The Worm Propagation Model with Dual Dynamic Quarantine Strategy

NASA Astrophysics Data System (ADS)

Yao, Yu; Xie, Xiao-Wu; Guo, Hao; Gao, Fu-Xiang; Yu, Ge

Internet worms are becoming more and more harmful with the rapid development of the Internet. Due to the extremely fast spread and great destructive power of network worms, strong dynamic quarantine strategies are necessary. Inspired by the real-world approach to the prevention and treatment of infectious diseases, this paper proposes a quarantine strategy based on dynamic worm propagation model: the SIQRV dual quarantine model. This strategy uses dynamic quarantine method to make the vulnerable host and infected host quarantined, and then release them after a certain period of time, regardless of whether quarantined host security is checked. Through mathematic modeling, it has been found that when the basic reproduction number R0 is less than a critical value, the system will stabilize in the disease-free equilibrium, that is, in theory, the infected hosts will be completely immune. Finally, by comparing the simulation results and numerical analysis, the basic agreement between the two curves supports the validity of the mathematical model. Our future work will be focusing on taking both the delay and double-quarantine strategy into account and further expanding the scale of our simulation work.

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

PubMed

Chen, Tinggui; Xiao, Renbin

2014-01-01

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

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

PubMed Central

Chen, Tinggui; Xiao, Renbin

2014-01-01

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

Basics of PD-1 in self-tolerance, infection, and cancer immunity.

PubMed

Chikuma, Shunsuke

2016-06-01

Successful cancer treatment requires understanding host immune response against tumor cells. PD-1 belongs to the CD28 superfamily of receptors that work as "checkpoints" of immune activation. PD-1 maintains immune self-tolerance to prevent autoimmunity and controls T-cell reaction during infection to prevent excessive tissue damage. Tumor cells that arise from normal tissue acquire mutations that can be targeted by lymphocytes. Accumulating lines of evidence suggest that tumor cells evade host immune attack by expressing physiological PD-1 ligands and stimulating PD-1 on the lymphocytes. Based on this idea, researchers have successfully demonstrated that systemic administration of monoclonal antibodies that inhibit the binding of PD-1 to the ligands reactivated T cells and augmented the anti-cancer immune response. In this review, I summarize the basics of T-cell biology and its regulation by PD-1 and discuss the current understanding and questions about this multifaceted molecule.

Immune checkpoint inhibitors: basics and challenges.

PubMed

Li, Bin; Chan, Ho Lam; Chen, Pingping

2017-08-04

Cancer is one of the most deadly diseases in modern world. The last decade has witnessed dramatic advances in the cancer treatment through immunotherapy. One extremely promising means to achieve anti-caner immunity is to block the immune checkpoint pathways, which mechanism was adopted by cancer cells to disguise themselves as regular components of human body. While checkpoint blockade is universally effective against a broad spectrum of cancer types and mostly unrestricted by certain gene mutation status, only a minority of patients achieved a complete response to such treatment. In this review we summarize the basic principles of immune checkpoint inhibitors and discuss potential mechanisms of resistance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effect of antibodies on pathogen dynamics with delays and two routes of infection

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Almatrafi, A. A.; Hobiny, A. D.

2018-06-01

We study the global stability of pathogen dynamics models with saturated pathogen-susceptible and infected-susceptible incidence. The models incorporate antibody immune response and three types of discrete or distributed time delays. We first show that the solutions of the model are nonnegative and ultimately bounded. We determine two threshold parameters, the basic reproduction number and antibody response activation number. We establish the existence and stability of the steady states. We study the global stability analysis of models using Lyapunov method. The numerical simulations have shown that antibodies can reduce the pathogen progression.

Effect of humoral immunity on HIV-1 dynamics with virus-to-target and infected-to-target infections

NASA Astrophysics Data System (ADS)

Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

2016-08-01

We consider an HIV-1 dynamics model by incorporating (i) two routes of infection via, respectively, binding of a virus to a receptor on the surface of a target cell to start genetic reactions (virus-to-target infection), and the direct transmission from infected cells to uninfected cells through the concept of virological synapse in vivo (infected-to-target infection); (ii) two types of distributed-time delays to describe the time between the virus or infected cell contacts an uninfected CD4+ T cell and the emission of new active viruses; (iii) humoral immune response, where the HIV-1 particles are attacked by the antibodies that are produced from the B lymphocytes. The existence and stability of all steady states are completely established by two bifurcation parameters, R 0 (the basic reproduction number) and R 1 (the viral reproduction number at the chronic-infection steady state without humoral immune response). By constructing Lyapunov functionals and using LaSalle's invariance principle, we have proven that, if R 0 ≤ 1 , then the infection-free steady state is globally asymptotically stable, if R 1 ≤ 1 < R 0 , then the chronic-infection steady state without humoral immune response is globally asymptotically stable, and if R 1 > 1 , then the chronic-infection steady state with humoral immune response is globally asymptotically stable. We have performed numerical simulations to confirm our theoretical results.

Immunology.

PubMed

Toskala, Elina

2014-09-01

Knowledge of our immune system functions is critical for understanding allergic airway disease development as well as for selection of appropriate diagnostic and therapeutic options for patients with respiratory allergies. This review explains the current understanding of the basic immunology of the upper airways and the pathophysiology of allergic responses, including the mechanisms behind allergic rhinitis. The immune system can be divided to 2 main defense systems that function differently-innate immunity and adaptive immunity. Innate immunity includes several defensive mechanisms such as anatomic or physical barriers, physiological barriers, phagocytosis, and inflammation. The adaptive immune response is activated in an antigen-specific way to provide for the elimination of antigen and induce lasting protection. Hypersensitivity reactions occur when an exaggerated adaptive immune response is activated. Allergic rhinitis is an example of a type I, immunoglobulin E, mediated hypersensitivity reaction. Today we have several immunomodulatory treatment options for patients with allergic airway diseases, such as subcutaneous and sublingual immunotherapy. An understanding of the basics of our immune system and its method of functions is key for using these therapies appropriately. © 2014 ARS-AAOA, LLC.

Expected Paradigm Shift in Brain Metastases Therapy-Immune Checkpoint Inhibitors.

PubMed

Jindal, Vishal; Gupta, Sorab

2018-01-30

Brain metastasis (BM) is one of the dreadful complications of malignancies. The prognosis after BM is extremely poor and life expectancy is meager. Currently, our treatment modalities are limited to radiotherapy and surgical resection, which also has poor outcomes and leads to various neurological deficits and affects the quality of life of patients. New treatment modality, i.e., immune checkpoint inhibitors, has brought revolution in management of melanoma, renal cancer, and non-small cell lung cancer (NSCLC). Immune checkpoint inhibitors basically enhance the immune response of the body to fight against cancers. Immune response in the brain is highly regulated; therefore, it is challenging to use immune-modulator drugs in BM. The microenvironment of BM is rich in cytotoxic T lymphocytes and which is the target of immune checkpoint inhibitors. Few studies have shown some hope regarding use of immune checkpoint inhibitors in management of BM. It works through inhibiting immune check point gates, i.e., CTLA-4 (cytotoxic T-lymphocyte-associated protein) and PD-1/PD-L1 (programmed cell death protein-1/program death ligand-1). This article explains the basic mechanism of immune check point inhibitors, rationale behind their usage in BM, and some of the clinical studies which have shown the efficacy of immune check point inhibitors in BM.

Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function.

PubMed

Balzar, Silvana

2017-01-01

Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

Routine Immunization Service Delivery Through the Basic Package of Health Services Program in Afghanistan: Gaps, Challenges, and Opportunities.

PubMed

Mbaeyi, Chukwuma; Kamawal, Noor Shah; Porter, Kimberly A; Azizi, Adam Khan; Sadaat, Iftekhar; Hadler, Stephen; Ehrhardt, Derek

2017-07-01

The Basic Package of Health Services (BPHS) program has increased access to immunization services for children living in rural Afghanistan. However, multiple surveys have indicated persistent immunization coverage gaps. Hence, to identify gaps in implementation, an assessment of the BPHS program was undertaken, with specific focus on the routine immunization (RI) component. A cross-sectional survey was conducted in 2014 on a representative sample drawn from a sampling frame of 1858 BPHS health facilities. Basic descriptive analysis was performed, capturing general characteristics of survey respondents and assessing specific RI components, and χ2 tests were used to evaluate possible differences in service delivery by type of health facility. Of 447 survey respondents, 27% were health subcenters (HSCs), 30% were basic health centers, 32% were comprehensive health centers, and 12% were district hospitals. Eighty-seven percent of all respondents offered RI services, though only 61% of HSCs did so. Compared with other facility types, HSCs were less likely to have adequate stock of vaccines, essential cold-chain equipment, or proper documentation of vaccination activities. There is an urgent need to address manpower and infrastructural deficits in RI service delivery through the BPHS program, especially at the HSC level. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Socioecological predictors of immune defences in wild spotted hyenas

PubMed Central

Flies, Andrew S.; Mansfield, Linda S.; Flies, Emily J.; Grant, Chris K.; Holekamp, Kay E.

2016-01-01

Summary Social rank can profoundly affect many aspects of mammalian reproduction and stress physiology, but little is known about how immune function is affected by rank and other socio-ecological factors in free-living animals.In this study we examine the effects of sex, social rank, and reproductive status on immune function in long-lived carnivores that are routinely exposed to a plethora of pathogens, yet rarely show signs of disease.Here we show that two types of immune defenses, complement-mediated bacterial killing capacity (BKC) and total IgM, are positively correlated with social rank in wild hyenas, but that a third type, total IgG, does not vary with rank.Female spotted hyenas, which are socially dominant to males in this species, have higher BKC, and higher IgG and IgM concentrations, than do males.Immune defenses are lower in lactating than pregnant females, suggesting the immune defenses may be energetically costly.Serum cortisol and testosterone concentrations are not reliable predictors of basic immune defenses in wild female spotted hyenas.These results suggest that immune defenses are costly and multiple socioecological variables are important determinants of basic immune defenses among wild hyenas. Effects of these variables should be accounted for when attempting to understand disease ecology and immune function. PMID:27833242

The Immunologic Revolution: Photoimmunology

PubMed Central

Ullrich, Stephen E.; Byrne, Scott N.

2011-01-01

UV radiation targets the skin and is a primary cause of skin cancer (both melanoma and non-melanoma skin cancer). Exposure to UV also suppresses the immune response, and UV-induced immune suppression is a major risk factor for skin cancer induction. The efforts of Dermatologists and Cancer Biologists to understand how UV exposure suppresses the immune response and contributes to skin cancer induction led to the development of the sub-discipline we call photoimmunology. Advances in photoimmunology have generally paralleled advances in immunology. However, there are a number of examples where investigations into the mechanisms underlying UV-induced immune suppression reshaped our understanding of basic immunological concepts. Unconventional immune regulatory roles for Langerhans cells, mast cells, and NKT cells as well as the immune suppressive function of lipid mediators of inflammation and alarmins, are just some examples of how advances in immunodermatology have altered our understanding of basic immunology. In this anniversary issue celebrating 75 years of Cutaneous Science, we will provide examples of how concepts that grew out of efforts by Immunologists and Dermatologists to understand immune regulation by UV radiation impacted on immunology in general. PMID:22170491

The stochastic dance of early HIV infection

NASA Astrophysics Data System (ADS)

Merrill, Stephen J.

2005-12-01

The stochastic nature of early HIV infection is described in a series of models, each of which captures aspects of the dance of HIV during the early stages of infection. It is to this highly variable target that the immune response must respond. The adaptability of the various components of the immune response is an important aspect of the system's operation, as the nature of the pathogens that the response will be required to respond to and the order in which those responses must be made cannot be known beforehand. As HIV infection has direct influence over cells responsible for the immune response, the dance predicts that the immune response will be also in a variable state of readiness and capability for this task of adaptation. The description of the stochastic dance of HIV here will use the tools of stochastic models, and for the most part, simulation. The justification for this approach is that the early stages and the development of HIV diversity require that the model to be able to describe both individual sample path and patient-to-patient variability. In addition, as early viral dynamics are best described using branching processes, the explosive growth of these models both predicts high variability and rapid response of HIV to changes in system parameters.In this paper, a basic viral growth model based on a time dependent continuous-time branching process is used to describe the growth of HIV infected cells in the macrophage and lymphocyte populations. Immigration from the reservoir population is added to the basic model to describe the incubation time distribution. This distribution is deduced directly from the modeling assumptions and the model of viral growth. A system of two branching processes, one in the infected macrophage population and one in the infected lymphocyte population is used to provide a description of the relationship between the development of HIV diversity as it relates to tropism (host cell preference). The role of the immune response to HIV and HIV infected cells is used to describe the movement of the infection from a few infected macrophages to a disease of infected CD4+ T lymphocytes.

Simulating the decentralized processes of the human immune system in a virtual anatomy model.

PubMed

Sarpe, Vladimir; Jacob, Christian

2013-01-01

Many physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spatial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation. Using agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project. Our current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a network of computers. As a future endeavour, we plan to use parameter tuning techniques on our model to further enhance its biological credibility. We consider these in silico experiments and their associated modeling and optimization techniques as essential components in further enhancing our capabilities of simulating a whole-body, decentralized immune system, to be used both for medical education and research as well as for virtual studies in immunoinformatics.

The epidemic threshold theorem with social and contact heterogeneity

NASA Astrophysics Data System (ADS)

Hincapié Palacio, Doracelly; Ospina Giraldo, Juan; Gómez Arias, Rubén Darío

2008-03-01

The threshold theorem of an epidemic SIR model was compared when infectious and susceptible individuals have homogeneous mixing and heterogeneous social status and when individuals of random networks have contact heterogeneity. Particularly the effect of vaccination in such models is considered when: individuals or nodes are exposed to impoverished, vaccination and loss of immunity. An equilibrium analysis and local stability of small perturbations about the equilibrium values were implemented using computer algebra. Numerical simulations were executed in order to describe the dynamic of transmission of diseases and changes of the basic reproductive rate. The implications of these results are examined around the threats to the global public health security.

The discontinuity theory of immunity

PubMed Central

Pradeu, Thomas; Vivier, Eric

2017-01-01

Some biological systems detect the rate of change in a stimulus rather than the stimulus itself only. We suggest that the immune system works in this way. According to the discontinuity theory of immunity, the immune system responds to sudden changes in antigenic stimulation and is rendered tolerant by slow or continuous stimulation. This basic principle, which is supported by recent data on immune checkpoints in viral infections, cancers, and allergies, can be seen as a unifying framework for diverse immune responses. PMID:28239677

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.

Analysis of a general SIS model with infective vectors on the complex networks

NASA Astrophysics Data System (ADS)

Juang, Jonq; Liang, Yu-Hao

2015-11-01

A general SIS model with infective vectors on complex networks is studied in this paper. In particular, the model considers the linear combination of three possible routes of disease propagation between infected and susceptible individuals as well as two possible transmission types which describe how the susceptible vectors attack the infected individuals. A new technique based on the basic reproduction matrix is introduced to obtain the following results. First, necessary and sufficient conditions are obtained for the global stability of the model through a unified approach. As a result, we are able to produce the exact basic reproduction number and the precise epidemic thresholds with respect to three spreading strengths, the curing strength or the immunization strength all at once. Second, the monotonicity of the basic reproduction number and the above mentioned epidemic thresholds with respect to all other parameters can be rigorously characterized. Finally, we are able to compare the effectiveness of various immunization strategies under the assumption that the number of persons getting vaccinated is the same for all strategies. In particular, we prove that in the scale-free networks, both targeted and acquaintance immunizations are more effective than uniform and active immunizations and that active immunization is the least effective strategy among those four. We are also able to determine how the vaccine should be used at minimum to control the outbreak of the disease.

Drivers of routine immunization coverage improvement in Africa: findings from district-level case studies

PubMed Central

LaFond, Anne; Kanagat, Natasha; Steinglass, Robert; Fields, Rebecca; Sequeira, Jenny; Mookherji, Sangeeta

2015-01-01

There is limited understanding of why routine immunization (RI) coverage improves in some settings in Africa and not in others. Using a grounded theory approach, we conducted in-depth case studies to understand pathways to coverage improvement by comparing immunization programme experience in 12 districts in three countries (Ethiopia, Cameroon and Ghana). Drawing on positive deviance or assets model techniques we compared the experience of districts where diphtheria–tetanus–pertussis (DTP3)/pentavalent3 (Penta3) coverage improved with districts where DTP3/Penta3 coverage remained unchanged (or steady) over the same period, focusing on basic readiness to deliver immunization services and drivers of coverage improvement. The results informed a model for immunization coverage improvement that emphasizes the dynamics of immunization systems at district level. In all districts, whether improving or steady, we found that a set of basic RI system resources were in place from 2006 to 2010 and did not observe major differences in infrastructure. We found that the differences in coverage trends were due to factors other than basic RI system capacity or service readiness. We identified six common drivers of RI coverage performance improvement—four direct drivers and two enabling drivers—that were present in well-performing districts and weaker or absent in steady coverage districts, and map the pathways from driver to improved supply, demand and coverage. Findings emphasize the critical role of implementation strategies and the need for locally skilled managers that are capable of tailoring strategies to specific settings and community needs. The case studies are unique in their focus on the positive drivers of change and the identification of pathways to coverage improvement, an approach that should be considered in future studies and routine assessments of district-level immunization system performance. PMID:24615431

Regulation of Adaptive Immunity in Health and Disease by Cholesterol Metabolism

PubMed Central

Fessler, Michael B.

2015-01-01

Four decades ago, it was observed that stimulation of T cells induces rapid changes in cellular cholesterol that are required before proliferation can commence. Investigators returning to this phenomenon have finally revealed its molecular underpinnings. Cholesterol trafficking and its dysregulation are now also recognized to strongly influence dendritic cell function, T cell polarization, and antibody responses. In this review, the state of the literature is reviewed on how cholesterol and its trafficking regulate the cells of the adaptive immune response and in vivo disease phenotypes of dysregulated adaptive immunity, including allergy, asthma, and autoimmune disease. Emerging evidence supporting a potential role for statins and other lipid-targeted therapies in the treatment of these diseases is presented. Just as vascular biologists have embraced immunity in the pathogenesis and treatment of atherosclerosis, so should basic and clinical immunologists in allergy, pulmonology, and other disciplines seek to encompass a basic understanding of lipid science. PMID:26149587

Oncolytic potency and reduced virus tumor-specificity in oncolytic virotherapy. A mathematical modelling approach.

PubMed

Mahasa, Khaphetsi Joseph; Eladdadi, Amina; de Pillis, Lisette; Ouifki, Rachid

2017-01-01

In the present paper, we address by means of mathematical modeling the following main question: How can oncolytic virus infection of some normal cells in the vicinity of tumor cells enhance oncolytic virotherapy? We formulate a mathematical model describing the interactions between the oncolytic virus, the tumor cells, the normal cells, and the antitumoral and antiviral immune responses. The model consists of a system of delay differential equations with one (discrete) delay. We derive the model's basic reproductive number within tumor and normal cell populations and use their ratio as a metric for virus tumor-specificity. Numerical simulations are performed for different values of the basic reproduction numbers and their ratios to investigate potential trade-offs between tumor reduction and normal cells losses. A fundamental feature unravelled by the model simulations is its great sensitivity to parameters that account for most variation in the early or late stages of oncolytic virotherapy. From a clinical point of view, our findings indicate that designing an oncolytic virus that is not 100% tumor-specific can increase virus particles, which in turn, can further infect tumor cells. Moreover, our findings indicate that when infected tissues can be regenerated, oncolytic viral infection of normal cells could improve cancer treatment.

Epidemic spreading on adaptively weighted scale-free networks.

PubMed

Sun, Mengfeng; Zhang, Haifeng; Kang, Huiyan; Zhu, Guanghu; Fu, Xinchu

2017-04-01

We introduce three modified SIS models on scale-free networks that take into account variable population size, nonlinear infectivity, adaptive weights, behavior inertia and time delay, so as to better characterize the actual spread of epidemics. We develop new mathematical methods and techniques to study the dynamics of the models, including the basic reproduction number, and the global asymptotic stability of the disease-free and endemic equilibria. We show the disease-free equilibrium cannot undergo a Hopf bifurcation. We further analyze the effects of local information of diseases and various immunization schemes on epidemic dynamics. We also perform some stochastic network simulations which yield quantitative agreement with the deterministic mean-field approach.

Global stability of an SIR model with differential infectivity on complex networks

NASA Astrophysics Data System (ADS)

Yuan, Xinpeng; Wang, Fang; Xue, Yakui; Liu, Maoxing

2018-06-01

In this paper, an SIR model with birth and death on complex networks is analyzed, where infected individuals are divided into m groups according to their infection and contact between human is treated as a scale-free social network. We obtain the basic reproduction number R0 as well as the effects of various immunization schemes. The results indicate that the disease-free equilibrium is locally and globally asymptotically stable in some conditions, otherwise disease-free equilibrium is unstable and exists an unique endemic equilibrium that is globally asymptotically stable. Our theoretical results are confirmed by numerical simulations and a promising way for infectious diseases control is suggested.

The effects of immunity and resistance on the development of AIDS

NASA Astrophysics Data System (ADS)

Abell, Martha; Braselton, James; Braselton, Lorraine

2007-09-01

We incorporate basic genetics into an AIDS model. We illustrate that if a homozygote is immune to the disease or is resistant to the effects of the disease, the corresponding allele goes to fixation. On the other hand, if the heterozygote is immune to the disease or is resistant to the effects of the disease, polymorphism usually occurs.

Glycan Arrays: From Basic Biochemical Research to Bioanalytical and Biomedical Applications

NASA Astrophysics Data System (ADS)

Geissner, Andreas; Seeberger, Peter H.

2016-06-01

A major branch of glycobiology and glycan-focused biomedicine studies the interaction between carbohydrates and other biopolymers, most importantly, glycan-binding proteins. Today, this research into glycan-biopolymer interaction is unthinkable without glycan arrays, tools that enable high-throughput analysis of carbohydrate interaction partners. Glycan arrays offer many applications in basic biochemical research, for example, defining the specificity of glycosyltransferases and lectins such as immune receptors. Biomedical applications include the characterization and surveillance of influenza strains, identification of biomarkers for cancer and infection, and profiling of immune responses to vaccines. Here, we review major applications of glycan arrays both in basic and applied research. Given the dynamic nature of this rapidly developing field, we focus on recent findings.

Immune responsiveness and risk of illness in U.S. Air Force Academy cadets during basic cadet training

NASA Technical Reports Server (NTRS)

Lee, David J.; Meehan, Richard T.; Robinson, Christine; Mabry, Thomas R.; Smith, Morey L.

1992-01-01

It has been proposed, but not confirmed, that environmental stressors alter immune function and increase the risk of viral infection among healthy individuals. This hypothesis was evaluated by examining the relationship among stress, immune function, and illness in 96 first-year U.S. Air Force Academy cadets during orientation and four weeks later during the stressful environment of basic cadet training (BCT). Perceived stress and well-being levels of cadets were assessed via questionnaire. Immune responsiveness was analyzed by PHA-stimulated thymidine uptake in mononuclear leucocytes and by serologic evidence of reactivation of the Epstein-Barr virus (EBV). Results showed significant declines in in vitro PHA-induced lymphocyte transformation (-35 percent)and subjective well-being (-19 percent) from orientation to BCT with corresponding, significant increases in perceived stress (+32 percent). Despite significantly altered in vitro immune responsiveness, there was no serologic evidence of EBV reactivation nor was there an association between these measures and risk of illness as determined by medical chart review and self-reported symptoms.

The twilight of immunity: emerging concepts in aging of the immune system.

