifications and implementations, focusing purely on thoroughly exploring the biology, recording hypotheses and assumptions, and serve as a communication medium detailing exactly how a simulation relates to the real biology.

Modelling biological behaviours with the unified modelling language: an immunological case study and critique

PubMed Central

Read, Mark; Andrews, Paul S.; Timmis, Jon; Kumar, Vipin

2014-01-01

We present a framework to assist the diagrammatic modelling of complex biological systems using the unified modelling language (UML). The framework comprises three levels of modelling, ranging in scope from the dynamics of individual model entities to system-level emergent properties. By way of an immunological case study of the mouse disease experimental autoimmune encephalomyelitis, we show how the framework can be used to produce models that capture and communicate the biological system, detailing how biological entities, interactions and behaviours lead to higher-level emergent properties observed in the real world. We demonstrate how the UML can be successfully applied within our framework, and provide a critique of UML's ability to capture concepts fundamental to immunology and biology more generally. We show how specialized, well-explained diagrams with less formal semantics can be used where no suitable UML formalism exists. We highlight UML's lack of expressive ability concerning cyclic feedbacks in cellular networks, and the compounding concurrency arising from huge numbers of stochastic, interacting agents. To compensate for this, we propose several additional relationships for expressing these concepts in UML's activity diagram. We also demonstrate the ambiguous nature of class diagrams when applied to complex biology, and question their utility in modelling such dynamic systems. Models created through our framework are non-executable, and expressly free of simulation implementation concerns. They are a valuable complement and precursor to simulation specifications and implementations, focusing purely on thoroughly exploring the biology, recording hypotheses and assumptions, and serve as a communication medium detailing exactly how a simulation relates to the real biology. PMID:25142524

Behavior and handling of physically and immunologically castrated market pigs on farm and going to market.

PubMed

Guay, K; Salgado, G; Thompson, G; Backus, B; Sapkota, A; Chaya, W; McGlone, J J

2013-11-01

Physical castration is a common management practice on commercial swine farms in the United States to reduce the incidence of boar taint and aggressive behavior. One alternative to physical castration (PC) is to immunologically castrate (IC) male pigs by blocking the gonadotropin-releasing factor (GnRF), thereby reducing levels of LH, FSH, testosterone, and androstenone. The objectives of this study were to evaluate the effects of IC on pig behavior, human-pig interactions, and handling during and after transport. Pigs were given the first immunization at wk 7 of the grower-finisher period, and second immunizations were given at wk 11, 13, or 14 of the grower-finisher period. Behaviors of PC and IC barrows were sampled at 3 time points after entering finishing at 9 wk of age: 7 wk before first injection, 16 wk (after immunization was complete) into finishing, and 1 d before marketing (16 to 19 wk into finishing). Handling during loading and unloading of trailers going to market was also quantified. Before the first injection, intact males showed increased aggression (P=0.014) and mounting (P=0.048), whereas PC barrows spent more (P=0.003) time feeding than intact males. There were treatment×time interactions for lying (P=0.018), aggression (P<0.001), and standing (P=0.009) behaviors. Few differences were observed in pig-human interactions between PC and IC barrows, with IC and PC approaching people in the same amount of time, but IC barrows were more (P<0.001) aggressive in chewing and rubbing on the test person's pant leg and boots. When handling and loading for processing in the home barn, PC barrows were more (P<0.05) vocal than IC barrows. Fewer dead and down pigs were observed among IC (0%) compared with PC barrows (1.17%). Immunological castration may result in similar or improved animal welfare compared to the stress of physical castration without pain relief.

Managing immune diseases in the smartphone era: how have apps impacted disease management and their future?

PubMed

Gallagher, Joe; O'Donoghue, John; Car, Josip

2015-04-01

Immunology, similar to other areas of clinical science, is a data-rich discipline that involves a great deal of interaction between healthcare professionals and their patients. The focus of this editorial is to review the challenges and opportunities for mobile healthcare applications within immunology. It is clear that further research is required to fully maximize the potential of mobile apps (e.g., regulations and guidelines, electronic health). However, it is equally clear that mobile healthcare applications have had a positive impact on patient outcomes (better response rates, more efficient usage of time and more accurate diagnosis). Overall, healthcare applications have a fundamental role to play in the future management of diseases as they will help to ensure that we deliver more effective patient care.

The use of the chick embryo chorioallantoic membrane as experimental model to study virus growth and to test the clonal selection hypothesis. The contribution of Sir Mac Farlane Burnet.

PubMed

Ribatti, Domenico

2018-06-07

Sir Mac Farlane Burnet was the most honored of all Australian scientists. In 1960, Burnet shared the Nobel Prize for Medicine with Peter Medawar of Britain for the discovery of acquired immunological tolerance. He developed techniques for growing influenza viruses in the chorioallantoic membrane of the chick embryo. This became a standard laboratory practice. He continued to work with chick embryos long after the use of cell cultures had become general. His virology research resulted in significant discoveries concerning the nature and replication of viruses and their interaction with the immune system. Copyright © 2018 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Immunomodulatory effects of temperature and pH of water in an Indian freshwater sponge.

PubMed

Mukherjee, Soumalya; Bhunia, Anindya Sundar; Bhunia, Niladri Sekhar; Ray, Mitali; Ray, Sajal

2016-07-01

Eunapius carteri, a freshwater sponge of India, inhabits the ponds and lakes and experiences variations of temperature and pH of water throughout the year. Sponges bear evolutionary and ecological importance with limited information on their immunological attribute and adaptational resilience in a changing environment. This paper reports temperature and pH specific responses of immune related parameters in sponge maintained in the experimental conditions of laboratory. Innate immunological parameters like phagocytosis and generation of cytotoxic molecules like superoxide anion, nitric oxide and phenoloxidase activity were estimated in E. carteri at different environmentally realistic water temperatures (10, 20, 30 and 40°C) and pH (6.4, 7.4 and 8.4). Phagocytosis and cytotoxicity are established as important immune parameters of invertebrates. Calalase, an antioxidant enzyme and phosphatases are involved in pathogen destruction and are considered as components of innate immunity. Activities of catalase, acid and alkaline phosphatases were estimated in E. carteri at different thermal regimes and pH. Modulation of phagocytic and cytotoxic responses and the activities of catalase and phosphatases at different water temperatures and pH indicated temperature and pH specific immunological status of E. carteri. Present investigation deals with the effects of selected hydrological parameters on the fundamental immune related parameters in sponge indicating its adaptational plasticity. Immunological resilience of this species in the face of variation of water temperature and pH is thought to be a special adaptive feature of sponge, a reported "living fossil". Copyright © 2016 Elsevier Ltd. All rights reserved.

100 Years Later: Celebrating the Contributions of X-ray Crystallography to Allergy and Clinical Immunology

PubMed Central

Pomés, Anna; Chruszcz, Maksymilian; Gustchina, Alla; Minor, Wladek; Mueller, Geoffrey A.; Pedersen, Lars C.; Wlodawer, Alexander; Chapman, Martin D.

2015-01-01

Current knowledge of molecules involved in immunology and allergic disease results from significant contributions of X-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and X-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact three-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and in mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind lipopolysaccharides may also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. This surface in turn determines antibody specificity and cross-reactivity that are important factors for the selection of allergen panels used for molecular diagnosis and for the interpretation of clinical symptoms. This review celebrates the contributions of X-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases. PMID:26145985

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

21 CFR 866.5590 - Lipoprotein X immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Lipoprotein X immunolog-ical test system. 866.5590... Lipoprotein X immunolog-ical test system. (a) Identification. A lipoprotein X immunological test system is a device that consists of the reagents used to measure by immunochemical techniques lipoprotein X (a high...

Genetic errors of the human CARD-BCL10-MALT1 (CBM) complex: molecular, immunological, and clinical heterogeneity

PubMed Central

de Diego, Rebeca Pérez; Sánchez-Ramón, Silvia; López-Collazo, Eduardo; Martínez-Barricarte, Rubén; Cubillos-Zapata, Carolina; Cerdán, Antonio Ferreira; Casanova, Jean-Laurent; Puel, Anne

2016-01-01

Three members of the caspase recruitment domain (CARD) family of adaptors (CARD9, CARD10, and CARD11) are known to form heterotrimers with B-cell lymphoma 10 (BCL10) and mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (MALT1). These three CARD-BCL10-MALT1 (CBM) complexes activate NF-κB in both the innate and adaptive arms of immunity. Human inherited defects of the three components of the CBM complex, including the two adaptors CARD9 and CARD11 and the two core components BCL10 and MALT1, have recently been reported. Bi-allelic loss-of-function (LOF) mutant alleles underlie several different immunological and clinical phenotypes, which can be assigned to two distinct categories. Isolated invasive fungal infections, of unclear cellular basis, are associated with CARD9 deficiency, whereas a broad range of clinical manifestations, including those characteristic of T- and B-lymphocyte defects, are associated with CARD11, MALT1 and BCL10 deficiencies. Interestingly, humans with these mutations have some features in common with the corresponding knockout mice, but other features are different between humans and mice. Moreover, germline and somatic gain-of-function (GOF) mutations of MALT1, BCL10 and CARD11 have also been found in other patients with lymphoproliferative disorders. This broad range of germline and somatic CBM lesions, including LOF and GOF mutations, highlights the contribution of each of the components of the CBM to human immunity. PMID:26277595

The bovine spleen: Interactions among splenic cell populations in the innate immunologic control of hemoparasitic infections

USDA-ARS?s Scientific Manuscript database

Over the past several years, innate immunity has been recognized as having an important role as a front-line defense mechanism and as an integral part of the adaptive immune response. Innate immunity in cattle exposed to hemoparasites is spleen-dependent and age-related. In this review, we discuss g...

IL-17A regulates Eimeria tenella schizont maturation and migration in avian coccidiosis

USDA-ARS?s Scientific Manuscript database

Although IL17A is associated with the immunological control of various infectious diseases, its role in host response to Eimeria infections is not well understood. In an effort to better dissect the role of IL17A in host-pathogen interactions in avian coccidiosis, a neutralizing antibody (Ab) to chi...

The Covalent Binding of Alkaline Phosphatase on Porous Supports and the Stability of the Immobilized Enzyme

DTIC Science & Technology

1988-08-11

and LiChrospher Si 4000 were obtained from Applied Science Laboratories, Inc. LiChrospher Si 100 was obtained from Alltech Assoc. The surface areas...Z U) w I < 0 The earliest attempt to take advantage of evanescent wave interactions in an optical waveguide to detect immunological reactions was made

An Interaction of LPS and RSV Infection in Augmenting the AHR and Airway Inflammation in Mice.

PubMed

Zhou, Na; Li, Wei; Ren, Luo; Xie, Xiaohong; Liu, Enmei

2017-10-01

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infection (LRTI) in children under 5 years of age, especially infants with severe bronchiolitis. Our preliminary clinical experiments showed that bacterial colonization was commonly observed in children with virus-induced wheezing, particularly in those with recurrent wheezing, suggesting that bacterial colonization with an accompanying viral infection may contribute to disease severity. In most cases, RSV-infected infants were colonized with pathogenic bacteria (mainly Gram-negative bacteria). LPS is the main component of Gram-negative bacteria and acts as a ligand for Toll-like receptor 4 (TLR4). Relevant studies have reported that the TLR family is crucial in mediating the link between viral components and immunologic responses to infection. Of note, TLR4 activation has been associated with disease severity during RSV infection. In the present study, we identified that LPS aggravated RSV-induced AHR and airway inflammation in BALB/c mice using an RSV coinfection model. We found that the airway inflammatory cells and cytokines present in BALF and TRIF in lung tissue play a role in inducing AHR and airway inflammation upon RSV and bacteria coinfection, which might occur through the TRIF-MMP-9-neutrophil-MMP-9 signalling pathway. These results may aid in the development of novel treatments and improve vaccine design.

Isolation of recombinant antibodies directed against surface proteins of Clostridium difficile.

PubMed

Shirvan, Ali Nazari; Aitken, Robert

2016-01-01

Clostridium difficile has emerged as an increasingly important nosocomial pathogen and the prime causative agent of antibiotic-associated diarrhoea and pseudomembranous colitis in humans. In addition to toxins A and B, immunological studies using antisera from patients infected with C. difficile have shown that a number of other bacterial factors contribute to the pathogenesis, including surface proteins, which are responsible for adhesion, motility and other interactions with the human host. In this study, various clostridial targets, including FliC, FliD and cell wall protein 66, were expressed and purified. Phage antibody display yielded a large panel of specific recombinant antibodies, which were expressed, purified and characterised. Reactions of the recombinant antibodies with their targets were detected by enzyme-linked immunosorbent assay; and Western blotting suggested that linear rather than conformational epitopes were recognised. Binding of the recombinant antibodies to surface-layer proteins and their components showed strain specificity, with good recognition of proteins from C. difficile 630. However, no reaction was observed for strain R20291-a representative of the 027 ribotype. Binding of the recombinant antibodies to C. difficile M120 extracts indicated that a component of a surface-layer protein of this strain might possess immunoglobulin-binding activities. The recombinant antibodies against FliC and FliD proteins were able to inhibit bacterial motility. Copyright © 2016. Published by Elsevier Editora Ltda.

Recommendations for Competency in Allergy Training for Undergraduates Qualifying as Medical Practitioners: A Position Paper of the World Allergy Organization

PubMed Central

2009-01-01

The Council acknowledges specific comments from: The American Academy of Allergy, Asthma and Immunology (AAAAI) (Amal H Assa'ad); The American College of Allergy, Asthma and Immunology (ACAAI) (Mark Dykewicz, D. Betty Lew, Bryan L. Martin); The Argentine Association of Allergy and Immunology (Ledit RF Ardusso); The Argentine Society of Allergy and Immunopathology (Estrella Asayag); The Australasian Society of Clinical Immunology and Allergy (ASCIA) (Jill Smith); The British Society for Allergy and Clinical Immunology (Stephen Durham); The Brazilian Society of Allergy and Immunopathology (Nelson Rosario); The Bulgarian Society of Allergology (Vasil Dimitrov); The Canadian Society of Allergy and Clinical Immunology (CSACI) (Richard Warrington); The Chilean Society of Allergy and Immunology (Jessica Salinas); The Chinese Society of Allergology (Zhang Hongyu, Yin Jia); The Czech Society of Allergology and Clinical Immunology (Jiri Litzman); The Danish Society of Allergology (Lone Winther, Peter Plaschke); The Egyptian Society of Allergy and Clinical Immunology (Kamal Maurice Hanna); The Egyptian Society of Pediatric Allergy and Immunology (Yehia El-Gamal); The German Society for Allergy and Clinical Immunology (Thilo Jakob, Claus Bachert, Bernhard Przybilla); The Hungarian Society of Allergology and Clinical Immunology (Kristof Nekam); The Icelandic Society of Allergy and Clinical Immunology (Björn R. Lúðvíksson); The Italian Association of Territorial and Hospital Allergists (Riccardo Asero); The Italian Society of Allergy and Clinical Immunology (Luigi Fontana); The Japanese Society of Allergology (Sankei Nishima); The Korean Academy of Asthma Allergy and Clinical Immunology (Joon Sung Lee, Hae-Sim Park); The Latvian Association of Allergists (Ieva Cirule); The Lebanese Society of Allergy & Immunology (Fares Zaitoun); The Mongolian Society of Allergology (S. Munkhbayarlakh); The Allergy and Clinical Immunology Society (Singapore) (Chng Hiok Hee); The Allergy Society of South Africa (Sharon Kling); The Spanish Society of Allergy and Clinical Immunology (Tomás Chivato); The Swiss Society for Allergology and Immunology (SSAI-SGAI) (Beat A. Imhof, Andreas Bircher); The Allergy and Immunology Society of Thailand (Pakit Vichyanond); The Turkish National Society of Allergy and Clinical Immunology (Omer Kalayci); and The Venezuelan Society of Allergy, Asthma and Immunology (Luis F Sarmiento). PMID:23283109

IMMUNOLOGIC MEMORY CELLS OF BONE MARROW ORIGIN

PubMed Central

Miller, Harold C.; Cudkowicz, Gustavo

1972-01-01

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F1 mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process. PMID:4553850

Associations between immunological function and memory recall in healthy adults.

PubMed

Wang, Grace Y; Taylor, Tamasin; Sumich, Alexander; Merien, Fabrice; Borotkanics, Robert; Wrapson, Wendy; Krägeloh, Chris; Siegert, Richard J

2017-12-01

Studies in clinical and aging populations support associations between immunological function, cognition and mood, although these are not always in line with animal models. Moreover, very little is known about the relationship between immunological measures and cognition in healthy young adults. The present study tested associations between the state of immune system and memory recall in a group of relatively healthy adults. Immediate and delayed memory recall was assessed in 30 participants using the computerised cognitive battery. CD4, CD8 and CD69 subpopulations of lymphocytes, Interleukin-6 (IL-6) and cortisol were assessed with blood assays. Correlation analysis showed significant negative relationships between CD4 and the short and long delay memory measures. IL-6 showed a significant positive correlation with long-delay recall. Generalized linear models found associations between differences in all recall challenges and CD4. A multivariate generalized linear model including CD4 and IL-6 exhibited a stronger association. Results highlight the interactions between CD4 and IL-6 in relation to memory function. Further study is necessary to determine the underlying mechanisms of the associations between the state of immune system and cognitive performance. Copyright © 2017 Elsevier Inc. All rights reserved.

Helminths in the hygiene hypothesis: sooner or later?

PubMed

Maizels, R M; McSorley, H J; Smyth, D J

2014-07-01

There is increasing recognition that exposures to infectious agents evoke fundamental effects on the development and behaviour of the immune system. Moreover, where infections (especially parasitic infections) have declined, immune responses appear to be increasingly prone to hyperactivity. For example, epidemiological studies of parasite-endemic areas indicate that prenatal or early-life experience of infections can imprint an individual's immunological reactivity. However, the ability of helminths to dampen pathology in established inflammatory diseases implies that they can have therapeutic effects even if the immune system has developed in a low-infection setting. With recent investigations of how parasites are able to modulate host immune pathology at the level of individual parasite molecules and host cell populations, we are now able to dissect the nature of the host-parasite interaction at both the initiation and recall phases of the immune response. Thus the question remains - is the influence of parasites on immunity one that acts primarily in early life, and at initiation of the immune response, or in adulthood and when recall responses occur? In short, parasite immunosuppression - sooner or later? © 2014 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

Myasthenia gravis: recent advances in immunopathology and therapy.

PubMed

Lee, John-Ih; Jander, Sebastian

2017-03-01

Myasthenia gravis is the most frequent acquired disorder of neuromuscular transmission. In the majority of cases, pathogenic antibodies against components of the postsynaptic muscle endplate membrane can be detected. In recent years there have been significant advances in the pathophysiological understanding and therapy of the disease. Areas covered: PubMed searches were conducted for the term 'myasthenia gravis' cross-referenced with the terms 'immunology', 'subgroups', 'antibody', 'ocular', 'thymoma', 'treatment' and 'thymectomy'. Additionally, we summarized the current state of immunopathology and therapy. Expert commentary: Immunological research defined new target antigens at the postsynaptic neuromuscular junction which along with clinical features allow a refined definition of disease subgroups. Overall the prognosis of myasthenia gravis with best possible symptomatic, immunosuppressive and supportive treatment is good but new immunomodulatory treatment options are developed for patients who do not respond well to the first line therapy. For most patients individually adapted long-term drug therapy is needed.

The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?

PubMed Central

Ochoa-Repáraz, Javier; Kasper, Lloyd H.

2016-01-01

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior. PMID:26865085

The Second Brain: Is the Gut Microbiota a Link Between Obesity and Central Nervous System Disorders?

PubMed

Ochoa-Repáraz, Javier; Kasper, Lloyd H

2016-03-01

The gut-brain axis is a bi-directional integrated system composed by immune, endocrine, and neuronal components by which the gap between the gut microbiota and the brain is significantly impacted. An increasing number of different gut microbial species are now postulated to regulate brain function in health and disease. The westernized diet is hypothesized to be the cause of the current obesity levels in many countries, a major socio-economical health problem. Experimental and epidemiological evidence suggest that the gut microbiota is responsible for significant immunologic, neuronal, and endocrine changes that lead to obesity. We hypothesize that the gut microbiota, and changes associated with diet, affect the gut-brain axis and may possibly contribute to the development of mental illness. In this review, we discuss the links between diet, gut dysbiosis, obesity, and immunologic and neurologic diseases that impact brain function and behavior.

Immunology and Immunotherapy of Head and Neck Cancer.

PubMed

Ferris, Robert L

2015-10-10

The immune system plays a key role in the development, establishment, and progression of head and neck squamous cell carcinoma (HNSCC). A greater understanding of the dysregulation and evasion of the immune system in the evolution and progression of HNSCC provides the basis for improved therapies and outcomes for patients. HNSCC cells evade the host immune system through manipulation of their own immunogenicity, production of immunosuppressive mediators, and promotion of immunomodulatory cell types. Through the tumor's influence on the microenvironment, the immune system can be exploited to promote metastasis, angiogenesis, and growth. This article provides a brief overview of key components of the immune infiltrating cells in the tumor microenvironment, reviewing immunological principles related to head and neck cancer, including the concept of cancer immunosurveillance and immune escape. Current immunotherapeutic strategies and emerging results from ongoing clinical trials are presented. © 2015 by American Society of Clinical Oncology.

An immune clock of human pregnancy

PubMed Central

Aghaeepour, Nima; Ganio, Edward A.; Mcilwain, David; Tsai, Amy S.; Tingle, Martha; Van Gassen, Sofie; Gaudilliere, Dyani K.; Baca, Quentin; McNeil, Leslie; Okada, Robin; Ghaemi, Mohammad S.; Furman, David; Wong, Ronald J.; Winn, Virginia D.; Druzin, Maurice L.; El-Sayed, Yaser Y.; Quaintance, Cecele; Gibbs, Ronald; Darmstadt, Gary L.; Shaw, Gary M.; Stevenson, David K.; Tibshirani, Robert; Nolan, Garry P.; Lewis, David B.; Angst, Martin S.; Gaudilliere, Brice

2017-01-01

The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling–based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2–dependent STAT5ab signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies. PMID:28864494

[Etiology and pathogenesis of inflammatory bowel diseases].