PubMed

Nikolich-Žugich, Janko

2018-01-01

Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

[What it means to be "infected"--how a human body, or health professionals combat "infection"].

PubMed

Arakawa, Soichi

2011-09-01

Human immunology and relationship between immune mechanism and infection were explained. Humoral immunity and cellular immunity collaborate properly and eliminate microorganisms. In immunocompromised host these mechanisms are broken. For prevention of healthcare associated infections, standard precausion is important basically. Additionary, according to the status of the patient, contact precaution, droplet precaution or airborne precaution should be applied.

Possible reasons for non-completion of immunization in an urban settlement of Papua New Guinea.

PubMed

Bukenya, G B; Freeman, P A

1991-03-01

A study to identify possible reasons for non-completion of immunization among children was carried out in an urban settlement of Port Moresby. It was found that the children's mothers lacked basic understanding about immunization and the potential seriousness of immunizable diseases. There was also poor social interaction between health workers and the mothers. It is recommended that emphasis be placed also on the social aspects of immunization if widespread coverage is to be achieved.

Conceptual Spaces of the Immune System.

PubMed

Fierz, Walter

2016-01-01

The immune system can be looked at as a cognitive system. This is often done in analogy to the neuro-psychological system. Here, it is demonstrated that the cognitive functions of the immune system can be properly described within a new theory of cognitive science. Gärdenfors' geometrical framework of conceptual spaces is applied to immune cognition. Basic notions, like quality dimensions, natural properties and concepts, similarities, prototypes, saliences, etc., are related to cognitive phenomena of the immune system. Constraints derived from treating the immune system within a cognitive theory, like Gärdenfors' conceptual spaces, might well prove to be instrumental for the design of vaccines, immunological diagnostic tests, and immunotherapy.

Suppression of Antigen-Specific Lymphocyte Activation in Simulated Microgravity

NASA Technical Reports Server (NTRS)

Cooper, David; Pride, Michael W.; Brown, Eric L.; Risin, Diana; Pellis, Neal R.

1999-01-01

Various parameters of immune suppression are observed in astronauts during and after spaceflight, and in isolated immune cells in true and simulated microgravity. Specifically, polyclonal activation of T cells is severely suppressed in true and simulated microgravity. These recent findings with various polyclonal activators suggests a suppression of oligoclonal lymphocyte activation in microgravity. We utilized rotating wall vessel (RWV) bioreactors that simulate aspects of microgravity for cell cultures to analyze three models of antigen-specific activation. A mixed-lymphocyte reaction (MLR), as a model for a primary immune response; a tetanus toxoid (TT) response and a B. burgdorferi (Bb) response, as models of a secondary immune response, were all suppressed in the RWV bioreactor. Our findings confirm that the suppression of activation observed with polyclonal models also encompasses oligoclonal antigen-specific activation.

Vaccination for protection of retinal ganglion cells against death from glutamate cytotoxicity and ocular hypertension: Implications for glaucoma

NASA Astrophysics Data System (ADS)

Schori, Hadas; Kipnis, Jonathan; Yoles, Eti; Woldemussie, Elizabeth; Ruiz, Guadalupe; Wheeler, Larry A.; Schwartz, Michal

2001-03-01

Our group recently demonstrated that autoimmune T cells directed against central nervous system-associated myelin antigens protect neurons from secondary degeneration. We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve. Here we attempted to determine whether similar immunizations are protective from retinal ganglion cell loss resulting from a direct biochemical insult caused, for example, by glutamate (a major mediator of degeneration in acute and chronic optic nerve insults) and in a rat model of ocular hypertension. Passive immunization with T cells reactive to myelin basic protein or active immunization with myelin oligodendrocyte glycoprotein-derived peptide, although neuroprotective after optic nerve injury, was ineffective against glutamate toxicity in mice and rats. In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 ± 270 and 1,329 ± 121, respectively, mean ± SEM; P < 0.02). A similar pattern was observed when mice were immunized on the day of glutamate injection (1,777 ± 101 compared with 1,414 ± 36; P <0.05), but not when they were immunized 48h later. These findings suggest that protection from glutamate toxicity requires reinforcement of the immune system by antigens that are different from those associated with myelin. The use of Cop-1 apparently circumvents this antigen specificity barrier. In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8%±6.8% to 4.3%±1.6%, without affecting the intraocular pressure. This study may point the way to a therapy for glaucoma, a neurodegenerative disease of the optic nerve often associated with increased intraocular pressure, as well as for acute and chronic degenerative disorders in which glutamate is a prominent participant.

Global threshold dynamics of an SIVS model with waning vaccine-induced immunity and nonlinear incidence.

PubMed

Yang, Junyuan; Martcheva, Maia; Wang, Lin

2015-10-01

Vaccination is the most effective method of preventing the spread of infectious diseases. For many diseases, vaccine-induced immunity is not life long and the duration of immunity is not always fixed. In this paper, we propose an SIVS model taking the waning of vaccine-induced immunity and general nonlinear incidence into consideration. Our analysis shows that the model exhibits global threshold dynamics in the sense that if the basic reproduction number is less than 1, then the disease-free equilibrium is globally asymptotically stable implying the disease dies out; while if the basic reproduction number is larger than 1, then the endemic equilibrium is globally asymptotically stable indicating that the disease persists. This global threshold result indicates that if the vaccination coverage rate is below a critical value, then the disease always persists and only if the vaccination coverage rate is above the critical value, the disease can be eradicated. Copyright © 2015 Elsevier Inc. All rights reserved.

The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

PubMed

Yin, Jinghua; Zhang, Jian; Lu, Qianjin

2017-07-01

Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

Array-Based Rational Design of Short Peptide Probe-Derived from an Anti-TNT Monoclonal Antibody.

PubMed

Okochi, Mina; Muto, Masaki; Yanai, Kentaro; Tanaka, Masayoshi; Onodera, Takeshi; Wang, Jin; Ueda, Hiroshi; Toko, Kiyoshi

2017-10-09

Complementarity-determining regions (CDRs) are sites on the variable chains of antibodies responsible for binding to specific antigens. In this study, a short peptide probe for recognition of 2,4,6-trinitrotoluene (TNT), was identified by testing sequences derived from the CDRs of an anti-TNT monoclonal antibody. The major TNT-binding site in this antibody was identified in the heavy chain CDR3 by antigen docking simulation and confirmed by an immunoassay using a spot-synthesis based peptide array comprising amino acid sequences of six CDRs in the variable region. A peptide derived from heavy chain CDR3 (RGYSSFIYWF) bound to TNT with a dissociation constant of 1.3 μM measured by surface plasmon resonance. Substitution of selected amino acids with basic residues increased TNT binding while substitution with acidic amino acids decreased affinity, an isoleucine to arginine change showed the greatest improvement of 1.8-fold. The ability to create simple peptide binders of volatile organic compounds from sequence information provided by the immune system in the creation of an immune response will be beneficial for sensor developments in the future.

Mathematical modeling on T-cell mediated adaptive immunity in primary dengue infections.

PubMed

Sasmal, Sourav Kumar; Dong, Yueping; Takeuchi, Yasuhiro

2017-09-21

At present, dengue is the most common mosquito-borne viral disease in the world, and the global dengue incidence is increasing day by day due to climate changing. Here, we present a mathematical model of dengue viruses (DENVs) dynamics in micro-environment (cellular level) consisting of healthy cells, infected cells, virus particles and T-cell mediated adaptive immunity. We have considered the explicit role of cytokines and antibody in our model. We find that the virus load goes down to zero within 6 days as it is common for DENV infection. From our analysis, we have identified the important model parameters and done the numerical simulation with respect to such important parameters. We have shown that the cytokine mediated virus clearance plays a very important role in dengue dynamics. It can change the dynamical behavior of the system and causes essential extinction of the virus. Finally, we have incorporated the antiviral treatment for dengue in our model and shown that the basic reproduction number is directly proportional to the antiviral treatment effects. Copyright © 2017 Elsevier Ltd. All rights reserved.

Localization of eosinophil granule major basic protein in paracoccidioidomycosis lesions.

PubMed

Wagner, J M; Franco, M; Kephart, G M; Gleich, G J

1998-07-01

Paracoccidioidomycosis is a chronic granulomatous disease caused by the fungus Paracoccidioides brasiliensis. Although eosinophils have long been associated with the immune defense against helminths, the role of eosinophils in the immune response to fungal diseases is not as well studied. The eosinophil granule major basic protein is toxic to helminths and mammalian cells in vitro, and its release has been used as a marker of eosinophil localization and degranulation. To determine whether eosinophil infiltration and degranulation, as evidenced by the deposition of major basic protein, occur in lesions of P. brasiliensis, we used an immunofluorescence technique to localize the P. brasiliensis organisms and eosinophils and major basic protein. Initially, all tissues were stained with polyclonal antibody to major basic protein; subsequently, colocalization of major basic protein and P. brasiliensis by double staining with mouse and rabbit antibodies, respectively, was performed. Nine biopsy tissues from seven patients were analyzed. All nine biopsies showed infiltration of intact eosinophils using both the monoclonal and the polyclonal anti-major basic protein antibodies, along with the presence of P. brasiliensis. Furthermore, using the polyclonal anti-major basic protein antibody, nine of nine tissues showed extracellular major basic protein deposition (granular or diffuse fluorescence staining outside of intact eosinophils). The double staining procedure using the anti-major basic protein monoclonal antibody showed extracellular deposition in five of eight biopsies; in these five biopsies, approximately 60% of the areas containing P. brasiliensis had extracellular major basic protein deposited on the organisms. These observations support the hypothesis that the eosinophil, through toxic granule proteins such as major basic protein, participates in the pathophysiology of paracoccidioidomycosis.

Chapter 2: Innate Immunity

PubMed Central

Turvey, Stuart E.; Broide, David H.

2009-01-01

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

25 CFR 36.99 - Are immunizations required for residential program students?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false Are immunizations required for residential program students? 36.99 Section 36.99 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...

25 CFR 36.99 - Are immunizations required for residential program students?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false Are immunizations required for residential program students? 36.99 Section 36.99 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...

25 CFR 36.99 - Are immunizations required for residential program students?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Are immunizations required for residential program students? 36.99 Section 36.99 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...

25 CFR 36.99 - Are immunizations required for residential program students?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true Are immunizations required for residential program students? 36.99 Section 36.99 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...

25 CFR 36.99 - Are immunizations required for residential program students?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false Are immunizations required for residential program students? 36.99 Section 36.99 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR EDUCATION MINIMUM ACADEMIC STANDARDS FOR THE BASIC EDUCATION OF INDIAN CHILDREN AND NATIONAL CRITERIA FOR DORMITORY...

Progress in the Utilization of High-Fidelity Simulation in Basic Science Education

ERIC Educational Resources Information Center

Helyer, Richard; Dickens, Peter

2016-01-01

High-fidelity patient simulators are mainly used to teach clinical skills and remain underutilized in teaching basic sciences. This article summarizes our current views on the use of simulation in basic science education and identifies pitfalls and opportunities for progress.

The use of simulation in teaching the basic sciences.

PubMed

Eason, Martin P

2013-12-01

To assess the current use of simulation in medical education, specifically, the teaching of the basic sciences to accomplish the goal of improved integration. Simulation is increasingly being used by the institutions to teach the basic sciences. Preliminary data suggest that it is an effective tool with increased retention and learner satisfaction. Medical education is undergoing tremendous change. One of the directions of that change is increasing integration of the basic and clinical sciences to improve the efficiency and quality of medical education, and ultimately to improve the patient care. Integration is thought to improve the understanding of basic science conceptual knowledge and to better prepare the learners for clinical practice. Simulation because of its unique effects on learning is currently being successfully used by many institutions as a means to produce that integration through its use in the teaching of the basic sciences. Preliminary data indicate that simulation is an effective tool for basic science education and garners high learner satisfaction.

Some basic properties of immune selection.

PubMed

Iwasa, Yoh; Michor, Franziska; Nowak, Martin

2004-07-21

We analyze models for the evolutionary dynamics of viral or other infectious agents within a host. We study how the invasion of a new strain affects the composition and diversity of the viral population. We show that--under strain-specific immunity--the equilibrium abundance of uninfected cells declines during viral evolution. In addition, for cytotoxic immunity the absolute force of infection, and for non-cytotoxic immunity the absolute cellular virulence increases during viral evolution. We prove global stability by means of Lyapunov functions. These unidirectional trends of virus evolution under immune selection do not hold for general cross-reactive immune responses, which introduce frequency-dependent selection among viral strains. Therefore, appropriate cross-reactive immunity can lead to a viral evolution within a host which limits the extent of the disease.

NCI’s Role in Immunotherapy Research

Cancer.gov

Advances in cancer immunotherapy are the result of several decades of basic research, much of it supported by NCI, on how the immune system responds to cancer. Learn how NCI continues to support a wide range of research, from basic research to clinical trials, to advance the field of cancer immunotherapy.

Laparoscopic skills acquisition: a study of simulation and traditional training.

PubMed

Marlow, Nicholas; Altree, Meryl; Babidge, Wendy; Field, John; Hewett, Peter; Maddern, Guy J

2014-12-01

Training in basic laparoscopic skills can be undertaken using traditional methods, where trainees are educated by experienced surgeons through a process of graduated responsibility or by simulation-based training. This study aimed to assess whether simulation trained individuals reach the same level of proficiency in basic laparoscopic skills as traditional trained participants when assessed in a simulated environment. A prospective study was undertaken. Participants were allocated to one of two cohorts according to surgical experience. Participants from the inexperienced cohort were randomized to receive training in basic laparoscopic skills on either a box trainer or a virtual reality simulator. They were then assessed on the simulator on which they did not receive training. Participants from the experienced cohort, considered to have received traditional training in basic laparoscopic skills, did not receive simulation training and were randomized to either the box trainer or virtual reality simulator for skills assessment. The assessment scores from different cohorts on either simulator were then compared. A total of 138 participants completed the assessment session, 101 in the inexperienced simulation-trained cohort and 37 on the experienced traditionally trained cohort. There was no statistically significant difference between the training outcomes of simulation and traditionally trained participants, irrespective of the simulator type used. The results demonstrated that participants trained on either a box trainer or virtual reality simulator achieved a level of basic laparoscopic skills assessed in a simulated environment that was not significantly different from participants who had been traditionally trained in basic laparoscopic skills. © 2013 Royal Australasian College of Surgeons.

Effect of simulated weightlessness on the immune system in rats

NASA Technical Reports Server (NTRS)

Caren, L. D.; Mandel, A. D.; Nunes, J. A.

1980-01-01

Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

Pathogenesis and spectrum of autoimmunity.

PubMed

Perl, Andras

2012-01-01

The immune system specifically recognizes and eliminates foreign antigens and, thus, protects integrity of the host. During maturation of the immune system, tolerance mechanisms develop that prevent or inhibit potentially harmful reactivities to self-antigens. Autoreactive B and T cells that are generated during immune responses are eliminated by apoptosis in the thymus, lymph nodes, or peripheral circulation or actively suppressed by regulatory T cells. However, autoreactive cells may survive due to failure of apoptosis or molecular mimicry, i.e., presentation and recognition of cryptic epitopes of self-antigens, or aberrant lymphokine production. Preservation of the host requires the development of immune responses to foreign antigen and tolerance to self-antigens. Autoimmunity results from a breakdown of tolerance to self-antigens through an interplay of genetic and environmental factors.One of the basic functions of the immune system is to specifically recognize and eliminate foreign antigens and, thus, protect integrity of the host. Through rearrangements and somatic mutations of various gene segments encoding T and B cell receptors and antibody molecules, the immune system acquires tremendous diversity. During maturation of the immune system, recognition of self-antigens plays an important role in shaping the repertoires of immune receptors. Tolerance mechanisms develop that prevent or inhibit potentially harmful reactivities to self-antigens. These self-defense mechanisms are mediated on the levels of central and peripheral tolerance, i.e., autoreactive T cells are either eliminated by apoptosis in the thymus, lymph nodes, or peripheral circulation or actively suppressed by regulatory T cells. Likewise, autoreactive B cells are eliminated in the bone marrow or peripheral lymphoid organs. However, immune responses triggered by foreign antigens may be sustained by molecular mimicry, i.e., presentation and recognition of cryptic epitopes of self-antigens. Further downstream, execution of immune responses depends on the functioning of intracellular signaling networks and the cooperation of many cell types communicating via surface receptors, cytokines, chemokines, and antibody molecules. Therefore, autoimmunity represents the end result of the breakdown of one or multiple basic mechanisms of immune tolerance (Table 1).

Allergy and immunology of the aging lung.

PubMed

Katial, Rohit; Zheng, Weihong

2007-12-01

The aging process is associated with progressively impaired immune surveillance and decreased ability to mount an appropriate immune response, which potentially leads to increased susceptibility to respiratory insults. In older patients, pneumonias rank high as a reason for hospitalization and cause significant morbidity and mortality. Currently, little is known about how the innate and adaptive immune responses change in the aged human lung or how the changes are linked to increasing susceptibility to respiratory disease. This article reviews the basics of pulmonary host defense and some recently published research on the immune response within the aging lung.

Immune memory: the basics and how to trigger an efficient long-term immune memory.

PubMed

Beverley, P C L

2010-01-01

Immunological memory consists of expanded clones of T and B lymphocytes that show an increased rate of cell division and shortened telomeres compared with naïve cells. However, exhaustion of clones is delayed by kinetic heterogeneity within clones and altered survival and up-regulation of telomerase. Prolonged maintenance of protective B-cell immunity is T-cell dependent and requires a balance between plasma cells and memory B cells. Protective T-cell immunity also requires correct quality of T cells and that they are located appropriately. Copyright 2009 Elsevier Ltd. All rights reserved.

T cell exhaustion: from pathophysiological basics to tumor immunotherapy.

PubMed

Catakovic, Kemal; Klieser, Eckhard; Neureiter, Daniel; Geisberger, Roland

2017-01-05

The immune system is capable of distinguishing between danger- and non-danger signals, thus inducing either an appropriate immune response against pathogens and cancer or inducing self-tolerance to avoid autoimmunity and immunopathology. One of the mechanisms that have evolved to prevent destruction by the immune system, is to functionally silence effector T cells, termed T cell exhaustion, which is also exploited by viruses and cancers for immune escape In this review, we discuss some of the phenotypic markers associated with T cell exhaustion and we summarize current strategies to reinvigorate exhausted T cells by blocking these surface marker using monoclonal antibodies.

Immunity to Diphtheria and Tetanus in Army Personnel and Adult Civilians in Mashhad, Iran.

PubMed

Hosseini Shokouh, Seyyed Javad; Mohammadi, Babak; Rajabi, Jalil; Mohammadian Roshan, Ghasem

2017-03-24

This study aimed to investigate serologic immunity to diphtheria and tetanus in army personnel and a sample population of adult civilians in Mashhad, Iran. Army personnel (n = 180) and civilians (n = 83) who presented at Mashhad army hospital participated in this study. Diphtheria and tetanus antitoxin levels were determined by enzyme-linked immunosorbent assay. Approximately 77% and 94% of army personnel aged 18-34 years had at least basic protection against diphtheria (antitoxin level ≥0.1 IU/mL) and tetanus (antitoxin level >0.1 IU/mL), respectively. For civilians in this age group, the proportions were 76% for both diseases. Antitoxin levels waned with age. Thus, participants older than 50 years had lower immunity; this decrease in immunity was more pronounced for tetanus than for diphtheria in both army personnel and civilians. For both diseases, geometric mean antitoxin titers and the proportion of participants with at least basic protection were higher in subjects with a history of vaccination in the last 10 years (P < 0.001), higher in men than women, and in army personnel than civilians in each age group. Young army personnel and civilians (18-34 years old) had adequate immunity to diphtheria and tetanus. However, the large number of susceptible older adults (>50 years old) calls for improved booster vaccination protocols.

Immunity, Life and Dancing Starlings: A Physician's Perspective.

PubMed

Bercovich, Dani; Goodman, Geoffrey; Gershwin, M Eric

2016-08-01

Immune function is the most basic physiological process in humans and indeed throughout the animal kingdom. Interestingly, the vast majority of textbooks of physiology do not include a chapter on immunity. Our species survival is dependent on the diversity of the immune response and the ability for antigen presentation and effector mechanisms to be enormously promiscuous. As physicians, we are likely all too aware of how brief our life span is and the myriad of diseases and events that shorten it. It is not surprising that we question where our life comes from and our relationship within the universe. Many hypotheses have been offered regarding the likelihood that intelligent life exists elsewhere. We propose that such issues be discussed in the context of basic biologic observations on earth, such as the sight of a dense flock of tens of thousands of starlings maneuvering in rapid twists and turns at dusk before settling in trees for the night. The mathematical likelihood for life elsewhere was proposed by Frank Drake in a classic equation whose 'thesis' has stimulated the search for alien civilizations and the nature of life. A fundamental gap in this equation is the presence of a diverse immune response, a feature essential for survival of Life, presumably also extra-terrestrially.

Vagal-immune interactions involved in cholinergic anti-inflammatory pathway.

PubMed

Zila, I; Mokra, D; Kopincova, J; Kolomaznik, M; Javorka, M; Calkovska, A

2017-09-22

Inflammation and other immune responses are involved in the variety of diseases and disorders. The acute response to endotoxemia includes activation of innate immune mechanisms as well as changes in autonomic nervous activity. The autonomic nervous system and the inflammatory response are intimately linked and sympathetic and vagal nerves are thought to have anti-inflammation functions. The basic functional circuit between vagus nerve and inflammatory response was identified and the neuroimmunomodulation loop was called cholinergic anti-inflammatory pathway. Unique function of vagus nerve in the anti-inflammatory reflex arc was found in many experimental and pre-clinical studies. They brought evidence on the cholinergic signaling interacting with systemic and local inflammation, particularly suppressing immune cells function. Pharmacological/electrical modulation of vagal activity suppressed TNF-alpha and other proinflammatory cytokines production and had beneficial therapeutic effects. Many questions related to mapping, linking and targeting of vagal-immune interactions have been elucidated and brought understanding of its basic physiology and provided the initial support for development of Tracey´s inflammatory reflex. This review summarizes and critically assesses the current knowledge defining cholinergic anti-inflammatory pathway with main focus on studies employing an experimental approach and emphasizes the potential of modulation of vagally-mediated anti-inflammatory pathway in the treatment strategies.

Development of an Agent-Based Model (ABM) to Simulate the Immune System and Integration of a Regression Method to Estimate the Key ABM Parameters by Fitting the Experimental Data

PubMed Central

Tong, Xuming; Chen, Jinghang; Miao, Hongyu; Li, Tingting; Zhang, Le

2015-01-01

Agent-based models (ABM) and differential equations (DE) are two commonly used methods for immune system simulation. However, it is difficult for ABM to estimate key parameters of the model by incorporating experimental data, whereas the differential equation model is incapable of describing the complicated immune system in detail. To overcome these problems, we developed an integrated ABM regression model (IABMR). It can combine the advantages of ABM and DE by employing ABM to mimic the multi-scale immune system with various phenotypes and types of cells as well as using the input and output of ABM to build up the Loess regression for key parameter estimation. Next, we employed the greedy algorithm to estimate the key parameters of the ABM with respect to the same experimental data set and used ABM to describe a 3D immune system similar to previous studies that employed the DE model. These results indicate that IABMR not only has the potential to simulate the immune system at various scales, phenotypes and cell types, but can also accurately infer the key parameters like DE model. Therefore, this study innovatively developed a complex system development mechanism that could simulate the complicated immune system in detail like ABM and validate the reliability and efficiency of model like DE by fitting the experimental data. PMID:26535589

A qualitatively validated mathematical-computational model of the immune response to the yellow fever vaccine.

PubMed

Bonin, Carla R B; Fernandes, Guilherme C; Dos Santos, Rodrigo W; Lobosco, Marcelo

2018-05-25

Although a safe and effective yellow fever vaccine was developed more than 80 years ago, several issues regarding its use remain unclear. For example, what is the minimum dose that can provide immunity against the disease? A useful tool that can help researchers answer this and other related questions is a computational simulator that implements a mathematical model describing the human immune response to vaccination against yellow fever. This work uses a system of ten ordinary differential equations to represent a few important populations in the response process generated by the body after vaccination. The main populations include viruses, APCs, CD8+ T cells, short-lived and long-lived plasma cells, B cells and antibodies. In order to qualitatively validate our model, four experiments were carried out, and their computational results were compared to experimental data obtained from the literature. The four experiments were: a) simulation of a scenario in which an individual was vaccinated against yellow fever for the first time; b) simulation of a booster dose ten years after the first dose; c) simulation of the immune response to the yellow fever vaccine in individuals with different levels of naïve CD8+ T cells; and d) simulation of the immune response to distinct doses of the yellow fever vaccine. This work shows that the simulator was able to qualitatively reproduce some of the experimental results reported in the literature, such as the amount of antibodies and viremia throughout time, as well as to reproduce other behaviors of the immune response reported in the literature, such as those that occur after a booster dose of the vaccine.

Overview of Basic Immunology for Clinical Investigators.

PubMed

Stephen, Bettzy; Hajjar, Joud

2017-01-01

Tumor exists as a complex network of structures with an ability to evolve and evade the host immune surveillance mechanism. The immune milieu which includes macrophages, dendritic cells, natural killer cells, neutrophils, mast cells, B cells, and T cells are found in the core, the invasive margin, or the adjacent stromal or lymphoid component of the tumor. The immune infiltrate is heterogeneous and varies within a patient and between patients of the same tumor histology. The location, density, functionality, and the cross talk between the immune cells in the tumor microenvironment influence the nature of immune response, prognosis, and treatment outcomes in cancer patients. Therefore, an understanding of the characteristics of the immune cells and their role in tumor immune surveillance is of paramount importance to identify immune targets and to develop novel immune therapeutics in the war against cancer. In this chapter, we provide an overview of the individual components of the human immune system and the translational relevance of predictive biomarkers.

Teaching AIDS. A Resource Guide on Acquired Immune Deficiency Syndrome. Third Edition.

ERIC Educational Resources Information Center

Quackenbush, Marcia; Sargent, Pamela

The first edition of this resource guide for educators on how to teach students about Acquired Immune Deficiency Syndrome (AIDS) was published in 1986. Since then, basic facts about the transmission and prevention of the AIDS virus have not changed substantially. The terminologies about the disease, however, have changed and the changing…

Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

USDA-ARS?s Scientific Manuscript database

Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

Estimating the basic reproduction rate of HFMD using the time series SIR model in Guangdong, China

PubMed Central

Du, Zhicheng; Zhang, Wangjian; Zhang, Dingmei; Yu, Shicheng

2017-01-01

Hand, foot, and mouth disease (HFMD) has caused a substantial burden of disease in China, especially in Guangdong Province. Based on notifiable cases, we use the time series Susceptible-Infected-Recovered model to estimate the basic reproduction rate (R0) and the herd immunity threshold, understanding the transmission and persistence of HFMD more completely for efficient intervention in this province. The standardized difference between the reported and fitted time series of HFMD was 0.009 (<0.2). The median basic reproduction rate of total, enterovirus 71, and coxsackievirus 16 cases in Guangdong were 4.621 (IQR: 3.907–5.823), 3.023 (IQR: 2.289–4.292) and 7.767 (IQR: 6.903–10.353), respectively. The heatmap of R0 showed semiannual peaks of activity, including a major peak in spring and early summer (about the 12th week) followed by a smaller peak in autumn (about the 36th week). The county-level model showed that Longchuan (R0 = 33), Gaozhou (R0 = 24), Huazhou (R0 = 23) and Qingxin (R0 = 19) counties have higher basic reproduction rate than other counties in the province. The epidemic of HFMD in Guangdong Province is still grim, and strategies like the World Health Organization’s expanded program on immunization need to be implemented. An elimination of HFMD in Guangdong might need a Herd Immunity Threshold of 78%. PMID:28692654

Transient immune impairment after a simulated long-haul flight.

PubMed

Wilder-Smith, Annelies; Mustafa, Fatima B; Peng, Chung Mien; Earnest, Arul; Koh, David; Lin, Gen; Hossain, Iqbal; MacAry, Paul A

2012-04-01

Almost 2 billion people travel aboard commercial airlines every year, with about 20% developing symptoms of the common cold within 1 wk after air travel. We hypothesize that hypobaric hypoxic conditions associated with air travel may contribute to immune impairment. We studied the effects of hypobaric hypoxic conditions during a simulated flight at 8000 ft (2438 m) cruising altitude on immune and stress markers in 52 healthy volunteers (mean age 31) before and on days 1, 4, and 7 after the flight. We did a cohort study using a generalized estimating equation to examine the differences in the repeated measures. Our findings show that the hypobaric hypoxic conditions of a 10-h overnight simulation flight are not associated with severe immune impairment or abnormal IgA or cortisol levels, but with transient impairment in some parameters: we observed a transient decrease in lymphocyte proliferative responses combined with an upregulation in CD69 and CD14 cells and a decrease in HLA-DR in the immediate days following the simulated flight that normalized by day 7 in most instances. These transient immune changes may contribute to an increased susceptibility to respiratory infections commonly seen after long-haul flights.

Environmental Terms--The Basics.

ERIC Educational Resources Information Center

Lee County School District, Ft. Myers, FL. Dept. of Environmental Education and Instructional Development Services.

One of the problems of the English language is that individual words can often convey such a breadth of meaning that people often find themselves speaking past each other. The jargon of the environment is not immune. The words included in this publication are some of those more basic to the understanding of the environment. Definitions offered…

Two Simple Macroeconomic Simulations and the Great Depression. Instructor's Notes [and] A Student Guide [and] Basic Program.

ERIC Educational Resources Information Center

Schenk, Robert E.

Intended for use with college students in introductory macroeconomics or American economic history courses, these two computer simulations of two basic macroeconomic models--a simple Keynesian-type model and a quantity-theory-of-money model--present largely incompatible explanations of the Great Depression. Written in Basic, the simulations are…

Measurements of Immune Responses for Establishing Correlates of Vaccine Protection Against HIV

PubMed Central

Burgers, Wendy A.; Manrique, Amapola; McKinnon, Lyle R.; Reynolds, Matthew R.; Rolland, Morgane; Blish, Catherine; Chege, Gerald K.; Curran, Rhonda; Fischer, William; Herrera, Carolina; Sather, D. Noah

2012-01-01

Abstract Well-defined correlates of protective immunity are an essential component of rational vaccine development. Despite years of basic science and three HIV vaccine efficacy trials, correlates of immunological protection from HIV infection remain undefined. In December 2010, a meeting of scientists engaged in basic and translational work toward developing HIV-1 vaccines was convened. The goal of this meeting was to discuss current opportunities and optimal approaches for defining correlates of protection, both for ongoing and future HIV-1 vaccine candidates; specific efforts were made to engage young scientists. We discuss here the highlights from the meeting regarding the progress made and the way forward for a protective HIV-1 vaccine. PMID:21861777

[Results from biomedical aging research. Trends and current examples from immunology].

PubMed

Pfister, G; Herndler-Brandstetter, D; Grubeck-Loebenstein, B

2006-06-01

The public health of our society is challenged by a continuous increase in life expectancy. Hence, biomedical aging research is enjoying a steadily increasing popularity but also enlightens our understanding of age-related diseases by a number of striking results from basic research. One of the most striking changes that occurs during normal human aging is an overall diminution of immune functions, a phenomenon often termed immunosenescence. Starting from some highly exciting examples from basic immunological research, this article sheds light on which impact normal human aging has on several immune defence mechanisms. In addition, clinical consequences in view of Alzheimer's disease, immunogenicity of vaccines and autoimmune diseases are discussed.

An Immune Agent for Web-Based AI Course

ERIC Educational Resources Information Center

Gong, Tao; Cai, Zixing

2006-01-01

To overcome weakness and faults of a web-based e-learning course such as Artificial Intelligence (AI), an immune agent was proposed, simulating a natural immune mechanism against a virus. The immune agent was built on the multi-dimension education agent model and immune algorithm. The web-based AI course was comprised of many files, such as HTML…

An IDEA for Short Term Outbreak Projection: Nearcasting Using the Basic Reproduction Number

PubMed Central

Fisman, David N.; Hauck, Tanya S.; Tuite, Ashleigh R.; Greer, Amy L.

2013-01-01

Background Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. Methodology The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R0, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). Principal Findings Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R0 is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1th serial interval using data from the ith serial interval within an average of 20% of actual incidence. Conclusions and Significance This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists. PMID:24391797

An IDEA for short term outbreak projection: nearcasting using the basic reproduction number.

PubMed

Fisman, David N; Hauck, Tanya S; Tuite, Ashleigh R; Greer, Amy L

2013-01-01

Communicable disease outbreaks of novel or existing pathogens threaten human health around the globe. It would be desirable to rapidly characterize such outbreaks and develop accurate projections of their duration and cumulative size even when limited preliminary data are available. Here we develop a mathematical model to aid public health authorities in tracking the expansion and contraction of outbreaks with explicit representation of factors (other than population immunity) that may slow epidemic growth. The Incidence Decay and Exponential Adjustment (IDEA) model is a parsimonious function that uses the basic reproduction number R0, along with a discounting factor to project the growth of outbreaks using only basic epidemiological information (e.g., daily incidence counts). Compared to simulated data, IDEA provides highly accurate estimates of total size and duration for a given outbreak when R0 is low or moderate, and also identifies turning points or new waves. When tested with an outbreak of pandemic influenza A (H1N1), the model generates estimated incidence at the i+1(th) serial interval using data from the i(th) serial interval within an average of 20% of actual incidence. This model for communicable disease outbreaks provides rapid assessments of outbreak growth and public health interventions. Further evaluation in the context of real-world outbreaks will establish the utility of IDEA as a tool for front-line epidemiologists.

Rumor Spreading Model with Immunization Strategy and Delay Time on Homogeneous Networks

NASA Astrophysics Data System (ADS)

Wang, Jing; Wang, Ya-Qi; Li, Ming

2017-12-01

In order to prevent and control the spread of rumors, the implementation of immunization strategies for ignorant individuals is very necessary, where the immunization usually means letting them learn the truth of rumors. Considering the facts that there is always a delay time between rumor spreading and implementing immunization, and that the truth of rumors can also be spread out, this paper constructs a novel susceptible-infected-removed (SIR) model. The propagation dynamical behaviors of the SIR model on homogeneous networks are investigated by using the mean-field theory and the Monte Carlo method. Research shows that the greater the delay time, the worse the immune effect of the immunization strategy. It is also found that the spread of the truth can inhibit to some extent the propagation of rumors, and the trend will become more obvious with the increase of reliability of the truth. Moreover, under the influence of delay time, the existence of nodes’ identification force still slightly reduces the propagation degree of rumors. Supported by the National Natural Science Foundation of China under Grant No. 61402531, the Natural Science Basic Research Plan in Shaanxi Province of China under Grant Nos. 2014JQ8358, 2015JQ6231, and 2014JQ8307, the China Postdoctoral Science Foundation under Grant No. 2015M582910, and the Basic Research Foundation of Engineering University of the Chinese People’s Armed Police Force under Grant Nos. WJY201419, WJY201605 and JLX201686

Immune modulation with high-dose heat-shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis.

PubMed

Chandawarkar, Rajiv Y; Wagh, Mihir S; Kovalchin, Joseph T; Srivastava, Pramod

2004-04-01

Immunization with heat-shock protein (HSP) gp96 elicits protective immunity to the cancer or virus-infected cells from which it is derived. Low doses of gp96 generate immunity, while doses 10 times the immunizing dose do not. We show here that injection of high doses of gp96 generates CD4(+) T cells that down-regulate a variety of ongoing immune responses. Immunization with high doses of gp96 prevents myelin basic protein- or proteolipid protein-induced autoimmune encephalomyelitis in SJL mice and the onset of diabetes in non-obese diabetic mice. The suppression of immune response can be adoptively transferred with CD4(+) cells and does not partition with the CD25 phenotype. The immunomodulatory properties of gp96 (and possibly other HSP) may be used for antigen-specific activation or suppression of cellular immune responses. The latter may form the basis for novel immunotherapies for autoimmune diseases.

Neuroimmunology of disordered sleep in depression and alcoholism.

PubMed

Irwin, M

2001-11-01

The specific functions of sleep are not known, although sleep is commonly considered a restorative process that is important for the proper functioning of the immune system. Severity of disordered sleep in depressed and alcoholic subjects correlates with declines in natural and cellular immunity and is associated with alterations in the complex cytokine network. Despite evidence that sleep and sleep loss have effects on immune processes and nocturnal secretion of cytokines, the physiological significance of these immune changes is not known. Moreover, in view of basic evidence of a reciprocal interaction between sleep and cytokines, further research is needed to understand whether alterations in cytokines contribute to disordered sleep.

Simulated climate change causes immune suppression and protein damage in the crustacean Nephrops norvegicus.

PubMed

Hernroth, Bodil; Sköld, Helen Nilsson; Wiklander, Kerstin; Jutfelt, Fredrik; Baden, Susanne

2012-11-01

Rising atmospheric carbon dioxide concentration is causing global warming, which affects oceans by elevating water temperature and reducing pH. Crustaceans have been considered tolerant to ocean acidification because of their retained capacity to calcify during subnormal pH. However, we report here that significant immune suppression of the Norway lobster, Nephrops norvegicus, occurs after a 4-month exposure to ocean acidification (OA) at a level predicted for the year 2100 (hypercapnic seawater with a pH lowered by 0.4 units). Experiments carried out at different temperatures (5, 10, 12, 14, 16, and 18°C) demonstrated that the temperature within this range alone did not affect lobster immune responses. In the OA-treatment, hemocyte numbers were reduced by almost 50% and the phagocytic capacity of the remaining hemocytes was inhibited by 60%. The reduction in hemocyte numbers was not due to increased apoptosis in hematopoetic tissue. Cellular responses to stress were investigated through evaluating advanced glycation end products (AGE) and lipid oxidation in lobster hepatopancreata, and OA-treatment was shown to significantly increase AGEs', indicating stress-induced protein alterations. Furthermore, the extracellular pH of lobster hemolymph was reduced by approximately 0.2 units in the OA-treatment group, indicating either limited pH compensation or buffering capacity. The negative effects of OA-treatment on the nephropidae immune response and tissue homeostasis were more pronounced at higher temperatures (12-18°C versus 5°C), which may potentially affect disease severity and spread. Our results signify that ocean acidification may have adverse effects on the physiology of lobsters, which previously had been overlooked in studies of basic parameters such as lobster growth or calcification. Copyright © 2012 Elsevier Ltd. All rights reserved.

A Simulated Heat Wave Has Diverse Effects on Immune Function and Oxidative Physiology in the Corn Snake (Pantherophis guttatus).

PubMed

Stahlschmidt, Z R; French, S S; Ahn, A; Webb, A; Butler, M W

Animals will continue to encounter increasingly warm environments, including more frequent and intense heat waves. Yet the physiological consequences of heat waves remain equivocal, potentially because of variation in adaptive plasticity (reversible acclimation) and/or aspects of experimental design. Thus, we measured a suite of physiological variables in the corn snake (Pantherophis guttatus) after exposure to field-parameterized, fluctuating temperature regimes (moderate temperature and heat wave treatments) to address two hypotheses: (1) a heat wave causes physiological stress, and (2) thermal performance of immune function exhibits adaptive plasticity in response to a heat wave. We found little support for our first hypothesis because a simulated heat wave had a negative effect on body mass, but it also reduced oxidative damage and did not affect peak performance of three immune metrics. Likewise, we found only partial support for our second hypothesis. After exposure to a simulated heat wave, P. guttatus exhibited greater performance breadth and reduced temperature specialization (the standardized difference between peak performance and performance breadth) for only one of three immune metrics and did so in a sex-dependent manner. Further, a simulated heat wave did not elicit greater performance of any immune metric at higher temperatures. Yet a heat wave likely reduced innate immune function in P. guttatus because each metric of innate immune performance in this species (as in most vertebrates) was lower at elevated temperatures. Together with previous research, our study indicates that a heat wave may have complex, modest, and even positive physiological effects in some taxa.

Anti–PD-1/PD-L1 therapy of human cancer: past, present, and future

PubMed Central

Chen, Lieping; Han, Xue

2015-01-01

Major progress has been made toward our understanding of the programmed death-1/programmed death ligand-1 (PD-1/PD-L1) pathway (referred to as the PD pathway). mAbs are already being used to block the PD pathway to treat human cancers (anti-PD therapy), especially advanced solid tumors. This therapy is based on principles that were discovered through basic research more than a decade ago, but the great potential of this pathway to treat a broad spectrum of advanced human cancers is just now becoming apparent. In this Review, we will briefly review the history and development of anti-PD therapy, from the original benchwork to the most up-to-date clinical results. We will then focus the discussion on three basic principles that define this unique therapeutic approach and highlight how anti-PD therapy is distinct from other immunotherapeutic approaches, namely tumor site immune modulation, targeting tumor-induced immune defects, and repairing ongoing (rather than generating de novo) tumor immunity. We believe that these fundamental principles set the standard for future immunotherapies and will guide our efforts to develop more efficacious and less toxic immune therapeutics to treat human cancers. PMID:26325035

Increased concentration of Pseudomonas aeruginosa and Staphylococcus sp. in small animals exposed to aerospace environments

NASA Technical Reports Server (NTRS)

Guthrie, R. K.

1976-01-01

The effects of increased concentrations of PSEUDOMONAS AERUGINOSA AND STAPHYLOCOCCUS in the total bacterial flora of small animals exposed to simulated spacecraft environments were evaluated. Tests to detect changes in infectivity, effects of antibiotic treatments, immune responses to bacterial antigens, and effectiveness of immune responses in the experimental environment were conducted. The most significant results appear to be the differences in immune responses at simulated altitudes and the production of infection in the presence of a specific antibody.

Influence of distributed delays on the dynamics of a generalized immune system cancerous cells interactions model

NASA Astrophysics Data System (ADS)

Piotrowska, M. J.; Bodnar, M.

2018-01-01

We present a generalisation of the mathematical models describing the interactions between the immune system and tumour cells which takes into account distributed time delays. For the analytical study we do not assume any particular form of the stimulus function describing the immune system reaction to presence of tumour cells but we only postulate its general properties. We analyse basic mathematical properties of the considered model such as existence and uniqueness of the solutions. Next, we discuss the existence of the stationary solutions and analytically investigate their stability depending on the forms of considered probability densities that is: Erlang, triangular and uniform probability densities separated or not from zero. Particular instability results are obtained for a general type of probability densities. Our results are compared with those for the model with discrete delays know from the literature. In addition, for each considered type of probability density, the model is fitted to the experimental data for the mice B-cell lymphoma showing mean square errors at the same comparable level. For estimated sets of parameters we discuss possibility of stabilisation of the tumour dormant steady state. Instability of this steady state results in uncontrolled tumour growth. In order to perform numerical simulation, following the idea of linear chain trick, we derive numerical procedures that allow us to solve systems with considered probability densities using standard algorithm for ordinary differential equations or differential equations with discrete delays.

The Knowledge of Staff in Day Nurseries about Some Basic Measures Which Promote Child Health

ERIC Educational Resources Information Center

Cavalcante, Suzy S.; Nunes de Melo, Maria Clotildes; Carneiro, Nadya Bustani; Silva, Luciana Rodrigues

2005-01-01

Purpose: This paper aims to determine the knowledge that staff in day nurseries in Brazil had of basic measures to promote child health which are connected with high child mortality. These measures included breastfeeding, oral rehydration therapy, child growth follow-up, immunization and the identification of signs that indicate that the child…

NIAID meeting report: improving malaria vaccine strategies through the application of immunological principles.

PubMed

Mo, Annie X Y; Augustine, Alison Deckhut

2014-02-26

A highly efficacious vaccine to prevent malaria infection or clinical disease is still far from reality despite several decades of intensive effort and a growing global commitment in malaria vaccine development. Further understanding of the mechanisms required for induction of effective host immune responses and maintenance of long-term protective immunity is needed to facilitate rational approaches for vaccine design and evaluation. The National Institute of Allergy and Infectious Diseases (NIAID) conducted a workshop on June 18-19, 2012 with experts in the fields of malaria vaccine development, malaria immunology, and basic immunology to address issues associated with improving our current understanding of malaria vaccine immunity. This report summarizes the discussion and major recommendations generated by the workshop participants regarding the application of recent advances in basic immunology and state-of-the-art immunological tools to improve progress and help address current challenges and knowledge gaps in malaria vaccine development. Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Motion Estimation Using the Single-row Superposition-type Planar Compound-like Eye

PubMed Central

Cheng, Chi-Cheng; Lin, Gwo-Long

2007-01-01

How can the compound eye of insects capture the prey so accurately and quickly? This interesting issue is explored from the perspective of computer vision instead of from the viewpoint of biology. The focus is on performance evaluation of noise immunity for motion recovery using the single-row superposition-type planar compound like eye (SPCE). The SPCE owns a special symmetrical framework with tremendous amount of ommatidia inspired by compound eye of insects. The noise simulates possible ambiguity of image patterns caused by either environmental uncertainty or low resolution of CCD devices. Results of extensive simulations indicate that this special visual configuration provides excellent motion estimation performance regardless of the magnitude of the noise. Even when the noise interference is serious, the SPCE is able to dramatically reduce errors of motion recovery of the ego-translation without any type of filters. In other words, symmetrical, regular, and multiple vision sensing devices of the compound-like eye have statistical averaging advantage to suppress possible noises. This discovery lays the basic foundation in terms of engineering approaches for the secret of the compound eye of insects.

Digital Simulation and Modelling.

ERIC Educational Resources Information Center

Hawthorne, G. B., Jr.

A basically tutorial point of view is taken in this general discussion. The author examines the basic concepts and principles of simulation and modelling and the application of digital computers to these tasks. Examples of existing simulations, a discussion of the applicability and feasibility of simulation studies, a review of simulation…

Global stability for an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response

NASA Astrophysics Data System (ADS)

Lv, Cuifang; Huang, Lihong; Yuan, Zhaohui

2014-01-01

In this paper, an HIV-1 infection model with Beddington-DeAngelis incidence rate and CTL immune response is investigated. One main feature of this model is that an eclipse stage for the infected cells is included and a portion of these cells is reverted to uninfected cells. We derive the basic reproduction number R1 and the immune response reproduction number R2 for the HIV-1 infection model. By constructing Lyapunov functions, the global stabilities for the equilibria have been analyzed.

The spreading dynamics of sexually transmitted diseases with birth and death on heterogeneous networks

NASA Astrophysics Data System (ADS)

Wang, Yi; Cao, Jinde; Alsaedi, Ahmed; Hayat, Tasawar

2017-02-01

In this paper, we formulate a deterministic model by including the vacant sites, which represent inactive individuals or potential contacts, to investigate the spreading dynamics of sexually transmitted diseases in heterogeneous networks. We first analytically derive the basic reproduction number R 0, which completely determines global dynamics of the system in the long run. Specifically, if R 0  <  1, the disease-free equilibrium is globally asymptotically stable, i.e. disease disappears from the network irrespective of initial infected numbers and distributions, whereas if R 0  >  1, the system is uniformly persistent around a unique endemic equilibrium, i.e. disease persists in the network. Furthermore, by using a suitable Lyapunov function the global stability of endemic equilibrium for low/high-risk infected individuals only is proved. Finally, the effects of three immunization schemes are studied and compared, and extensive numerical simulations are performed to investigate the effect of network topology and population turnover on disease spread. Our results suggest that population turnover could have great impact on the sexually transmitted disease system in heterogeneous networks, including the basic reproduction number and infection prevalence.