PubMed

Lukáš, Milan

2014-01-01

Zdenek Mařatka has been the first physician, who had brought a new information for the Czech medical community with topic of inflammatory bowel diseases, which had been systematic studied for him. He had prepared an original theory - two component hypothesis about origin of ulcerative colitis, which had been developed and innovated by him for long time. From the international point of view, Mařatka has had an extraordinary impact and significant contribution for recognition of ulcerative colitis and Crohn´s disease. Despite the fact that the true origin of ulcerative colitis and Crohn´s disease (UC) still remain elusive, basic as well as clinical research bring many new data on etiology and pathogenesis of this inflammatory condition. It seems clear that IBD originate from interaction of several intrinsic and extrinsic factors that contribute individually in a particular patient. Among internal factors the genes play an important role, because its influence on the mucosal immunity system and immunological response. Among the external factors importance are recognized the gut microbiota content, cigarette smoking and psychological stress.

Fidelity in Animal Modeling: Prerequisite for a Mechanistic Research Front Relevant to the Inflammatory Incompetence of Acute Pediatric Malnutrition.

PubMed

Woodward, Bill

2016-04-11

Inflammatory incompetence is characteristic of acute pediatric protein-energy malnutrition, but its underlying mechanisms remain obscure. Perhaps substantially because the research front lacks the driving force of a scholarly unifying hypothesis, it is adrift and research activity is declining. A body of animal-based research points to a unifying paradigm, the Tolerance Model, with some potential to offer coherence and a mechanistic impetus to the field. However, reasonable skepticism prevails regarding the relevance of animal models of acute pediatric malnutrition; consequently, the fundamental contributions of the animal-based component of this research front are largely overlooked. Design-related modifications to improve the relevance of animal modeling in this research front include, most notably, prioritizing essential features of pediatric malnutrition pathology rather than dietary minutiae specific to infants and children, selecting windows of experimental animal development that correspond to targeted stages of pediatric immunological ontogeny, and controlling for ontogeny-related confounders. In addition, important opportunities are presented by newer tools including the immunologically humanized mouse and outbred stocks exhibiting a magnitude of genetic heterogeneity comparable to that of human populations. Sound animal modeling is within our grasp to stimulate and support a mechanistic research front relevant to the immunological problems that accompany acute pediatric malnutrition.

Capture stress and the bactericidal competence of blood and plasma in five species of tropical birds.

PubMed

Matson, Kevin D; Tieleman, B Irene; Klasing, Kirk C

2006-01-01

In wild birds, relatively little is known about intra- or interspecific variation in immunological capabilities, and even less is known about the effects of stress on immune function. Immunological assays adaptable to field settings and suitable for a wide variety of taxa will prove most useful for addressing these issues. We describe a novel application of an in vitro technique that measures the intrinsic bacteria-killing abilities of blood. We assessed the capacities of whole blood and plasma from free-living individuals of five tropical bird species to kill a nonpathogenic strain of E. coli before and after the birds experienced an acute stress. Killing invasive bacteria is a fundamental immune function, and the bacteria-killing assay measures constitutive, innate immunity integrated across circulating cell and protein components. Killing ability varied significantly across species, with common ground doves exhibiting the lowest levels and blue-crowned motmots exhibiting the highest levels. Across species, plasma killed bacteria as effectively as whole blood, and higher concentrations of plasma killed significantly better. One hour of acute stress reduced killing ability by up to 40%. This assay is expected to be useful in evolutionary and ecological studies dealing with physiological and immunological differences in birds.

The sea urchin Paracentrotus lividus immunological response to chemical pollution exposure: The case of lindane.

PubMed

Stabili, Loredana; Pagliara, Patrizia

2015-09-01

In the marine environment organochlorine insecticides can be broadly detected in water, sediments, and biota. These pollutants may have major ecological consequences since they may affect marine organisms and endanger organismal growth, reproduction or survival. In this study we investigated the modification of some sea urchin immunological parameters in response to subchronic lindane (γ-HCH) exposure. Adult specimens of the sea urchin Paracentrotus lividus were exposed to two different concentrations (0.1 and 0.5 mg L(-1)) of lindane. After 24 and 48h of treatment, we examined the lindane influence on coelomocytes vitality and enumeration as well on some humoral parameters. Our results showed that the presence of the pesticide affected both cellular and humoral components of the immune system. In particular, P. lividus coelomocytes vitality did not change but a decrease of the total cell number and an increase of the red cells was recorded. Haemolytic and lysozyme-like activities as well as antibacterial activity on Vibrio alginolyticus of treated animals decreased. Sea urchin immunological competence modifications might represent a tool for monitoring disease susceptibility thus providing biological criteria for the implementation of water quality standards to protect marine organisms. Copyright © 2015 Elsevier Ltd. All rights reserved.

21 CFR 866.5230 - Colostrum immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5230 Colostrum immunological test system. (a) Identification. A colostrum immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Colostrum immunological test system. 866.5230...

21 CFR 866.5570 - Lactoferrin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5570 Lactoferrin immunological test system. (a) Identification. A lactoferrin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactoferrin immunological test system. 866.5570...

21 CFR 866.5340 - Ferritin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5340 Ferritin immunological test system. (a) Identification. A ferritin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Ferritin immunological test system. 866.5340...

21 CFR 866.5735 - Prothrombin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5735 Prothrombin immunological test system. (a) Identification. A prothrombin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prothrombin immunological test system. 866.5735...

21 CFR 866.5680 - Myoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5680 Myoglobin immunological test system. (a) Identification. A myoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Myoglobin immunological test system. 866.5680...

21 CFR 866.5715 - Plasminogen immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5715 Plasminogen immunological test system. (a) Identification. A plasminogen immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Plasminogen immunological test system. 866.5715...

21 CFR 866.5470 - Hemoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5470 Hemoglobin immunological test system. (a) Indentification. A hemoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hemoglobin immunological test system. 866.5470...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5880 Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Transferrin immunological test system. 866.5880...

21 CFR 866.5060 - Prealbumin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5060 Prealbumin immunological test system. (a) Identification. A prealbumin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Prealbumin immunological test system. 866.5060...

21 CFR 866.5460 - Haptoglobin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5460 Haptoglobin immunological test system. (a) Identification. A haptoglobin immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Haptoglobin immunological test system. 866.5460...

21 CFR 866.5400 - Alpha-globulin immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5400 Alpha-globulin immuno-logical test system. (a) Identification. An alpha-globulin immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-globulin immuno-logical test system. 866...

21 CFR 866.5350 - Fibrinopeptide A immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5350 Fibrinopeptide A immuno-logical test system. (a) Identification. A fibrinopeptide A immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fibrinopeptide A immuno-logical test system. 866...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5170 Breast milk immunological test system. (a) Identification. A breast milk immunological test system is a device... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Breast milk immunological test system. 866.5170...

21 CFR 866.5360 - Cohn fraction IV immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5360 Cohn fraction IV immuno-logical test system. (a) Identification. A Cohn fraction IV immunological... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Cohn fraction IV immuno-logical test system. 866...

21 CFR 866.5040 - Albumin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... (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 of... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Albumin immunological test system. 866.5040...

Rab11-FIP3 Regulation of Lck Endosomal Traffic Controls TCR Signal Transduction.

PubMed

Bouchet, Jérôme; Del Río-Iñiguez, Iratxe; Vázquez-Chávez, Elena; Lasserre, Rémi; Agüera-González, Sonia; Cuche, Céline; McCaffrey, Mary W; Di Bartolo, Vincenzo; Alcover, Andrés

2017-04-01

The role of endosomes in receptor signal transduction is a long-standing question, which remains largely unanswered. The T cell Ag receptor and various components of its proximal signaling machinery are associated with distinct endosomal compartments, but how endosomal traffic affects T cell signaling remains ill-defined. In this article, we demonstrate in human T cells that the subcellular localization and function of the protein tyrosine kinase Lck depends on the Rab11 effector FIP3 (Rab11 family interacting protein-3). FIP3 overexpression or silencing and its ability to interact with Rab11 modify Lck subcellular localization and its delivery to the immunological synapse. Importantly, FIP3-dependent Lck localization controls early TCR signaling events, such as tyrosine phosphorylation of TCRζ, ZAP70, and LAT and intracellular calcium concentration, as well as IL-2 gene expression. Interestingly, FIP3 controls both steady-state and poststimulation phosphotyrosine and calcium levels. Finally, our findings indicate that FIP3 modulates TCR-CD3 cell surface expression via the regulation of steady-state Lck-mediated TCRζ phosphorylation, which in turn controls TCRζ protein levels. This may influence long-term T cell activation in response to TCR-CD3 stimulation. Therefore, our data underscore the importance of finely regulated endosomal traffic in TCR signal transduction and T cell activation leading to IL-2 production. Copyright © 2017 by The American Association of Immunologists, Inc.

Structural basis for pH-insensitive inhibition of immunoglobulin G recycling by an anti-neonatal Fc receptor antibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kenniston, Jon A.; Taylor, Brandy M.; Conley, Gregory P.

The neonatal Fc receptor FcRn plays a critical role in the trafficking of IgGs across tissue barriers and in retaining high circulating concentrations of both IgG and albumin. Although generally beneficial from an immunological perspective in maintaining IgG populations, FcRn can contribute to the pathogenesis of autoimmune disorders when an abnormal immune response targets normal biological components. We previously described a monoclonal antibody (DX-2507) that binds to FcRn with high affinity at both neutral and acidic pH, prevents the simultaneous binding of IgG, and reduces circulating IgG levels in preclinical animal models. Here, we report a 2.5 Å resolution X-raymore » crystal structure of an FcRn–DX-2507 Fab complex, revealing a nearly complete overlap of the IgG–Fc binding site in FcRn by complementarity-determining regions in DX-2507. This overlap explains how DX-2507 blocks IgG binding to FcRn and thereby shortens IgG half-life by preventing IgGs from recycling back into circulation. Moreover, the complex structure explains how the DX-2507 interaction is pH-insensitive unlike normal Fc interactions and how serum albumin levels are unaffected by DX-2507 binding. These structural studies could inform antibody-based therapeutic approaches for limiting the effects of IgG-mediated autoimmune disease.« less

Interaction between IL-6 and TNF-α genotypes associated with bacteremia in multiple myeloma patients submitted to autologous stem cell transplantation (ASCT).

PubMed

Trigo, Fernanda M B; Luizon, Marcelo R; Dutra, Hélio S; Maiolino, Angelo; Nucci, Márcio; Simões, Belinda P

2014-01-01

Stem cell transplantation affects patient׳s vulnerability to infections due to immunological changes related to chemotherapy. Multiple myeloma is characterized by susceptibility to infections, and IL-6 and TNF-α increased levels affect immune response (IR). Polymorphisms in promoter region of cytokine genes may alter expression levels and affect IR. We performed interaction analysis of IL-6 (-174G/C) and TNF-α (-308G/A) polymorphisms with infection susceptibility in 148 patients classified accordingly to infection status and found an interaction when compared groups with and without bacteremia (p=0.0380). The interaction may be more important than single effects for the IR associated with the infection susceptibility in ASCT.

Transmission Dynamics of the Four Dengue Serotypes in Southern Vietnam and the Potential Impact of Vaccination

PubMed Central

Coudeville, Laurent; Garnett, Geoff P.

2012-01-01

Background With approximately 2.5 billion people at risk, dengue is a major international public health concern. Dengue vaccines currently in development should help reduce the burden associated with this disease but the most efficient way of using future dengue vaccines remains to be defined. Mathematical models of transmission can provide insight into the expected impact of different vaccination strategies at a population level and contribute to this definition. Methods and Findings We developed and analyzed an age-structured, host-vector and serotype-specific compartmental model, including seasonality. We first used this transmission model to identify the immunological interactions between serotypes that affect the risks and consequences of secondary infections (cross-protection, increased susceptibility, increased severity, and increased infectiousness) and reproduce the observed epidemiology of dengue. For populating this model, we used routine surveillance data from Southern Vietnam and the results of a prospective cohort study conducted in the same area. The model provided a good fit to the observed data for age, severity of cases, serotype distribution, and dynamics over time, using two scenarios of immunological interaction : short term cross-protection alone (6–17 months) or a combination of short term cross-protection with cross-enhancement (increased susceptibility, severity and infectiousness in the case of secondary infections). Finally, we explored the potential impact of vaccination for these two scenarios. Both highlighted that vaccination can substantially decrease dengue burden by reducing the magnitude and frequency of outbreaks. Conclusion Our model suggests that seasonality and short term cross-protection are key factors for explaining dengue dynamics in Southern Vietnam. Vaccination was predicted to significantly reduce the disease burden, even in the situation where immunological cross-enhancement affects the risks and consequences of secondary infections. PMID:23251466

The complex contributions of genetics and nutrition to immunity in Drosophila melanogaster.

PubMed

Unckless, Robert L; Rottschaefer, Susan M; Lazzaro, Brian P

2015-03-01

Both malnutrition and undernutrition can lead to compromised immune defense in a diversity of animals, and "nutritional immunology" has been suggested as a means of understanding immunity and determining strategies for fighting infection. The genetic basis for the effects of diet on immunity, however, has been largely unknown. In the present study, we have conducted genome-wide association mapping in Drosophila melanogaster to identify the genetic basis for individual variation in resistance, and for variation in immunological sensitivity to diet (genotype-by-environment interaction, or GxE). D. melanogaster were reared for several generations on either high-glucose or low-glucose diets and then infected with Providencia rettgeri, a natural bacterial pathogen of D. melanogaster. Systemic pathogen load was measured at the peak of infection intensity, and several indicators of nutritional status were taken from uninfected flies reared on each diet. We find that dietary glucose level significantly alters the quality of immune defense, with elevated dietary glucose resulting in higher pathogen loads. The quality of immune defense is genetically variable within the sampled population, and we find genetic variation for immunological sensitivity to dietary glucose (genotype-by-diet interaction). Immune defense was genetically correlated with indicators of metabolic status in flies reared on the high-glucose diet, and we identified multiple genes that explain variation in immune defense, including several that have not been previously implicated in immune response but which are confirmed to alter pathogen load after RNAi knockdown. Our findings emphasize the importance of dietary composition to immune defense and reveal genes outside the conventional "immune system" that can be important in determining susceptibility to infection. Functional variation in these genes is segregating in a natural population, providing the substrate for evolutionary response to pathogen pressure in the context of nutritional environment.

Replication capacity in relation to immunologic and virologic outcomes in HIV-1-infected treatment-naive subjects.

PubMed

Skowron, Gail; Spritzler, John G; Weidler, Jodi; Robbins, Gregory K; Johnson, Victoria A; Chan, Ellen S; Asmuth, David M; Gandhi, Rajesh T; Lie, Yolanda; Bates, Michael; Pollard, Richard B

2009-03-01

To evaluate the association between baseline (BL) replication capacity (RC) (RCBL) and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1-infected subjects initiating antiretroviral therapy. RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naive subjects from AIDS Clinical Trials Group 384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Higher RCBL was associated with lower baseline CD4 (CD4BL) (r = -0.23, P < 0.0001), higher baseline HIV-1 RNA (r = 0.25, P < 0.0001), higher CD4BL activation percent (r = 0.23, P < 0.0001), and lower CD4BL memory count (r = -0.21, P = 0.0002). In a multivariable model, week 48 CD4 increase (DeltaCD448) was associated with lower CD4BL memory count and higher CD4BL-naive percent (P = 0.004, P = 0.015, respectively). The interaction between CD4BL and RCBL was significant (P = 0.018), with a positive association between RCBL and DeltaCD448 in subjects with higher CD4BL and a negative association at lower absCD4BL. At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different CD4BL counts.

Replication Capacity in Relation to Immunologic and Virologic Outcomes in HIV-1 infected, Treatment-Naïve Subjects

PubMed Central

Skowron, Gail; Spritzler, John G.; Weidler, Jodi; Robbins, Gregory K.; Johnson, Victoria A.; Chan, Ellen S.; Asmuth, David M.; Gandhi, Rajesh T.; Lie, Yolanda; Bates, Michael; Pollard, Richard B.

2012-01-01

Objectives To evaluate the association between baseline (BL) replication capacity (RC) [RCBL] and immunologic/virologic parameters (at BL and after 48 weeks on therapy) in HIV-1 infected subjects initiating antiretroviral therapy. Methods RCBL was determined using a modified Monogram PhenoSense HIV drug susceptibility assay on plasma HIV-1 from 321 treatment-naïve subjects from ACTG384. Univariate and multivariable analyses were performed to determine the association of RCBL with BL and on-therapy virologic and immunologic outcomes. Results Higher RCBL was associated with lower baseline CD4 (CD4BL) (r=−0.23, p<0.0001), higher baseline HIV-1 (RNABL) (r=0.25, p<0.0001), higher CD4BL activation percent (r=0.23, p<0.0001) and lower CD4BL memory count (r=−0.21, p=0.0002). In a multivariable model, week 48 CD4 increase (ΔCD448) was associated with lower CD4BL memory count and higher CD4BL naive percent (p=0.004, p=0.015, respectively). The interaction between CD4BL and RCBL was significant (p=0.018), with a positive association between RCBL and ΔCD448 in subjects with higher CD4BL, and a negative association at lower absCD4BL. Conclusions At baseline, higher RC was significantly associated with higher HIV-1 RNA, higher CD4 cell activation, lower CD4 cell count, and lower CD4 memory cell count. These factors may interact, directly or indirectly, to modify the extent to which CD4 recovery occurs in patients starting antiretroviral therapy at different baseline CD4 counts. PMID:19194319

Performance of a compact, hybrid optical evanescent-wave sensor for chemical and biological applications

NASA Astrophysics Data System (ADS)

Helmers, H.; Greco, Pierre; Benech, Pierre; Rustad, Rolf; Kherrat, Rochdi; Bouvier, Gérard

1996-02-01

We describe a hybrid evanescent-wave sensor component that we fabricated by using an integrated optical interferometer with a specially adapted photodetector array. The design of the interferometer is based on the use of tapered waveguides to obtain two intersecting collimated beams. Phase shifts can be measured with an angular precision of better than 10-3 rad, which corresponds to a superstrate index change inferior of 10-6 with our structure. The interest in the device as a chemical sensor is experimentally demonstrated. The same optical component could be used in a variety of other sensor applications, e.g., biological and immunological sensors.

Influenza, immune system, and pregnancy.

PubMed

Raj, Renju S; Bonney, Elizabeth A; Phillippe, Mark

2014-12-01

Influenza is a major health problem worldwide. Both seasonal influenza and pandemics take a major toll on the health and economy of our country. The present review focuses on the virology and complex immunology of this RNA virus in general and in relation to pregnancy. The goal is to attempt to explain the increased morbidity and mortality seen in infection during pregnancy. We discuss elements of innate and adaptive immunity as well as placental cellular responses to infection. In addition, we delineate findings in animal models as well as human disease. Increased knowledge of maternal and fetal immunologic responses to influenza is needed. However, enhanced understanding of nonimmune, pregnancy-specific factors influencing direct interaction of the virus with host cells is also important for the development of more effective prevention and treatment options in the future. © The Author(s) 2014.

COMPARATIVE HISTOLOGIC AND IMMUNOLOGIC STUDIES IN RABBITS OF INDUCED HYPERSENSITIVITY OF THE SERUM SICKNESS TYPE

PubMed Central

Germuth, Frederick G.; Pace, Mary Geraldine; Tippett, Jack C.

1955-01-01

Sensitization of rabbits with bovine albumin and the cross-reactive antigen, egg albumin, increased the rate of bovine albumin elimination following its intravenous administration. Elimination of this antigen was complete in 7 and 10 days respectively instead of approximately 2 weeks as in unsensitized normal animals. The peak incidence of allergic tissue alteration was proportionately accelerated. Certain qualitative and quantitative differences between the histologic responses of the sensitized and unsensitized rabbits were noted. These differences were probably due to the shorter period of antigen-antibody interaction in the sensitized animals in which the antigen was quickly eliminated. The temporal relationship between the histologic and immunologic responses in sensitized animals adds further support to the hypothesis that the lesions which occur after the injection of foreign protein are the result of antigen-antibody combination. PMID:13233442

Hydrogel-based encapsulation of biological, functional tissue: fundamentals, technologies and applications

NASA Astrophysics Data System (ADS)

Zimmermann, H.; Ehrhart, F.; Zimmermann, D.; Müller, K.; Katsen-Globa, A.; Behringer, M.; Feilen, P. J.; Gessner, P.; Zimmermann, G.; Shirley, S. G.; Weber, M. M.; Metze, J.; Zimmermann, U.

2007-12-01

Replacing dysfunctional endocrine cells or tissues (e.g. islets, parathyroid tissue) by functional, foreign material without using immunosuppressives could soon become reality. Immunological reactions are avoided by encapsulating cells/tissues in hydrogel (e.g. alginate) microcapsules, preventing interaction of the enclosed material with the host’s immune system while permitting the unhindered passage of nutrients, oxygen and secreted therapeutic factors. Detailed investigations of the physical, physico-chemical and immunological parameters of alginate-based microcapsules have led recently to the development of a novel class of cell-entrapping microcapsules that meet the demands of biocompatibility, long-term integrity and function. This together with the development of ‘good medical practice’ microfluidic chip technology and of advanced cryopreservation technology for generation and storage of immunoisolated transplants will bring cell-based therapy to clinics and the market.

IMMUNOLOGY OF TAENIA SOLIUM TAENIASIS AND HUMAN CYSTICERCOSIS

PubMed Central

Garcia, Hector H.; Rodriguez, Silvia; Friedland, Jon S.

2018-01-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by fecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data is limited by the relative lack of animal models. This manuscript manuscript revises the available information on the immunology of human taeniasis and cysticercosis. PMID:24962350

Immunology of Taenia solium taeniasis and human cysticercosis.