HIV infection and specific mucosal immunity: workshop 4B.

PubMed

Challacombe, S J; Fidel, P L; Tugizov, S; Tao, L; Wahl, S M

2011-04-01

Most HIV infections are transmitted across mucosal epithelium. An area of fundamental importance is understanding the role of innate and specific mucosal immunity in susceptibility or protection against HIV infection, as well as the effect of HIV infection on mucosal immunity, which leads to increased susceptibility to bacterial, fungal, and viral infections of oral and other mucosae. This workshop attempted to address 5 basic issues-namely, HIV acquisition across mucosal surfaces, innate and adaptive immunity in HIV resistance, antiviral activity of breast milk as a model mucosal fluid, neutralizing immunoglobulin A antibodies against HIV, and progress toward a mucosal vaccine against HIV. The workshop attendants agreed that progress had been made in each area covered, with much recent information. However, these advances revealed how little work had been performed on stratified squamous epithelium compared with columnar epithelium, and the attendants identified several important biological questions that had not been addressed. It is increasingly clear that innate immunity has an important biological role, although basic understanding of the mechanisms of normal homeostasis is still being investigated. Application of the emerging knowledge was lacking with regard to homeostatic mucosal immunity to HIV and its role in changing this homeostasis. With regard to breast milk, a series of studies have demonstrated the differences between transmitters and nontransmitters, although whether these findings could be generalized to other secretions such as saliva was less clear. Important progress toward an oral mucosal HIV vaccine has been made, demonstrating proof of principle for administering vaccine candidates into oral lymphoid tissues to trigger anti-HIV local and systemic immune responses. Similarly, experimental data emphasized the central role of neutralizing antibodies to prevent HIV infection via mucosal routes.

[The extraneuronal cholinergic system of the skin. Basic facts and clinical relevance].

PubMed

Kurzen, H

2004-05-01

Acetylcholine (ACh) is a prototypical neurotransmitter that has recently been recognized to occur extraneuronally in a large variety of cells. ACh and its nicotinic and muscarinic receptors are produced in the epidermis and in the adnexal structures of the skin in a highly complicated pattern. They are also produced in melanocytes, fibroblasts, endothelial cells and immune cells. Through autocrine, paracrine and endocrine mechanisms, the cholinergic system is involved in the basic functions of the skin, such as keratinocyte differentiation, epidermal barrier formation, sweating, sebum production, blood circulation, angiogenesis and a variety of immune reactions. Hence diseases like acne vulgaris, vitiligo, psoriasis, pemphigus vulgaris and atopic dermatitis may be influenced. The exploration of the extraneuronal cholinergic system of the skin has only just begun.

Invasive meningococcal disease epidemiology and control measures: a framework for evaluation.

PubMed

Caro, J Jaime; Möller, Jörgen; Getsios, Denis; Coudeville, L; El-Hadi, Wissam; Chevat, Catherine; Nguyen, Van Hung; Caro, Ingrid

2007-06-29

Meningococcal disease can have devastating consequences. As new vaccines emerge, it is necessary to assess their impact on public health. In the absence of long-term real world data, modeling the effects of different vaccination strategies is required. Discrete event simulation provides a flexible platform with which to conduct such evaluations. A discrete event simulation of the epidemiology of invasive meningococcal disease was developed to quantify the potential impact of implementing routine vaccination of adolescents in the United States with a quadrivalent conjugate vaccine protecting against serogroups A, C, Y, and W-135. The impact of vaccination is assessed including both the direct effects on individuals vaccinated and the indirect effects resulting from herd immunity. The simulation integrates a variety of epidemiologic and demographic data, with core information on the incidence of invasive meningococcal disease and outbreak frequency derived from data available through the Centers for Disease Control and Prevention. Simulation of the potential indirect benefits of vaccination resulting from herd immunity draw on data from the United Kingdom, where routine vaccination with a conjugate vaccine has been in place for a number of years. Cases of disease are modeled along with their health consequences, as are the occurrence of disease outbreaks. When run without a strategy of routine immunization, the simulation accurately predicts the age-specific incidence of invasive meningococcal disease and the site-specific frequency of outbreaks in the Unite States. 2,807 cases are predicted annually, resulting in over 14,000 potential life years lost due to invasive disease. In base case analyses of routine vaccination, life years lost due to infection are reduced by over 45% (to 7,600) when routinely vaccinating adolescents 12 years of age at 70% coverage. Sensitivity analyses indicate that herd immunity plays an important role when this population is targeted for vaccination. While 1,100 cases are avoided annually when herd immunity effects are included, in the absence of any herd immunity, the number of cases avoided with routine vaccination falls to 380 annually. The duration of vaccine protection also strongly influences results. In the absence of appropriate real world data on outcomes associated with large-scale vaccination programs, decisions on optimal immunization strategies can be aided by discrete events simulations such as the one described here. Given the importance of herd immunity on outcomes associated with routine vaccination, published estimates of the economic efficiency of routine vaccination with a quadrivalent conjugate vaccine in the United States may have considerably underestimated the benefits associated with a policy of routine immunization of adolescents.

Senescence in immune priming and attractiveness in a beetle.

PubMed

Daukšte, J; Kivleniece, I; Krama, T; Rantala, M J; Krams, I

2012-07-01

Age-related decline in immune activity is referred to as immunosenescence and has been observed for both the adaptive immune response of vertebrates and the innate immune system of invertebrates. Because maintaining a basic level of immune defence and mounting an immune response is costly, optimal investment in immune function should vary over a wide range of individual states such as the individual's age. In this study, we tested whether the immune response and immunological priming within individuals become less efficient with age using mealworm beetles, Tenebrio molitor, as a model organism. We also tested whether ageing and immunological priming affected the odours produced by males. We found that young males of T. molitor were capable of mounting an immune response a sterile nylon monofilament implant with the potential to exhibit a simple form of immune memory through mechanisms of immune priming. Older males did not increase their immune response to a second immune challenge, which negatively affected their sexual attractiveness and remaining life span. Our results indicate that the immune system of older males in T. molitor is less effective, suggesting complex evolutionary trade-offs between ageing, immune response and sexual attractiveness. © 2012 The Authors. Journal of Evolutionary Biology © 2012 European Society For Evolutionary Biology.

WntD and Diedel: Two immunomodulatory cytokines in Drosophila immunity.

PubMed

Lamiable, Olivier; Meignin, Carine; Imler, Jean-Luc

2016-10-01

Remarkable progress has been made on the understanding of the basic mechanisms of innate immunity in flies, from sensing infection to production of effector molecules. However, how the immune response is orchestrated at the level of the organism remains poorly understood. While cytokines activating immune responses, such as Spaetzle or Unpaired-3, have been identified and characterized in Drosophila, much less is known regarding immunosuppressor cytokines. In a recent publication, we reported the identification of a novel cytokine, Diedel, which acts as systemic negative regulator of the IMD pathway. Here, we discuss the similarities between Diedel and WntD, another immunomodulatory cytokine and present evidence that the 2 molecules act independently from one another.

Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems.

PubMed

Okamoto, Kazuo; Nakashima, Tomoki; Shinohara, Masahiro; Negishi-Koga, Takako; Komatsu, Noriko; Terashima, Asuka; Sawa, Shinichiro; Nitta, Takeshi; Takayanagi, Hiroshi

2017-10-01

The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system. Copyright © 2017 the American Physiological Society.

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine.

PubMed

Hartl, Dominik; Tirouvanziam, Rabindra; Laval, Julie; Greene, Catherine M; Habiel, David; Sharma, Lokesh; Yildirim, Ali Önder; Dela Cruz, Charles S; Hogaboam, Cory M

2018-02-13

The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract. © 2018 S. Karger AG, Basel.

Surgical Assisting

MedlinePlus

... CPR/BLS certification Acceptable health and immunization records Computer literacy Students also must be able to show proof of successful completion of basic science (college level) instruction, including: Microbiology Pathophysiology Pharmacology Anatomy ...

Review of the systems biology of the immune system using agent-based models.

PubMed

Shinde, Snehal B; Kurhekar, Manish P

2018-06-01

The immune system is an inherent protection system in vertebrate animals including human beings that exhibit properties such as self-organisation, self-adaptation, learning, and recognition. It interacts with the other allied systems such as the gut and lymph nodes. There is a need for immune system modelling to know about its complex internal mechanism, to understand how it maintains the homoeostasis, and how it interacts with the other systems. There are two types of modelling techniques used for the simulation of features of the immune system: equation-based modelling (EBM) and agent-based modelling. Owing to certain shortcomings of the EBM, agent-based modelling techniques are being widely used. This technique provides various predictions for disease causes and treatments; it also helps in hypothesis verification. This study presents a review of agent-based modelling of the immune system and its interactions with the gut and lymph nodes. The authors also review the modelling of immune system interactions during tuberculosis and cancer. In addition, they also outline the future research directions for the immune system simulation through agent-based techniques such as the effects of stress on the immune system, evolution of the immune system, and identification of the parameters for a healthy immune system.

Evaluation of the Immunization Program in the Federation of Bosnia and Herzegovina - Possible Modalities for Improvement

PubMed Central

Husic, Fuad; Jatic, Zaim; Joguncic, Anes; Sporisevic, Lutvo

2018-01-01

Introduction: Immunization is a lifelong preventive activity that helps prevent/reduce disease, prevent/ reduce mortality and prevent disability from specific infectious diseases. Material and Methods: Authors of this paper researched the WHO extended program of mandatory immunization of children from birth to the age of 18 years and analyzed how it has been implemented in the Federation of Bosnia and Herzegovina (FB&H), because the guidelines of the specialist physician societies on immunization of adults, elderly people and risk groups of the population are missing. Results: The paper presents the basic characteristics of the immunization program in the FB&H and the world, points to the most frequent problems that the doctor practitioner has in carrying out immunization, and also presents possible modalities of improving immunization. It is pointed out the need to develop the national guidelines and individual immunization booklets, introduction of electronic registration of immunization, and continuous education of health professionals of all profiles, population, educators, teachers and harmonious partnership relations of health workers, population, social entities and the media with the aim of achieving an appropriate lifelong vaccination. PMID:29670482

Evaluation of the Immunization Program in the Federation of Bosnia and Herzegovina - Possible Modalities for Improvement.

PubMed

Husic, Fuad; Jatic, Zaim; Joguncic, Anes; Sporisevic, Lutvo

2018-03-01

Immunization is a lifelong preventive activity that helps prevent/reduce disease, prevent/ reduce mortality and prevent disability from specific infectious diseases. Authors of this paper researched the WHO extended program of mandatory immunization of children from birth to the age of 18 years and analyzed how it has been implemented in the Federation of Bosnia and Herzegovina (FB&H), because the guidelines of the specialist physician societies on immunization of adults, elderly people and risk groups of the population are missing. The paper presents the basic characteristics of the immunization program in the FB&H and the world, points to the most frequent problems that the doctor practitioner has in carrying out immunization, and also presents possible modalities of improving immunization. It is pointed out the need to develop the national guidelines and individual immunization booklets, introduction of electronic registration of immunization, and continuous education of health professionals of all profiles, population, educators, teachers and harmonious partnership relations of health workers, population, social entities and the media with the aim of achieving an appropriate lifelong vaccination.

Design and simulation study of the immunization Data Quality Audit (DQA).

PubMed

Woodard, Stacy; Archer, Linda; Zell, Elizabeth; Ronveaux, Olivier; Birmingham, Maureen

2007-08-01

The goal of the Data Quality Audit (DQA) is to assess whether the Global Alliance for Vaccines and Immunization-funded countries are adequately reporting the number of diphtheria-tetanus-pertussis immunizations given, on which the "shares" are awarded. Given that this sampling design is a modified two-stage cluster sample (modified because a stratified, rather than a simple, random sample of health facilities is obtained from the selected clusters); the formula for the calculation of the standard error for the estimate is unknown. An approximated standard error has been proposed, and the first goal of this simulation is to assess the accuracy of the standard error. Results from the simulations based on hypothetical populations were found not to be representative of the actual DQAs that were conducted. Additional simulations were then conducted on the actual DQA data to better access the precision of the DQ with both the original and the increased sample sizes.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits.

PubMed

Jia, Keran; An, Liyun; Wang, Fukun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-04-01

To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C(14)-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C(14)-urea breath-test values were significantly higher compared with before training - thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4(+) and CD8(+) T-cell percentages and the CD4(+)/CD8(+) ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. © The Author(s) 2016.

Aggravation of Helicobacter pylori stomach infections in stressed military recruits

PubMed Central

Jia, Keran; An, Liyun; Shi, Lanchun; Ran, Xiangyang; Wang, Xianling; He, Zhanguo; Chen, Jing

2016-01-01

Objective To investigate the effect of military stress on immune response and Helicobacter pylori stomach infections. Methods In this prospective, observational study, the Symptom Checklist-90 questionnaire was completed by military recruits before and following a 3-month basic training programme. H. pylori immunoglobulin (Ig)G levels, C14-urea breath-test values and levels of cortisol, catecholamine, and certain humoral and cellular immune responses were measured before and after the basic training. Results For 60 military recruits, somatization, depression and paranoid ideation scores were significantly increased after, compared with before, basic training. Post-training H. pylori IgG detection revealed three additional cases of H. pylori infection. Post-training C14-urea breath-test values were significantly higher compared with before training – thus suggesting higher levels of H. pylori colonization in the stomach. Post-training cortisol and catecholamine levels were increased, while serum IgG levels were decreased; complement component (C)3 and C4 levels remained unchanged. Post-training CD4+ and CD8+ T-cell percentages and the CD4+/CD8+ ratio were significantly reduced compared with before training. Serum interleukin (IL)-2 levels were lower and IL-10 levels were higher following training and there was a significant decrease in the IL-2/IL-10 ratio. Conclusion Military stress may reduce humoral and cellular immune responses and may aggravate the severity of H. pylori infection. PMID:26800706

Gastrointestinal immune system and its disorders.

PubMed

Keren, D F

1990-01-01

Over the past 15 years the basic details of the mucosal immune response have been described. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes in the gastrointestinal tract. It is now clear that secretory IgA is the main immunoglobulin produced by the mucosa. Further, we know that oral rather than parenteral priming preferentially stimulates a secretory IgA response. IgA protects mainly by binding to an intraluminal microorganism or toxin and thereby interfering with its absorption across the gut epithelium. The cellular basis for the IgA response has also been elucidated to some degree. It is clear that the response is highly T cell dependent and requires both helper T cells and switch T cells. With the use of monoclonal antibodies, we have begun to learn about cell-mediated functions in the gut. Suppressor/cytotoxic lymphocytes are largely sequestered in the epithelium whereas helper/inducer lymphocytes mainly reside in the lamina propria. In diseases such as celiac disease and inflammatory bowel disease, several alterations in the gastrointestinal immune system have been described. Some, such as the finding of antibody to gliaden, may be causally related to the disease. Others, such as antibodies to luminal bacteria, likely are secondary events. The challenge of the next decade is to expand these details and to relate this basic information to pathologic processes along the gastrointestinal tract.

The development of a fully-integrated immune response model (FIRM) simulator of the immune response through integration of multiple subset models

PubMed Central

2013-01-01

Background The complexity and multiscale nature of the mammalian immune response provides an excellent test bed for the potential of mathematical modeling and simulation to facilitate mechanistic understanding. Historically, mathematical models of the immune response focused on subsets of the immune system and/or specific aspects of the response. Mathematical models have been developed for the humoral side of the immune response, or for the cellular side, or for cytokine kinetics, but rarely have they been proposed to encompass the overall system complexity. We propose here a framework for integration of subset models, based on a system biology approach. Results A dynamic simulator, the Fully-integrated Immune Response Model (FIRM), was built in a stepwise fashion by integrating published subset models and adding novel features. The approach used to build the model includes the formulation of the network of interacting species and the subsequent introduction of rate laws to describe each biological process. The resulting model represents a multi-organ structure, comprised of the target organ where the immune response takes place, circulating blood, lymphoid T, and lymphoid B tissue. The cell types accounted for include macrophages, a few T-cell lineages (cytotoxic, regulatory, helper 1, and helper 2), and B-cell activation to plasma cells. Four different cytokines were accounted for: IFN-γ, IL-4, IL-10 and IL-12. In addition, generic inflammatory signals are used to represent the kinetics of IL-1, IL-2, and TGF-β. Cell recruitment, differentiation, replication, apoptosis and migration are described as appropriate for the different cell types. The model is a hybrid structure containing information from several mammalian species. The structure of the network was built to be physiologically and biochemically consistent. Rate laws for all the cellular fate processes, growth factor production rates and half-lives, together with antibody production rates and half-lives, are provided. The results demonstrate how this framework can be used to integrate mathematical models of the immune response from several published sources and describe qualitative predictions of global immune system response arising from the integrated, hybrid model. In addition, we show how the model can be expanded to include novel biological findings. Case studies were carried out to simulate TB infection, tumor rejection, response to a blood borne pathogen and the consequences of accounting for regulatory T-cells. Conclusions The final result of this work is a postulated and increasingly comprehensive representation of the mammalian immune system, based on physiological knowledge and susceptible to further experimental testing and validation. We believe that the integrated nature of FIRM has the potential to simulate a range of responses under a variety of conditions, from modeling of immune responses after tuberculosis (TB) infection to tumor formation in tissues. FIRM also has the flexibility to be expanded to include both complex and novel immunological response features as our knowledge of the immune system advances. PMID:24074340

DCB - Cancer Immunology, Hematology, and Etiology Research

Cancer.gov

Part of NCI’s Division of Cancer Biology’s research portfolio, studies supported include the characterization of basic mechanisms relevant to anti-tumor immune responses and hematologic malignancies.

A core viral protein binds host nucleosomes to sequester immune danger signals

PubMed Central

Avgousti, Daphne C.; Herrmann, Christin; Kulej, Katarzyna; Pancholi, Neha J.; Sekulic, Nikolina; Petrescu, Joana; Molden, Rosalynn C.; Blumenthal, Daniel; Paris, Andrew J.; Reyes, Emigdio D.; Ostapchuk, Philomena; Hearing, Patrick; Seeholzer, Steven H.; Worthen, G. Scott; Black, Ben E.; Garcia, Benjamin A.; Weitzman, Matthew D.

2016-01-01

Viral proteins mimic host protein structure and function to redirect cellular processes and subvert innate defenses1. Small basic proteins compact and regulate both viral and cellular DNA genomes. Nucleosomes are the repeating units of cellular chromatin and play an important role in innate immune responses2. Viral encoded core basic proteins compact viral genomes but their impact on host chromatin structure and function remains unexplored. Adenoviruses encode a highly basic protein called protein VII that resembles cellular histones3. Although protein VII binds viral DNA and is incorporated with viral genomes into virus particles4,5, it is unknown whether protein VII impacts cellular chromatin. Our observation that protein VII alters cellular chromatin led us to hypothesize that this impacts antiviral responses during adenovirus infection. We found that protein VII forms complexes with nucleosomes and limits DNA accessibility. We identified post-translational modifications on protein VII that are responsible for chromatin localization. Furthermore, proteomic analysis demonstrated that protein VII is sufficient to alter protein composition of host chromatin. We found that protein VII is necessary and sufficient for retention in chromatin of members of the high-mobility group protein B family (HMGB1, HMGB2, and HMGB3). HMGB1 is actively released in response to inflammatory stimuli and functions as a danger signal to activate immune responses6,7. We showed that protein VII can directly bind HMGB1 in vitro and further demonstrated that protein VII expression in mouse lungs is sufficient to decrease inflammation-induced HMGB1 content and neutrophil recruitment in the bronchoalveolar lavage fluid. Together our in vitro and in vivo results show that protein VII sequesters HMGB1 and can prevent its release. This study uncovers a viral strategy in which nucleosome binding is exploited to control extracellular immune signaling. PMID:27362237

Bruton's Tyrosine Kinase: An Emerging Key Player in Innate Immunity.

PubMed

Weber, Alexander N R; Bittner, Zsofia; Liu, Xiao; Dang, Truong-Minh; Radsak, Markus Philipp; Brunner, Cornelia

2017-01-01

Bruton's tyrosine kinase (BTK) was initially discovered as a critical mediator of B cell receptor signaling in the development and functioning of adaptive immunity. Growing evidence also suggests multiple roles for BTK in mononuclear cells of the innate immune system, especially in dendritic cells and macrophages. For example, BTK has been shown to function in Toll-like receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. Most recently, BTK was additionally identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome. BTK has thus attracted interest not only for gaining a more thorough basic understanding of the human innate immune system but also as a target to therapeutically modulate innate immunity. We here review the latest developments on the role of BTK in mononuclear innate immune cells in mouse versus man, with specific emphasis on the sensing of infectious agents and the induction of inflammation. Therapeutic implications for modulating innate immunity and critical open questions are also discussed.

Oral immunization of rainbow trout (Salmo gairdneri) against an etiologic agent of "redmouth disease"

USGS Publications Warehouse

1965-01-01

Rainbow trout were fed a pelleted diet containing killed cells of the etiologic agent of a bacterial disease, redmouth. These fish in addition to appropriate controls were subsequently challenged with virulent homologous organisms. Ninety per cent of the redmouth immunized fish survived the basic challenge using virulent organisms in contrast to 20% survival for the controls. Multiple challenge doses at increased levels also are discussed.

What Vaccines Do You Need?

MedlinePlus

... Recommendations Why Immunize? Vaccines: The Basics The Adult Vaccine Quiz Language: English Español (Spanish) Recommend on Facebook Tweet Share Compartir Vaccines are recommended for adults based on age, health ...

Host Control of Fungal Infections: Lessons from Basic Studies and Human Cohorts.

PubMed

Lionakis, Michail S; Levitz, Stuart M

2018-04-26

In the last few decades, the AIDS pandemic and the significant advances in the medical management of individuals with neoplastic and inflammatory conditions have resulted in a dramatic increase in the population of immunosuppressed patients with opportunistic, life-threatening fungal infections. The parallel development of clinically relevant mouse models of fungal disease and the discovery and characterization of several inborn errors of immune-related genes that underlie inherited human susceptibility to opportunistic mycoses have significantly expanded our understanding of the innate and adaptive immune mechanisms that protect against ubiquitous fungal exposures. This review synthesizes immunological knowledge derived from basic mouse studies and from human cohorts and provides an overview of mammalian antifungal host defenses that show promise for informing therapeutic and vaccination strategies for vulnerable patients.

Slow and fast dynamics model of a Malaria with Sickle-Cell genetic disease with multi-stage infections of the mosquitoes population

NASA Astrophysics Data System (ADS)

Dewi Siawanta, Shanti; Adi-Kusumo, Fajar; Irwan Endrayanto, Aluicius

2018-03-01

Malaria, which is caused by Plasmodium, is a common disease in tropical areas. There are three types of Plasmodium i.e. Plasmodium Vivax, Plasmodium Malariae, and Plasmodium Falciparum. The most dangerous cases of the Malaria are mainly caused by the Plasmodium Falciparum. One of the important characteristics for the Plasmodium infection is due to the immunity of erythrocyte that contains HbS (Haemoglobin Sickle-cell) genes. The individuals who has the HbS gene has better immunity against the disease. In this paper, we consider a model that shows the spread of malaria involving the interaction between the mosquitos population, the human who has HbS genes population and the human with normal gene population. We do some analytical and numerical simulation to study the basic reproduction ratio and the slow-fast dynamics of the phase-portrait. The slow dynamics in our model represents the response of the human population with HbS gene to the Malaria disease while the fast dynamics show the response of the human population with the normal gene to the disease. The slow and fast dynamics phenomena are due to the fact that the population of the individuals who have HbS gene is much smaller than the individuals who has normal genes.

Contextualizing the relevance of basic sciences: small-group simulation with debrief for first- and second-year medical students in an integrated curriculum.

PubMed

Ginzburg, Samara B; Brenner, Judith; Cassara, Michael; Kwiatkowski, Thomas; Willey, Joanne M

2017-01-01

There has been a call for increased integration of basic and clinical sciences during preclinical years of undergraduate medical education. Despite the recognition that clinical simulation is an effective pedagogical tool, little has been reported on its use to demonstrate the relevance of basic science principles to the practice of clinical medicine. We hypothesized that simulation with an integrated science and clinical debrief used with early learners would illustrate the importance of basic science principles in clinical diagnosis and management of patients. Small groups of first- and second-year medical students were engaged in a high-fidelity simulation followed by a comprehensive debrief facilitated by a basic scientist and clinician. Surveys including anchored and open-ended questions were distributed at the conclusion of each experience. The majority of the students agreed that simulation followed by an integrated debrief illustrated the clinical relevance of basic sciences (mean ± standard deviation: 93.8% ± 2.9% of first-year medical students; 96.7% ± 3.5% of second-year medical students) and its importance in patient care (92.8% of first-year medical students; 90.4% of second-year medical students). In a thematic analysis of open-ended responses, students felt that these experiences provided opportunities for direct application of scientific knowledge to diagnosis and treatment, improving student knowledge, simulating real-world experience, and developing clinical reasoning, all of which specifically helped them understand the clinical relevance of basic sciences. Small-group simulation followed by a debrief that integrates basic and clinical sciences is an effective means of demonstrating the relationship between scientific fundamentals and patient care for early learners. As more medical schools embrace integrated curricula and seek opportunities for integration, our model is a novel approach that can be utilized.

Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology

PubMed Central

Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; dos Santos, Rodrigo Weber; Lobosco, Marcelo

2017-01-01

ABSTRACT New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus. PMID:28027002

Mathematical modeling based on ordinary differential equations: A promising approach to vaccinology.

PubMed

Bonin, Carla Rezende Barbosa; Fernandes, Guilherme Cortes; Dos Santos, Rodrigo Weber; Lobosco, Marcelo

2017-02-01

New contributions that aim to accelerate the development or to improve the efficacy and safety of vaccines arise from many different areas of research and technology. One of these areas is computational science, which traditionally participates in the initial steps, such as the pre-screening of active substances that have the potential to become a vaccine antigen. In this work, we present another promising way to use computational science in vaccinology: mathematical and computational models of important cell and protein dynamics of the immune system. A system of Ordinary Differential Equations represents different immune system populations, such as B cells and T cells, antigen presenting cells and antibodies. In this way, it is possible to simulate, in silico, the immune response to vaccines under development or under study. Distinct scenarios can be simulated by varying parameters of the mathematical model. As a proof of concept, we developed a model of the immune response to vaccination against the yellow fever. Our simulations have shown consistent results when compared with experimental data available in the literature. The model is generic enough to represent the action of other diseases or vaccines in the human immune system, such as dengue and Zika virus.

Skin Immune Landscape: Inside and Outside the Organism.

PubMed

Abdallah, Florence; Mijouin, Lily; Pichon, Chantal

2017-01-01

The skin is an essential organ to the human body protecting it from external aggressions and pathogens. Over the years, the skin was proven to have a crucial immunological role, not only being a passive protective barrier but a network of effector cells and molecular mediators that constitute a highly sophisticated compound known as the "skin immune system" (SIS). Studies of skin immune sentinels provided essential insights of a complex and dynamic immunity, which was achieved through interaction between the external and internal cutaneous compartments. In fact, the skin surface is cohabited by microorganisms recognized as skin microbiota that live in complete harmony with the immune sentinels and contribute to the epithelial barrier reinforcement. However, under stress, the symbiotic relationship changes into a dysbiotic one resulting in skin disorders. Hence, the skin microbiota may have either positive or negative influence on the immune system. This review aims at providing basic background information on the cutaneous immune system from major cellular and molecular players and the impact of its microbiota on the well-coordinated immune responses in host defense.

Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune System Simulation under the Framework of History Matching: A Case Study on Influenza A Virus Infection

PubMed Central

Li, Tingting; Cheng, Zhengguo; Zhang, Le

2017-01-01

Since they can provide a natural and flexible description of nonlinear dynamic behavior of complex system, Agent-based models (ABM) have been commonly used for immune system simulation. However, it is crucial for ABM to obtain an appropriate estimation for the key parameters of the model by incorporating experimental data. In this paper, a systematic procedure for immune system simulation by integrating the ABM and regression method under the framework of history matching is developed. A novel parameter estimation method by incorporating the experiment data for the simulator ABM during the procedure is proposed. First, we employ ABM as simulator to simulate the immune system. Then, the dimension-reduced type generalized additive model (GAM) is employed to train a statistical regression model by using the input and output data of ABM and play a role as an emulator during history matching. Next, we reduce the input space of parameters by introducing an implausible measure to discard the implausible input values. At last, the estimation of model parameters is obtained using the particle swarm optimization algorithm (PSO) by fitting the experiment data among the non-implausible input values. The real Influeza A Virus (IAV) data set is employed to demonstrate the performance of our proposed method, and the results show that the proposed method not only has good fitting and predicting accuracy, but it also owns favorable computational efficiency. PMID:29194393

Developing a Novel Parameter Estimation Method for Agent-Based Model in Immune System Simulation under the Framework of History Matching: A Case Study on Influenza A Virus Infection.

PubMed

Li, Tingting; Cheng, Zhengguo; Zhang, Le

2017-12-01

Since they can provide a natural and flexible description of nonlinear dynamic behavior of complex system, Agent-based models (ABM) have been commonly used for immune system simulation. However, it is crucial for ABM to obtain an appropriate estimation for the key parameters of the model by incorporating experimental data. In this paper, a systematic procedure for immune system simulation by integrating the ABM and regression method under the framework of history matching is developed. A novel parameter estimation method by incorporating the experiment data for the simulator ABM during the procedure is proposed. First, we employ ABM as simulator to simulate the immune system. Then, the dimension-reduced type generalized additive model (GAM) is employed to train a statistical regression model by using the input and output data of ABM and play a role as an emulator during history matching. Next, we reduce the input space of parameters by introducing an implausible measure to discard the implausible input values. At last, the estimation of model parameters is obtained using the particle swarm optimization algorithm (PSO) by fitting the experiment data among the non-implausible input values. The real Influeza A Virus (IAV) data set is employed to demonstrate the performance of our proposed method, and the results show that the proposed method not only has good fitting and predicting accuracy, but it also owns favorable computational efficiency.

Assessing the impact of the Lebanese National Polio Immunization Campaign using a population-based computational model.

PubMed

Alawieh, Ali; Sabra, Zahraa; Langley, E Farris; Bizri, Abdul Rahman; Hamadeh, Randa; Zaraket, Fadi A

2017-11-25

After the re-introduction of poliovirus to Syria in 2013, Lebanon was considered at high transmission risk due to its proximity to Syria and the high number of Syrian refugees. However, after a large-scale national immunization initiative, Lebanon was able to prevent a potential outbreak of polio among nationals and refugees. In this work, we used a computational individual-simulation model to assess the risk of poliovirus threat to Lebanon prior and after the immunization campaign and to quantitatively assess the healthcare impact of the campaign and the required standards that need to be maintained nationally to prevent a future outbreak. Acute poliomyelitis surveillance in Lebanon was along with the design and coverage rate of the recent national polio immunization campaign were reviewed from the records of the Lebanese Ministry of Public Health. Lebanese population demographics including Syrian and Palestinian refugees were reviewed to design individual-based models that predicts the consequences of polio spread to Lebanon and evaluate the outcome of immunization campaigns. The model takes into account geographic, demographic and health-related features. Our simulations confirmed the high risk of polio outbreaks in Lebanon within 10 days of case introduction prior to the immunization campaign, and showed that the current immunization campaign significantly reduced the speed of the infection in the event poliomyelitis cases enter the country. A minimum of 90% national immunization coverage was found to be required to prevent exponential propagation of potential transmission. Both surveillance and immunization efforts should be maintained at high standards in Lebanon and other countries in the area to detect and limit any potential outbreak. The use of computational population simulation models can provide a quantitative approach to assess the impact of immunization campaigns and the burden of infectious diseases even in the context of population migration.

Acting Out Immunity: A Simulation of a Complicated Concept.

ERIC Educational Resources Information Center

Bealer, Jonathan; Bealer, Virginia

1996-01-01

Presents a lecture and play in which the students themselves become the elements of the immune system. Aims at facilitating student comprehension and retention of the complicated processes associated with the immune system. Includes objectives, outline, background information sources, instructor guide, student narrator guide, extension, and topics…

Immunological cross-reactivity between acid extracts of myelin, liver and neoplastic tissues: studies in immunized guinea-pigs.

PubMed Central

Flavell, D. J.; Goepel, J.; Wilson, A. P.; Potter, C. W.

1979-01-01

Groups of 4 guinea-pigs were immunized with acid extracts prepared from bovine myelin (EF), normal human liver tissue and malignant or benign neoplastic tissues in Freund's complete adjuvant (FCA1. The animals were weighed daily and examined for clinical signs of experimental allergic encephalomyelitis (EAE). All the animals immunized with EF developed clinical symptoms of EAE within 21 days of the initial immunization, whilst some of the animals immunized with certain tumour extracts developed symptoms which closely resembled those of EAE. Control animals immunized with FCA only remained asymptomatic. Cellular immunity to the various extracts in immunized animals was assessed 20 days after immunization by i.d. skin testing, and upon killing at Day 21 with the direct peritoneal-exudate macrophage migration inhibition (MMI) test. Brains and spinal cords were removed at killing, fixed in formalin and processed for histological examination. I.d. skin testing was shown to be most consistent in demonstrating positive delayed hypersensitivity, whilst the MMI test frequently gave negative results in the presence of pronounced skin responses to specific extracts. Thus it was shown that 3/4 animals immunized with basic proteins extracted from an adenocarcinoma of the lung or related hepatic metastases, and 1/2 animals immunized with an extract of a carcinoma of the breast, gave intense erythema and induration responses 5 mm in diameter 24 h after i.d. challenge with EF. No such response was obtained in animals immunized with basic proteins extracted from normal human liver, any of the other neoplastic tissues, or in control animals immunized with FCA only. Examination of brains and spinal cords from animals immunized with EF revealed dense infiltration by mononuclear cells in the ependyma and choroid plexus of levels in the spinal cord. Examination of brains and spinal cords from animals immunized with the lung-tumour extract or related hepatic metastases which showed demonstrable immunological cross-reactivity with EF in immunized animals, revealed a number of inflammatory changes characterized by dense infiltrates of mononuclear cells sub-ependymally, and perivascular cuffing in the cortex. However, no significant lesions were seen in the spinal cords of these animals. Polyacrylamide-gel electrophoresis of the 2 tumour extracts exerting this apparent encephalitogenic effect did not reveal proteins within the mol. wt range of EF. Thus the observed pathological effects and cross-reactivity with EF were probably not due to contamination with nervous-tissue components. It is suggested that these tumour extracts may have contained a component or components other than EF, immunologically cross-reactive with EF, and capable of inducing the observed encephalitis. Images Fig. 2 Fig. 3a, b Fig. 3c, d PMID:92328

Twelve tips for postgraduate or undergraduate medics building a basic microsurgery simulation training course.

PubMed

Mason, Katrina A; Theodorakopoulou, Evgenia; Pafitanis, Georgios; Ghanem, Ali M; Myers, Simon R

2016-09-01

Microsurgery is used in a variety of surgical specialties, including Plastic Surgery, Maxillofacial Surgery, Ophthalmic Surgery, Otolaryngology and Neurosurgery. It is considered one of the most technically challenging fields of surgery. Microsurgical skills demand fine, precise and controlled movements, and microsurgical skill acquisition has a steep initial learning curve. Microsurgical simulation provides a safe environment for skill acquisition before operating clinically. The traditional starting point for anyone wanting to pursue microsurgery is a basic simulation training course. We present twelve tips for postgraduate and undergraduate medics on how to set up and run a basic ex-vivo microsurgery simulation training course suitable for their peers.

GenASiS Basics: Object-oriented utilitarian functionality for large-scale physics simulations

DOE PAGES

Cardall, Christian Y.; Budiardja, Reuben D.

2015-06-11

Aside from numerical algorithms and problem setup, large-scale physics simulations on distributed-memory supercomputers require more basic utilitarian functionality, such as physical units and constants; display to the screen or standard output device; message passing; I/O to disk; and runtime parameter management and usage statistics. Here we describe and make available Fortran 2003 classes furnishing extensible object-oriented implementations of this sort of rudimentary functionality, along with individual `unit test' programs and larger example problems demonstrating their use. Lastly, these classes compose the Basics division of our developing astrophysics simulation code GenASiS (General Astrophysical Simulation System), but their fundamental nature makes themmore » useful for physics simulations in many fields.« less

Bat-mouse bone marrow chimera: a novel animal model for dissecting the uniqueness of the bat immune system.

PubMed

Yong, Kylie Su Mei; Ng, Justin Han Jia; Her, Zhisheng; Hey, Ying Ying; Tan, Sue Yee; Tan, Wilson Wei Sheng; Irac, Sergio Erdal; Liu, Min; Chan, Xue Ying; Gunawan, Merry; Foo, Randy Jee Hiang; Low, Dolyce Hong Wen; Mendenhall, Ian Hewitt; Chionh, Yok Teng; Dutertre, Charles-Antoine; Chen, Qingfeng; Wang, Lin-Fa

2018-03-16

Bats are an important animal model with long lifespans, low incidences of tumorigenesis and an ability to asymptomatically harbour pathogens. Currently, in vivo studies of bats are hampered due to their low reproduction rates. To overcome this, we transplanted bat cells from bone marrow (BM) and spleen into an immunodeficient mouse strain NOD-scid IL-2R -/- (NSG), and have successfully established stable, long-term reconstitution of bat immune cells in mice (bat-mice). Immune functionality of our bat-mouse model was demonstrated through generation of antigen-specific antibody response by bat cells following immunization. Post-engraftment of total bat BM cells and splenocytes, bat immune cells survived, expanded and repopulated the mouse without any observable clinical abnormalities. Utilizing bat's remarkable immunological functions, this novel model has a potential to be transformed into a powerful platform for basic and translational research.

Immunization of pregnant women: Future of early infant protection

PubMed Central

Faucette, Azure N; Pawlitz, Michael D; Pei, Bo; Yao, Fayi; Chen, Kang

2015-01-01

Children in early infancy do not mount effective antibody responses to many vaccines against commons infectious pathogens, which results in a window of increased susceptibility or severity infections. In addition, vaccine-preventable infections are among the leading causes of morbidity in pregnant women. Immunization during pregnancy can generate maternal immune protection as well as elicit the production and transfer of antibodies cross the placenta and via breastfeeding to provide early infant protection. Several successful vaccines are now recommended to all pregnant women worldwide. However, significant gaps exist in our understanding of the efficacy and safety of other vaccines and in women with conditions associated with increased susceptible to high-risk pregnancies. Public acceptance of maternal immunization remained to be improved. Broader success of maternal immunization will rely on the integration of advances in basic science in vaccine design and evaluation and carefully planned clinical trials that are inclusive to pregnant women. PMID:26366844

Clinical Implications of Basic Science Discoveries: Immune Homeostasis and the Microbiome-Dietary and Therapeutic Modulation and Implications for Transplantation.

PubMed

Fishman, J A; Thomson, A W

2015-07-01

Links between the human microbiome and the innate and adaptive immune systems and their impact on autoimmune and inflammatory diseases are only beginning to be recognized. Characterization of the complex human microbial community is facilitated by culture-independent nucleic acid sequencing tools and bioinformatics systems. Specific organisms and microbial antigens are linked with initiation of innate immune responses that, depending on the context, may be associated with tolerogenic or effector immune responses. Further complexity is introduced by preclinical data that demonstrate the impacts of dietary manipulation on the prevention of genetically determined, systemic autoimmune disorders and on gastrointestinal microbiota. Investigation of interactions of complex microbial populations with the human immune system may provide new targets for clinical management in allotransplantation. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Methods for Posttranslational Induction of Polyreactivity of Antibodies.

PubMed

Lecerf, Maxime; Jarossay, Annaelle; Kaveri, Srinivas V; Lacroix-Desmazes, Sébastien; Dimitrov, Jordan D

2017-01-01

An antibody molecule that recognizes multiple unrelated antigens is defined as polyreactive. Polyreactivity is an intrinsic characteristic of immune repertoires. Degenerated antigen binding diversifies the repertoire of specificities, thus contributing to immune defense and immune regulation. Immune repertoire contains also a fraction of immunoglobulins, which acquire polyreactivity only following contact with various protein-destabilizing or pro-oxidative substances. Posttranslational induction of the antibody polyreactivity may have important repercussion for laboratory practice, as well as in cases of pathological conditions accompanied by liberation of large quantities of pro-oxidative substances such as heme, labile iron, or reactive oxygen species. Antibodies with induced polyreactivity have been demonstrated to exert pathogen neutralization and immune regulatory potential in inflammatory conditions, suggesting that this phenomenon may be exploited for design of therapeutic strategies. In this article, we provide description of the basic procedures for uncovering of the cryptic polyreactivity of antibodies by heme, ferrous ions, and acid pH solution.

Kidney dendritic cells in acute and chronic renal disease.

PubMed

Hochheiser, Katharina; Tittel, André; Kurts, Christian

2011-06-01

Dendritic cells are not only the master regulators of adaptive immunity, but also participate profoundly in innate immune responses. Much has been learned about their basic immunological functions and their roles in various diseases. Comparatively little is still known about their role in renal disease, despite their obvious potential to affect immune responses in the kidney, and immune responses that are directed against renal components. Kidney dendritic cells form an abundant network in the renal tubulointerstitium and constantly survey the environment for signs of injury or infection, in order to alert the immune system to the need to initiate defensive action. Recent studies have identified a role for dendritic cells in several murine models of acute renal injury and chronic nephritis. Here we summarize the current knowledge on the role of kidney dendritic cells that has been obtained from the study of murine models of renal disease. © 2010 The Authors. Journal compilation © 2010 Blackwell Publishing Ltd.

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

Validation of a novel basic virtual reality simulator, the LAP-X, for training basic laparoscopic skills.

PubMed

Kawaguchi, Koji; Egi, Hiroyuki; Hattori, Minoru; Sawada, Hiroyuki; Suzuki, Takahisa; Ohdan, Hideki

2014-10-01

Virtual reality surgical simulators are becoming popular as a means of providing trainees with an opportunity to practice laparoscopic skills. The Lap-X (Epona Medical, Rotterdam, the Netherlands) is a novel VR simulator for training basic skills in laparoscopic surgery. The objective of this study was to validate the LAP-X laparoscopic virtual reality simulator by assessing the face and construct validity in order to determine whether the simulator is adequate for basic skills training. The face and content validity were evaluated using a structured questionnaire. To assess the construct validity, the participants, nine expert surgeons (median age: 40 (32-45)) (>100 laparoscopic procedures) and 11 novices performed three basic laparoscopic tasks using the Lap-X. The participants reported a high level of content validity. No significant differences were found between the expert surgeons and the novices (Ps > 0.246). The performance of the expert surgeons on the three tasks was significantly better than that of the novices in all parameters (Ps < 0.05). This study demonstrated the face, content and construct validity of the Lap-X. The Lap-X holds real potential as a home and hospital training device.

Intraindividual variability in basic reaction time predicts middle-aged and older pilots' flight simulator performance.

PubMed

Kennedy, Quinn; Taylor, Joy; Heraldez, Daniel; Noda, Art; Lazzeroni, Laura C; Yesavage, Jerome

2013-07-01

Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Two-hundred and thirty-six pilots (40-69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%-12% of the negative age effect on initial flight performance. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance.

Intraindividual Variability in Basic Reaction Time Predicts Middle-Aged and Older Pilots’ Flight Simulator Performance

PubMed Central

2013-01-01

Objectives. Intraindividual variability (IIV) is negatively associated with cognitive test performance and is positively associated with age and some neurological disorders. We aimed to extend these findings to a real-world task, flight simulator performance. We hypothesized that IIV predicts poorer initial flight performance and increased rate of decline in performance among middle-aged and older pilots. Method. Two-hundred and thirty-six pilots (40–69 years) completed annual assessments comprising a cognitive battery and two 75-min simulated flights in a flight simulator. Basic and complex IIV composite variables were created from measures of basic reaction time and shifting and divided attention tasks. Flight simulator performance was characterized by an overall summary score and scores on communication, emergencies, approach, and traffic avoidance components. Results. Although basic IIV did not predict rate of decline in flight performance, it had a negative association with initial performance for most flight measures. After taking into account processing speed, basic IIV explained an additional 8%–12% of the negative age effect on initial flight performance. Discussion. IIV plays an important role in real-world tasks and is another aspect of cognition that underlies age-related differences in cognitive performance. PMID:23052365

Predicting the impact of combined therapies on myeloma cell growth using a hybrid multi-scale agent-based model.

PubMed

Ji, Zhiwei; Su, Jing; Wu, Dan; Peng, Huiming; Zhao, Weiling; Nlong Zhao, Brian; Zhou, Xiaobo

2017-01-31

Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth. We constructed a hybrid multi-scale agent-based model (HABM) that combines an ODE system and Agent-based model (ABM). The ODEs was used for modeling the dynamic changes of intracellular signal transductions and ABM for modeling the cell-cell interactions between stromal cells, tumor, and immune components in the BM. This model simulated myeloma growth in the bone marrow microenvironment and revealed the important role of immune system in this process. The predicted outcomes were consistent with the experimental observations from previous studies. Moreover, we applied this model to predict the treatment effects of three key therapeutic drugs used for MM, and found that the combination of these three drugs potentially suppress the growth of myeloma cells and reactivate the immune response. In summary, the proposed model may serve as a novel computational platform for simulating the formation of MM and evaluating the treatment response of MM to multiple drugs.

[Ilya Ilich Metchnikov and Paul Ehrlich: 1908 Nobel Prize winners for their research on immunity].

PubMed

Lokaj, J; John, C

2008-11-01

The Nobel Prize in Physiology or Medicine in 1908 was awarded to Ilya I. Mechnikov and Paul Ehrlich for recognition of their work on immunity. Mechnikov have discovered phagocytes and phagocytosis as the basis of natural cellular immunity. His ,,phagocytic theory" is the principle of immunological concept "self and not self" as the prerequisition of physiological inflammation, and selfmaintaining of organism. Ehrlich developed the methods for standardization of antibody activity in immune sera, described neutralizing and complement-depending effect of antibodies and enunciated the ,"ide-chain" theory of the formation of antibodies. Their concept of the key-stone of immunity was different, but they expressed the basic paradigma of immunology: immunity imply the protection of identity and guarantee the integrity of organism. Both are the founders of immunology as the scientific discipline. Discoveries and conceptions of I. Mechnikov and P. Ehrlich exceedingly influenced development of immunology and are also applicable, instructive and suggestive in contemporary immunology and microbiology.