PubMed

Garcia, H H; Rodriguez, S; Friedland, J S

2014-08-01

The life cycle of Taenia solium, the pork tapeworm, is continuously closed in many rural settings in developing countries when free roaming pigs ingest human stools containing T. solium eggs and develop cysticercosis, and humans ingest pork infected with cystic larvae and develop intestinal taeniasis, or may also accidentally acquire cysticercosis by faecal-oral contamination. Cysticercosis of the human nervous system, neurocysticercosis, is a major cause of seizures and other neurological morbidity in most of the world. The dynamics of exposure, infection and disease as well as the location of parasites result in a complex interaction which involves immune evasion mechanisms and involutive or progressive disease along time. Moreover, existing data are limited by the relative lack of animal models. This manuscript revises the available information on the immunology of human taeniasis and cysticercosis. © 2014 John Wiley & Sons Ltd.

Trichuris muris research revisited: a journey through time.

PubMed

Hurst, Rebecca J M; Else, Kathryn J

2013-09-01

The mouse whipworm Trichuris muris has long been used as a tractable model of human Trichuriasis. Here we look back at the history of T. muris research; from the definition of the species and determination of its life cycle, through to the complex immune responses that we study today. We highlight the key research papers that have developed our understanding of immune responses to this parasite, and reflect on how original concepts have been transformed, as our knowledge of immunology has grown. Although we have a good understanding of host–parasite interactions in the context of the underlying cellular immunology, there are still many aspects of the biology of the Trichuris parasite that remain undefined. We predict that advances in parasite biology will be key in the future development of new and improved treatments for Trichuriasis.

[Development of an incubation system for an inverted microscopy for long-term observation of cell cultures using chamber slides].

PubMed

Feicht, W; Buchner, A; Riesenberg, R

2001-05-01

Trifunctional bispecific antibodies open up new immunological possibilities in tumour treatment. Prior to clinical application, comprehensive investigations using animal models and in vitro examinations need to be done. To investigate long-term interactions between various immunologically active blood cells and individual tumour cells in the presence of antibodies, we developed an incubation system for experimental cell cultures on an inverted microscope. The system consists of a perspex box with a central moisture chamber with integrated water reservoir, external air circulation heating, and a CO2 supply. The sterile cell cultures are located in the wells of a slide positioned within a depression in the water reservoir. The newly developed incubation system enables continuous observation over the long term of experiments under optimal cell cultures conditions in combination with modern video techniques.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients.

PubMed

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-06-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (T(regs)) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4(+) T cell count (> or < 500/mm(3)). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4(+) lymphocytes, including T(reg) subsets, and CD8(+) T cells was performed. Percentages of activated CD4(+) T cells, T(regs), effector T(regs) and terminal effector T(regs) were found to be significantly elevated in iIR. Neither the percentage of activated CD8(+) T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4(+) T cell count and percentage of T(regs) were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4(+) and CD8(+) T cells, T(reg) percentages and very low-level viraemia. Causative interactions between T(regs) and CD4(+) T cells should now be explored prospectively in a large patients cohort. © 2014 British Society for Immunology.

Interaction of Bacteriophages with the Immune System: Induction of Bacteriophage-Specific Antibodies.

PubMed

Dąbrowska, Krystyna

2018-01-01

In all cases when a bacteriophage makes direct contact with a mammalian organism, it may challenge the mammalian immunological system. Its major consequence is production of antibodies specific to the bacteriophage. Here we present protocols applicable in studies of bacteriophage ability to induce specific antibodies. The protocols have been divided into three parts: purification, immunization, and detection (ELISA).

Susceptibility of broiler chickens to coccidiosis when fed subclinical doses of deoxynivalenol and fumonisins – special emphasis on the immunological response and the mycotoxin interaction

USDA-ARS?s Scientific Manuscript database

Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these ...

FDDI information management system for centralizing interactive, computerized multimedia clinical experiences in pediatric rheumatology/Immunology.

PubMed

Rouhani, R; Cronenberger, H; Stein, L; Hannum, W; Reed, A M; Wilhelm, C; Hsiao, H

1995-01-01

This paper describes the design, authoring, and development of interactive, computerized, multimedia clinical simulations in pediatric rheumatology/immunology and related musculoskeletal diseases, the development and implementation of a high speed information management system for their centralized storage and distribution, and analytical methods for evaluating the total system's educational impact on medical students and pediatric residents. An FDDI fiber optic network with client/server/host architecture is the core. The server houses digitized audio, still-image video clips and text files. A host station houses the DB2/2 database containing case-associated labels and information. Cases can be accessed from any workstation via a customized interface in AVA/2 written specifically for this application. OS/2 Presentation Manager controls, written in C, are incorporated into the interface. This interface allows SQL searches and retrievals of cases and case materials. In addition to providing user-directed clinical experiences, this centralized information management system provides designated faculty with the ability to add audio notes and visual pointers to image files. Users may browse through case materials, mark selected ones and download them for utilization in lectures or for editing and converting into 35mm slides.

Effects of testosterone undecanoate as a male contraceptive candidate on rat immunological features.

PubMed

Yu, Mingcan; Cao, Xiaomei; Xu, Jinju; Wang, Xiaolei; Yang, Jing; Wang, Xinghai; Ben, Kunlong

2003-11-01

Testosterone undecanoate (TU) is under phase III clinical trial as a hormonal male contraceptive in China. Sex hormones can modulate the immune system. Female hormonal contraceptives may affect SIV/HIV-1 transmission. To evaluate the safety of TU and to understand whether long-term use of TU for a male contraceptive affects users' immunological features, adult male rats were treated for a 32-week TU-treated phase at the dose of 20 mg TU/kg body weight and a 24-week recovery phase. The reproductive and immunological parameters of 4-6 rats in each subgroup were examined at the stated time point. The mean sperm count and viability in the treated rats were significantly suppressed (p < 0.01). In the TU-treated group: the mean blood leukocyte and lymphocyte counts; the proliferation indexes of T cells from peripheral blood mononuclear cells (PBMC) and spleen; and, of B cells from spleen, as well as the mean counts of blood T, NK, and B cells decreased in comparison with those of control group. These decreases were not significant (p > 0.01). Similarly, the mean serum IgM, IgG, and IgA levels and complement activity in TU-treated rats were lower than those in control group (p > 0.01), and the changes in the antibody levels of the examined genital secretions were not significant (p > 0.01). The changes in the thickness of urethra epithelium, and in secretory component (SC) expression in genitals were not observed in the treated group. These results demonstrated that long-term supraphysiological TU injection did not obviously affect the examined rat immunological parameters.

Modelling the immunological response to a tetravalent dengue vaccine from multiple phase-2 trials in Latin America and South East Asia.

PubMed

Dorigatti, Ilaria; Aguas, Ricardo; Donnelly, Christl A; Guy, Bruno; Coudeville, Laurent; Jackson, Nicholas; Saville, Melanie; Ferguson, Neil M

2015-07-17

The most advanced dengue vaccine candidate is a live-attenuated recombinant vaccine containing the four dengue viruses on the yellow fever vaccine backbone (CYD-TDV) developed by Sanofi Pasteur. Several analyses have been published on the safety and immunogenicity of the CYD-TDV vaccine from single trials but none modelled the heterogeneity observed in the antibody responses elicited by the vaccine. We analyse the immunogenicity data collected in five phase-2 trials of the CYD-TDV vaccine. We provide a descriptive analysis of the aggregated datasets and fit the observed post-vaccination PRNT50 titres against the four dengue (DENV) serotypes using multivariate regression models. We find that the responses to CYD-TDV are principally predicted by the baseline immunological status against DENV, but the trial is also a significant predictor. We find that the CYD-TDV vaccine generates similar titres against all serotypes following the third dose, though DENV4 is immunodominant after the first dose. This study contributes to a better understanding of the immunological responses elicited by CYD-TDV. The recent availability of phase-3 data is a unique opportunity to further investigate the immunogenicity and efficacy of the CYD-TDV vaccine, especially in subjects with different levels of pre-existing immunity against DENV. Modelling multiple immunological outcomes with a single multivariate model offers advantages over traditional approaches, capturing correlations between response variables, and the statistical method adopted in this study can be applied to a variety of infections with interacting strains. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Immunology for rheumatology residents: working toward a Canadian national curriculum consensus.

PubMed

Chow, Shirley L; Herman-Kideckel, Sari; Mahendira, Dharini; McDonald-Blumer, Heather

2015-01-01

Immunologic mechanisms play an integral role in understanding the pathogenesis and management of rheumatic conditions. Currently, there is limited access to formal instruction in immunology for rheumatology trainees across Canada. The aims of this study were (1) to describe current immunology curricula among adult rheumatology training programs across Canada and (2) to compare the perceived learning needs of rheumatology trainees from the perspective of program directors and trainees to help develop a focused nationwide immunology curriculum. Rheumatology trainees and program directors from adult rheumatology programs across Canada completed an online questionnaire and were asked to rank a comprehensive list of immunology topics. A modified Delphi approach was implemented to obtain consensus on immunology topics. Only 42% of program directors and 31% of trainees felt the current method of teaching immunology was effective. Results illustrate concordance between program directors and trainees for the highest-ranked immunology topics including innate immunity, adaptive immunity, and cells and tissues of the immune system. However, there was discordance among other topics, such as diagnostic laboratory immunology and therapeutics. There is a need to improve immunology teaching in rheumatology training programs. Results show high concordance between the basic immunology topics. This study provides the groundwork for development of future immunology curricula.

EpitopeViewer: a Java application for the visualization and analysis of immune epitopes in the Immune Epitope Database and Analysis Resource (IEDB).

PubMed

Beaver, John E; Bourne, Philip E; Ponomarenko, Julia V

2007-02-21

Structural information about epitopes, particularly the three-dimensional (3D) structures of antigens in complex with immune receptors, presents a valuable source of data for immunology. This information is available in the Protein Data Bank (PDB) and provided in curated form by the Immune Epitope Database and Analysis Resource (IEDB). With continued growth in these data and the importance in understanding molecular level interactions of immunological interest there is a need for new specialized molecular visualization and analysis tools. The EpitopeViewer is a platform-independent Java application for the visualization of the three-dimensional structure and sequence of epitopes and analyses of their interactions with antigen-specific receptors of the immune system (antibodies, T cell receptors and MHC molecules). The viewer renders both 3D views and two-dimensional plots of intermolecular interactions between the antigen and receptor(s) by reading curated data from the IEDB and/or calculated on-the-fly from atom coordinates from the PDB. The 3D views and associated interactions can be saved for future use and publication. The EpitopeViewer can be accessed from the IEDB Web site http://www.immuneepitope.org through the quick link 'Browse Records by 3D Structure.' The EpitopeViewer is designed and been tested for use by immunologists with little or no training in molecular graphics. The EpitopeViewer can be launched from most popular Web browsers without user intervention. A Java Runtime Environment (RJE) 1.4.2 or higher is required.

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia.

PubMed

Yirdaw, Kesetebirhan Delele; Hattingh, Susan

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources.

Prevalence and Predictors of Immunological Failure among HIV Patients on HAART in Southern Ethiopia

PubMed Central

2015-01-01

Immunological monitoring is part of the standard of care for patients on antiretroviral treatment. Yet, little is known about the routine implementation of immunological laboratory monitoring and utilization in clinical care in Ethiopia. This study assessed the pattern of immunological monitoring, immunological response, level of immunological treatment failure and factors related to it among patients on antiretroviral therapy in selected hospitals in southern Ethiopia. A retrospective longitudinal analytic study was conducted using documents of patients started on antiretroviral therapy. Adequacy of timely immunological monitoring was assessed every six months the first year and every one year thereafter. Immunological response was assessed every six months at cohort level. Immunological failure was based on the criteria: fall of follow-up CD4 cell count to baseline (or below), or CD4 levels persisting below 100 cells/mm3, or 50% fall from on-treatment peak value. A total of 1,321 documents of patients reviewed revealed timely immunological monitoring were inadequate. There was adequate immunological response, with pediatric patients, females, those with less advanced illness (baseline WHO Stage I or II) and those with higher baseline CD4 cell count found to have better immunological recovery. Thirty-nine patients (3%) were not evaluated for immunological failure because they had frequent treatment interruption. Despite overall adequate immunological response at group level, the prevalence of those who ever experienced immunological failure was 17.6% (n=226), while after subsequent re-evaluation it dropped to 11.5% (n=147). Having WHO Stage III/IV of the disease or a higher CD4 cell count at baseline was identified as a risk for immunological failure. Few patients with confirmed failure were switched to second line therapy. These findings highlight the magnitude of the problem of immunological failure and the gap in management. Prioritizing care for high risk patients may help in effective utilization of meager resources. PMID:25961732

21 CFR 866.5090 - Antimitochondrial antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5090 Antimitochondrial antibody immunological test system. (a) Identification. An... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antimitochondrial antibody immunological test...

21 CFR 866.5750 - Radioallergosorbent (RAST) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5750 Radioallergosorbent (RAST) immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Radioallergosorbent (RAST) immunological test...

21 CFR 866.5500 - Hypersensitivity pneumonitis immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5500 Hypersensitivity pneumonitis immunological test system. (a) Identification. A... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Hypersensitivity pneumonitis immunological test...

The Importance of TLR2 and Macrophages in Modulating a Humoral Response after Encountering Streptococcus pneumoniae

DTIC Science & Technology

2008-03-26

Response after Encountering Streptococcus Pneumoniae" Brian Schae:5 ,Ph.D. Department of Microbi ogy & Immunology Committee Chairperson Masters...presenting cells (APCs), such as macrophages (M ) and dendritic cells (DC) recognize microbial surface components via cell surface receptors (i.e...stimulating factor (GM-CSF). TH1 cells are able to secrete IFN- , which is important in activating M to produce mediators important for microbial

21 CFR 866.5180 - Fecal calprotectin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5180 Fecal calprotectin immunological test system. (a) Identification. A fecal calprotectin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fecal calprotectin immunological test system. 866...

21 CFR 866.5560 - Lactic dehydrogenase immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5560 Lactic dehydrogenase immunological test system. (a) Identification. A lactic dehydrogenase... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Lactic dehydrogenase immunological test system...

21 CFR 866.5660 - Multiple autoantibodies immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5660 Multiple autoantibodies immunological test system. (a) Identification. A multiple autoantibodies... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Multiple autoantibodies immunological test system...

21 CFR 866.5870 - Thyroid autoantibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5870 Thyroid autoantibody immunological test system. (a) Identification. A thyroid autoantibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Thyroid autoantibody immunological test system...

21 CFR 866.5110 - Antiparietal antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5110 Antiparietal antibody immunological test system. (a) Identification. An antiparietal antibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antiparietal antibody immunological test system...

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5100 Antinuclear antibody immunological test system. (a) Identification. An antinuclear antibody... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antinuclear antibody immunological test system...

Two subunits of the 55 K porcine zona pellucida glycoprotein family are immunologically distinct

DOE Office of Scientific and Technical Information (OSTI.GOV)

Subramanian, M.G.; Yurewicz, E.C.; Sacco, A.G.

1986-03-01

The 55K glycoprotein family (ZP3) of the porcine zona pellucida is comprised of two subunits of 46 K and 45 K which can be resolved by endo-..beta..-galactosidase digestion of ZP3 followed by reversed phase HPLC on Vydac C4 resin. Gel electrophoresis revealed that the 46 K component (EBDG..cap alpha..) is approx. 95% pure and the 45 K component (EBGD..beta..) is 100% pure. In the present study, these two subunits were evaluated immunologically by RIA. Under similar reaction protocols (chloramine-T iodination procedure) comparable specific activities were obtained for EBGD..cap alpha.. (33.06 +/- 7.5 ..mu..ci/..mu..gm), EBGD..beta.. (30.45 +/- 1.6) and ZP3 (26.3more » +/- 1.3). Antibody (Ab) titration studies revealed that EBGD..cap alpha.. and ..beta.. are potent immunogens and /sup 125/I-EBGD..cap alpha.. showed minimal cross reactivity to EBGD..beta..-Ab (8% bound at 1:500 dilution), whereas, /sup 125/I-EBGD..beta.. showed a greater degree of cross reactivity to EBGD..cap alpha..-Ab (23% bound at 1:500 dilution). Maximum binding for the two labeled antigens against homologous Abs (1:500) was > 60%. Dose response studies revealed that in the /sup 125/I-EBGD..cap alpha.. vs EBGD..cap alpha.. -Ab system, the 50% intercept was 3.25 +/- 0.32 ng for EBGD..cap alpha.. and 472.43 +/- 30.26 ng for EBGD..beta.. (p < 0.01), whereas, in the /sup 125/I-EBGD..beta.. vs EBGD..beta..-Ab system the 50% intercept was 3.51 +/- 0.58 for EBGD..beta.. and 166.77 +/- 49.20 for EBGD..cap alpha.. (p < 0.01). No significant differences were observed in the slopes of the dose response curves. It is concluded that the two subunits of ZP3 possess distinct immunologic characteristics as evaluated by RIA.« less

21 CFR 866.5080 - Alpha-1-antichymotrypsin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5080 Alpha-1-antichymotrypsin immunological test system. (a) Identification. An alpha-1... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antichymotrypsin immunological test system...

21 CFR 866.5120 - Antismooth muscle antibody immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5120 Antismooth muscle antibody immunological test system. (a) Identification. An antismooth... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Antismooth muscle antibody immunological test...

Design of three-component vaccines against group A streptococcal infections: importance of spatial arrangement of vaccine components.

PubMed

Abdel-Aal, Abu-Baker M; Zaman, Mehfuz; Fujita, Yoshio; Batzloff, Michael R; Good, Michael F; Toth, Istvan

2010-11-25

Immunological assessment of group A streptococcal (GAS) branched lipopeptides demonstrated the impact of spatial arrangement of vaccine components on both the quality and quantity of their immune responses. Each lipopeptide was composed of three components: a GAS B-cell epitope (J14), a universal CD4(+) T-cell helper epitope (P25), and an immunostimulant lipid moiety that differs only in its spatial arrangement. The best systemic immune responses were demonstrated by a lipopeptide featuring the lipid moiety at the lipopeptide C-terminus. However, this candidate did not achieve protection against bacterial challenge. The best protection (100%) was shown by a lipopeptide featuring a C-terminal J14, conjugated through a lysine residue to P25 at the N-terminus, and a lipid moiety on the lysine side chain. The former candidate features α-helical conformation required to produce protective J14-specific antibodies. Our results highlight the importance of epitope orientation and lipid position in the design of three-component synthetic vaccines.

21 CFR 866.5630 - Beta-2-microglobulin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5630 Beta-2-microglobulin immunological test system. (a) Identification. A beta-2-microglobulin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-microglobulin immunological test system...

21 CFR 866.5530 - Immunoglobulin G (Fc fragment specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) immunological test system. 866.5530 Section 866.5530 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5530 Immunoglobulin G (Fc fragment specific) immunological test system. (a...

21 CFR 866.5620 - Alpha-2-macroglobulin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5620 Alpha-2-macroglobulin immunological test system. (a) Identification. An alpha-2-macroglobulin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-2-macroglobulin immunological test system...

21 CFR 866.5540 - Immunoglobulin G (Fd fragment specific) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) immunological test system. 866.5540 Section 866.5540 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5540 Immunoglobulin G (Fd fragment specific) immunological test system. (a...

21 CFR 866.5130 - Alpha-1-antitrypsin immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5130 Alpha-1-antitrypsin immunological test system. (a) Identification. An alpha-1-antitrypsin... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-antitrypsin immunological test system. 866...

21 CFR 866.5800 - Seminal fluid (sperm) immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5800 Seminal fluid (sperm) immunological test system. (a) Identification. A seminal fluid (sperm... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Seminal fluid (sperm) immunological test system...

21 CFR 866.5600 - Low-density lipoprotein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5600 Low-density lipoprotein immunological test system. (a) Identification. A low-density lipoprotein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Low-density lipoprotein immunological test system...

21 CFR 866.5890 - Inter-alpha trypsin inhibitor immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5890 Inter-alpha trypsin inhibitor immunological test system. (a) Identification. An inter... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Inter-alpha trypsin inhibitor immunological test...

21 CFR 866.5065 - Human allotypic marker immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5065 Human allotypic marker immunological test system. (a) Identification. A human allotypic marker... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human allotypic marker immunological test system...

21 CFR 866.5765 - Retinol-binding protein immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5765 Retinol-binding protein immunological test system. (a) Identification. A retinol-binding protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Retinol-binding protein immunological test system...

21 CFR 866.6010 - Tumor-associated antigen immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tumor-associated antigen immunological test system... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6010 Tumor-associated antigen immunological test system. (a) Identification. A...

Development of the infant intestinal microbiome: A bird's eye view of a complex process.

PubMed

Meropol, Sharon B; Edwards, Amy

2015-12-01

Infants undergo profound shifts in colonizing intestinal microorganisms during their first year, especially during and after birth and during weaning. Microbiota are passed to infants through the placenta, during the vaginal birth process, and from early diet and other environmental exposures. These microbiota play an active role in the development of healthy infant metabolic and immunologic systems; profound shifts in microbiotal populations can be persistent, are associated with immediate alterations in gene expression, metabolic, immunologic, and neurologic function, and with downstream metabolic and immunologic consequences such as obesity, allergies, asthma, autoimmune diseases, and potentially neurologic conditions. Many modern exposures, including Cesarean section, formula feeding, and antibiotics, have been associated with microbiome shifts, and also with downstream diseases; while many published studies considered exposures individually, a more comprehensive understanding of their interaction and impact will consider the entirety of the infant's environment. It is not possible, nor desirable, to return to a world without toilets, sewers, tap water, delivery room antisepsis, Cesarean sections, antibiotics, immunizations, and refrigerators; our other alternative is to better understand these complex changes in infant developmental and molecular physiology. Protecting and repairing the developmental processes of the healthy infant microbiome is the modern medical frontier. © 2015 Wiley Periodicals, Inc.

The importance of antineuraminidase antibodies in resistance to influenza A and immunologic memory for their synthesis.

PubMed Central

Naikhin, A. N.; Tsaritsina, I. M.; Oleinikova, E. V.; Syrodoeva, L. G.; Korchanova, N. L.; Denisov, G. M.; Shvartsman YaS

1983-01-01

Eight hundred and seventy-seven sera from 360 adults aged 18-50 who were under permanent observation from October 1980 to March 1981 have been studied by haemagglutination-inhibition (HI) and erythrocyte elution-inhibition (EI) tests--a simplified method of antineuraminidase antibody titration. It was demonstrated in some subjects infected with influenza A H1N1 and H3N2 viruses that the antibody rise was to one of the surface antigens only--haemagglutinin or neuraminidase. These subjects made up 5.2-25.8% of all examinees. The protective effect of antibodies to neuraminidase was similar to that of antihaemagglutinins. Interaction of both types of antibodies was observed in protection against the disease. Data have been obtained on the influence of antineuraminidase antibodies in decreasing the severity of natural infection with influenza A. A study of heterologous immunologic responses to haemagglutinin and neuraminidase among persons immunized with live influenza A H1N1 and H3N2 vaccines and among children naturally infected with influenza A H3N2 demonstrated the presence of immunologic memory for antineuraminidase antibody synthesis. Thus, the suggestion of a common antigenic structure for neuraminidase N1 and N2 is made. PMID:6886409

Granulocyte-associated IgG in neutropenic disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cines, D.B.; Passero, F.; Guerry, D. IV

We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevatedmore » PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from noneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.« less

Granulocyte-associated IgG in neutropenic disorders

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cines, D.B.; Passero, F.; Guerry, D.

We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevatedmore » PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from nonneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder.« less

Grooming Behavior as a Mechanism of Insect Disease Defense.

PubMed

Zhukovskaya, Marianna; Yanagawa, Aya; Forschler, Brian T

2013-11-04

Grooming is a well-recognized, multipurpose, behavior in arthropods and vertebrates. In this paper, we review the literature to highlight the physical function, neurophysiological mechanisms, and role that grooming plays in insect defense against pathogenic infection. The intricate relationships between the physical, neurological and immunological mechanisms of grooming are discussed to illustrate the importance of this behavior when examining the ecology of insect-pathogen interactions.

A comparison of the biological properties of small molecular weight agonists and antagonists of CD200:CD200R interactions.

PubMed

Gorczynski, Reg; Boudakov, Ivo; Khatri, Ismat

2008-11-01

Our laboratory and others have documented in some detail the immunological consequences which follow from interaction of the ubiquitously expressed molecule CD200 with its receptor(s) CD200R (expressed predominantly on cells of myeloid and lymphoid origin). In particular, there is evidence that these interactions lead to immunosuppressive signals which modulate graft rejection responses; decrease the manifestations of arthritis in rodent models; diminish mast cell mediator release in models of allergic disease; and favour the growth of tumors in both mice and humans. The development of small molecular weight agonists (and/or antagonists) of these interactions would thus likely have significant clinical importance. The data reported herein characterizes several such molecules in a number of rodent models.

A roadmap towards personalized immunology.

PubMed

Delhalle, Sylvie; Bode, Sebastian F N; Balling, Rudi; Ollert, Markus; He, Feng Q

2018-01-01

Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions. There is still a long way ahead on translating our capability to identify potentially targetable personalized biomarkers into effective personalized therapy in immune-centralized diseases. Here, we discuss the recent advances and successful applications in "Omics" data utilization and network analysis on patients' samples of clinical trials and studies, as well as the major challenges and strategies towards personalized stratification and treatment for infectious or non-communicable inflammatory diseases such as autoimmune diseases or allergies. We provide a roadmap and highlight experimental, clinical, computational analysis, data management, ethical and regulatory issues to accelerate the implementation of personalized immunology.

Neuroinflammation in Alzheimer's Disease

PubMed Central

Heneka, Michael T.; Carson, Monica J.; El Khoury, Joseph; Landreth, Gary E.; Brosseron, Frederik; Feinstein, Douglas L.; Jacobs, Andreas H.; Wyss-Coray, Tony; Vitorica, Javier; Ransohoff, Richard M.; Herrup, Karl; Frautschy, Sally A.; Finsen, Bente; Brown, Guy C.; Verkhratsky, Alexei; Yamanaka, Koji; Koistinaho, Jari; Latz, Eicke; Halle, Annett; Petzold, Gabor C.; Town, Terrence; Morgan, Dave; Shinohara, Mari L.; Perry, V. Hugh; Holmes, Clive; Bazan, Nicolas G.; Brooks, David J.; Hunot, Stephane; Joseph, Bertrand; Deigendesch, Nikolaus; Garaschuk, Olga; Boddeke, Erik; Dinarello, Charles A.; Breitner, John C.; Cole, Greg M.; Golenbock, Douglas T.; Kummer, Markus P.

2018-01-01

Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment but strongly interacts with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on micro- and astroglia and trigger an innate immune response, characterized by the release of inflammatory mediators, which contribute to disease progression and severity. Genome wide analysis suggests that several genes, which increase the risk for sporadic Alzheimer's disease en-code for factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity are likely to interfere with the immunological processes of the brain and further promote disease progression. This re-view provides an overview on the current knowledge and focuses on the most recent and exciting findings. Modulation of risk factors and intervention with the described immune mechanisms are likely to lead to future preventive or therapeutic strategies for Alzheimer's disease. PMID:25792098

Nanoparticles and direct immunosuppression

PubMed Central

Ngobili, Terrika A

2016-01-01

Targeting the immune system with nanomaterials is an intensely active area of research. Specifically, the capability to induce immunosuppression is a promising complement for drug delivery and regenerative medicine therapies. Many novel strategies for immunosuppression rely on nanoparticles as delivery vehicles for small-molecule immunosuppressive compounds. As a consequence, efforts in understanding the mechanisms in which nanoparticles directly interact with the immune system have been overshadowed. The immunological activity of nanoparticles is dependent on the physiochemical properties of the nanoparticles and its subsequent cellular internalization. As the underlying factors for these reactions are elucidated, more nanoparticles may be engineered and evaluated for inducing immunosuppression and complementing immunosuppressive drugs. This review will briefly summarize the state-of-the-art and developments in understanding how nanoparticles induce immunosuppressive responses, compare the inherent properties of nanomaterials which induce these immunological reactions, and comment on the potential for using nanomaterials to modulate and control the immune system. PMID:27229901

Antisperm antibodies and fertility association.

PubMed

Restrepo, B; Cardona-Maya, W

2013-10-01

To evaluate the relation between antisperm antibodies (ASA) and human fertility by reviewing the scientific literature of the last 45 years. We carried out a review of scientific literature about antisperm antibodies and infertility published in spanish or english in databases as Pubmed, Medline, Scielo, some books and another gray literature include information related to this review and that is published in the last 45 years. Infertile couples suffer infertility by immunological mechanisms mainly by the presence of antisperm antibodies ASA in blood, semen or cervicovaginal secretions; the formation of ASA in men and women may be associated with disturbance in immunomodulatory mechanisms that result in functional impairment of sperm and thus its inability to fertilize the oocyte. Immunological infertility caused by ASA is the result of interference of these antibodies in various stages of fertilization process, inhibiting the ability of interaction between sperm and oocyte. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

Immunological multimetal deposition for rapid visualization of sweat fingerprints.

PubMed

He, Yayun; Xu, Linru; Zhu, Yu; Wei, Qianhui; Zhang, Meiqin; Su, Bin

2014-11-10

A simple method termed immunological multimetal deposition (iMMD) was developed for rapid visualization of sweat fingerprints with bare eyes, by combining the conventional MMD with the immunoassay technique. In this approach, antibody-conjugated gold nanoparticles (AuNPs) were used to specifically interact with the corresponding antigens in the fingerprint residue. The AuNPs serve as the nucleation sites for autometallographic deposition of silver particles from the silver staining solution, generating a dark ridge pattern for visual detection. Using fingerprints inked with human immunoglobulin G (hIgG), we obtained the optimal formulation of iMMD, which was then successfully applied to visualize sweat fingerprints through the detection of two secreted polypeptides, epidermal growth factor and lysozyme. In comparison with the conventional MMD, iMMD is faster and can provide additional information than just identification. Moreover, iMMD is facile and does not need expensive instruments. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

21 CFR 866.5270 - C-reactive protein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5270 C-reactive protein immuno-logical test system. (a) Identification. A C-reactive protein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false C-reactive protein immuno-logical test system. 866...

21 CFR 866.5440 - Beta-2-glycoprotein III immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5440 Beta-2-glycoprotein III immunological test system. (a) Identification. A beta-2-glycoprotein III... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-glycoprotein III immunological test system...

21 CFR 866.5200 - Carbonic anhydrase B and C immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5200 Carbonic anhydrase B and C immunological test system. (a) Identification. A carbonic... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Carbonic anhydrase B and C immunological test...

21 CFR 866.5430 - Beta-2-glycoprotein I immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5430 Beta-2-glycoprotein I immunological test system. (a) Identification. A beta-2-glycoprotein I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Beta-2-glycoprotein I immunological test system...

21 CFR 866.5260 - Complement C3b inactivator immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5260 Complement C3b inactivator immunological test system. (a) Identification. A complement... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Complement C3b inactivator immunological test...

21 CFR 866.5580 - Alpha-1-lipoprotein immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5580 Alpha-1-lipoprotein immuno-logical test system. (a) Identification. An alpha-1-lipoprotein... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Alpha-1-lipoprotein immuno-logical test system...

21 CFR 866.5330 - Factor XIII, A, S, immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5330 Factor XIII, A, S, immuno-logical test system. (a) Identification. A factor XIII, A, S... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Factor XIII, A, S, immuno-logical test system. 866...

Genetically detoxified pertussis toxin (PT-9K/129G): implications for immunization and vaccines.

PubMed

Seubert, Anja; D'Oro, Ugo; Scarselli, Maria; Pizza, Mariagrazia

2014-10-01

Pertussis toxin (PT) is one of the major virulence factors of Bordetella pertussis and the primary component of all pertussis vaccines available to date. Because of its various noxious effects the toxin needs to be detoxified. In all currently available vaccines, detoxification is achieved by treatment with high quantity of chemical agents such as formaldehyde, glutaraldehyde or hydrogen peroxide. Although effective in detoxification, this chemical treatment alters dramatically the immunological properties of the toxin. In contrast, PT genetically detoxified through the substitution of two residues necessary for its enzymatic activity maintains all functional and immunological properties. This review describes in detail the characteristics of this PT-9K/129G mutant and shows that it is non-toxic and a superior immunogen compared with chemically detoxified PT. Importantly, data from an efficacy trial show that the PT-9K/129G-based vaccine induces earlier and longer-lasting protection, further supporting the hypothesis that PT-9K/129G represents an ideal candidate for future pertussis vaccine formulations.

Quantitative imaging assay for NF-κB nuclear translocation in primary human macrophages

PubMed Central

Noursadeghi, Mahdad; Tsang, Jhen; Haustein, Thomas; Miller, Robert F.; Chain, Benjamin M.; Katz, David R.

2008-01-01

Quantitative measurement of NF-κB nuclear translocation is an important research tool in cellular immunology. Established methodologies have a number of limitations, such as poor sensitivity, high cost or dependence on cell lines. Novel imaging methods to measure nuclear translocation of transcriptionally active components of NF-κB are being used but are also partly limited by the need for specialist imaging equipment or image analysis software. Herein we present a method for quantitative detection of NF-κB rel A nuclear translocation, using immunofluorescence microscopy and the public domain image analysis software ImageJ that can be easily adopted for cellular immunology research without the need for specialist image analysis expertise and at low cost. The method presented here is validated by demonstrating the time course and dose response of NF-κB nuclear translocation in primary human macrophages stimulated with LPS, and by comparison with a commercial NF-κB activation reporter cell line. PMID:18036607

The Impact of Neuroimmune Alterations in Autism Spectrum Disorder

PubMed Central

Gottfried, Carmem; Bambini-Junior, Victorio; Francis, Fiona; Riesgo, Rudimar; Savino, Wilson

2015-01-01

Autism spectrum disorder (ASD) involves a complex interplay of both genetic and environmental risk factors, with immune alterations and synaptic connection deficiency in early life. In the past decade, studies of ASD have substantially increased, in both humans and animal models. Immunological imbalance (including autoimmunity) has been proposed as a major etiological component in ASD, taking into account increased levels of pro-inflammatory cytokines observed in postmortem brain from patients, as well as autoantibody production. Also, epidemiological studies have established a correlation of ASD with family history of autoimmune diseases; associations with major histocompatibility complex haplotypes and abnormal levels of immunological markers in the blood. Moreover, the use of animal models to study ASD is providing increasing information on the relationship between the immune system and the pathophysiology of ASD. Herein, we will discuss the accumulating literature for ASD, giving special attention to the relevant aspects of factors that may be related to the neuroimmune interface in the development of ASD, including changes in neuroplasticity. PMID:26441683

No more non-model species: the promise of next generation sequencing for comparative immunology.

PubMed

Dheilly, Nolwenn M; Adema, Coen; Raftos, David A; Gourbal, Benjamin; Grunau, Christoph; Du Pasquier, Louis

2014-07-01

Next generation sequencing (NGS) allows for the rapid, comprehensive and cost effective analysis of entire genomes and transcriptomes. NGS provides approaches for immune response gene discovery, profiling gene expression over the course of parasitosis, studying mechanisms of diversification of immune receptors and investigating the role of epigenetic mechanisms in regulating immune gene expression and/or diversification. NGS will allow meaningful comparisons to be made between organisms from different taxa in an effort to understand the selection of diverse strategies for host defence under different environmental pathogen pressures. At the same time, it will reveal the shared and unique components of the immunological toolkit and basic functional aspects that are essential for immune defence throughout the living world. In this review, we argue that NGS will revolutionize our understanding of immune responses throughout the animal kingdom because the depth of information it provides will circumvent the need to concentrate on a few "model" species. Copyright © 2014 Elsevier Ltd. All rights reserved.

Recycling endosomes in human cytotoxic T lymphocytes constitute an auxiliary intracellular trafficking pathway for newly synthesized perforin.

PubMed

Lesteberg, Kelsey; Orange, Jordan; Makedonas, George

2017-10-01

Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein, we aimed to determine how new perforin transits to the synapse if not via lytic granules. We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin. The recycling endosome compartments identified by rab8, rab11a, rab4, and rab37 co-localized with new perforin, as well as the SNAREs vti1b and VAMP4. After ablating the function of the recycling endosome pathway, we observed a relative accumulation of new perforin in rab8 vesicles. The recycling endosome pathway may serve as an auxiliary intracellular route for the delivery of new perforin to an immunologic synapse in order to perpetuate a cytotoxic response.

Recycling endosomes in human cytotoxic T lymphocytes constitute an auxiliary intracellular trafficking pathway for newly synthesized perforin

PubMed Central

Lesteberg, Kelsey E.; Orange, Jordan S.; Makedonas, George

2018-01-01

Background Although cytotoxic T lymphocytes (CTLs) store perforin within cytoplasmic secretory granules for immediate use, perforin is synthesized anew within hours of TCR stimulation. Previously, we observed new perforin protein at an immunologic synapse independent of secretory lysosomes; herein we aimed to determine how new perforin transits to the synapse if not via lytic granules. Results We analyzed antigen-specific human CTLs via imaging flow cytometry and high-resolution confocal microscopy, with attention to intracellular trafficking components and new perforin. The recycling endosome compartments identified by rab8, rab11a, rab4, and rab37 co-localized with new perforin, as well as the SNAREs vti1b and VAMP4. After ablating the function of the recycling endosome pathway, we observed a relative accumulation of new perforin in rab8 vesicles. Conclusions The recycling endosome pathway may serve as an auxiliary intracellular route for the delivery of new perforin to an immunologic synapse in order to perpetuate a cytotoxic response. PMID:28822075

Immunology for physicists

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perelson, A.S.; Weisbuch, G.

1997-10-01

The immune system is a complex system of cells and molecules that can provide us with a basic defense against pathogenic organisms. Like the nervous system, the immune system performs pattern recognition tasks, learns, and retains a memory of the antigens that it has fought. The immune system contains more than 10{sup 7} different clones of cells that communicate via cell-cell contact and the secretion of molecules. Performing complex tasks such as learning and memory involves cooperation among large numbers of components of the immune system and hence there is interest in using methods and concepts from statistical physics. Furthermore,more » the immune response develops in time and the description of its time evolution is an interesting problem in dynamical systems. In this paper, the authors provide a brief introduction to the biology of the immune system and discuss a number of immunological problems in which the use of physical concepts and mathematical methods has increased our understanding. {copyright} {ital 1997} {ital The American Physical Society}« less

Photothermal therapy with immune-adjuvant nanoparticles together with checkpoint blockade for effective cancer immunotherapy

NASA Astrophysics Data System (ADS)

Chen, Qian; Xu, Ligeng; Liang, Chao; Wang, Chao; Peng, Rui; Liu, Zhuang

2016-10-01

A therapeutic strategy that can eliminate primary tumours, inhibit metastases, and prevent tumour relapses is developed herein by combining adjuvant nanoparticle-based photothermal therapy with checkpoint-blockade immunotherapy. Indocyanine green (ICG), a photothermal agent, and imiquimod (R837), a Toll-like-receptor-7 agonist, are co-encapsulated by poly(lactic-co-glycolic) acid (PLGA). The formed PLGA-ICG-R837 nanoparticles composed purely by three clinically approved components can be used for near-infrared laser-triggered photothermal ablation of primary tumours, generating tumour-associated antigens, which in the presence of R837-containing nanoparticles as the adjuvant can show vaccine-like functions. In combination with the checkpoint-blockade using anti-cytotoxic T-lymphocyte antigen-4 (CTLA4), the generated immunological responses will be able to attack remaining tumour cells in mice, useful in metastasis inhibition, and may potentially be applicable for various types of tumour models. Furthermore, such strategy offers a strong immunological memory effect, which can provide protection against tumour rechallenging post elimination of their initial tumours.

Towards integrating extracellular matrix and immunological pathways.

PubMed

Boyd, David F; Thomas, Paul G

2017-10-01

The extracellular matrix (ECM) is a complex and dynamic structure made up of an estimated 300 different proteins. The ECM is also a rich source of cytokines and growth factors in addition to numerous bioactive ECM degradation products that influence cell migration, proliferation, and differentiation. The ECM is constantly being remodeled during homeostasis and in a wide range of pathological contexts. Changes in the ECM modulate immune responses, which in turn regulate repair and regeneration of tissues. Here, we review the many components of the ECM, enzymes involved in ECM remodeling, and the signals that feed into immunological pathways in the context of a dynamic ECM. We highlight studies that have taken an integrative approach to studying immune responses in the context of the ECM and studies that use novel proteomic strategies. Finally, we discuss research challenges relevant to the integration of immune and ECM networks and propose experimental and translational approaches to resolve these issues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Modeling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.

PubMed

Baral, Subhasish; Roy, Rahul; Dixit, Narendra M

2018-05-09

A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT + /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT + /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment. Whether the hypothesis is consistent with data of viral load changes in patients who experienced EOT + /SVR is unknown. Here, we constructed a mathematical model of viral kinetics incorporating the immunologic hypothesis and compared its predictions with patient data. We found the predictions to be in quantitative agreement with patient data. Using the model, we unraveled an underlying bistability that gives rise to EOT + /SVR and presents a new avenue to optimize treatment durations. Infected cells trigger both activation and exhaustion of CTLs. CTLs in turn kill infected cells. Due to these competing interactions, two stable steady states, chronic infection and viral clearance, emerge, separated by an unstable steady state with intermediate viremia. When treatment during chronic infection drives viremia sufficiently below the unstable state, spontaneous viral clearance results post-treatment, marking EOT + /SVR. The duration to achieve this desired reduction in viremia defines the minimum treatment duration required for ensuring SVR, which our model can quantify. Estimating parameters defining the CTL response of individuals to HCV infection would enable the application of our model to personalize treatment durations. © 2018 The Authors Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of Australasian Society for Immunology Inc.

Association between discordant immunological response to highly active anti-retroviral therapy, regulatory T cell percentage, immune cell activation and very low-level viraemia in HIV-infected patients

PubMed Central

Saison, J; Ferry, T; Demaret, J; Maucort Boulch, D; Venet, F; Perpoint, T; Ader, F; Icard, V; Chidiac, C; Monneret, G

2014-01-01

The mechanisms sustaining the absence of complete immune recovery in HIV-infected patients upon long-term effective highly active anti-retroviral therapy (HAART) remain elusive. Immune activation, regulatory T cells (Tregs) or very low-level viraemia (VLLV) have been alternatively suspected, but rarely investigated simultaneously. We performed a cross-sectional study in HIV-infected aviraemic subjects (mean duration of HAART: 12 years) to concomitantly assess parameters associated independently with inadequate immunological response. Patients were classified as complete immunological responders (cIR, n = 48) and inadequate immunological responders (iIR, n = 39), depending on the CD4+ T cell count (> or < 500/mm3). Clinical and virological data (including very low-level viraemia) were collected. In parallel, immunophenotyping of CD4+ lymphocytes, including Treg subsets, and CD8+ T cells was performed. Percentages of activated CD4+ T cells, Tregs, effector Tregs and terminal effector Tregs were found to be significantly elevated in iIR. Neither the percentage of activated CD8+ T cells nor VLLV were found to be associated with iIR. In the multivariate analysis, nadir of CD4+ T cell count and percentage of Tregs were the only two parameters associated independently with iIR [odds ratio (OR) = 2·339, P = 0·001, and OR = 0·803, P = 0·041]. We present here the largest study investigating simultaneously the immune response to long-term HAART, activation of CD4+ and CD8+ T cells, Treg percentages and very low-level viraemia. Causative interactions between Tregs and CD4+ T cells should now be explored prospectively in a large patients cohort. PMID:24460818

21 CFR 866.6030 - AFP-L3% immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false AFP-L3% immunological test system. 866.6030 Section 866.6030 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Tumor Associated Antigen immunological Test Systems § 866.6030 AFP-L3% immunological test...

The interplay between pH sensitivity and label-free protein detection in immunologically modified nano-scaled field-effect transistor.