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

New Simulation Methods to Facilitate Achieving a Mechanistic Understanding of Basic Pharmacology Principles in the Classroom

ERIC Educational Resources Information Center

Grover, Anita; Lam, Tai Ning; Hunt, C. Anthony

2008-01-01

We present a simulation tool to aid the study of basic pharmacology principles. By taking advantage of the properties of agent-based modeling, the tool facilitates taking a mechanistic approach to learning basic concepts, in contrast to the traditional empirical methods. Pharmacodynamics is a particular aspect of pharmacology that can benefit from…

Tuberculosis vaccine development: strength lies in tenacity.

PubMed

Kaufmann, Stefan H E

2012-07-01

The past decade has witnessed a tremendous increase in the development of novel vaccines against tuberculosis (TB). In mice, each of these vaccine candidates stimulates an immune response that reduces the bacillary load, reflecting control but not sterilization of infection. Yet, the immune mechanisms underlying vaccine efficacy are only partially understood. In parallel to clinical assessment of current candidates, the next generation of vaccine candidates still needs to be developed. This requires basic research on how to induce the most efficacious immune response. Equally important is the dissection of immune responses in patients, latently infected healthy individuals, and participants of clinical vaccine trials. Amalgamation of this information will foster the way towards more efficacious vaccination strategies that not only prevent disease, but prevent or abolish infection. Copyright © 2012 Elsevier Ltd. All rights reserved.

Advances in sepsis research derived from animal models.

PubMed

Männel, Daniela N

2007-09-01

Inflammation is the basic process by which tissues of the body respond to infection. Activation of the immune system normally leads to removal of microbial pathogens, and after resolution of the inflammation immune homeostasis is restored. This controlled process, however, can be disturbed resulting in disease. Therefore, many studies using infection models have investigated the participating immune mechanisms aiming at possible therapeutic interventions. Defined model substances such as bacterial lipopolysaccharide (endotoxin) have been used to mimic bacterial infections and analyze their immune stimulating functions. A complex network of molecular mechanisms involved in the recognition and activation processes of bacterial infections and their regulation has developed from these studies. More complex infection models will now help to interpret earlier observations leading to the design of relevant new infection models.

Human immune circadian system in prolonged mild hypoxia during simulated flights.

PubMed

Coste, Olivier; Van Beers, Pascal; Bogdan, André; Touitou, Yvan

2007-01-01

An impairment of immunity is reported after long-haul flights, and the mild hypobaric hypoxia caused by pressurization in the passenger airline cabin may contribute to it. In this controlled crossover study, the effects of two levels of hypoxia, equivalent to 8000 and 12,000 feet above sea level, on the rhythm of CD3, CD4, and CD8 lymphocytes and plasma concentrations of the immunoglobulins A, G, and M were assessed. Fourteen healthy male volunteers, aged 23 to 39 years, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), simulating an altitude condition at 8,000 feet. This was followed by an additional 8.5 h study four weeks later simulating altitude conditions at 12,000 feet. The variables were assayed every 2 h over two 24 h cycles (control and hypoxic-exposure cycles). No significant effect of hypoxia on the studied circadian immune profiles were found. Therefore, the authors conclude that mild hypobaric hypoxia does not seem to be responsible for any quantitative changes during long-haul flights in the immune assays commonly used in routine clinical medicine practice.

The threshold of a stochastic delayed SIR epidemic model with temporary immunity

NASA Astrophysics Data System (ADS)

Liu, Qun; Chen, Qingmei; Jiang, Daqing

2016-05-01

This paper is concerned with the asymptotic properties of a stochastic delayed SIR epidemic model with temporary immunity. Sufficient conditions for extinction and persistence in the mean of the epidemic are established. The threshold between persistence in the mean and extinction of the epidemic is obtained. Compared with the corresponding deterministic model, the threshold affected by the white noise is smaller than the basic reproduction number R0 of the deterministic system.

[Indicators of the persistent pro-inflammatory activation of the immune system in depression].

PubMed

Cubała, Wiesław Jerzy; Godlewska, Beata; Trzonkowski, Piotr; Landowski, Jerzy

2006-01-01

The aetiology of depression remains tentative. Current hypotheses on the aetiology of the depressive disorder tend to integrate monoaminoergic, neuroendocrine and immunological concepts of depression. A number of research papers emphasise the altered hormonal and immune status of patients with depression with pronounced cytokine level variations. Those studies tend to link the variable course of depression in relation to the altered proinflammatory activity of the immune system. The results of the studies on the activity of the selected elements of the immune system are ambiguous indicating both increased and decreased activities of its selected elements. However, a number of basic and psychopharmacological studies support the hypothesis of the increased proinflammatory activity of the immune system in the course of depression which is the foundation for the immunological hypothesis of depression. The aim of this paper is to review the functional abnormalities that are observed in depression focusing on the monoaminoergic deficiency and increased immune activation as well as endocrine dysregulation. This paper puts together and discusses current studies related to this subject with a detailed insight into interactions involving nervous, endocrine and immune systems.

Basic problems of serological laboratory diagnosis.

PubMed

Fierz, Walter

2004-01-01

Serological laboratory diagnosis of infectious diseases is inflicted with several kinds of basic problems. One difficulty relates to the fact that the serological diagnosis of infectious diseases is double indirect: The first indirect aim in diagnosing an infectious disease is to identify the microbial agent that caused the disease. The second indirect aim is to identify this infectious agent by measuring the patient's immune response to the potential agent. Thus, the serological test is neither measuring directly disease nor the cause of the disease, but the patient's immune system. The latter poses another type of problem, because each person's immune system is unique. The immune response to an infectious agent is usually of polyclonal nature, and the exact physicochemical properties of antibodies are unique for each clone of antibody. The clonal makeup and composition and, therefore, the way an individual's immune system sees an infectious agent, depends not only on the genetic background of the person but also on the individual experience from former encounters with various infectious agents. In consequence, the reaction of a patient's serum in an analytical system is not precisely predictable. Also, the antigenic makeup of an infectious agent is not always foreseeable. Antigenic variations leading to different serotypes is a quite common phenomenon. Altogether, these biological problems lead to complexities in selecting the appropriate tests and strategies for testing, in interpreting the results, and in standardizing serological test systems. For that reason, a close collaboration of the laboratory with the clinic is mandatory to avoid erroneous conclusions from serological test results, which might lead to wrong decisions in patient care.

Modulation of macrophage functions by sheeppox virus provides clues to understand interaction of the virus with host immune system.

PubMed

Abu-El-Saad, Abdel-Aziz S; Abdel-Moneim, Ahmed S

2005-03-22

Poxviruses encode a range of immunomodulatory genes to subvert or evade the challenges posed by the innate and adaptive immune responses. However, the inactivated poxviruses possessed immunostimulating capacity and were used as a prophylactic or metaphylactic application that efficiently reduced susceptibility to infectious diseases in different species. This fact is intensively studied in different genera of poxviruses. However, little is known about the basic mechanisms adopted by sheeppox virus (SPPV). SPPV causes an acute disease of sheep that recently, has been observed to reinfect its host in spite of vaccination. By injecting inactivated or attenuated sheeppox virus SPPV vaccine in adult male Swiss mice, SPPV was found to reduce macrophages' functions in a local event that occurs at the site of application 12 h after vaccine administration as indicated by increased level of IL-10 and decreased level of SOD from cultured peritoneal macrophages. In contrast increased levels of IL-12, and SOD activity from cultured splenic macrophages, lymphocyte response to PHA-P, and in-vivo response to T-dependant Ag were detected. These effects were observed in both attenuated and inactivated SPPV, but more prominent in attenuated one. The results of this study help to elucidate, the phenomenon of existence natural SPPV infections in sheep instead of vaccination and the basic mechanisms responsible for the immunostimulating capacity of sheeppox virus. Locally, SPPV shows evidence for an immune escape mechanism that alleviates the host's immune response. Later and systemically, the virus protects the host from any fatal consequences of the immune system suppression.

Oral testosterone in male rats and the development of experimental autoimmune encephalomyelitis.

PubMed

Macció, Daniela R; Calfa, Gastón; Roth, German A

2005-01-01

Considering that sex steroids can influence the immune system, we studied the development of experimental autoimmune encephalomyelitis (EAE), a T-cell-mediated autoimmune disease of the central nervous system, and the concomitant cell-mediated immunity in gonadally intact and gonadectomized male Wistar rats given testosterone supplementation. Sham-operated rats and surgically castrated animals were orally self-administered with vehicle or testosterone added in the water bottle for 20 days before EAE induction. The androgenic effect of oral testosterone self-administration was evidenced by changes in body weight, and in the weights of androgen-dependent testes and seminal vesicles. Testosterone administration reduced the incidence of clinical signs of EAE in sham-operated animals and reversed the clinical symptoms of the disease associated with castrated EAE animals. The clinical signs observed in the different groups correlated with changes in delayed-type hypersensitivity and mononuclear cell-proliferative responses to the encephalitogenic myelin basic protein. Moreover, testosterone but not cholesterol supplementation in vitro suppressed the proliferative response of mononuclear cells to myelin basic protein suggesting that testosterone may affect specific immune functions through direct actions on immune cells. Finally, self-administration of testosterone induced also elevated corticosterone levels that in sham-operated rats correlated with the low incidence of the disease and in gonadectomized animals could be involved in the remission of clinical symptoms of EAE. These results suggest that orally self-administered testosterone can modulate specific cellular immune responses and serum corticosterone levels leading to changes in the development of EAE. Copyright 2005 S. Karger AG, Basel.

Qa-1/HLA-E-restricted regulatory CD8+ T cells and self-nonself discrimination: an essay on peripheral T-cell regulation.

PubMed

Jiang, Hong; Chess, Leonard

2008-11-01

By discriminating self from nonself and controlling the magnitude and class of immune responses, the immune system mounts effective immunity against virtually any foreign antigens but avoids harmful immune responses to self. These are two equally important and related but distinct processes, which function in concert to ensure an optimal function of the immune system. Immunologically relevant clinical problems often occur because of failure of either process, especially the former. Currently, there is no unified conceptual framework to characterize the precise relationship between thymic negative selection and peripheral immune regulation, which is the basis for understanding self-non-self discrimination versus control of magnitude and class of immune responses. In this article, we explore a novel hypothesis of how the immune system discriminates self from nonself in the periphery during adaptive immunity. This hypothesis permits rational analysis of various seemingly unrelated biomedical problems inherent in immunologic disorders that cannot be uniformly interpreted by any currently existing paradigms. The proposed hypothesis is based on a unified conceptual framework of the "avidity model of peripheral T-cell regulation" that we originally proposed and tested, in both basic and clinical immunology, to understand how the immune system achieves self-nonself discrimination in the periphery.

[Anti-infective defence strategies and methods of escape from entomologic pathogens under immunologic control of insects].

PubMed

Jarosz, J

1996-01-01

Insect immunity comprises a complex of several distinct systems, both haemocytic and humoral in nature, that cooperate together in a more or less coordinated way to provide protection of the body cavity from invading microorganisms. Insects can respond to infections by a selective synthesis of haemolymph immune proteins that are responsible for antibacterial immunity. Antibacterial activity of insect blood is attributable to innate compounds such as lysozome, and to induced polypeptides or small basic proteins absent in non-immunized insects. The cecropins and attacins in Lepidoptera, and diptericins in Diptera are the inducible antibacterial immune proteins well defined biochemically. Bacterial pathogens and some parasites of insects, preferably entomogenous rhabditid nematodes, have developed the mechanism by which they may counteract insect immunity. This phenomenon is realized either by escaping immune reactions or by degrading antimicrobial factors of haemolymph in an active process. Passive resistance of parasites to insect immunity is a result of a strong evolutionary pressure on parasites to develop mechanisms to escape insect immune reactions or to minimize their effectiveness through changes in the parasite itself. Active resistance to the insect non-self response system involves a partial or total destruction of immune proteins by extracellular proteinases released during parasitism.

Heat and immunity: an experimental heat wave alters immune functions in three-spined sticklebacks (Gasterosteus aculeatus).

PubMed

Dittmar, Janine; Janssen, Hannah; Kuske, Andra; Kurtz, Joachim; Scharsack, Jörn P

2014-07-01

Global climate change is predicted to lead to increased temperatures and more extreme climatic events. This may influence host-parasite interactions, immunity and therefore the impact of infectious diseases on ecosystems. However, little is known about the effects of rising temperatures on immune defence, in particular in ectothermic animals, where the immune system is directly exposed to external temperature change. Fish are ideal models for studying the effect of temperature on immunity, because they are poikilothermic, but possess a complete vertebrate immune system with both innate and adaptive immunity. We used three-spined sticklebacks ( Gasterosteus aculeatus) originating from a stream and a pond, whereby the latter supposedly were adapted to higher temperature variation. We studied the effect of increasing and decreasing temperatures and a simulated heat wave with subsequent recovery on body condition and immune parameters. We hypothesized that the immune system might be less active at low temperatures, but will be even more suppressed at temperatures towards the upper tolerable temperature range. Contrary to our expectation, we found innate and adaptive immune activity to be highest at a temperature as low as 13 °C. Exposure to a simulated heat wave induced long-lasting immune disorders, in particular in a stickleback population that might be less adapted to temperature variation in its natural environment. The results show that the activity of the immune system of an ectothermic animal species is temperature dependent and suggest that heat waves associated with global warming may immunocompromise host species, thereby potentially facilitating the spread of infectious diseases. © 2014 The Authors. Journal of Animal Ecology © 2014 British Ecological Society.

Basic Operational Robotics Instructional System

NASA Technical Reports Server (NTRS)

Todd, Brian Keith; Fischer, James; Falgout, Jane; Schweers, John

2013-01-01

The Basic Operational Robotics Instructional System (BORIS) is a six-degree-of-freedom rotational robotic manipulator system simulation used for training of fundamental robotics concepts, with in-line shoulder, offset elbow, and offset wrist. BORIS is used to provide generic robotics training to aerospace professionals including flight crews, flight controllers, and robotics instructors. It uses forward kinematic and inverse kinematic algorithms to simulate joint and end-effector motion, combined with a multibody dynamics model, moving-object contact model, and X-Windows based graphical user interfaces, coordinated in the Trick Simulation modeling environment. The motivation for development of BORIS was the need for a generic system for basic robotics training. Before BORIS, introductory robotics training was done with either the SRMS (Shuttle Remote Manipulator System) or SSRMS (Space Station Remote Manipulator System) simulations. The unique construction of each of these systems required some specialized training that distracted students from the ideas and goals of the basic robotics instruction.

Medicine.

ERIC Educational Resources Information Center

Ingelfinger, Franz J.

1980-01-01

Selected for discussion are certain advances in basic research and technologic innovation which shape the past, present, and future of medical care. Included are infectious diseases, especially hepatitis, immunology, clinical disorders of the immune system and the histocompatability system. (Author/SA)

A brief simulation intervention increasing basic science and clinical knowledge.

PubMed

Sheakley, Maria L; Gilbert, Gregory E; Leighton, Kim; Hall, Maureen; Callender, Diana; Pederson, David

2016-01-01

The United States Medical Licensing Examination (USMLE) is increasing clinical content on the Step 1 exam; thus, inclusion of clinical applications within the basic science curriculum is crucial. Including simulation activities during basic science years bridges the knowledge gap between basic science content and clinical application. To evaluate the effects of a one-off, 1-hour cardiovascular simulation intervention on a summative assessment after adjusting for relevant demographic and academic predictors. This study was a non-randomized study using historical controls to evaluate curricular change. The control group received lecture (n l=515) and the intervention group received lecture plus a simulation exercise (n l+s=1,066). Assessment included summative exam questions (n=4) that were scored as pass/fail (≥75%). USMLE-style assessment questions were identical for both cohorts. Descriptive statistics for variables are presented and odds of passage calculated using logistic regression. Undergraduate grade point ratio, MCAT-BS, MCAT-PS, age, attendance at an academic review program, and gender were significant predictors of summative exam passage. Students receiving the intervention were significantly more likely to pass the summative exam than students receiving lecture only (P=0.0003). Simulation plus lecture increases short-term understanding as tested by a written exam. A longitudinal study is needed to assess the effect of a brief simulation intervention on long-term retention of clinical concepts in a basic science curriculum.

A brief simulation intervention increasing basic science and clinical knowledge.

PubMed

Sheakley, Maria L; Gilbert, Gregory E; Leighton, Kim; Hall, Maureen; Callender, Diana; Pederson, David

2016-01-01

Background The United States Medical Licensing Examination (USMLE) is increasing clinical content on the Step 1 exam; thus, inclusion of clinical applications within the basic science curriculum is crucial. Including simulation activities during basic science years bridges the knowledge gap between basic science content and clinical application. Purpose To evaluate the effects of a one-off, 1-hour cardiovascular simulation intervention on a summative assessment after adjusting for relevant demographic and academic predictors. Methods This study was a non-randomized study using historical controls to evaluate curricular change. The control group received lecture (n l =515) and the intervention group received lecture plus a simulation exercise (n l+s =1,066). Assessment included summative exam questions (n=4) that were scored as pass/fail (≥75%). USMLE-style assessment questions were identical for both cohorts. Descriptive statistics for variables are presented and odds of passage calculated using logistic regression. Results Undergraduate grade point ratio, MCAT-BS, MCAT-PS, age, attendance at an academic review program, and gender were significant predictors of summative exam passage. Students receiving the intervention were significantly more likely to pass the summative exam than students receiving lecture only (P=0.0003). Discussion Simulation plus lecture increases short-term understanding as tested by a written exam. A longitudinal study is needed to assess the effect of a brief simulation intervention on long-term retention of clinical concepts in a basic science curriculum.

Gold kiwifruit ( Actinidia chinensis 'Hort16A') for immune support.

PubMed

Skinner, Margot A; Loh, Jacelyn M S; Hunter, Denise C; Zhang, Jingli

2011-05-01

Kiwifruit is a good source of several vitamins and minerals and dietary fibre, and contains a number of phytochemicals; so kiwifruit potentially provides health benefits beyond basic nutrition. Consumption of green kiwifruit can have positive effects on cardiovascular health through antioxidant activity, inhibition of platelet aggregation and lowered TAG levels, and gut health through improving laxation, aiding digestion and promoting a healthy gut microflora. The importance of nutrition on immune function is well recognised, with deficiencies in vitamins A, C, E, B6 and B12, folic acid, Zn, Cu, Fe and Se being associated with impaired immune function and increased susceptibility to diseases. Evidence is growing that kiwifruit enhances immunity, with several small murine studies showing enhancement of innate and adaptive immune function. Few studies have examined the effect of kiwifruit on immune function in human subjects, but a recent study has revealed that kiwifruit up-regulates several 'immune' and 'DNA and repair'-related gene sets, and down-regulates one gene set related to Ig secretion. Taken together, the evidence from the literature provides supporting data for designing a human intervention trial to validate the ability of kiwifruit to support immune function in healthy and immunocompromised populations.

Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances.

PubMed

Haapakoski, Rita; Ebmeier, Klaus P; Alenius, Harri; Kivimäki, Mika

2016-04-03

The inflammation theory of depression, proposed over 20years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced 'omics' technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Innate and adaptive immunity in the development of depression: An update on current knowledge and technological advances

PubMed Central

Haapakoski, Rita; Ebmeier, Klaus P.; Alenius, Harri; Kivimäki, Mika

2016-01-01

The inflammation theory of depression, proposed over 20 years ago, was influenced by early studies on T cell responses and since then has been a stimulus for numerous research projects aimed at understanding the relationship between immune function and depression. Observational studies have shown that indicators of immunity, especially C reactive protein and proinflammatory cytokines, such as interleukin 6, are associated with an increased risk of depressive disorders, although the evidence from randomized trials remains limited and only few studies have assessed the interplay between innate and adaptive immunity in depression. In this paper, we review current knowledge on the interactions between central and peripheral innate and adaptive immune molecules and the potential role of immune-related activation of microglia, inflammasomes and indoleamine-2,3-dioxygenase in the development of depressive symptoms. We highlight how combining basic immune methods with more advanced ‘omics’ technologies would help us to make progress in unravelling the complex associations between altered immune function and depressive disorders, in the identification of depression-specific biomarkers and in developing immunotherapeutic treatment strategies that take individual variability into account. PMID:26631274

Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

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

Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.

HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation processmore » including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Furthermore, our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.« less

Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

DOE PAGES

Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; ...

2015-12-22

HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation processmore » including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness landscapes influenced the shape of phylogenies, diversity trends, and survival of virus with latent genomic fragments. Furthermore, our model predicts that the persistence of latent genomic fragments from multiple different ancestral origins increases sequence diversity in plasma for reasonable fitness landscapes.« less

Design and implementation of a combined influenza immunization and tuberculosis screening campaign with simulation modelling.

PubMed

Heim, Joseph A; Huang, Hao; Zabinsky, Zelda B; Dickerson, Jane; Wellner, Monica; Astion, Michael; Cruz, Doris; Vincent, Jeanne; Jack, Rhona

2015-08-01

Design and implement a concurrent campaign of influenza immunization and tuberculosis (TB) screening for health care workers (HCWs) that can reduce the number of clinic visits for each HCW. A discrete-event simulation model was developed to support issues of resource allocation decisions in planning and operations phases. The campaign was compressed to100 days in 2010 and further compressed to 75 days in 2012 and 2013. With more than 5000 HCW arrivals in 2011, 2012 and 2013, the 14-day goal of TB results was achieved for each year and reduced to about 4 days in 2012 and 2013. Implementing a concurrent campaign allows less number of visiting clinics and the compressing of campaign length allows earlier immunization. The support of simulation modelling can provide useful evaluations of different configurations. © 2015 John Wiley & Sons, Ltd.

HIV-1 Strategies of Immune Evasion

NASA Astrophysics Data System (ADS)

Castiglione, F.; Bernaschi, M.

We simulate the progression of the HIV-1 infection in untreated host organisms. The phenotype features of the virus are represented by the replication rate, the probability of activating the transcription, the mutation rate and the capacity to stimulate an immune response (the so-called immunogenicity). It is very difficult to study in-vivo or in-vitro how these characteristics of the virus influence the evolution of the disease. Therefore we resorted to simulations based on a computer model validated in previous studies. We observe, by means of computer experiments, that the virus continuously evolves under the selective pressure of an immune response whose effectiveness downgrades along with the disease progression. The results of the simulations show that immunogenicity is the most important factor in determining the rate of disease progression but, by itself, it is not sufficient to drive the disease to a conclusion in all cases.

Characterization of immune response to Eimeria tenella antigens in a natural immunity model with hosts which differ serologically at the B locus of the major histocompatibility complex.

PubMed Central

Brake, D A; Fedor, C H; Werner, B W; Miller, T J; Taylor, R L; Clare, R A

1997-01-01

A model to simulate natural immunity to Eimeria tenella was developed in three chicken lines which differ at the B locus of the major histocompatibility complex. Homozygous, 1-day-old chicks of the B19B19, B24B24, or B30B30 genotype were trickle immunized by being orally fed a small infectious dose of E. tenella oocysts for 5 consecutive days. These naturally exposed birds were then challenged at different times between 5 and 24 days after the final dose, and the level of protection was assessed 6 days after challenge, using body weight gain and intestinal lesion scores. The duration of immunity in naturally exposed birds differed among the major histocompatibility complex lines. Trickle immunization of the B19B19 haplotype afforded the longest and strongest level of protection compared to the other two haplotypes tested. In addition, in vitro splenic and peripheral blood lymphocyte proliferative responses in trickle-immunized birds were measured against sporozoite, merozoite, and tissue culture-derived E. tenella parasite antigens isolated from the recently described SB-CEV-1/F7 established cell line. The lymphocytes obtained from B19B19 birds trickle immunized responded in vitro to the E. tenella-infected SB-CEV-1/F7 tissue culture-derived parasite antigen. Furthermore, antigen-specific immune responses appeared earlier in immune, challenged B19B19 birds than in their naive, challenged counterparts. The development of a model simulating natural immunization will serve as a foundation to further characterize both humoral and cell-mediated responses to E. tenella tissue culture-derived parasite antigens and to better understand host protective immune responses to avian coccidiosis. PMID:9119452

The role of myelin lipids in experimental allergic encephalomyelitis. Part 1. Influence on disease production by non-encephalitogenic doses of myelin basic protein.