PubMed

Shalev, Gil; Rosenwaks, Yossi; Levy, Ilan

2012-01-15

We present experimental results in order to establish a correlation between pH sensitivity of immunologically modified nano-scaled field-effect transistor (NS-ImmunoFET) with their sensing capacity for label-free detection. The NS-ImmunoFETs are fabricated from silicon-on-insulator (SOI) wafers and are fully-depleted with thickness of ~20 nm. The data shows that higher sensitivity to pH entails enhanced sensitivity to analyte detection. This suggests that the mechanism of analyte detection as pure electrostatic perturbation induced by antibody-analyte interaction is over simplified. The fundamental assumption, in existing models for field-effect sensing mechanism assumes that the analyte molecules do not directly interact with the surface but rather stand 'deep' in the solution and away from the dielectric surface. Recent studies clearly provide contradicting evidence demonstrating that antibodies lie down flat on the surface. These observations led us to propose that the proteins that cover the gate area intimately interact with active sites on the surface thus forming a network of interacting sites. Since sensitivity to pH is directly correlated with the amount of amphoteric sites, we witness a direct correlation between sensitivity to pH and analyte detection. The highest and lowest threshold voltage shift for a label-free and specific detection of 6.5 nM IgG were 40 mV and 2.3 mV for NS-ImmunoFETs with pH sensitivity of 35 mV/decade and 15 mV/decade, respectively. Finally, physical modeling of the NS-ImmunoFET is presented and charge of a single IgG protein at pH 6 is calculated. The obtained value is consistent with charge of IgG protein cited in literature. Copyright © 2011 Elsevier B.V. All rights reserved.

Randomized trial of vitamin supplements in relation to transmission of HIV-1 through breastfeeding and early child mortality.

PubMed

Fawzi, Wafaie W; Msamanga, Gernard I; Hunter, David; Renjifo, Boris; Antelman, Gretchen; Bang, Heejung; Manji, Karim; Kapiga, Saidi; Mwakagile, Davis; Essex, Max; Spiegelman, Donna

2002-09-27

HIV-1 transmission through breastfeeding is a global problem and has been associated with poor maternal micronutrient status. A total of 1078 HIV-infected pregnant women from Tanzania were randomly assigned to vitamin A or multivitamins excluding A from approximately 20 weeks' gestation and throughout lactation. Multivitamins excluding A had no effect on the total risk of HIV-1 transmission (RR 1.04, 95% CI 0.82-1.32, P= 0.76). Vitamin A increased the risk of transmission (RR 1.38, 95% CI 1.09-1.76, P = 0.009). Multivitamins were associated with non-statistically significant reductions in transmission through breastfeeding, and mortality by 24 months among those alive and not infected at 6 weeks. Multivitamins significantly reduced breastfeeding transmission in infants of mothers with low baseline lymphocyte counts (RR 0.37; 95% CI 0.16-0.85, P = 0.02) compared with infants of mothers with higher counts (RR 0.99, 95% CI 0.68-1.45, P = 0.97; -for-interaction 0.03). Multivitamins also protected against transmission among mothers with a high erythrocyte sedimentation rate (P-for-interaction 0.06), low hemoglobin (P-for-interaction 0.06), and low birthweight babies (P-for-interaction 0.04). Multivitamins reduced death and prolonged HIV-free survival significantly among children born to women with low maternal immunological or nutritional status. Vitamin A alone increased breastfeeding transmission but had no effect on mortality by 24 months. Vitamin A increased the risk of HIV-1 transmission. Multivitamin (B, C, and E) supplementation of breastfeeding mothers reduced child mortality and HIV-1 transmission through breastfeeding among immunologically and nutritionally compromised women. The provision of these supplements to HIV-infected lactating women should be considered.

Photocrosslinking approaches to interactome mapping

PubMed Central

Pham, Nam D.; Parker, Randy B.; Kohler, Jennifer J.

2012-01-01

Photocrosslinking approaches can be used to map interactome networks within the context of living cells. Photocrosslinking methods rely on use of metabolic engineering or genetic code expansion to incorporate photocrosslinking analogs of amino acids or sugars into cellular biomolecules. Immunological and mass spectrometry techniques are used to analyze crosslinked complexes, thereby defining specific interactomes. Because photocrosslinking can be conducted in native, cellular settings, it can be used to define context-dependent interactions. Photocrosslinking methods are also ideally suited for determining interactome dynamics, mapping interaction interfaces, and identifying transient interactions in which intrinsically disordered proteins and glycoproteins engage. Here we discuss the application of cell-based photocrosslinking to the study of specific problems in immune cell signaling, transcription, membrane protein dynamics, nucleocytoplasmic transport, and chaperone-assisted protein folding. PMID:23149092

A Comparison of CAL with a Conventional Method of Delivery of Cell Biology to Undergraduate Nursing Students Using an Experimental Design.

ERIC Educational Resources Information Center

Wharrad, Heather J.; Kent, Christine; Allcock, Nick; Wood, Barry

2001-01-01

In study 1, 12 nursing students attended slide lectures on cell biology; 13 used interactive computer-assisted learning (CAL). Study 2 surveyed 38 students who used CAL to study immunology. Students preferred CAL and felt confident in their grasp of the material, even without the presence of lecturers to answer questions. (Contains 16 references.)…

Immunologic Intervention in HIV Infection: Anti-Polymerase Responses and Hormonal Regulation

DTIC Science & Technology

1993-09-01

chronic human immunodeficiency virus infection is blocked in vitro by a methylphosphonate oligodeoxynucleoside targeted to a U3/enhancer element. J...Grimison B, Gonenne A. 1992. Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. Blood 79...Kong X-B, Chou T-C. Interactions of recombinant human growth hormone with dideoxynucleoside inhibitors of human immunodeficiency virus. Blood, in

Buffalo's Center for Immunology: A New Answer to an Old Dilemma

ERIC Educational Resources Information Center

Rose, Noel R.; Bogazzi, Pierluigi E.

1972-01-01

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)

Nature and Consequences of Biological Reductionism for the Immunological Study of Infectious Diseases.

PubMed

Rivas, Ariel L; Leitner, Gabriel; Jankowski, Mark D; Hoogesteijn, Almira L; Iandiorio, Michelle J; Chatzipanagiotou, Stylianos; Ioannidis, Anastasios; Blum, Shlomo E; Piccinini, Renata; Antoniades, Athos; Fazio, Jane C; Apidianakis, Yiorgos; Fair, Jeanne M; Van Regenmortel, Marc H V

2017-01-01

Evolution has conserved "economic" systems that perform many functions, faster or better, with less. For example, three to five leukocyte types protect from thousands of pathogens. To achieve so much with so little, biological systems combine their limited elements, creating complex structures. Yet, the prevalent research paradigm is reductionist. Focusing on infectious diseases, reductionist and non-reductionist views are here described. The literature indicates that reductionism is associated with information loss and errors, while non-reductionist operations can extract more information from the same data. When designed to capture one-to-many/many-to-one interactions-including the use of arrows that connect pairs of consecutive observations-non-reductionist (spatial-temporal) constructs eliminate data variability from all dimensions, except along one line, while arrows describe the directionality of temporal changes that occur along the line. To validate the patterns detected by non-reductionist operations, reductionist procedures are needed. Integrated (non-reductionist and reductionist) methods can (i) distinguish data subsets that differ immunologically and statistically; (ii) differentiate false-negative from -positive errors; (iii) discriminate disease stages; (iv) capture in vivo , multilevel interactions that consider the patient, the microbe, and antibiotic-mediated responses; and (v) assess dynamics. Integrated methods provide repeatable and biologically interpretable information.

How advances in immunology provide insight into improving vaccine efficacy

PubMed Central

Slifka, Mark K.; Amanna, Ian

2014-01-01

Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations. PMID:24709587

Elongated fibrillar structure of a streptococcal adhesin assembled by the high-affinity association of [alpha]- and PPII-helices

DOE Office of Scientific and Technical Information (OSTI.GOV)

Larson, Matthew R.; Rajashankar, Kanagalaghatta R.; Patel, Manisha H.

2010-08-18

Streptococcus mutans antigen I/II (AgI/II) is a cell surface-localized protein adhesin that interacts with salivary components within the salivary pellicle. AgI/II contributes to virulence and has been studied as an immunological and structural target, but a fundamental understanding of its underlying architecture has been lacking. Here we report a high-resolution (1.8 {angstrom}) crystal structure of the A{sub 3}VP{sub 1} fragment of S. mutans AgI/II that demonstrates a unique fibrillar form (155 {angstrom}) through the interaction of two noncontiguous regions in the primary sequence. The A{sub 3} repeat of the alanine-rich domain adopts an extended {alpha}-helix that intertwines with the P{submore » 1} repeat polyproline type II (PPII) helix to form a highly extended stalk-like structure heretofore unseen in prokaryotic or eukaryotic protein structures. Velocity sedimentation studies indicate that full-length AgI/II that contains three A/P repeats extends over 50 nanometers in length. Isothermal titration calorimetry revealed that the high-affinity association between the A{sub 3} and P{sub 1} helices is enthalpically driven. Two distinct binding sites on AgI/II to the host receptor salivary agglutinin (SAG) were identified by surface plasmon resonance (SPR). The current crystal structure reveals that AgI/II family proteins are extended fibrillar structures with the number of alanine- and proline-rich repeats determining their length.« less

Vaccination ecosystem health check: achieving impact today and sustainability for tomorrow.

PubMed

Saadatian-Elahi, Mitra; Bloom, David; Plotkin, Stanley; Picot, Valentina; Louis, Jacques; Watson, Michael

2017-01-01

Vaccination is a complex ecosystem with several components that interact with one another and with the environment. Today's vaccine ecosystem is defined by the pursuit of polio eradication, the drive to get as many of the new vaccines to as many people as possible and the research and development against immunologically challenging diseases. Despite these successes, vaccine ecosystem is facing keys issues with regard to supply/distribution and cost/profitability asymmetry that risk slowing its global growth. The conference "Vaccination ecosystem health check: achieving impact today and sustainability for tomorrow" held in Annecy-France (January 19-21, 2015) took stock of the health of today's vaccination ecosystem and its ability to reliably and sustainably supply high-quality vaccines while investing in tomorrow's needed innovation. Small and decreasing numbers of suppliers/manufacturing facilities; paucity of research-driven companies; regulatory pressures; market uncertainties; political prioritization; anti-vaccine movements/complacency; and technological and programmatic issues were acknowledged as the major challenges that could weaken today's vaccination ecosystem. The expert panel discussed also drivers and barriers to a sustainable vaccination ecosystem; the metrics of a vaccination ecosystem; and what should be added, removed, increased, or reduced to maintain the health of the vaccination ecosystem.

Involvement of Dynein and Spectrin with Early Melanosome Transport and Melanosomal Protein Trafficking

PubMed Central

Watabe, Hidenori; Valencia, Julio C.; Le Pape, Elodie; Yamaguchi, Yuji; Nakamura, Masayuki; Rouzaud, François; Hoashi, Toshihiko; Kawa, Yoko; Mizoguchi, Masako; Hearing, Vincent J.

2007-01-01

Melanosomes are unique membrane-bound organelles specialized for the synthesis and distribution of melanin. Mechanisms involved in the trafficking of proteins to melanosomes and in the transport of mature pigmented melanosomes to the dendrites of melanocytic cells are being characterized but details about those processes during early stages of melanosome maturation are not well understood. Early melanosomes must remain in the perinuclear area until critical components are assembled. In this study, we characterized the processing of two distinct melanosomal proteins, TYR and Pmel17, to elucidate protein processing in early or late steps of the secretory pathway, respectively, and to determine mechanisms underlying the subcellular localization and transport of early melanosomes. We used immunological, biochemical and molecular approaches to demonstrate that the movement of early melanosomes in the perinuclear area depends primarily on microtubules but not on actin filaments. In contrast, the trafficking of TYR and Pmel17 depends on cytoplasmic dynein and its interaction with the spectrin/ankyrin system which is involved with the sorting of cargo from the plasma membrane. These results provide important clues towards understanding the processes involved with early events in melanosome formation and transport. PMID:17687388

The type III secretion system needle tip complex mediates host cell sensing and translocon insertion.

PubMed

Veenendaal, Andreas K J; Hodgkinson, Julie L; Schwarzer, Lynn; Stabat, David; Zenk, Sebastian F; Blocker, Ariel J

2007-03-01

Type III secretion systems (T3SSs) are essential virulence determinants of many Gram-negative bacterial pathogens. The Shigella T3SS consists of a cytoplasmic bulb, a transmembrane region and a hollow 'needle' protruding from the bacterial surface. Physical contact with host cells initiates secretion and leads to assembly of a pore, formed by IpaB and IpaC, in the host cell membrane, through which proteins that facilitate host cell invasion are translocated. As the needle is implicated in host cell sensing and secretion regulation, its tip should contain components that initiate host cell contact. Through biochemical and immunological studies of wild-type and mutant Shigella T3SS needles, we reveal tip complexes of differing compositions and functional states, which appear to represent the molecular events surrounding host cell sensing and pore formation. Our studies indicate that the interaction between IpaB and IpaD at needle tips is key to host cell sensing, orchestration of IpaC secretion and its subsequent assembly at needle tips. This allows insertion into the host cell membrane of a translocation pore that is continuous with the needle.

Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

PubMed

Debnath, Monojit; Berk, Michael

2017-12-01

The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

Decidualization and angiogenesis in early pregnancy: unravelling the functions of DC and NK cells.

PubMed

Blois, Sandra M; Klapp, Burghard F; Barrientos, Gabriela

2011-03-01

Differentiation of endometrial stromal cells and formation of new maternal blood vessels at the time of embryo implantation are critical for the establishment and maintenance of gestation. The regulatory functions of decidual leukocytes during early pregnancy, particularly dendritic cells (DC) and NK cells, may be important not only for the generation of maternal immunological tolerance but also in the regulation of stromal cell differentiation and the vascular responses associated with the implantation process. However, the specific contributions of DC and NK cells during implantation are still difficult to dissect mainly due to reciprocal regulatory interactions established between them within the decidualizing microenvironment. The present review article discusses current evidence on the regulatory pathways driving decidualization in mice, suggesting that NK cells promote uterine vascular modifications that assist decidual growth but DC directly control stromal cell proliferation, angiogenesis and the homing and maturation of NK cell precursors in the pregnant uterus. Thus, successful implantation appears to result from an interplay between cellular components of the decidualizing endometrium involving immunoregulatory and pro-angiogenic functions of DC and NK cells. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

PolySac3DB: an annotated data base of 3 dimensional structures of polysaccharides.

PubMed

Sarkar, Anita; Pérez, Serge

2012-11-14

Polysaccharides are ubiquitously present in the living world. Their structural versatility makes them important and interesting components in numerous biological and technological processes ranging from structural stabilization to a variety of immunologically important molecular recognition events. The knowledge of polysaccharide three-dimensional (3D) structure is important in studying carbohydrate-mediated host-pathogen interactions, interactions with other bio-macromolecules, drug design and vaccine development as well as material science applications or production of bio-ethanol. PolySac3DB is an annotated database that contains the 3D structural information of 157 polysaccharide entries that have been collected from an extensive screening of scientific literature. They have been systematically organized using standard names in the field of carbohydrate research into 18 categories representing polysaccharide families. Structure-related information includes the saccharides making up the repeat unit(s) and their glycosidic linkages, the expanded 3D representation of the repeat unit, unit cell dimensions and space group, helix type, diffraction diagram(s) (when applicable), experimental and/or simulation methods used for structure description, link to the abstract of the publication, reference and the atomic coordinate files for visualization and download. The database is accompanied by a user-friendly graphical user interface (GUI). It features interactive displays of polysaccharide structures and customized search options for beginners and experts, respectively. The site also serves as an information portal for polysaccharide structure determination techniques. The web-interface also references external links where other carbohydrate-related resources are available. PolySac3DB is established to maintain information on the detailed 3D structures of polysaccharides. All the data and features are available via the web-interface utilizing the search engine and can be accessed at http://polysac3db.cermav.cnrs.fr.

Empirical evaluation of neutral interactions in host-parasite networks.

PubMed

Canard, E F; Mouquet, N; Mouillot, D; Stanko, M; Miklisova, D; Gravel, D

2014-04-01

While niche-based processes have been invoked extensively to explain the structure of interaction networks, recent studies propose that neutrality could also be of great importance. Under the neutral hypothesis, network structure would simply emerge from random encounters between individuals and thus would be directly linked to species abundance. We investigated the impact of species abundance distributions on qualitative and quantitative metrics of 113 host-parasite networks. We analyzed the concordance between neutral expectations and empirical observations at interaction, species, and network levels. We found that species abundance accurately predicts network metrics at all levels. Despite host-parasite systems being constrained by physiology and immunology, our results suggest that neutrality could also explain, at least partially, their structure. We hypothesize that trait matching would determine potential interactions between species, while abundance would determine their realization.

The Functional Impact of the Intestinal Microbiome on Mucosal Immunity and Systemic Autoimmunity

PubMed Central

Longman, Randy S.; Littman, Dan R.

2016-01-01

Purpose of Review This review will highlight recent advances functionally linking the gut microbiome with mucosal and systemic immune cell activation potentially underlying autoimmunity. Recent Findings Dynamic interactions between the gut microbiome and environmental cues (including diet and medicines) shape the effector potential of the microbial organ. Key bacteria and viruses have emerged, that, in defined microenvironments, play a critical role in regulating effector lymphocyte functions. The coordinated interactions between these different microbial kingdoms—including bacteria, helminths, and viruses (termed transkingdom interactions)—play a critical role in shaping immunity. Emerging strategies to identify immunologically-relevant microbes with the potential to regulate immune cell functions both at mucosal sites and systemically will likely define key diagnostic and therapeutic targets. Summary The microbiome constitutes a critical microbial organ with coordinated interactions that shape host immunity. PMID:26002030

Frequent and seasonally variable sublethal anthrax infections are accompanied by short-lived immunity in an endemic system

PubMed Central

Cizauskas, Carrie A.; Bellan, Steven E.; Turner, Wendy C.; Vance, Russell E.; Getz, Wayne M.

2014-01-01

Summary Few studies have examined host-pathogen interactions in wildlife from an immunological perspective, particularly in the context of seasonal and longitudinal dynamics. In addition, though most ecological immunology studies employ serological antibody assays, endpoint titer determination is usually based on subjective criteria and needs to be made more objective. Despite the fact that anthrax is an ancient and emerging zoonotic infectious disease found worldwide, its natural ecology is not well understood. In particular, little is known about the adaptive immune responses of wild herbivore hosts against Bacillus anthracis. Working in the natural anthrax system of Etosha National Park, Namibia, we collected 154 serum samples from plains zebra (Equus quagga), 21 from springbok (Antidorcas marsupialis), and 45 from African elephants (Loxodonta africana) over 2-3 years, resampling individuals when possible for seasonal and longitudinal comparisons. We used enzyme-linked immunosorbent assays to measure anti-anthrax antibody titers and developed three increasingly conservative models to determine endpoint titers with more rigorous, objective mensuration. Between 52-87% of zebra, 0-15% of springbok, and 3-52% of elephants had measurable anti-anthrax antibody titers, depending on the model used. While the ability of elephants and springbok to mount anti-anthrax adaptive immune responses is still equivocal, our results indicate that zebra in ENP often survive sublethal anthrax infections, encounter most B. anthracis in the wet season, and can partially booster their immunity to B. anthracis. Thus, rather than being solely a lethal disease, anthrax often occurs as a sublethal infection in some susceptible hosts. Though we found that adaptive immunity to anthrax wanes rapidly, subsequent and frequent sublethal B. anthracis infections cause maturation of anti-anthrax immunity. By triggering host immune responses, these common sublethal infections may act as immunomodulators and affect population dynamics through indirect immunological and co-infection effects. In addition, with our three endpoint titer models, we introduce more mensuration rigor into serological antibody assays, even under the often-restrictive conditions that come with adapting laboratory immunology methods to wild systems. With these methods we identified significantly more zebras responding immunologically to anthrax than have previous studies using less comprehensive titer analyses. PMID:24499424

Laboratory guidelines for the diagnosis and follow-up of patients with monoclonal gammopathies.

PubMed

Bravo García-Morato, M; Padilla-Merlano, B; Nozal, P; Espiño, M; Juárez, C; Villar, L M; López-Trascasa, M

2016-04-01

We present guidelines from the Immunochemistry group of the Spanish Society for Immunology that are designed to provide a practical tool for the diagnosis and follow-up of monoclonal gammopathies. We review the clinical and analytical features of various monoclonal gammopathies, international consensus guidelines and techniques used to detect and follow-up monoclonal components. Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI). All rights reserved.

Research in Biological and Medical Sciences Including Biochemistry, Communicable Disease and Immunology, Internal Medicine, Nuclear Medicine, Physiology, Psychiatry, Surgery, and Veterinary Medicine. Volume 2

DTIC Science & Technology

1974-06-30

Sprinz and Formal 1968). Fat seen in colonic epithelial cells of monkeys infected by Shigella flexneri occurred before penetration of...cellular or non-cellular components of the peripheral blood such as fat , fibrin, denatured protein, red blood cells, intact neutrophils or other...in vitro, and imply their embolic character when infused into the recipient’s vasculature. Corclusion Storage of whole blood under normal blood bank

Differential segregation in a cell-cell contact interface: the dynamics of the immunological synapse.

PubMed Central

Burroughs, Nigel John; Wülfing, Christoph

2002-01-01

Receptor-ligand couples in the cell-cell contact interface between a T cell and an antigen-presenting cell form distinct geometric patterns and undergo spatial rearrangement within the contact interface. Spatial segregation of the antigen and adhesion receptors occurs within seconds of contact, central aggregation of the antigen receptor then occurring over 1-5 min. This structure, called the immunological synapse, is becoming a paradigm for localized signaling. However, the mechanisms driving its formation, in particular spatial segregation, are currently not understood. With a reaction diffusion model incorporating thermodynamics, elasticity, and reaction kinetics, we examine the hypothesis that differing bond lengths (extracellular domain size) is the driving force behind molecular segregation. We derive two key conditions necessary for segregation: a thermodynamic criterion on the effective bond elasticity and a requirement for the seeding/nucleation of domains. Domains have a minimum length scale and will only spontaneously coalesce/aggregate if the contact area is small or the membrane relaxation distance large. Otherwise, differential attachment of receptors to the cytoskeleton is required for central aggregation. Our analysis indicates that differential bond lengths have a significant effect on synapse dynamics, i.e., there is a significant contribution to the free energy of the interaction, suggesting that segregation by differential bond length is important in cell-cell contact interfaces and the immunological synapse. PMID:12324401

Exosomes in fetal bovine serum dampen primary macrophage IL-1β response to lipopolysaccharide (LPS) challenge.