PubMed

Hosein, Z Z; Gilbert, J J; Strejan, G H

1984-12-01

Hartley guinea pig central nervous system (CNS) myelin has been purified and fractionated into its protein and lipid components. Experimental allergic encephalomyelitis (EAE) was induced in juvenile strain 13 guinea pigs with both lyophilized and fresh 'wet' myelin. However, a larger dose of lyophilized myelin was required to induce chronic EAE. Total myelin lipids, galactocerebrosides, gangliosides, phospholipids or proteolipids were combined with a non-encephalitogenic dose of myelin basic protein (MBP) and injected in juvenile Hartley guinea pigs. No clinical or histological manifestations of disease were observed. Parameters of immune functions indicated that the total myelin lipids augmented cell-mediated immune responses as measured by in vitro lymphocyte transformation and by a significant decrease in the percentage of peripheral early T cells. Only the proteolipids elicited delayed hypersensitivity reactions. Animals that received the phospholipid-MBP combination showed no changes when compared to animals injected with MBP alone. The results suggest that although the myelin lipids did not act synergistically with a non-encephalitogenic dose of MBP to induce EAE, they induced immunological changes and potentiated the immune response to MBP.

Outcomes of a virtual-reality simulator-training programme on basic surgical skills in robot-assisted laparoscopic surgery.

PubMed

Phé, Véronique; Cattarino, Susanna; Parra, Jérôme; Bitker, Marc-Olivier; Ambrogi, Vanina; Vaessen, Christophe; Rouprêt, Morgan

2017-06-01

The utility of the virtual-reality robotic simulator in training programmes has not been clearly evaluated. Our aim was to evaluate the impact of a virtual-reality robotic simulator-training programme on basic surgical skills. A simulator-training programme in robotic surgery, using the da Vinci Skills Simulator, was evaluated in a population including junior and seasoned surgeons, and non-physicians. Their performances on robotic dots and suturing-skin pod platforms before and after virtual-simulation training were rated anonymously by surgeons experienced in robotics. 39 participants were enrolled: 14 medical students and residents in surgery, 14 seasoned surgeons, 11 non-physicians. Junior and seasoned surgeons' performances on platforms were not significantly improved after virtual-reality robotic simulation in any of the skill domains, in contrast to non-physicians. The benefits of virtual-reality simulator training on several tasks to basic skills in robotic surgery were not obvious among surgeons in our initial and early experience with the simulator. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of Simulated Microgravity on a Host-Pathogen System

NASA Technical Reports Server (NTRS)

Gilbert, Rachel; Lo, Rachel; Bhattacharya, Sharmila

2017-01-01

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Health Services in Afghanistan: USAID Continues Providing Millions of Dollars to the Ministry of Public Health Despite the Risk of Misuse of Funds

DTIC Science & Technology

2013-09-01

funding to the MoPH for the delivery of health services throughout Afghanistan, ranging from immunizations and prenatal care to hospital services...for the Afghan people through a two-tiered system : • Basic Package of Health Services provides primary health care services—such as immunizations and... prenatal care —at small and rural health clinics and forms the core of health service delivery for all primary care facilities in Afghanistan

Applied Research on Laparoscopic Simulator in the Resident Surgical Laparoscopic Operation Technical Training.

PubMed

Fu, Shangxi; Liu, Xiao; Zhou, Li; Zhou, Meisheng; Wang, Liming

2017-08-01

The purpose of this study was to estimate the effects of surgical laparoscopic operation course on laparoscopic operation skills after the simulated training for medical students with relatively objective results via data gained before and after the practice course of laparoscopic simulator of the resident standardized trainees. Experiment 1: 20 resident standardized trainees with no experience in laparoscopic surgery were included in the inexperienced group and finished simulated cholecystectomy according to simulator videos. Simulator data was collected (total operation time, path length, average speed of instrument movement, movement efficiency, number of perforations, the time cautery is applied without appropriate contact with adhesions, number of serious complications). Ten attending doctors were included in the experienced group and conducted the operation of simulated cholecystectomy directly. Data was collected with simulator. Data of two groups was compared. Experiment 2: Participants in inexperienced group were assigned to basic group (receiving 8 items of basic operation training) and special group (receiving 8 items of basic operation training and 4 items of specialized training), and 10 persons for each group. They received training course designed by us respectively. After training level had reached the expected target, simulated cholecystectomy was performed, and data was collected. Experimental data between basic group and special group was compared and then data between special group and experienced group was compared. Results of experiment 1 showed that there is significant difference between data in inexperienced group in which participants operated simulated cholecystectomy only according to instructors' teaching and operation video and data in experienced group. Result of experiment 2 suggested that, total operation time, number of perforations, number of serious complications, number of non-cauterized bleeding and the time cautery is applied without appropriate contact with adhesions in special group were all superior to those in basic group. There was no statistical difference on other data between special group and basic group. Comparing special group with experienced group, data of total operation time and the time cautery is applied without appropriate contact with adhesions in experienced group was superior to that in special group. There was no statistical difference on other data between special group and experienced group. Laparoscopic simulators are effective for surgical skills training. Basic courses could mainly improve operator's hand-eye coordination and perception of sense of the insertion depth for instruments. Specialized training courses could not only improve operator's familiarity with surgeries, but also reduce operation time and risk, and improve safety.

[Yellow fever: nurse counseling on travelers' health at basic health clinics].

PubMed

Mallet, Anna Paula; Dall'Agnol, Clarice Maria; Souza, Dirciara Barañano

2010-06-01

The objective of this qualitative, exploratory and descriptive study is to investigate the nursing practices related to travelers' health counseling. Data were collected from nursing professionals who work in the immunization sector of three Basic Health Units in Porto Alegre, Rio Grande do Sul, Brazil, using the technique of semi-structured interview. Five categories emerged from content analysis: care profile, health orientation, referrals to exchange the National Immunization Card for the International Certificate of Vaccination, information source and information material. The results signal the beginning of an organization of nursing practices focused on travelers' health, going beyond the focus on yellow fever. Failures in guidelines for acquisition of International Certificate of Vaccination still occur and information materials are missing. It points out to the need of broadening the discussion on travelers' health for a review of strategies for care organization and referrals for the construction of a specific policy.

Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

PubMed

Hess, Christoph; Kemper, Claudia

2016-08-16

Complement is well appreciated as a critical arm of innate immunity. It is required for the removal of invading pathogens and works by directly destroying them through the activation of innate and adaptive immune cells. However, complement activation and function is not confined to the extracellular space but also occurs within cells. Recent work indicates that complement activation regulates key metabolic pathways and thus can impact fundamental cellular processes, such as survival, proliferation, and autophagy. Newly identified functions of complement include a key role in shaping metabolic reprogramming, which underlies T cell effector differentiation, and a role as a nexus for interactions with other effector systems, in particular the inflammasome and Notch transcription-factor networks. This review focuses on the contributions of complement to basic processes of the cell, in particular the integration of complement with cellular metabolism and the potential implications in infection and other disease settings. Copyright © 2016 Elsevier Inc. All rights reserved.

The critical proportion of immune individuals needed to control hepatitis B

NASA Astrophysics Data System (ADS)

Ospina, Juan; Hincapié-Palacio, Doracelly

2016-05-01

We estimate the critical proportion of immunity (Pc) to control hepatitis B in Medellin - Colombia, based on a random population survey of 2077 individuals of 6-64 years of age. The force of infection (Fi) was estimated according to empirical data of susceptibility by age S(a), assuming a quadratic expression. Parameters were estimated by adjusting data to a nonlinear regression. Fi was defined by -(ds(a)/da)/s(a) and according to the form of the empirical curve S(a) we assume a quadratic expression given by S(a)= Ea2+Ba+C. Then we have the explicit expression for the accumulated Fi by age given by F(a) = -a(Ea+B)/c. The expression of average infection age A is obtained as A = L + EL3/(3C)+BL2/(2C) and the basic reproductive number R0 is obtained as R0 = 1 + 6C/(6C+2EL2+3BL). From the las result we obtain the Pc given by Pc= 6C/(12C+2EL2+3BL). Numerical simulations were performed with the age-susceptibility proportion and initial values (a=0.02, b=20, c=100), obtaining an adjusted coefficient of multiple determination of 64.83%. According to the best estimate, the algebraic expressions for S(a) and the Fi were derived. Using the result of Fi, we obtain A = 30, L =85; R0 CI 95%: 1.42 - 1.64 and Pc: 0-0.29. These results indicate that at the worst case, to maintain control of the disease should be immunes at least 30% of susceptible individuals. Similar results were obtained by sex and residential area.

Modular, high power, variable R dynamic electrical load simulator

NASA Technical Reports Server (NTRS)

Joncas, K. P.

1974-01-01

The design of a previously developed basic variable R load simulator was entended to increase its power dissipation and transient handling capabilities. The delivered units satisfy all design requirements, and provides for a high power, modular simulation capability uniquely suited to the simulation of complex load responses. In addition to presenting conclusions and recommendations and pertinent background information, the report covers program accomplishments; describes the simulator basic circuits, transfer characteristic, protective features, assembly, and specifications; indicates the results of simulator evaluation, including burn-in and acceptance testing; provides acceptance test data; and summarizes the monthly progress reports.

[The 40th anniversary of RAMS institute of human morphology].

PubMed

Kakturskiĭ, L V; Shakhlamov, V A

2002-01-01

Institute of Human Morphology of Russian Academy of Medical Sciences was established in 1961 and united efforts of morphologists of various profile--pathologists, cytologists, embryologists. The role of outstanding Russian morphologists and the first Institute heads is shown. Basic achievements in four research fields are characterized: in geographic pathology; structural basis of immune homeostasis in health and pathology; pathologic anatomy and pathogenesis of basic human diseases; human morpho- and embriogenesis in health and disease.

Second Breakdown of 18V Grounded Gate NMOS induced by the Kirk Effect under Electrostatic Discharge

NASA Astrophysics Data System (ADS)

Jeon, Byung-Chul; Lee, Seung-Chul; Han, Min-Koo

2003-09-01

Electrostatic Discharge (ESD) failure mechanisms of 18V grounded gate NMOS (GGNMOS) for liquid crystal display driver IC (LDI) applications are investigated and effects of layout design parameters on the ESD immunity level are analyzed. Experimental results show that 18V GGNMOS exhibits snapback characteristics and the ESD immunity level is rather high when XO (N-drift overlap over n+ source/drain) is sufficiently large, while GGNMOS does not exhibit the sustaining region and is very vulnerable to ESD stress when XO is relatively small. Simulation results show that the ESD failure mechanism of 18V GGNMOS could be the low-temperature second breakdown induced by the Kirk effect. It is inferred that a certain amount of XO is indispensable to ensure snapback characteristics and high ESD immunity level. Simulation results also show that the ESD immunity level is increased as drain contact to gate space (DCGS) is increased.

Glassy Dynamics in the Adaptive Immune Response Prevents Autoimmune Disease

NASA Astrophysics Data System (ADS)

Sun, Jun; Deem, Michael

2006-03-01

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

T-cell epitope prediction and immune complex simulation using molecular dynamics: state of the art and persisting challenges

PubMed Central

2010-01-01

Atomistic Molecular Dynamics provides powerful and flexible tools for the prediction and analysis of molecular and macromolecular systems. Specifically, it provides a means by which we can measure theoretically that which cannot be measured experimentally: the dynamic time-evolution of complex systems comprising atoms and molecules. It is particularly suitable for the simulation and analysis of the otherwise inaccessible details of MHC-peptide interaction and, on a larger scale, the simulation of the immune synapse. Progress has been relatively tentative yet the emergence of truly high-performance computing and the development of coarse-grained simulation now offers us the hope of accurately predicting thermodynamic parameters and of simulating not merely a handful of proteins but larger, longer simulations comprising thousands of protein molecules and the cellular scale structures they form. We exemplify this within the context of immunoinformatics. PMID:21067546

Quantifying the Impact of Natural Immunity on Rotavirus Vaccine Efficacy Estimates: A Clinical Trial in Dhaka, Bangladesh (PROVIDE) and a Simulation Study.

PubMed

Rogawski, Elizabeth T; Platts-Mills, James A; Colgate, E Ross; Haque, Rashidul; Zaman, K; Petri, William A; Kirkpatrick, Beth D

2018-03-05

The low efficacy of rotavirus vaccines in clinical trials performed in low-resource settings may be partially explained by acquired immunity from natural exposure, especially in settings with high disease incidence. In a clinical trial of monovalent rotavirus vaccine in Bangladesh, we compared the original per-protocol efficacy estimate to efficacy derived from a recurrent events survival model in which children were considered naturally exposed and potentially immune after their first rotavirus diarrhea (RVD) episode. We then simulated trial cohorts to estimate the expected impact of prior exposure on efficacy estimates for varying rotavirus incidence rates and vaccine efficacies. Accounting for natural immunity increased the per-protocol vaccine efficacy estimate against severe RVD from 63.1% (95% confidence interval [CI], 33.0%-79.7%) to 70.2% (95% CI, 44.5%-84.0%) in the postvaccination period, and original year 2 efficacy was underestimated by 14%. The simulations demonstrated that this expected impact increases linearly with RVD incidence, will be greatest for vaccine efficacies near 50%, and can reach 20% in settings with high incidence and low efficacy. High rotavirus incidence leads to predictably lower vaccine efficacy estimates due to the acquisition of natural immunity in unvaccinated children, and this phenomenon should be considered when comparing efficacy estimates across settings. NCT01375647.

Response of basic structural elements and B-52 structural components to simulated nuclear overpressure. Volume II-program data (basic structural elements). Final report, 1 June 1977-30 September 1979

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

Syring, R.P.; Grubb, R.L.

1979-09-30

This document reports on the following: (1) experimental determination of the response of 16 basic structural elements and 7 B-52 components to simulated nuclear overpressure environments (utilizing Sandia Corporation's Thunderpipe Shock Tube), (2) analysis of these test specimens utilizing the NOVA-2 computer program, and (3) correlation of test and analysis results.

GENASIS Basics: Object-oriented utilitarian functionality for large-scale physics simulations (Version 2)

NASA Astrophysics Data System (ADS)

Cardall, Christian Y.; Budiardja, Reuben D.

2017-05-01

GenASiS Basics provides Fortran 2003 classes furnishing extensible object-oriented utilitarian functionality for large-scale physics simulations on distributed memory supercomputers. This functionality includes physical units and constants; display to the screen or standard output device; message passing; I/O to disk; and runtime parameter management and usage statistics. This revision -Version 2 of Basics - makes mostly minor additions to functionality and includes some simplifying name changes.

The influence of the microbiota on the immune response to transplantation

PubMed Central

Bartman, Caroline; Chong, Anita S.; Alegre, Maria-Luisa

2015-01-01

Purpose of review In the past decade, appreciation of the important effects of commensal microbes on immunity has grown exponentially. The effect of the microbiota on transplantation has only recently begun to be explored; however, our understanding of the mechanistic details of host-microbe interactions is still lacking. Recent findings It has become clear that transplantation is associated with changes in the microbiota in many different settings although what clinical events and therapeutic interventions contribute to these changes remains to be parsed out. Research groups have begun to identify associations between specific communities of organisms and transplant outcomes but it remains to be established whether microbial changes precede or follow transplant rejection episodes. Finally, results from continuing exploration of basic mechanisms by which microbial communities affect innate and adaptive immunity in various animal models of disease continues to inform research on the microbiota’s effects on immune responses against transplanted organs. Summary Commensal microbes may alter immune responses to organ transplantation, but direct experiments are only beginning in the field to identify species and immune pathways responsible for these putative effects. PMID:25563985

Immunity to fish rhabdoviruses

USGS Publications Warehouse

Purcell, Maureen K.; Laing, Kerry J.; Winton, James R.

2012-01-01

Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non-virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

Immunity to fish rhabdoviruses.

PubMed

Purcell, Maureen K; Laing, Kerry J; Winton, James R

2012-01-01

Members of the family Rhabdoviridae are single-stranded RNA viruses and globally important pathogens of wild and cultured fish and thus relatively well studied in their respective hosts or other model systems. Here, we review the protective immune mechanisms that fish mount in response to rhabdovirus infections. Teleost fish possess the principal components of innate and adaptive immunity found in other vertebrates. Neutralizing antibodies are critical for long-term protection from fish rhabdoviruses, but several studies also indicate a role for cell-mediated immunity. Survival of acute rhabdoviral infection is also dependent on innate immunity, particularly the interferon (IFN) system that is rapidly induced in response to infection. Paradoxically, rhabdoviruses are sensitive to the effects of IFN but virulent rhabdoviruses can continue to replicate owing to the abilities of the matrix (M) protein to mediate host-cell shutoff and the non‑virion (NV) protein to subvert programmed cell death and suppress functional IFN. While many basic features of the fish immune response to rhabdovirus infections are becoming better understood, much less is known about how factors in the environment affect the ecology of rhabdovirus infections in natural populations of aquatic animals.

Impact of early treatment programs on HIV epidemics: An immunity-based mathematical model.

PubMed

Rahman, S M Ashrafur; Vaidya, Naveen K; Zou, Xingfu

2016-10-01

While studies on pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) have demonstrated substantial advantages in controlling HIV transmission, the overall benefits of the programs with early initiation of antiretroviral therapy (ART) have not been fully understood and are still on debate. Here, we develop an immunity-based (CD4+ T cell count based) mathematical model to study the impacts of early treatment programs on HIV epidemics and the overall community-level immunity. The model is parametrized using the HIV prevalence data from South Africa and fully analyzed for stability of equilibria and infection persistence criteria. Using our model, we evaluate the effects of early treatment on the new infection transmission, disease death, basic reproduction number, HIV prevalence, and the community-level immunity. Our model predicts that the programs with early treatments significantly reduce the new infection transmission and increase the community-level immunity, but the treatments alone may not be enough to eliminate HIV epidemics. These findings, including the community-level immunity, might provide helpful information for proper implementation of HIV treatment programs. Copyright © 2016 Elsevier Inc. All rights reserved.

Vaccine financing in Nigeria: are we making progress towards self-financing/sustenance?

PubMed

Faniyan, Olumide; Opara, Chidiabere; Oyinade, Akinyede; Botchway, Pamela; Soyemi, Kenneth

2017-01-01

Nigeria has an estimated population of 186 million with 23% of eligible children aged 12-23 months fully immunized. Government spending on routine immunization per surviving infant has declined since 2006 meaning the immunization budget needs to improve. By 2020, Nigeria will be ineligible for additional Global Alliance for Vaccination and Immunization (Gavi) grants and will be facing an annual vaccine bill of around US$426.3m. There are several potential revenue sources that could be utilized to fill the potential funding gap, these are however subject to timely legislation and appropriation of funds by the legislative body. Innovative funding sources that should be considered include tiered levies on tele-communications, airline, hotel, alcohol, tobacco, sugar beverage taxes, lottery sales, crowd-sourcing, optimized federal state co-financing etc. To demonstrate monthly income that will be derived from a single tax revenue source, we modelled using Monte Carlo simulation trials the Communication Service Tax that is being introduced by the National Assembly. We used number of active telephone subscribers, penetration ratio, monthly charges, and percent of immunization levy as model scenario inputs and dollars generated monthly as output. The simulation generated a modest mean (SD) monthly amount of $3,649,289.38 ($1,789,651); 88% certainty range $1,282,719.90 to $7,450,906.26. The entire range for the simulation was $528,903.26 to $7,966,287.26 with a standard error of mean of $17,896.52. Sensitivity analysis revealed that percentage of immunization levy contributed 97.9 percent of the variance in the model, number of active subscribers and charges per month contributed 1.5%, and 0.6% respectively. Our modest simulation analysis demonstrated the potential to raise revenue from one possible tax source; when combined, the revenue sources will potentially surpass Nigeria's long-term financing needs. The ROI of vaccine should supersede all other considerations and prompt urgent activities to cover the impending finance coverage gap.

Vaccine financing in Nigeria: are we making progress towards self-financing/sustenance?

PubMed Central

Faniyan, Olumide; Opara, Chidiabere; Oyinade, Akinyede; Botchway, Pamela; Soyemi, Kenneth

2017-01-01

Nigeria has an estimated population of 186 million with 23% of eligible children aged 12-23 months fully immunized. Government spending on routine immunization per surviving infant has declined since 2006 meaning the immunization budget needs to improve. By 2020, Nigeria will be ineligible for additional Global Alliance for Vaccination and Immunization (Gavi) grants and will be facing an annual vaccine bill of around US$426.3m. There are several potential revenue sources that could be utilized to fill the potential funding gap, these are however subject to timely legislation and appropriation of funds by the legislative body. Innovative funding sources that should be considered include tiered levies on tele-communications, airline, hotel, alcohol, tobacco, sugar beverage taxes, lottery sales, crowd-sourcing, optimized federal state co-financing etc. To demonstrate monthly income that will be derived from a single tax revenue source, we modelled using Monte Carlo simulation trials the Communication Service Tax that is being introduced by the National Assembly. We used number of active telephone subscribers, penetration ratio, monthly charges, and percent of immunization levy as model scenario inputs and dollars generated monthly as output. The simulation generated a modest mean (SD) monthly amount of $3,649,289.38 ($1,789,651); 88% certainty range $1,282,719.90 to $7,450,906.26. The entire range for the simulation was $528,903.26 to $7,966,287.26 with a standard error of mean of $17,896.52. Sensitivity analysis revealed that percentage of immunization levy contributed 97.9 percent of the variance in the model, number of active subscribers and charges per month contributed 1.5%, and 0.6% respectively. Our modest simulation analysis demonstrated the potential to raise revenue from one possible tax source; when combined, the revenue sources will potentially surpass Nigeria’s long-term financing needs. The ROI of vaccine should supersede all other considerations and prompt urgent activities to cover the impending finance coverage gap. PMID:29296144

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.

[Invitation to the immunoglobulin world].

PubMed

Mafune, Naoki

2010-04-01

One of the most basic characteristics of the organism is to recognize self and non-self. Immune system is a typical system that fulfills this characteristic, and the immunoglobulins play important roles in it. The immunoglobulins circulating in internal or secreting to external space of the body, are basically characterized as a soluble form of cell surface receptors. The immunoglobulin has two kinds of domains. One is the variable domain that binds the antigen and the other is the constant domain that has the effecter functions. The immunoglobulin molecule can be obviously identified in vertebrates. In mammals, five immunoglobulin classes, IgG, IgA, IgM, IgD and IgE are classified. It is important to recognize that our immune system assign immunological roles among classes especially between IgG and IgA after class switch from IgM. IgG, the major immunoglobulin in plasma or extra vascular spaces, has the most versatile function of immunoglobulin molecules; such as placenta transfer, complement fixation and cell binding. On the other hand, IgA, the major immunoglobulin in secretions, does not show any complement fixation unless denatured. These facts implicate an aggressive characteristic of IgG in systemic immune response inside of the body, and a defensive characteristic of IgA in mucosal immune response on the surface of the body. Further, they allot the immunological roles to fetus or baby, in other words, IgG transferred from placenta protects fetus and newborn, and then IgA secreted in milk protects baby from mucosal invasion of pathogenic organisms.