PubMed

Beninson, Lida A; Fleshner, Monika

2015-02-01

This study identifies a previously unknown immunological function of exosomes present in fetal bovine serum (FBS). Exosomes are small (40-100 nm), biologically active nanoparticles released from cells that associate with a variety of proteins and miRNA. Exosomes are present in nearly all biological fluids, including FBS, a common supplement to cell culture media. While there are a growing number of studies examining cellular responses to exosomes, there is no assessment of how FBS exosomes impact cellular responses to immunological challenges. Our results demonstrate that primary macrophages from Fisher 344 rats cultured with lipopolysaccharide (LPS) in the presence of FBS exosomes exhibit a dose-dependent reduction in IL-1β compared to macrophages cultured in medium supplemented with exosome-depleted FBS. The addition of fetal bovine exosomes also reduced macrophage tumor necrosis factor-alpha (TNF-α) and IL-6, but not IL-10, monocyte chemotactic factor-1 (MCP-1), nitric oxide (NO), or lactose dehydrogenase (LDH) response to LPS. The selectivity of exosomal impact on macrophage IL-1β and pro-inflammatory protein responses may implicate the potential role of exosome-inflammasome interactions. These findings suggest that researchers should consider the immunological influence of FBS exosomes, particularly on IL-1β activity, when studying cells in culture. Copyright © 2015. Published by Elsevier B.V.

Soya Saponins Induce Enteritis in Atlantic Salmon (Salmo salar L.).

PubMed

Krogdahl, Åshild; Gajardo, Karina; Kortner, Trond M; Penn, Michael; Gu, Min; Berge, Gerd Marit; Bakke, Anne Marie

2015-04-22

Soybean meal-induced enteritis (SBMIE) is a well-described condition in the distal intestine of salmonids, and saponins have been implicated as the causal agent. However, the question remains whether saponins alone cause SBMIE. Moreover, the dose-response relationship has not been described. In a 10 week feeding trial with Atlantic salmon, a highly purified (95%) soya saponin preparation was supplemented (0, 2, 4, 6, or 10 g/kg) to two basal diets, one containing fishmeal as the major protein source (FM) and the other 25% lupin meal (LP). Saponins caused dose-dependent increases in the severity of inflammation independent of the basal diet, with concomitant alterations in digestive functions and immunological marker expression. Thus, saponins induced inflammation whether the diet contained other legume components or not. However, responses were often the same or stronger in fish fed the corresponding saponin-supplemented LP diets despite lower saponin exposure, suggesting potentiation by other legume component(s).

Clinical review: Extracorporeal blood purification in severe sepsis

PubMed Central

Venkataraman, Ramesh; Subramanian, Sanjay; Kellum, John A

2003-01-01

Sepsis and septic shock are the leading causes of acute renal failure, multiple organ system dysfunction, and death in the intensive care unit. The pathogenesis of sepsis is complex and comprises a mosaic of interconnected pathways. Several attempts to improve patient outcomes by targeting specific components of this network have been unsuccessful. For these reasons, the ideal immunomodulating strategy would be one that restores immunologic stability rather than blindly inhibiting or stimulating one or another component of this complex network. Hence, the recent focus of immunomodulatory therapy in sepsis has shifted to nonspecific methods of influencing the entire inflammatory response without suppressing it. Here, we discuss the various modalities of extracorporeal blood purification, the existing evidence, and future prospects. PMID:12720560

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 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 serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 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 serology...

42 CFR 493.833 - Condition: Diagnostic immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 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 serology...

Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation.

PubMed

He, YingYing; Lawlor, Nathan T; Newburg, David S

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2'-fucosyllactose attenuate TLR4 signaling; 3'-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. © 2016 American Society for Nutrition.

Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

PubMed Central

He, YingYing; Lawlor, Nathan T

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

Consortium biology in immunology: the perspective from the Immunological Genome Project.

PubMed

Benoist, Christophe; Lanier, Lewis; Merad, Miriam; Mathis, Diane

2012-10-01

Although the field has a long collaborative tradition, immunology has made less use than genetics of 'consortium biology', wherein groups of investigators together tackle large integrated questions or problems. However, immunology is naturally suited to large-scale integrative and systems-level approaches, owing to the multicellular and adaptive nature of the cells it encompasses. Here, we discuss the value and drawbacks of this organization of research, in the context of the long-running 'big science' debate, and consider the opportunities that may exist for the immunology community. We position this analysis in light of our own experience, both positive and negative, as participants of the Immunological Genome Project.

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 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 syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 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 syphilis...

Virtual Immunology: Software for Teaching Basic Immunology

ERIC Educational Resources Information Center

Berçot, Filipe Faria; Fidalgo-Neto, Antônio Augusto; Lopes, Renato Matos; Faggioni, Thais; Alves, Luiz Anastácio

2013-01-01

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…

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 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 syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 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 syphilis...

42 CFR 493.921 - Diagnostic immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 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 syphilis...

In silico polypharmacology of natural products.

PubMed

Fang, Jiansong; Liu, Chuang; Wang, Qi; Lin, Ping; Cheng, Feixiong

2017-04-27

Natural products with polypharmacological profiles have demonstrated promise as novel therapeutics for various complex diseases, including cancer. Currently, many gaps exist in our knowledge of which compounds interact with which targets, and experimentally testing all possible interactions is infeasible. Recent advances and developments of systems pharmacology and computational (in silico) approaches provide powerful tools for exploring the polypharmacological profiles of natural products. In this review, we introduce recent progresses and advances of computational tools and systems pharmacology approaches for identifying drug targets of natural products by focusing on the development of targeted cancer therapy. We survey the polypharmacological and systems immunology profiles of five representative natural products that are being considered as cancer therapies. We summarize various chemoinformatics, bioinformatics and systems biology resources for reconstructing drug-target networks of natural products. We then review currently available computational approaches and tools for prediction of drug-target interactions by focusing on five domains: target-based, ligand-based, chemogenomics-based, network-based and omics-based systems biology approaches. In addition, we describe a practical example of the application of systems pharmacology approaches by integrating the polypharmacology of natural products and large-scale cancer genomics data for the development of precision oncology under the systems biology framework. Finally, we highlight the promise of cancer immunotherapies and combination therapies that target tumor ecosystems (e.g. clones or 'selfish' sub-clones) via exploiting the immunological and inflammatory 'side' effects of natural products in the cancer post-genomics era. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Avian macrophage: effector functions in health and disease.

PubMed

Qureshi, M A; Heggen, C L; Hussain, I

2000-01-01

Monocytes-macrophages, cells belonging to the mononuclear phagocytic system, are considered as the first line of immunological defense. Being mobile scavenger cells, macrophages participate in innate immunity by serving as phagocytic cells. These cells arise in the bone marrow and subsequently enter the blood circulation as blood monocytes. Upon migration to various tissues, monocytes mature and differentiate into tissue macrophages. Macrophages then initiate the 'acquired' immune response in their capacity as antigen processing and presenting cells. While responding to their tissue microenvironment or exogenous antigenic challenge, macrophages may secrete several immunoregulatory cytokines or metabolites. Being the first line of immunological defense, macrophages therefore represent an important step during interaction with infectious agents. The outcome of the macrophage-pathogen interaction depends upon several factors including the stage of macrophage activation, the nature of the infectious agent, the level of genetic control on macrophage function as well as environmental and nutritional factors that may modulate macrophage activation and functions. Research in avian macrophages has lagged behind that in mammals. This has been largely due to the lack of harvestable resident macrophages from the chicken peritoneal cavity. However, the development of elicitation protocols to harvest inflammatory abdominal macrophages and the availability of transformed chicken macrophage cell lines, has enabled researchers to address several questions related to chicken macrophage biology and function in health and disease. In this manuscript the basic profiles of several macrophage effector functions are described. In addition, the interaction of macrophages with various pathogens as well as the effect of genetic and environmental factors on macrophage functional modulation is described.

Learning from epidemiological, clinical, and immunological studies on Mycobacterium africanum for improving current understanding of host-pathogen interactions, and for the development and evaluation of diagnostics, host-directed therapies, and vaccines for tuberculosis.

PubMed

Zumla, Alimuddin; Otchere, Isaac Darko; Mensah, Gloria Ivy; Asante-Poku, Adwoa; Gehre, Florian; Maeurer, Markus; Bates, Matthew; Mwaba, Peter; Ntoumi, Francine; Yeboah-Manu, Dorothy

2017-03-01

Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host-pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)-those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host-M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Need for immunologic stimulators during immunosuppression produced by major cancer surgery.

PubMed Central

Cole, W H; Humphrey, L

1985-01-01

Although surgery, radiology, and anticancer chemicals have been effective in the treatment of cancer, the immunologic phase of therapy deserves more effort and thought, because the possibilities are considerable. However, the immunologic phase is so complicated that, without the advances made during the past few years, little could be expected from immunology. The focus of this paper is on the immunosuppression produced by major cancer operations, at which time the patient needs immunologic help. PMID:3893336

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 5 2011-10-01 2011-10-01 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 §§ 493...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 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 §§ 493...

Graduate Students' Interest in Immunology as a Discipline

ERIC Educational Resources Information Center

Kwarteng, Alexander; Frimpong, Michael; Sylverken, Augustina Angelina; Arthur, Yarhands D.; Ahuno, Samuel T.; Owusu-Dabo, Ellis

2017-01-01

Interest and motivation significantly influence achievement; however, interest in immunology remains to be determined. Using a structured questionnaire, the current study assessed for the first time interest in immunology among biomedical graduate students in Ghana after a one-week introduction to immunology course. Our results revealed that…

21 CFR 866.5510 - Immunoglobulins A, G, M, D, and E immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... test system. 866.5510 Section 866.5510 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866.5510 Immunoglobulins A, G, M, D, and E immunological test system. (a) Identification...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5860 - Total spinal fluid immuno-logical test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... diagnosis of multiple sclerosis and other diseases of the nervous system. (b) Classification. Class I... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Total spinal fluid immuno-logical test system. 866... SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Immunological Test Systems § 866...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5210 - Ceruloplasmin immunolog-ical test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... (copper-transporting serum protein) in serum, other body fluids, or tissues. Measurements of ceruloplasmin... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Ceruloplasmin immunolog-ical test system. 866.5210 Section 866.5210 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES...

21 CFR 866.5230 - Colostrum immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Colostrum immunological test system. 866.5230... Colostrum immunological test system. (a) Identification. A colostrum immunological test system is a device... colostrum. Colostrum is a substance excreted by the mammary glands during pregnancy and until production of...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 5 2014-10-01 2014-10-01 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 §§ 493...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 5 2013-10-01 2013-10-01 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 §§ 493...

SPECIAL ISSUE VETERINARY IMMUNOLOGY IMMUNOPATHOLOGY: PROCEEDINGS 8TH INTERNATIONAL VETERINARY IMMUNOLOGY SYMPOSIUM

USDA-ARS?s Scientific Manuscript database

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...

42 CFR 493.1208 - Condition: General immunology.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 5 2012-10-01 2012-10-01 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 §§ 493...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

21 CFR 866.5170 - Breast milk immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Breast milk immunological test system. 866.5170... milk immunological test system. (a) Identification. A breast milk immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the breast milk proteins. (b...

Interactions between Autophagy and Inhibitory Cytokines

PubMed Central

Wu, Tian-tian; Li, Wei-Min; Yao, Yong-Ming

2016-01-01

Autophagy is a degradative pathway that plays an essential role in maintaining cellular homeostasis. Most early studies of autophagy focused on its involvement in age-associated degeneration and nutrient deprivation. However, the immunological functions of autophagy have become more widely studied in recent years. Autophagy has been shown to be an intrinsic cellular defense mechanism in the innate and adaptive immune responses. Cytokines belong to a broad and loose category of proteins and are crucial for innate and adaptive immunity. Inhibitory cytokines have evolved to permit tolerance to self while also contributing to the eradication of invading pathogens. Interactions between inhibitory cytokines and autophagy have recently been reported, revealing a novel mechanism by which autophagy controls the immune response. In this review, we discuss interactions between autophagy and the regulatory cytokines IL-10, transforming growth factor-β, and IL-27. We also mention possible interactions between two newly discovered cytokines, IL-35 and IL-37, and autophagy. PMID:27313501

T cell-B cell interactions in primary immunodeficiencies.

PubMed

Tangye, Stuart G; Deenick, Elissa K; Palendira, Umaimainthan; Ma, Cindy S

2012-02-01

Regulated interactions between cells of the immune system facilitate the generation of successful immune responses, thereby enabling efficient neutralization and clearance of pathogens and the establishment of both cell- and humoral-mediated immunological memory. The corollary of this is that impediments to efficient cell-cell interactions, normally necessary for differentiation and effector functions of immune cells, underly the clinical features and disease pathogenesis of primary immunodeficiencies. In affected individuals, these defects manifest as impaired long-term humoral immunity and susceptibility to infection by specific pathogens. In this review, we discuss the importance of, and requirements for, effective interactions between B cells and T cells during the formation of CD4(+) T follicular helper cells and the elicitation of cytotoxic function of virus-specific CD8(+) T cells, as well as how these processes are abrogated in primary immunodeficiencies due to loss-of-function mutations in defined genes. © 2012 New York Academy of Sciences.

[A Concept Analysis for Mind-Body Interaction].

PubMed

Chen, Hsing-Wen; Yeh, Mei-Ling; Rong, Jiin-Ru

2015-08-01

Mind-body interaction (MBI) refers the holistic association and interactive process between wisdom, thinking, belief, and physiological reaction, which critically affects health. The main goal of nursing is to maintain mind and body in a healthy state of well being. Few reports in the literatures have addressed the evaluation and application of MBI. Thus, a conceptual analysis of this subject is worth exploring in depth. This paper analyzes the MBI concept step by step based on the procedures of Walker and Avant. The result defines the characteristics of MBI as (1) being aware of psychosomatic effects, (2) interacting between psychology, neurology, immunology and others, and (3) turning out a bio-psycho-social status. Antecedents include geography, culture, race, gender, age, education, profession, values, personality, experience, and health status. Consequences of MBI include well-being, illness, and death. This paper provides new information on MBI that clarifies its meaning, provides comprehensive cognition, and suggests useful applications.

Salivary markers in patients with chronic renal failure.

PubMed

Pallos, Debora; Leão, Mariella V P; Togeiro, Fernanda C F B; Alegre, Larissa; Ricardo, Lucilene Hernandes; Perozini, Caroline; Ruivo, Gilson Fernandes

2015-12-01

Chronic renal failure (CRF) is a progressive loss of renal function over a period of months or years. The major function of the kidneys is the removal of metabolic waste products, electrolytes and water. When this function is impaired, systemic changes, oral complications and alterations in salivary composition may occur. This study aimed to compare the levels of immunological and inflammatory components in the saliva samples from patients that undergo to hemodialysis treatment (HD), without HD and control. This study evaluated IgA, IgG, C reactive protein (CRP) and nitric oxide (NO) in saliva samples from 119 patients, who were divided into the control group (C), chronic renal failure (CRF) patient group and CRF patients on hemodialysis treatment (HD) group. IgA and IgG levels were analyzed by ELISA. Nitric oxide levels were determined indirectly by the nitrite concentration using Griess reagent; CRP by agglutination tests; and total proteins, by Bradford assay. The HD group showed significantly higher levels of IgG, IgA and CRP compared with the control and CRF groups. The CRF group presented the same amounts of IgG, IgA and CRP as the C group but significantly higher levels of NO similar to the HD group. Renal disease, particularly hemodialysis treatment during renal disease, seems to alter salivary immunological and inflammatory components. Thus, analyzing the levels of IgA, IgG, NO and CRP in saliva may be beneficial for monitoring renal disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

Formulation and immunological evaluation of a trivalent vaccine comprising emulsified submicron particles and inactivated virions of H5N1/EV71/JEV

PubMed Central

Lin, Chih-Wei; Chang, Ching-Yun; Chen, Wei-Lin; Lin, Shih-Chang; Liao, Chien-Chun; Chang, Jui-Yuan; Liu, Chia-Chyi; Hu, Alan Yung-Chih; Lu, Tsung-Chun; Chou, Ai-Hsiang; Wu, Suh-Chin; Chong, Pele; Huang, Ming-Hsi

2013-01-01

Combination vaccines can reduce the number of injections and simplify the immunization schedule required to prevent different diseases. Here we assessed the immunogenicity in a mouse model of a vaccine composition comprising inactivated influenza viruses (H5N1/H1N1), enterovirus 71 (EV71), and/or Japanese encephalitis virus (JEV) and investigated whether the vaccine formulations can overcome the immunologic interference between the individual vaccine components. We demonstrated that the antigenic competition happens between H5N1/H1N1 or H5N1/EV71 inactivated virions when the vaccine combinations either formulated with Alum suspensions or without adjuvant. In the presence of PELC emulsified particles, EV71-specific immune responses before and after incorporating H5N1 virus into EV71 vaccine were detected of no significant difference; in addition, H5N1- and EV71-specific immune responses were found at the same level when H5N1/EV71/JEV consolidating into combination vaccine. Emulsified vaccine formulation was represented as a potential tool that is found to reduce the number of injections required to prevent multiple infectious strains causing the same disease (H5N1/H1N1) and/or that protect against different diseases (H5N1/EV71). Combination vaccines can also include a third component to protect against H5N1/EV71/JEV at the same time. PMID:23838466

Immunological characteristics of patients infected with common intestinal helminths: results of a study based on reverse-transcriptase PCR.

PubMed

Lertanekawattana, S; Wichatrong, T; Chaisari, K; Uchikawa, R; Arizono, N

2005-01-01

To determine whether common helminth infections could modify the intestinal immunopathological status of the host, the expression in the human duodenal mucosa of cytokines, eosinophil- and mast-cell-specific molecules and monosaccharide transporters of the glucose-transporter (GLUT) family was explored. The 31 subjects were all patients at the gastro-intestinal disease unit of Nongkhai Hospital, Thailand. Four of the 10 patients who presented with eosinophilia (> or = 6.0% of their leucocytes were eosinophils), and five of the other 21 patients, had intestinal infections with helminths when they presented or within the previous 3 months. Studies based on semi-quantitative, reverse-transcriptase PCR revealed that the interleukin-5/interferon-gamma ratio was significantly higher in the noneosinophilic, helminth-infected patients than in the non-eosinophilic, uninfected patients, whereas the IgE receptor type I (Fc epsilon RI)/mast-cell tryptase ratio was significantly higher in the eosinophilic, helminth-infected patients than in the eosinophilic, uninfected patients. Expression of Charcot-Leyden-crystal protein, GLUT-1 and GLUT-5, however, showed no significant inter-group differences. Principal-components analysis of the data on eosinophils, interleukin-5, interferon-gamma, Fc epsilon RI and mast-cell tryptase revealed that one principal component could discriminate the patients who had helminth infection from the non-eosinophilic, uninfected patients, but not from the eosinophilic, uninfected patients. These results indicate that, whatever the intestinal pathology, patients infected with common intestinal helminths tend to develop a mucosal immunological response of the Th2 type.

Immunology-directed methods for distributed robotics: a novel immunity-based architecture for robust control and coordination

NASA Astrophysics Data System (ADS)

Singh, Surya P. N.; Thayer, Scott M.

2002-02-01

This paper presents a novel algorithmic architecture for the coordination and control of large scale distributed robot teams derived from the constructs found within the human immune system. Using this as a guide, the Immunology-derived Distributed Autonomous Robotics Architecture (IDARA) distributes tasks so that broad, all-purpose actions are refined and followed by specific and mediated responses based on each unit's utility and capability to timely address the system's perceived need(s). This method improves on initial developments in this area by including often overlooked interactions of the innate immune system resulting in a stronger first-order, general response mechanism. This allows for rapid reactions in dynamic environments, especially those lacking significant a priori information. As characterized via computer simulation of a of a self-healing mobile minefield having up to 7,500 mines and 2,750 robots, IDARA provides an efficient, communications light, and scalable architecture that yields significant operation and performance improvements for large-scale multi-robot coordination and control.

Immunology of Bats and Their Viruses: Challenges and Opportunities

PubMed Central

Schountz, Tony

2014-01-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock. PMID:25494448

Dichotomal effect of space flight-associated microgravity on stress-activated protein kinases in innate immunity

PubMed Central

Verhaar, Auke P.; Hoekstra, Elmer; Tjon, Angela S. W.; Utomo, Wesley K.; Deuring, J. Jasper; Bakker, Elvira R. M.; Muncan, Vanesa; Peppelenbosch, Maikel P.

2014-01-01

Space flight strongly moderates human immunity but is in general well tolerated. Elucidation of the mechanisms by which zero gravity interacts with human immunity may provide clues for developing rational avenues to deal with exaggerated immune responses, e.g. as in autoimmune disease. Using two sounding rockets and one manned Soyuz launch, the influence of space flight on immunological signal transduction provoked by lipopolysaccharide (LPS) stimulation was investigated in freshly isolated peripheral blood monocytes and was compared to samples obtained from on-board centrifuge-loaded 1 g controls. The effect of microgravity on immunological signal transduction is highly specific, since LPS dependent Jun-N-terminal kinase activation is impaired in the 0 g condition, while the corresponding LPS dependent activation of p38 MAP kinase remains unaffected. Thus our results identify Jun-N-terminal kinase as a relevant target in immunity for microgravity and support using Jun-N-terminal kinase specific inhibitors for combating autoimmune disease. PMID:24968806

Immunology of bats and their viruses: challenges and opportunities.

PubMed

Schountz, Tony

2014-12-01

Bats are reservoir hosts of several high-impact viruses that cause significant human diseases, including Nipah virus, Marburg virus and rabies virus. They also harbor many other viruses that are thought to have caused disease in humans after spillover into intermediate hosts, including SARS and MERS coronaviruses. As is usual with reservoir hosts, these viruses apparently cause little or no pathology in bats. Despite the importance of bats as reservoir hosts of zoonotic and potentially zoonotic agents, virtually nothing is known about the host/virus relationships; principally because few colonies of bats are available for experimental infections, a lack of reagents, methods and expertise for studying bat antiviral responses and immunology, and the difficulty of conducting meaningful field work. These challenges can be addressed, in part, with new technologies that are species-independent that can provide insight into the interactions of bats and viruses, which should clarify how the viruses persist in nature, and what risk factors might facilitate transmission to humans and livestock.

The role of virologic and immunologic factors in mother-to-child transmission of HIV-1.

PubMed

Colognesi, C; Halapi, E; Jansson, M; Hodara, V; Steuer, G; Tresoldi, E; Leitner, T; Scarlatti, G

1997-09-01

More than 90% of human immunodeficiency virus type 1 (HIV-1) infection in children is acquired by mother-to-child transmission. However, infection of the child occurs in between 14 and 35% of cases. To understand the mechanisms involved in HIV-1 transmission, we have investigated the antigenic, molecular, and phenotypic characteristics of the virus harbored in infected mothers and their children. A clear correlation was observed between the transmission of the virus and the isolation of viral variants with a rapidly replicating and syncytium-inducing phenotype from the mother. Furthermore, non-transmitting mothers were able to neutralize several primary isolates more frequently than transmitting mothers. The comparison of the viral phenotype and genotype of mother-child pairs showed that the transmitted virus did not have common features, suggesting that transmission is usually not a selective process. This study suggests that transmission is governed by an interaction of both viral and immunological factors. The results obtained indicate that different strategies can be applied for the prevention of transmission.

Quantitative Enzymatic and Immunologic Histophotometry of Diseased Human Kid-Ney Tissues Using Tv-Camera and Computer Assisted Image Processing Systems.

NASA Astrophysics Data System (ADS)

Heinert, G.; Mondorf, W.

1982-11-01

High speed image processing was used to analyse morphologic and metabolic characteristics of clinically relevant kidney tissue alterations.Qualitative computer-assisted histophotometry was performed to measure alterations in levels of the enzymes alkaline phosphatase (Ap),alanine aminopeptidase (AAP),g-glutamyltranspepti-dase (GGTP) and A-glucuronidase (B-G1) and AAP and GGTP immunologically determined in prepared renal and cancer tissue sections. A "Mioro-Videomat 2" image analysis system with a "Tessovar" macroscope,a computer-assisted "Axiomat" photomicroscope and an "Interactive Image Analysis System (IBAS)" were employed for analysing changes in enzyme activities determined by changes in absorbance or transmission.Diseased kidney as well as renal neoplastic tissues could be distinguished by significantly (wilcoxon test,p<0,05) decreased enzyme concentrations as compared to those found in normal human kidney tissues.This image analysis techniques might be of potential use in diagnostic and prognostic evaluation of renal cancer and diseased kidney tissues.

Fcγ1 fragment of IgG1 as a powerful affinity tag in recombinant Fc-fusion proteins: immunological, biochemical and therapeutic properties.

PubMed

Soleimanpour, Saman; Hassannia, Tahereh; Motiee, Mahdieh; Amini, Abbas Ali; Rezaee, S A R

2017-05-01

Affinity tags are vital tools for the production of high-throughput recombinant proteins. Several affinity tags, such as the hexahistidine tag, maltose-binding protein, streptavidin-binding peptide tag, calmodulin-binding peptide, c-Myc tag, glutathione S-transferase and FLAG tag, have been introduced for recombinant protein production. The fragment crystallizable (Fc) domain of the IgG1 antibody is one of the useful affinity tags that can facilitate detection, purification and localization of proteins and can improve the immunogenicity, modulatory effects, physicochemical and pharmaceutical properties of proteins. Fcγ recombinant forms a group of recombinant proteins called Fc-fusion proteins (FFPs). FFPs are widely used in drug discovery, drug delivery, vaccine design and experimental research on receptor-ligand interactions. These fusion proteins have become successful alternatives to monoclonal antibodies for drug developments. In this review, the physicochemical, biochemical, immunological, pharmaceutical and therapeutic properties of recombinant FFPs were discussed as a new generation of bioengineering strategies.

Dichotomal effect of space flight-associated microgravity on stress-activated protein kinases in innate immunity.

PubMed

Verhaar, Auke P; Hoekstra, Elmer; Tjon, Angela S W; Utomo, Wesley K; Deuring, J Jasper; Bakker, Elvira R M; Muncan, Vanesa; Peppelenbosch, Maikel P

2014-06-27

Space flight strongly moderates human immunity but is in general well tolerated. Elucidation of the mechanisms by which zero gravity interacts with human immunity may provide clues for developing rational avenues to deal with exaggerated immune responses, e.g. as in autoimmune disease. Using two sounding rockets and one manned Soyuz launch, the influence of space flight on immunological signal transduction provoked by lipopolysaccharide (LPS) stimulation was investigated in freshly isolated peripheral blood monocytes and was compared to samples obtained from on-board centrifuge-loaded 1 g controls. The effect of microgravity on immunological signal transduction is highly specific, since LPS dependent Jun-N-terminal kinase activation is impaired in the 0 g condition, while the corresponding LPS dependent activation of p38 MAP kinase remains unaffected. Thus our results identify Jun-N-terminal kinase as a relevant target in immunity for microgravity and support using Jun-N-terminal kinase specific inhibitors for combating autoimmune disease.

21 CFR 866.5820 - Systemic lupus erythema-tosus immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Systemic lupus erythema-tosus immunological test... Systems § 866.5820 Systemic lupus erythema-tosus immunological test system. (a) Identification. A systemic lupus erythematosus (SLE) immunological test system is a device that consists of the reagents used to...

A fine-tuned vector-parasite dialogue in tsetse's cardia determines peritrophic matrix integrity and trypanosome transmission success

PubMed Central

Aksoy, Emre; Weiss, Brian L.; Zhao, Xin; Awuoche, Erick O.; Wu, Yineng; Aksoy, Serap

2018-01-01

Arthropod vectors have multiple physical and immunological barriers that impede the development and transmission of parasites to new vertebrate hosts. These barriers include the peritrophic matrix (PM), a chitinous barrier that separates the blood bolus from the midgut epithelia and modulates vector-pathogens interactions. In tsetse flies, a sleeve-like PM is continuously produced by the cardia organ located at the fore- and midgut junction. African trypanosomes, Trypanosoma brucei, must bypass the PM twice; first to colonize the midgut and secondly to reach the salivary glands (SG), to complete their transmission cycle in tsetse. However, not all flies with midgut infections develop mammalian transmissible SG infections—the reasons for which are unclear. Here, we used transcriptomics, microscopy and functional genomics analyses to understand the factors that regulate parasite migration from midgut to SG. In flies with midgut infections only, parasites fail to cross the PM as they are eliminated from the cardia by reactive oxygen intermediates (ROIs)—albeit at the expense of collateral cytotoxic damage to the cardia. In flies with midgut and SG infections, expression of genes encoding components of the PM is reduced in the cardia, and structural integrity of the PM barrier is compromised. Under these circumstances trypanosomes traverse through the newly secreted and compromised PM. The process of PM attrition that enables the parasites to re-enter into the midgut lumen is apparently mediated by components of the parasites residing in the cardia. Thus, a fine-tuned dialogue between tsetse and trypanosomes at the cardia determines the outcome of PM integrity and trypanosome transmission success. PMID:29614112

Infectious Agents as Stimuli of Trained Innate Immunity.

PubMed

Rusek, Paulina; Wala, Mateusz; Druszczyńska, Magdalena; Fol, Marek

2018-02-03

The discoveries made over the past few years have modified the current immunological paradigm. It turns out that innate immunity cells can mount some kind of immunological memory, similar to that observed in the acquired immunity and corresponding to the defense mechanisms of lower organisms, which increases their resistance to reinfection. This phenomenon is termed trained innate immunity. It is based on epigenetic changes in innate immune cells (monocytes/macrophages, NK cells) after their stimulation with various infectious or non-infectious agents. Many infectious stimuli, including bacterial or fungal cells and their components (LPS, β-glucan, chitin) as well as viruses or even parasites are considered potent inducers of innate immune memory. Epigenetic cell reprogramming occurring at the heart of the phenomenon may provide a useful basis for designing novel prophylactic and therapeutic strategies to prevent and protect against multiple diseases. In this article, we present the current state of art on trained innate immunity occurring as a result of infectious agent induction. Additionally, we discuss the mechanisms of cell reprogramming and the implications for immune response stimulation/manipulation.

Lactate - A new frontier in the immunology and therapy of prostate cancer.

PubMed

Nenu, Iuliana; Gafencu, Grigore-Aristide; Popescu, Tiberiu; Kacso, Gabriel

2017-01-01

Prostate cancer, one of the most common male malignancies with an increasing incidence in the recent years, requires the development of new methods of treatment. One of the most debated subjects is the tumor-associated macrophages (TAM). Although, the pathophysiological mechanisms are still a subject of intense research, TAM acts as procarcinogenic factors. It was also demonstrated that hypoxia-inducible factor 1 (HIF1) induces the expression of TAM genes involved in prostate carcinogenesis. Furthermore, it should be noted that the stromal extracellular lactate, the result of tumoral glycolysis process is one of the HIF1 activators. In addition, lactate inhibits the differentiation of monocytes and dendritic cells and also induces the inactivation of the cytotoxic T-lymphocytes. Through an analysis of recent studies, we conclude that lactate is a vital component of several ways of modulating the immune response at the stromal prostatic adenocarcinoma including TAM activation and cytotoxic T lymphocytes immunosuppression. Our review focuses on the impact of lactate on prostatic adenocarcinoma progression in terms of its immunology, and how this influences the therapy of this condition and the clinical outcome.

The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies.

PubMed

Brunner, Patrick M; Guttman-Yassky, Emma; Leung, Donald Y M

2017-04-01

Atopic dermatitis (AD), the most common chronic inflammatory skin disease, is driven by both terminal keratinocyte differentiation defects and strong type 2 immune responses. In contrast to chronic plaque-type psoriasis, AD is now understood to be a much more heterogeneous disease, with additional activation of T H 22, T H 17/IL-23, and T H 1 cytokine pathways depending on the subtype of the disease. In this review we discuss our current understanding of the AD immune map in both patients with early-onset and those with chronic disease. Clinical studies with broad and targeted therapeutics have helped to elucidate the contribution of various immune axes to the disease phenotype. Importantly, immune activation extends well beyond lesional AD because nonlesional skin and the blood component harbor AD-specific inflammatory changes. For this reason, future therapeutics will need to focus on a systemic treatment approach, especially in patients with moderate-to-severe disease. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Differences between h-index measures from different bibliographic sources and search engines.

PubMed

Barreto, Mauricio Lima; Aragão, Erika; Sousa, Luis Eugenio Portela Fernandes de; Santana, Táris Maria; Barata, Rita Barradas

2013-04-01

To analyze the use of the h-index as a measure of the bibliometric impact of Brazilian researchers' scientific publications. The scientific production of Brazilian CNPq 1-A researchers in the areas of public health, immunology and medicine were compared. The mean h-index of the groups of researchers in each area were estimated and nonparametric Kruskal Wallis test and multiple comparisons Behrens-Fisher test were used to compare the differences. The h-index means were higher in the area of Immunology than in Public Health and Medicine when the Web of Science base was used. However, this difference disappears when the comparison is made using Scopus or Google Scholar. The emergence of Google Scholar brings a new level to discussions on the measure of the bibliometric impact of scientific publications. Areas with strong professional components, in which knowledge is produced and must also be published in the native language, vis-a-vis its dissemination to the international community, necessarily have a standard of scientific publications and citations different from areas exclusively or predominantly academic and they are best captured by Google Scholar.

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

Type 2 diabetes mellitus(DM) is a major risk factor for the development of active pulmonary tuberculosis (TB), with development of DM pandemic in countries where TB is also endemic. Understanding the impact of DM on TB and the determinants of co-morbidity is essential in responding to this growing public health problem with improved therapeutic approaches. Despite the clinical and public health significance posed by the dual burden of TB and DM, little is known about the immunological and biochemical mechanisms of susceptibility. One possible mechanism is that an impaired immune response in patients with DM facilitates either primary infection with Mycobacterium tuberculosis or reactivation of latent TB. Diabetes is associated with immune dysfunction and alterations in the components of the immune system, including altered levels of specific cytokines and chemokines. Some effects of DM on adaptive immunity that are potentially relevant to TB defence have been identified in humans. In this review, we summarize current findings regarding the alterations in the innate and adaptive immune responses and immunological mechanisms of susceptibility of patients with DM to M. tuberculosis infection and disease. © 2017 John Wiley & Sons Ltd.

Scavenger Receptors: Emerging Roles in Cancer Biology and Immunology

PubMed Central

Yu, Xiaofei; Guo, Chunqing; Fisher, Paul B.; Subjeck, John R.; Wang, Xiang-Yang

2015-01-01

Scavenger receptors constitute a large family of evolutionally conserved protein molecules that are structurally and functionally diverse. Although scavenger receptors were originally identified based on their capacity to scavenge modified lipoproteins, these molecules have been shown to recognize and bind to a broad spectrum of ligands, including modified and unmodified host-derived molecules or microbial components. As a major subset of innate pattern recognition receptors, scavenger receptors are mainly expressed on myeloid cells and function in a wide range of biological processes, such as endocytosis, adhesion, lipid transport, antigen presentation, and pathogen clearance. In addition to playing a crucial role in maintenance of host homeostasis, scavenger receptors have been implicated in the pathogenesis of a number of diseases, e.g., atherosclerosis, neurodegeneration, or metabolic disorders. Emerging evidence has begun to reveal these receptor molecules as important regulators of tumor behavior and host immune responses to cancer. This review summarizes our current understanding on the newly identified, distinct functions of scavenger receptors in cancer biology and immunology. The potential of scavenger receptors as diagnostic biomarkers and novel targets for therapeutic interventions to treat malignancies is also highlighted. PMID:26216637

Health surveillance for occupational asthma.

PubMed

Fishwick, David; Forman, Steve

2018-04-01

The outcome for workers with occupational asthma is improved for those with an earlier diagnosis. Health surveillance at work is in principle designed to identify such cases, so that the risks to the individual worker, and coworkers, can be reduced. There is recent evidence to suggest that the uptake and quality of such surveillance could be improved. This review has assessed current approaches to health surveillance for occupational asthma. The article covers a review of the utility of questionnaires, lung function testing, immunological investigations, and other tests, including exhaled nitric oxide, sputum eosinophilia, and exhaled breath condensate specifically in the context of workplace-based health surveillance. Questionnaires remain a key component of respiratory health surveillance, although maybe limited by both sensitivity and specificity for early occupational asthma. The role of lung function testing is debated, although is recommended for higher level health surveillance. Various examples of immunological testing in health surveillance are discussed, but more evidence is needed in many specific areas before more general recommendations can be made. Evidence is discussed in relation to the utility of newer approaches such as exhaled nitric oxide, sputum eosinophilia, and exhaled breath condensate.

Alphavirus-based DNA vaccine breaks immunological tolerance by activating innate antiviral pathways

PubMed Central

Leitner, Wolfgang W.; Hwang, Leroy N.; Deveer, Michael J.; Zhou, Aimin; Silverman, Robert H.; Williams, Bryan R.G.; Dubensky, Thomas W.; Ying, Han; Restifo, Nicholas P.

2006-01-01

Cancer vaccines targeting ‘self’ antigens that are expressed at consistently high levels by tumor cells are potentially useful in immunotherapy, but immunological tolerance may block their function. Here, we describe a novel, naked DNA vaccine encoding an alphavirus replicon (self-replicating mRNA) and the self/tumor antigen tyrosinase-related protein-1. Unlike conventional DNA vaccines, this vaccine can break tolerance and provide immunity to melanoma. The vaccine mediates production of double-stranded RNA, as evidenced by the autophosphorylation of protein kinase R. Double-stranded RNA is critical to vaccine function because both the immunogenicity and the anti-tumor activity of the vaccine are blocked in mice deficient for the RNase L enzyme, a key component of the 2′,5′-linked oligoadenylate synthetase antiviral pathway involved in double-stranded RNA recognition. This study shows for the first time that alphaviral replicon-encoding DNA vaccines activate innate immune pathways known to drive antiviral immune responses, and points the way to strategies for improving the efficacy of immunization with naked DNA. PMID:12496961

Developments in rabies vaccines.

PubMed

Hicks, D J; Fooks, A R; Johnson, N

2012-09-01

The development of vaccines that prevent rabies has a long and distinguished history, with the earliest preceding modern understanding of viruses and the mechanisms of immune protection against disease. The correct application of inactivated tissue culture-derived vaccines is highly effective at preventing the development of rabies, and very few failures are recorded. Furthermore, oral and parenteral vaccination is possible for wildlife, companion animals and livestock, again using inactivated tissue culture-derived virus. However, rabies remains endemic in many regions of the world and causes thousands of human deaths annually. There also remain no means of prophylaxis for rabies once the virus enters the central nervous system (CNS). One reason for this is the poor immune response within the CNS to infection with rabies virus (RABV). New approaches to vaccination using modified rabies viruses that express components of the innate immune system are being applied to this problem. Preliminary reports suggest that direct inoculation of such viruses could trigger an effective anti-viral response and prevent a fatal outcome from RABV infection. © 2012 Crown copyright. Clinical and Experimental Immunology © 2012 British Society for Immunology.

Porphyromonas gingivalis Promotes Unrestrained Type I Interferon Production by Dysregulating TAM Signaling via MYD88 Degradation.

PubMed

Mizraji, Gabriel; Nassar, Maria; Segev, Hadas; Sharawi, Hafiz; Eli-Berchoer, Luba; Capucha, Tal; Nir, Tsipora; Tabib, Yaara; Maimon, Avraham; Dishon, Shira; Shapira, Lior; Nussbaum, Gabriel; Wilensky, Asaf; Hovav, Avi-Hai

2017-01-10

Whereas type I interferons (IFNs-I) were proposed to be elevated in human periodontitis, their role in the disease remains elusive. Using a bacterial-induced model of murine periodontitis, we revealed a prolonged elevation in IFN-I expression. This was due to the downregulation of TAM signaling, a major negative regulator of IFN-I. Further examination revealed that the expression of certain TAM components was reduced as a result of prolonged degradation of MYD88 by the infection. As a result of such prolonged IFN-I production, innate immunological functions of the gingiva were disrupted, and CD4 + T cells were constitutively primed by dendritic cells, leading to elevated RANKL expression and, subsequently, alveolar bone loss (ABL). Blocking IFN-I signaling restored proper immunological function and prevented ABL. Importantly, a loss of negative regulation on IFN-I expression by TAM signaling was also evident in periodontitis patients. These findings thus suggest a role for IFN-I in the pathogenesis of periodontitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

The Phagocyte, Metchnikoff, and the Foundation of Immunology.

PubMed

Teti, Giuseppe; Biondo, Carmelo; Beninati, Concetta

2016-04-01

Since the ability of some cells to engulf particulate material was observed before Metchnikoff, he did not "discover" phagocytosis, as is sometimes mentioned in textbooks. Rather, he assigned to particle internalization the role of defending the host against noxious stimuli, which represented a new function relative to the previously recognized task of intracellular digestion. With this proposal, Metchnikoff built the conceptual framework within which immunity could finally be seen as an active host function triggered by noxious stimuli. In this sense, Metchnikoff can be rightly regarded as the father of all immunological sciences and not only of innate immunity or myeloid cell biology. Moreover, the recognition properties of his phagocyte fit surprisingly well with recent discoveries and modern models of immune sensing. For example, rather than assigning to immune recognition exclusively the function of eliminating nonself components (as others did after him), Metchnikoff viewed phagocytes as homeostatic agents capable of monitoring the internal environment and promoting tissue remodeling, thereby continuously defining the identity of the organism. No doubt, Metchnikoff's life and creativity can provide, still today, a rich source of inspiration.

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

21 CFR 866.5700 - Whole human plasma or serum immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Whole human plasma or serum immunological test... Systems § 866.5700 Whole human plasma or serum immunological test system. (a) Identification. A whole human plasma or serum immunological test system is a device that consists of reagents used to measure by...

Medical immunology: two-way bridge connecting bench and bedside.

PubMed

Rijkers, Ger T; Damoiseaux, Jan G M C; Hooijkaas, Herbert

2014-12-01

Medical immunology in The Netherlands is a laboratory specialism dealing with immunological analyses as well as pre- and post-analytical consultation to clinicians (clinical immunologists and other specialists) involved in patients with immune mediated diseases. The scope of medical immunology includes immunodeficiencies, autoimmune diseases, allergy, transfusion and transplantation immunology, and lymphoproliferative disorders plus the monitoring of these patients. The training, professional criteria, quality control of procedures and laboratories is well organized. As examples of the bridge function of medical immunology between laboratory (bench) and patient (bedside) the contribution of medical immunologists to diagnosis and treatment of primary immunodeficiency diseases (in particular: humoral immunodeficiencies) as well as autoantibodies (anti-citrullinated proteins in rheumatoid arthritis) are given. Copyright © 2014 Elsevier B.V. All rights reserved.

Potential of mean force for human lysozyme camelid vhh hl6 antibody interaction studies

NASA Astrophysics Data System (ADS)

Wang, Yeng-Tseng; Liao, Jun-Min; Chen, Cheng-Lung; Su, Zhi-Yuan; Chen, Chang-Hung; Hu, Jeu-Jiun

2008-04-01

Calculating antigen-antibody interaction energies is crucial for understanding antigen-antibody associations in immunology. To shed further light into this equation, we study a separation of human lysozyme-camelid vhh hl6 antibody (cAb-HuL6) complex. The c-terminal end-to-end stretching of the lysozyme-antibody complex structures have been studied using potential of mean force (PMF) calculations based on molecular dynamics (MD) and explicit water model. For the lysozyme-antibody complex, there are six important intermediates in the c-terminal extensions process. Inclusion of our simulations may help to understand the binding mechanics of lysozyme-cAb-HuL6 antibody complex.

Immunological dysregulation in multiple myeloma microenvironment.

PubMed

Romano, Alessandra; Conticello, Concetta; Cavalli, Maide; Vetro, Calogero; La Fauci, Alessia; Parrinello, Nunziatina Laura; Di Raimondo, Francesco

2014-01-01

Multiple Myeloma (MM) is a systemic hematologic disease due to uncontrolled proliferation of monoclonal plasma cells (PC) in bone marrow (BM). Emerging in other solid and liquid cancers, the host immune system and the microenvironment have a pivotal role for PC growth, proliferation, survival, migration, and resistance to drugs and are responsible for some clinical manifestations of MM. In MM, microenvironment is represented by the cellular component of a normal bone marrow together with extracellular matrix proteins, adhesion molecules, cytokines, and growth factors produced by both stromal cells and PC themselves. All these components are able to protect PC from cytotoxic effect of chemo- and radiotherapy. This review is focused on the role of immunome to sustain MM progression, the emerging role of myeloid derived suppressor cells, and their potential clinical implications as novel therapeutic target.

Consensus Communication on Early Peanut Introduction and Prevention of Peanut Allergy in High-Risk Infants.

PubMed

Fleischer, David M; Sicherer, Scott; Greenhawt, Matthew; Campbell, Dianne; Chan, Edmond; Muraro, Antonella; Halken, Susanne; Katz, Yitzhak; Ebisawa, Motohiro; Eichenfield, Lawrence; Sampson, Hugh; Lack, Gideon; Du Toit, George; Roberts, Graham; Bahnson, Henry; Feeney, Mary; Hourihane, Jonathan; Spergel, Jonathan; Young, Michael; As'aad, Amal; Allen, Katrina; Prescott, Susan; Kapur, Sandeep; Saito, Hirohisa; Agache, Ioana; Akdis, Cezmi A; Arshad, Hasan; Beyer, Kirsten; Dubois, Anthony; Eigenmann, Philippe; Fernandez-Rivas, Monserrat; Grimshaw, Kate; Hoffman-Sommergruber, Karin; Host, Arne; Lau, Susanne; O'Mahony, Liam; Mills, Clare; Papadopoulos, Nikolaus; Venter, Carina; Agmon-Levin, Nancy; Kessel, Aaron; Antaya, Richard; Drolet, Beth; Rosenwasser, Lanny

2016-01-01

The purpose of this brief communication is to highlight emerging evidence regarding potential benefits of supporting early rather than delayed peanut introduction during the period of complementary food introduction in infants. This document should be considered as interim guidance based on consensus among the following organizations: American Academy of Allergy, Asthma, and Immunology, American Academy of Pediatrics, American College of Allergy, Asthma, and Immunology, Australasian Society of Clinical Immunology and Allergy, Canadian Society of Allergy and Clinical Immunology, European Academy of Allergy and Clinical Immunology, Israel Association of Allergy and Clinical Immunology, Japanese Society for Allergology, Society for Pediatric Dermatology, and World Allergy Organization. More formal guidelines regarding early-life, complementary feeding practices and the risk of allergy development will follow in the next year from the National Institute of Allergy and Infectious Diseases-sponsored Working Group and the European Academy of Allergy and Clinical Immunology. © 2015 the Authors. Published by Wiley Periodicals, Inc.

The 14th European Immunology Meeting--EFIS 2000. 23-27 September 2000, Poznañ, Poland.

PubMed

Wysocki, P J; Nawrocki, S; Mackiewicz, A

2001-01-01

The 14th European Immunology Meeting--EFIS 2000, held in Poznan, Poland on 23-27 September 2000, was the last major meeting of European immunologists in the second millennium. This conference was intended to summarise past achievements and to present future prospects in immunology. The philosophy of the scientific program was to fuse fundamental and clinical immunology and give a chance for basic scientists and clinicians to discuss mutual topics in a general view. There were eight state-of-art lectures, 12 'meet an expert' sessions, 20 plenary sessions and 46 workshops. More than 900 works were presented. Significant interest was focused on several aspects of cancer immunology and immunotherapy. EFIS 2000 was accompanied by six pre-congress satellite symposia held in various Polish cities. The topics were, 'Heat shock proteins: immune, stress response and apoptosis' (Gdansk), 'Infectious immunity and vaccines' (Kazimierz Dolny), 'Mononuclear phagocytes in basic and clinical immunology' (Cracow), 'Immunology of reproduction' (Poznan), 'Primary immunodeficiencies' (Warsaw) and 'Glycoimmunology' (Wroclaw).

Precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae.

PubMed

Adeyefa, C A

1992-07-01

The precipitin response of the mitogen produced by Strongylus vulgaris arterial larvae was investigated. IgG (T) from the sera of horses naturally infected with S. vulgaris adults and arterial larvae recognised the presence of two antigenic components of the mitogenic fractions. The results obtained seem to confirm that these antigens are immunogenic in stimulating the production of increased levels of IgG(T) in infected animals, and showed that the procedures could be used as immunological tools in the diagnosis of S. vulgaris infection.

Immunopathogenesis of inflammatory bowel disease and mechanisms of biological therapies.

PubMed

Ahluwalia, Bani; Moraes, Luiza; Magnusson, Maria K; Öhman, Lena

2018-04-01

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract with a multifactorial pathophysiology. Full comprehension of IBD pathology is still out of reach and, therefore, treatment is far from ideal. Nevertheless, components involved in IBD pathogenesis including environmental, genetic, microbial, and immunological factors are continuously being investigated and the improved knowledge contributes to the development of new therapies. In this article we review the aspects of the immunopathogenesis of IBD, with focus on mucosal immunity, and discuss mechanisms of action for current and emerging biological therapies.

[Botulism: structure and function of botulinum toxin and its clinical application].

PubMed

Oguma, Keiji; Yamamoto, Yumiko; Suzuki, Tomonori; Fatmawati, Ni Nengah Dwi; Fujita, Kumiko

2012-08-01

Clostridium botulinum produces seven immunological distinct poisonous neurotoxins, A to G, with molecular masses of approximately 150kDa. In acidic foods and culture fluid, the neurotoxins associate with non-toxic components, and form large complexes designated progenitor toxins. The progenitor toxins are found in three forms named LL, L, and M. These neurotoxins and progenitor toxins were purified, and whole nucleotide sequences of their structure genes were determined. In this manuscript, the structure and function of these toxins, and the application of these toxins to clinical usage have been described.

SOME CHARACTERISTICS OF THE ORAL CAVITY AND TEETH OF COSMONAUTS ON MISSIONS TO THE INTERNATIONAL SPACE STATION.

PubMed

Ilyin, V K; Shumilina, G A; Solovieva, Z O; Nosovsky, A M; Kaminskaya, E V

Earlier studies were furthered by examination of parodentium anaerobic microbiota and investigation of gingival liquid immunological factors in space flight. Immunoglobulins were measured using the .enzyme immunoassay (EM). The qualitative content of keya parodentium pathogens is determined with state-of-the-art molecular biology technologies such as the polymerase chain reaction. Statistical data processing was performed using the principle component analysis and ensuing standard statistical analysis. Thereupon, recommendations on cosmonaut's oral and dental hygiene during space mission were developed.

Absence of cellular hypersensitivity to muscle and thymic antigens in myasthenia gravis.

PubMed Central

Behan, W M; Behan, P O; Simpson, J A

1975-01-01

Humoral antibodies to skeletal muscle and its components and to thymus have been demonstrated in the sera of patients with myasthenia gravis. A role for cellular hypersensitivity to similar antigens in the pathogenesis of the disease has been suggested by some reports of the presence of cellular immunity. A detailed immunological study using muscle and thymic antigens, including those prepared from the patients' own tissues, failed to confirm these findings. It is suggested that previous reports of cellular hypersensitivity represent the demonstration of an epiphenomenon. PMID:1206412

Face-offs in reproductive immunology: the Montreal forum meeting report.

PubMed

Croy, B Anne; Baines, Malcolm G

2004-10-01

The combined 12th International Congress of Immunology (ICI) and the 4th Annual Conference of the Federation of Clinical Immunological Societies (FOCIS) was held in Montreal, Canada July 18-23, 2004 and attracted over 6000 immunologists and almost 4000 abstracts. The host society, the Canadian Society for Immunology (CSI) spent many years in preparation for this large meeting and encouraged its members to propose topics for symposia and mini-symposia and to sponsor satellite meetings. With sponsorship of CSI; the Canadian Institutes of Health Research; the University of Guelph, Guelph, ON; Queen's University, Kingston, ON; McGill University, Montreal, QU, Canada; and the American Society for Reproductive Immunology, a focused, highly successful, one day satellite meeting on human uterine immunology was held. The highlights of the presentations and discussions are reported.

Molecular and immunological characterisation of the glycosylated orange allergen Cit s 1

PubMed Central

Pöltl, Gerald; Ahrazem, Oussama; Paschinger, Katharina; Ibañez, M. Dolores; Salcedo, Gabriel; Wilson, Iain B. H.

2010-01-01

The IgE of sera from patients with a history of allergy to oranges (Citrus sinensis) bind a number of proteins in orange extract, including Cit s 1, a germin-like protein. In the present study, we have analysed its immunological cross-reactivity and its molecular nature. Sera from many of the patients examined recognise a range of glycoproteins and neoglycoconjugates containing β1,2-xylose and core α1,3-fucose on their N-glycans. These reagents also inhibited the interaction of Cit s 1 with patients’ sera, thus underlining the critical role of glycosylation in the recognition of this protein by patients’ IgE and extending previous data showing that deglycosylated Cit s 1 does not possess IgE epitopes. In parallel, we examined the peptide sequence and glycan structure of Cit s 1 using mass spectrometric techniques. Indeed, we achieved complete sequence coverage of the mature protein as compared to the translation of an expressed sequence tag cDNA clone and demonstrated that the single N-glycosylation site of this protein carries oligosaccharides with xylose and fucose residues. Due to the presumed requirement for multivalency for in vivo allergenicity, our molecular data showing that Cit s 1 is monovalent as regards glycosylation and that the single N-glycan is the target of the IgE response to this protein, therefore, explain the immunological cross-reactive properties of Cit s 1 as well as its equivocal nature as a clinically-relevant allergen. PMID:17095532

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer.

PubMed

Roberts, David D; Kaur, Sukhbir; Isenberg, Jeffrey S

2017-10-20

In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

21 CFR 866.5880 - Transferrin immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... transferrin levels aids in the diagnosis of malnutrition, acute inflammation, infection, and red blood cell... Transferrin immunological test system. (a) Identification. A transferrin immunological test system is a device...

Multicentre physiological reference intervals for serum concentrations of immunoglobulins A, G and M, complement C3c and C4 measured with Tina-Quant reagents systems.

PubMed

Fuentes-Arderiu, Xavier; Alonso-Gregorio, Eduardo; Alvarez-Funes, Virtudes; Ambrós-Marigómez, Carmen; Coca-Fábregas, Lluís; Cruz-Placer, Marta; Díaz-Fernández, Julián; Pinel-Julián, María Pilar; Gutiérrez-Cecchini, Beatriz; Herrero-Bernal, Pilar; Sempere-Alcocer, Marcos; García-Caballero, Francisca; Del Mar Larrea-Ortiz-Quintana, María; La-Torre-Marcellán, Pedro; Del Señor López-Vélez, María; Mar-Medina, Carmen; Martín-Oncina, Javier; Rodríguez-Hernández, María Victoria; Romero-Sotomayor, María Victoria; Serrano-López, Cándido; Sicilia-Enríquez-de-Salamanca, Adolfo; Velasco-Romero, Ana María; Juvé-Cuxart, Santiago

2007-01-01

Clinical laboratories seeking accreditation for compliance with ISO 15189:2003 need to demonstrate that the physiological reference intervals communicated to all users of the laboratory service are appropriate for the patient population served and for the measurement systems used. In the case of immunological quantities, few articles have been published in peer-reviewed journals. A total of 21 clinical laboratories in different regions of Spain collaborated in identifying reference individuals and determining adult reference intervals for some immunological quantities measured using RD/Hitachi Modular Analytics analysers and Tina-Quant reagent systems. These immunological quantities are the mass concentrations of immunoglobulin A, immunoglobulin G, immunoglobulin M, complement C3c and complement C4 in serum. All the logistic work was carried out in co-operation with the supplier of the reagents and analysers (Roche Diagnostics España, S.L., Sant Cugat del Vallès, Catalonia, Spain). From the set of reference values obtained by each laboratory, multicentre reference limits were estimated non-parametrically. The reference intervals estimated in this study for concentrations of serum components under consideration are: complement C3c, 0.62-1.64 g/L for women and men; complement C4, 0.14-0.72 g/L for women and men; immunoglobulin A, 0.89-4.80 g/L for women and men; immunoglobulin G, 6.5-14.3 g/L for women and men; and immunoglobulin M, 0.48-3.38 g/L for women and 0.41-2.46 g/L for men.

The Immunology of Wild Rodents: Current Status and Future Prospects

PubMed Central

Viney, Mark; Riley, Eleanor M.

2017-01-01

Wild animals’ immune responses contribute to their evolutionary fitness. These responses are moulded by selection to be appropriate to the actual antigenic environment in which the animals live, but without imposing an excessive energetic demand which compromises other component of fitness. But, exactly what these responses are, and how they compare with those of laboratory animals, has been little studied. Here, we review the very small number of published studies of immune responses of wild rodents, finding general agreement that their humoral (antibody) responses are highly elevated when compared with those of laboratory animals, and that wild rodents’ cellular immune system reveals extensive antigenic exposure. In contrast, proliferative and cytokine responses of ex vivo-stimulated immune cells of wild rodents are typically depressed compared with those of laboratory animals. Collectively, these responses are appropriate to wild animals’ lives, because the elevated responses reflect the cumulative exposure to infection, while the depressed proliferative and cytokine responses are indicative of effective immune homeostasis that minimizes immunopathology. A more comprehensive understanding of the immune ecology of wild animals requires (i) understanding the antigenic load to which wild animals are exposed, and identification of any key antigens that mould the immune repertoire, (ii) identifying immunoregulatory processes of wild animals and the events that induce them, and (iii) understanding the actual resource state of wild animals, and the immunological consequences that flow from this. Together, by extending studies of wild rodents, particularly addressing these questions (while drawing on our immunological understanding of laboratory animals), we will be better able to understand how rodents’ immune responses contribute to their fitness in the wild. PMID:29184549

The Immunology of Wild Rodents: Current Status and Future Prospects.

PubMed

Viney, Mark; Riley, Eleanor M

2017-01-01

Wild animals' immune responses contribute to their evolutionary fitness. These responses are moulded by selection to be appropriate to the actual antigenic environment in which the animals live, but without imposing an excessive energetic demand which compromises other component of fitness. But, exactly what these responses are, and how they compare with those of laboratory animals, has been little studied. Here, we review the very small number of published studies of immune responses of wild rodents, finding general agreement that their humoral (antibody) responses are highly elevated when compared with those of laboratory animals, and that wild rodents' cellular immune system reveals extensive antigenic exposure. In contrast, proliferative and cytokine responses of ex vivo -stimulated immune cells of wild rodents are typically depressed compared with those of laboratory animals. Collectively, these responses are appropriate to wild animals' lives, because the elevated responses reflect the cumulative exposure to infection, while the depressed proliferative and cytokine responses are indicative of effective immune homeostasis that minimizes immunopathology. A more comprehensive understanding of the immune ecology of wild animals requires (i) understanding the antigenic load to which wild animals are exposed, and identification of any key antigens that mould the immune repertoire, (ii) identifying immunoregulatory processes of wild animals and the events that induce them, and (iii) understanding the actual resource state of wild animals, and the immunological consequences that flow from this. Together, by extending studies of wild rodents, particularly addressing these questions (while drawing on our immunological understanding of laboratory animals), we will be better able to understand how rodents' immune responses contribute to their fitness in the wild.

The Effect of Immunologically Safe Plasma Rich in Growth Factor Eye Drops in Patients with Sjögren Syndrome.

PubMed

Sanchez-Avila, Ronald Mauricio; Merayo-Lloves, Jesus; Riestra, Ana Cristina; Anitua, Eduardo; Muruzabal, Francisco; Orive, Gorka; Fernández-Vega, Luis

2017-06-01

The objective was to provide preliminary information about the efficacy and safety of immunologically safe plasma rich in growth factor (immunosafe PRGF) eye drops in the treatment of moderate to severe dry eye in patients with primary and secondary Sjögren's syndrome (SS) and to analyze the influence of several variables on treatment outcomes. This retrospective study included patients with SS. All patients were treated with previously immunosafe PRGF eye drops to reduce the immunologic component contents. Ocular Surface Disease Index (OSDI) scale, best-corrected visual acuity (BCVA), visual analog scale (VAS) frequency, and VAS severity outcome measures were evaluated before and after treatment with immunosafe PRGF. The potential influence of some patient clinical variables on results was also assessed. Safety assessment was also performed reporting all adverse events. Twenty-six patients (12 patients with primary SS, and 14 patients suffering secondary SS) with a total of 52 affected eyes were included and evaluated. Immunosafe PRGF treatment showed a significant reduction (P < 0.05) in OSDI scale (41.86%), in BCVA (62.97%), in VAS frequency (34.75%), and in VAS severity (41.50%). BCVA and VAS frequency scores improved significantly (P < 0.05) after concomitant treatment of PRGF with corticosteroids. Only 2 adverse events were reported in 2 patients (7.7% of patients). Signs and symptoms of dry eye syndrome in patients with SS were reduced after treatment with PRGF-Endoret eye drops. Immunosafe PRGF-Endoret is safe and effective for treating patients with primary and secondary SS.

Hepatitis E and Pregnancy- Understanding the pathogenesis

PubMed Central

Navaneethan, Udayakumar; Mohajer, Mayar Al; Shata, Mohamed T

2008-01-01

Hepatitis E virus (HEV) is a single-stranded RNA virus that causes large-scale epidemics of acute viral hepatitis, particularly in developing countries. In men and non pregnant women, the disease is usually self-limited and has a case-fatality rate of less than <0.1%. However in pregnant women particularly from certain geographic areas in India, HEV infection is more severe, often leading to fulminant hepatic failure and death in a significant proportion of patients. In contrast, reports from Egypt, Europe and the USA have shown that the course and severity of viral hepatitis during pregnancy is not different from that in non-pregnant women. The reasons for this geographical difference are not clear. The high mortality rate in pregnancy has been thought to be secondary to the associated hormonal (estrogen and progesterone) changes during pregnancy and consequent immunological changes. These immunological changes include down regulation of p65 component of NF κB with a predominant Th2 bias in the T-cell response along with host susceptibility factors, mediated by HLA expression. Thus far, researchers were unable to explain the high HEV morbidity in pregnancy, why it is different from other hepatitis viruses such as hepatitis A with similar epidemiological features, and the reason behind the difference in HEV morbidity in pregnant women in different geographical regions. The recent developments in understanding the immune response to HEV have encouraged us to review possible mechanisms for these differences. Further research in the immunology of HEV and pregnancy is required to conquer this disease in the near future. PMID:18662274

Intensive educational course in allergy and immunology.

PubMed

Elizalde, A; Perez, E E; Sriaroon, P; Nguyen, D; Lockey, R F; Dorsey, M J

2012-09-01

A one-day intensive educational course on allergy and immunology theory and diagnostic procedure significantly increased the competency of allergy and immunology fellows-in-training. © 2012 John Wiley & Sons A/S.

Pediatric allergy and immunology in Turkey.

PubMed

Celik, Gülfem; Bakirtas, Arzu; Sackesen, Cansin; Reisli, Ismail; Tuncer, Ayfer

2011-06-01

Allergic diseases constitute a significant health problem in Turkey. According to a recent multicenter study, which used the ISAAC questionnaire, the mean prevalence of wheezing, rhinoconjunctivitis, and eczema in 10-yr-old school children during the past year was 15.8%, 23.5%, and 8.1%, respectively. A healthcare level system, regulated by Ministry of Health, is available in Turkey. Pediatric allergists and pediatric immunologists provide patient care at the tertiary level. Currently, 48 centers deliver care for allergic and immunologic diseases in children. There are 136 pediatric and 61 adult allergists/immunologists. Although the number of allergy/clinical immunology specialists is limited, these centers are capable of delivering many of the procedures required for the proper management and diagnosis of allergy/immunology. Pediatric allergy and/or immunology is a subspecialty lasting 3 yr and follows a 4-yr pediatric specialist training. Fellow training involves gaining knowledge in basic and clinical allergy and immunology as well as the performance and interpretation of laboratory procedures in the field of allergy and clinical immunology. The Turkish National Society of Allergy and Clinical Immunology (TNSACI) was officially established in 1989 and currently has 356 members. The society organizes a national congress annually and winter schools for fellowship training as well as training courses for patients and their relatives. TNSACI also has a strong representation in European Academy of Allergy and Clinical Immunology (EAACI) and European Society for Immunodeficiencies (ESID) through its participation in the executive committee, consensus reports, and initiatives in the diagnosis of allergic and immunologic diseases of children. The 30th Congress of the EAACI is also due to be held in Istanbul, Turkey, between June 11 and 15, 2011. © 2011 John Wiley & Sons A/S.

[Human milk, immune responses and health effects].

PubMed

Løland, Beate Fossum; Baerug, Anne B; Nylander, Gro

2007-09-20

Besides providing optimal nutrition to infants, human milk contains a multitude of immunological components. These components are important for protection against infections and also support the development and maturation of the infant's own immune system. This review focuses on the function of some classical immunocomponents of human milk. Relevant studies are presented that describe health benefits of human milk for the child and of lactation for the mother. Relevant articles were found mainly by searching PubMed. Humoral and cellular components of human milk confer protection against infections in the respiratory--, gastrointestinal--and urinary tract. Human milk also protects premature children from neonatal sepsis and necrotizing enterocolitis. There is evidence that human milk may confer long-term benefits such as lower risk of certain autoimmune diseases, inflammatory bowel disease and probably some malignancies. Human milk possibly affects components of the metabolic syndrome. Recent studies demonstrate long-term health benefits of lactation also for the mother. A reduced incidence of breast cancer is best documented. An increasing number of studies indicate protection against ovarian cancer, rheumatoid arthritis and type II diabetes.