Influence of the Cholinergic System on the Immune Response of Teleost Fishes: Potential Model in Biomedical Research

PubMed Central

Toledo-Ibarra, G. A.; Rojas-Mayorquín, A. E.; Girón-Pérez, M. I.

2013-01-01

Fishes are the phylogenetically oldest vertebrate group, which includes more than one-half of the vertebrates on the planet; additionally, many species have ecological and economic importance. Fish are the first evolved group of organisms with adaptive immune mechanisms; consequently, they are an important link in the evolution of the immune system, thus a potential model for understanding the mechanisms of immunoregulation. Currently, the influence of the neurotransmitter acetylcholine (ACh) on the cells of the immune system is widely studied in mammalian models, which have provided evidence on ACh production by immune cells (the noncholinergic neuronal system); however, these neuroimmunomodulation mechanisms in fish and lower vertebrates are poorly studied. Therefore, the objective of this review paper was to analyze the influence of the cholinergic system on the immune response of teleost fish, which could provide information concerning the possibility of bidirectional communication between the nervous and immune systems in these organisms and provide data for a better understanding of basic issues in neuroimmunology in lower vertebrates, such as bony fishes. Thus, the use of fish as a model in biomedical research may contribute to a better understanding of human diseases and diseases in other animals. PMID:24324508

Influence of the cholinergic system on the immune response of teleost fishes: potential model in biomedical research.

PubMed

Toledo-Ibarra, G A; Rojas-Mayorquín, A E; Girón-Pérez, M I

2013-01-01

Fishes are the phylogenetically oldest vertebrate group, which includes more than one-half of the vertebrates on the planet; additionally, many species have ecological and economic importance. Fish are the first evolved group of organisms with adaptive immune mechanisms; consequently, they are an important link in the evolution of the immune system, thus a potential model for understanding the mechanisms of immunoregulation. Currently, the influence of the neurotransmitter acetylcholine (ACh) on the cells of the immune system is widely studied in mammalian models, which have provided evidence on ACh production by immune cells (the noncholinergic neuronal system); however, these neuroimmunomodulation mechanisms in fish and lower vertebrates are poorly studied. Therefore, the objective of this review paper was to analyze the influence of the cholinergic system on the immune response of teleost fish, which could provide information concerning the possibility of bidirectional communication between the nervous and immune systems in these organisms and provide data for a better understanding of basic issues in neuroimmunology in lower vertebrates, such as bony fishes. Thus, the use of fish as a model in biomedical research may contribute to a better understanding of human diseases and diseases in other animals.

The differential expression of IL-4 and IL-13 and its impact on type-2 immunity.

PubMed

Bao, Katherine; Reinhardt, R Lee

2015-09-01

Allergic disease represents a significant global health burden, and disease incidence continues to rise in urban areas of the world. As such, a better understanding of the basic immune mechanisms underlying disease pathology are key to developing therapeutic interventions to both prevent disease onset as well as to ameliorate disease morbidity in those individuals already suffering from a disorder linked to type-2 inflammation. Two factors central to type-2 immunity are interleukin (IL)-4 and IL-13, which have been linked to virtually all major hallmarks associated with type-2 inflammation. Therefore, IL-4 and IL-13 and their regulatory pathways represent ideal targets to suppress disease. Despite sharing many common regulatory pathways and receptors, these cytokines perform very distinct functions during a type-2 immune response. This review summarizes the literature surrounding the function and expression of IL-4 and IL-13 in CD4+ T cells and innate immune cells. It highlights recent findings in vivo regarding the differential expression and non-canonical regulation of IL-4 and IL-13 in various immune cells, which likely play important and underappreciated roles in type-2 immunity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Virtual reality simulators and training in laparoscopic surgery.

PubMed

Yiannakopoulou, Eugenia; Nikiteas, Nikolaos; Perrea, Despina; Tsigris, Christos

2015-01-01

Virtual reality simulators provide basic skills training without supervision in a controlled environment, free of pressure of operating on patients. Skills obtained through virtual reality simulation training can be transferred on the operating room. However, relative evidence is limited with data available only for basic surgical skills and for laparoscopic cholecystectomy. No data exist on the effect of virtual reality simulation on performance on advanced surgical procedures. Evidence suggests that performance on virtual reality simulators reliably distinguishes experienced from novice surgeons Limited available data suggest that independent approach on virtual reality simulation training is not different from proctored approach. The effect of virtual reality simulators training on acquisition of basic surgical skills does not seem to be different from the effect the physical simulators. Limited data exist on the effect of virtual reality simulation training on the acquisition of visual spatial perception and stress coping skills. Undoubtedly, virtual reality simulation training provides an alternative means of improving performance in laparoscopic surgery. However, future research efforts should focus on the effect of virtual reality simulation on performance in the context of advanced surgical procedure, on standardization of training, on the possibility of synergistic effect of virtual reality simulation training combined with mental training, on personalized training. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

A Large Scale Dynamical System Immune Network Modelwith Finite Connectivity

NASA Astrophysics Data System (ADS)

Uezu, T.; Kadono, C.; Hatchett, J.; Coolen, A. C. C.

We study a model of an idiotypic immune network which was introduced by N. K. Jerne. It is known that in immune systems there generally exist several kinds of immune cells which can recognize any particular antigen. Taking this fact into account and assuming that each cell interacts with only a finite number of other cells, we analyze a large scale immune network via both numerical simulations and statistical mechanical methods, and show that the distribution of the concentrations of antibodies becomes non-trivial for a range of values of the strength of the interaction and the connectivity.

An improved immune algorithm for optimizing the pulse width modulation control sequence of inverters

NASA Astrophysics Data System (ADS)

Sheng, L.; Qian, S. Q.; Ye, Y. Q.; Wu, Y. H.

2017-09-01

In this article, an improved immune algorithm (IIA), based on the fundamental principles of the biological immune system, is proposed for optimizing the pulse width modulation (PWM) control sequence of a single-phase full-bridge inverter. The IIA takes advantage of the receptor editing and adaptive mutation mechanisms of the immune system to develop two operations that enhance the population diversity and convergence of the proposed algorithm. To verify the effectiveness and examine the performance of the IIA, 17 cases are considered, including fixed and disturbed resistances. Simulation results show that the IIA is able to obtain an effective PWM control sequence. Furthermore, when compared with existing immune algorithms (IAs), genetic algorithms (GAs), a non-traditional GA, simplified simulated annealing, and a generalized Hopfield neural network method, the IIA can achieve small total harmonic distortion (THD) and large magnitude. Meanwhile, a non-parametric test indicates that the IIA is significantly better than most comparison algorithms. Supplemental data for this article can be accessed at http://dx.doi.org/10.1080/0305215X.2016.1250894.

Bivalve immunity and response to infections: Are we looking at the right place?

PubMed

Allam, Bassem; Pales Espinosa, Emmanuelle

2016-06-01

Significant progress has been made in the understanding of cellular and molecular mediators of immunity in invertebrates in general and bivalve mollusks in particular. Despite this information, there is a lack of understanding of factors affecting animal resistance and specific responses to infections. This in part results from limited consideration of the spatial (and to some extent temporal) heterogeneity of immune responses and very limited information on host-pathogen (and microbes in general) interactions at initial encounter/colonization sites. Of great concern is the fact that most studies on molluscan immunity focus on the circulating hemocytes and the humoral defense factors in the plasma while most relevant host-microbe interactions occur at mucosal interfaces. This paper summarizes information available on the contrasting value of information available on focal and systemic immune responses in infected bivalves, and highlights the role of mucosal immune factors in host-pathogen interactions. Available information underlines the diversity of immune effectors at molluscan mucosal interfaces and highlights the tailored immune response to pathogen stimuli. This context raises fascinating basic research questions around host-microbe crosstalk and feedback controls of these interactions and may lead to novel disease mitigation strategies and improve the assessment of resistant crops or the screening of probiotic candidates. Copyright © 2016 Elsevier Ltd. All rights reserved.

Basics of cancer immunotherapy.

PubMed

Fujioka, Yuki; Nishikawa, Hiroyoshi

2016-01-01

The immune system is the body's defense against infectious organisms and other invaders including cancer cells. Cancer immunotherapy, which employs our own immune systems to attack cancer cells, is now emerging as a promising modality of cancer treatment based upon the clinical successes of immune checkpoint blockade and adoptive T cell transfer. In hematologic malignancies, clinical application of anti-PD-1 mAb and CAR (chimeric antigen receptor) T therapy is now being extensively tested in Hodgkin's disease, multiple myeloma, and CD19 + acute lymphocytic leukemia. In sharp contrast to conventional anti-cancer reagents which directly kill cancer cells, cancer immunotherapy activates various types of immune effector cells to attack cancer cells. However, more than half of the treated patients showed no activation of anti-tumor CD8 + killer T cells and CD4 + helper T cells and failed to respond to immune therapies such as immune checkpoint blockade, even when administered in combination regimens. Thus, development of novel immunotherapies to achieve more effective activation of anti-cancer immunity and immuno-monitoring of biomarkers, allowing proper evaluation of immune responses in cancer patients in order to detect responders, are urgent issues. Additionally, we must pay attention to characteristic immunological side effects not observed following treatment with conventional anti-cancer reagents. Herein, we present a summary outline and discuss the future direction of cancer immunotherapy.

Basic and applied problems in developmental biology and immunobiology of cestode infections: Hymenolepis, Taenia and Echinococcus.

PubMed

Ito, A

2015-02-01

Differentiation and development of parasites, including longevity in host animals, are thought to be governed by host-parasite interactions. In this review, several topics on the developmental biology of cestode infections are discussed from immunobiological perspective with a focus on Hymenolepis, Taenia and Echinococcus infections. The basic premise of this review is that 'differentiation and development of cestodes' are somehow affected by host immune responses with an evolutionary history. © 2014 John Wiley & Sons Ltd.

Miming the cancer-immune system competition by kinetic Monte Carlo simulations

NASA Astrophysics Data System (ADS)

Bianca, Carlo; Lemarchand, Annie

2016-10-01

In order to mimic the interactions between cancer and the immune system at cell scale, we propose a minimal model of cell interactions that is similar to a chemical mechanism including autocatalytic steps. The cells are supposed to bear a quantity called activity that may increase during the interactions. The fluctuations of cell activity are controlled by a so-called thermostat. We develop a kinetic Monte Carlo algorithm to simulate the cell interactions and thermalization of cell activity. The model is able to reproduce the well-known behavior of tumors treated by immunotherapy: the first apparent elimination of the tumor by the immune system is followed by a long equilibrium period and the final escape of cancer from immunosurveillance.

Response of basic structural elements and B-52 structural components to simulated nuclear overpressure. Volume I-program description and results (basic structural elements). Final report, 1 June 1977-30 September 1979

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

Syring, R.P.; Grubb, R.L.

1979-09-30

This document reports on the following: (1) experimental determination of the response of 16 basic structural elements and 7 B-52 components to simulated nuclear overpressure environments (utilizing Sandia Corporation's Thunderpipe Shock Tube), (2) analysis of these test specimens utilizing the NOVA-2 computer program, and (3) correlation of test and analysis results.

Basophil (close-up) (image)

MedlinePlus

... a specific type of white blood cell. These cells are readily stained with basic dyes (this is where the name comes from). Note the dark grains inside the cellular fluid (cytoplasm) of this ... white blood cells but are important parts of the body's immune ...

PEG-PLA-PEG block copolymeric nanoparticles for oral immunization against hepatitis B.

PubMed

Jain, Arvind K; Goyal, Amit K; Mishra, Neeraj; Vaidya, Bhuvaneshwar; Mangal, Sharad; Vyas, Suresh P

2010-03-15

PLA/PLGA nanoparticles are well known as efficient vaccine delivery systems, but they have got limitation in oral vaccine delivery because of their sensitivity to harsh gastric environment. The aim of present study was to improve the stability of PLA nanoparticles in such environment by copolymerizing PLA with PEG. Nanoparticles were formulated using different block copolymers AB, ABA and BAB (where 'A' is PLA and 'B' is PEG) encapsulating hepatitis B surface antigen (HBsAg) to evaluate their efficacy as oral vaccine delivery system. The results of in vitro studies engrave the efficiency of copolymeric nanoparticles to retain encapsulated antigen and average particle size even after 2 h incubation in simulated gastric fluid and simulated intestinal fluid. Fluorescence microscopic studies indicated efficient uptake of copolymeric nanoparticles by gut mucosa of immunized mice model as compared to control. Finally copolymeric and PLA nanoparticles, encapsulating HBsAg, were evaluated for their adjuvancity in generating immune response after oral administration. PLA nanoparticles could not generate an effective immune response due to stability issues. On the other hand, oral administration of copolymeric nanoparticles exhibited effective levels of humoral immunity along with the mucosal (sIgA) and cellular immune response (T(H)1). The results of in vitro and in vivo studies demonstrate that BAB nanoparticles depict enhanced mucosal uptake leading to effective immune response as compared to other copolymeric nanoparticles. Present study indicates the efficacy of BAB nanoparticles as a promising carrier for oral immunization. 2009 Elsevier B.V. All rights reserved.

Osteopathic lymphatic pump techniques to enhance immunity and treat pneumonia.

PubMed

Hodge, Lisa M

2012-03-01

Pneumonia is a common cause of morbidity and mortality worldwide. While antibiotics are generally effective for the treatment of infection, the emergence of resistant strains of bacteria threatens their success. The osteopathic medical profession has designed a set of manipulative techniques called lymphatic pump techniques (LPT), to enhance the flow of lymph through the lymphatic system. Clinically, LPT is used to treat infection and oedemaand might be an effective adjuvant therapy in patients with pneumonia.The immune system uses the lymphatic and blood systems to survey to rid the body of pathogens; however, only recently have the effects of LPT on the lymphatic and immune systems been investigated. This short review highlightsclinical and basic science research studies that support the use of LPT to enhance the lymphatic and immune systems and treat pneumonia, and discusses the potential mechanisms by which LPT benefits patients with pneumonia.

Low dosages: new chemotherapeutic weapons on the battlefield of immune-related disease

PubMed Central

Liu, Jing; Zhao, Jie; Hu, Liang; Cao, Yuchun; Huang, Bo

2011-01-01

Chemotherapeutic drugs eliminate tumor cells at relatively high doses and are considered weapons against tumors in clinics and hospitals. However, despite their ability to induce cellular apoptosis, chemotherapeutic drugs should probably be regarded more as a class of cell regulators than cell killers, if the dosage used and the fact that their targets are involved in basic molecular events are considered. Unfortunately, the regulatory properties of chemotherapeutic drugs are usually hidden or masked by the massive cell death induced by high doses. Recent evidence has begun to suggest that low dosages of chemotherapeutic drugs might profoundly regulate various intracellular aspects of normal cells, especially immune cells. Here, we discuss the immune regulatory roles of three kinds of chemotherapeutic drugs under low-dose conditions and propose low dosages as potential new chemotherapeutic weapons on the battlefield of immune-related disease. PMID:21423201

Autoimmunity in the pathogenesis and treatment of keratoconjunctivitis sicca.

PubMed

Liu, Katy C; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M

2014-01-01

Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. Keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren's syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets.

CMV and Immunosenescence: from basics to clinics

PubMed Central

2012-01-01

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates “immunosenescence”. This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop. PMID:23114110

Clinical implications of basic science discoveries: janus resurrected--two faces of B cell and plasma cell biology.

PubMed

Woodle, E S; Rothstein, D M

2015-01-01

B cells play a complex role in the immune response. In addition to giving rise to plasma cells (PCs) and promoting T cell responses via antigen presentation, they perform immunoregulatory functions. This knowledge has created concerns regarding nonspecific B cell depletional therapy because of the potential to paradoxically augment immune responses. Recent studies now indicate that PCs have immune functions beyond immunoglobulin synthesis. Evidence for a new role for PCs as potent regulatory cells (via IL-10 and IL-35 production) is discussed including the implications for PC-targeted therapies currently being developed for clinical transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

DNA vaccination for prostate cancer, from preclinical to clinical trials - where we stand?

PubMed Central

2012-01-01

Development of various vaccines for prostate cancer (PCa) is becoming an active research area. PCa vaccines are perceived to have less toxicity compared with the available cytotoxic agents. While various immune-based strategies can elicit anti-tumour responses, DNA vaccines present increased efficacy, inducing both humoural and cellular immunity. This immune activation has been proven effective in animal models and initial clinical trials are encouraging. However, to validate the role of DNA vaccination in currently available PCa management paradigms, strong clinical evidence is still lacking. This article provides an overview of the basic principles of DNA vaccines and aims to provide a summary of preclinical and clinical trials outlining the benefits of this immunotherapy in the management of PCa. PMID:23046944

CMV and Immunosenescence: from basics to clinics.

PubMed

Solana, Rafael; Tarazona, Raquel; Aiello, Allison E; Akbar, Arne N; Appay, Victor; Beswick, Mark; Bosch, Jos A; Campos, Carmen; Cantisán, Sara; Cicin-Sain, Luka; Derhovanessian, Evelyna; Ferrando-Martínez, Sara; Frasca, Daniela; Fulöp, Tamas; Govind, Sheila; Grubeck-Loebenstein, Beatrix; Hill, Ann; Hurme, Mikko; Kern, Florian; Larbi, Anis; López-Botet, Miguel; Maier, Andrea B; McElhaney, Janet E; Moss, Paul; Naumova, Elissaveta; Nikolich-Zugich, Janko; Pera, Alejandra; Rector, Jerrald L; Riddell, Natalie; Sanchez-Correa, Beatriz; Sansoni, Paolo; Sauce, Delphine; van Lier, Rene; Wang, George C; Wills, Mark R; Zieliński, Maciej; Pawelec, Graham

2012-10-31

Alone among herpesviruses, persistent Cytomegalovirus (CMV) markedly alters the numbers and proportions of peripheral immune cells in infected-vs-uninfected people. Because the rate of CMV infection increases with age in most countries, it has been suggested that it drives or at least exacerbates "immunosenescence". This contention remains controversial and was the primary subject of the Third International Workshop on CMV & Immunosenescence which was held in Cordoba, Spain, 15-16th March, 2012. Discussions focused on several main themes including the effects of CMV on adaptive immunity and immunosenescence, characterization of CMV-specific T cells, impact of CMV infection and ageing on innate immunity, and finally, most important, the clinical implications of immunosenescence and CMV infection. Here we summarize the major findings of this workshop.

A mathematical model for foreign body reactions in 2D.

PubMed

Su, Jianzhong; Gonzales, Humberto Perez; Todorov, Michail; Kojouharov, Hristo; Tang, Liping

2011-02-01

The foreign body reactions are commonly referred to the network of immune and inflammatory reactions of human or animals to foreign objects placed in tissues. They are basic biological processes, and are also highly relevant to bioengineering applications in implants, as fibrotic tissue formations surrounding medical implants have been found to substantially reduce the effectiveness of devices. Despite of intensive research on determining the mechanisms governing such complex responses, few mechanistic mathematical models have been developed to study such foreign body reactions. This study focuses on a kinetics-based predictive tool in order to analyze outcomes of multiple interactive complex reactions of various cells/proteins and biochemical processes and to understand transient behavior during the entire period (up to several months). A computational model in two spatial dimensions is constructed to investigate the time dynamics as well as spatial variation of foreign body reaction kinetics. The simulation results have been consistent with experimental data and the model can facilitate quantitative insights for study of foreign body reaction process in general.

Qualitative analysis of a stochastic epidemic model with specific functional response and temporary immunity

NASA Astrophysics Data System (ADS)

Hattaf, Khalid; Mahrouf, Marouane; Adnani, Jihad; Yousfi, Noura

2018-01-01

In this paper, we propose a stochastic delayed epidemic model with specific functional response. The time delay represents temporary immunity period, i.e., time from recovery to becoming susceptible again. We first show that the proposed model is mathematically and biologically well-posed. Moreover, the extinction of the disease and the persistence in the mean are established in the terms of a threshold value R0S which is smaller than the basic reproduction number R0 of the corresponding deterministic system.

Garlic Revisited: Therapeutic for the Major Diseases of Our Times?

PubMed Central

Abdullah, Tariq H.; Kandil, O.; Elkadi, A.; Carter, J.

1988-01-01

Garlic may play an invaluable role in the prevention and therapy of the major causes of death. Anecdotal, basic, and clinical research data are confirming the efficacy of this herb in the treatment of hyperlipemia, cancer, heavy-metal intoxication, infectious diseases, hypertension, free-radical damage, and immune deficiency states. Garlic's broad antimicrobial spectra and its ability to modulate immunity may play a strategic role in the acquired immunodeficiency syndrome pandemic. A review of the literature supports a greater scrutiny of this herb's therapeutic potential. PMID:3290502

A structurally oriented simulation system

NASA Technical Reports Server (NTRS)

Aran, Z.

1973-01-01

The computer program SOSS (Structurally Oriented Simulation System) is designed to be used as an experimental aid in the study of reliable systems. Basically, SOSS can simulate the structure and behavior of a discrete-time, finite-state, time-invariant system at various levels of structural definition. A general description of the program is given along with its modes of operation, command language of the basic system, future features to be incorporated in SOSS, and an example of usage.

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection

PubMed Central

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close “neighborhood” of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa. PMID:26327290

Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.

PubMed

Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

2015-01-01

Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.

Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November–December 2017

PubMed Central

Matsuyama, Ryota; Lee, Hyojung; Yamaguchi, Takayuki; Tsuzuki, Shinya

2018-01-01

Background A Rohingya refugee camp in Cox’s Bazar, Bangladesh experienced a large-scale diphtheria epidemic in 2017. The background information of previously immune fraction among refugees cannot be explicitly estimated, and thus we conducted an uncertainty analysis of the basic reproduction number, R0. Methods A renewal process model was devised to estimate the R0 and ascertainment rate of cases, and loss of susceptible individuals was modeled as one minus the sum of initially immune fraction and the fraction naturally infected during the epidemic. To account for the uncertainty of initially immune fraction, we employed a Latin Hypercube sampling (LHS) method. Results R0 ranged from 4.7 to 14.8 with the median estimate at 7.2. R0 was positively correlated with ascertainment rates. Sensitivity analysis indicated that R0 would become smaller with greater variance of the generation time. Discussion Estimated R0 was broadly consistent with published estimate from endemic data, indicating that the vaccination coverage of 86% has to be satisfied to prevent the epidemic by means of mass vaccination. LHS was particularly useful in the setting of a refugee camp in which the background health status is poorly quantified. PMID:29629244

Daidzein enhances immune function in late lactation cows under heat stress.

PubMed

Liu, De-Yi; He, Shao-Jun; Liu, Shi-Qing; Tang, Yi-Guo; Jin, Er-Hui; Chen, Hui-Liang; Li, Sheng-He; Zhong, Liang-Ting

2014-01-01

Heat stress decreases natural immunity making cows more vulnerable to diseases. A previous study reported that daidzein can enhance animal resistance to heat stress and regulate animal immunocompetence. However, it is unclear whether daidzein regulates the immune performance of late lactation cows under heat stress. In this study, late lactation cows in four groups were raised in hot weather and fed with basic diet, basic diet plus 200, 300, 400 mg/day daidzein, respectively, and the experimental period was 60 days. Blood was collected to examine the changes of serum total protein (TP), albumin (ALB), immunoglobulin G (IgG), interferon alpha (IFN-α), and interleukin-2 (IL-2). We found the levels of serum IgG and INF-α were significantly higher in late lactation cows after 300 and 400 mg/day daidzein treatment compared to those in the control group and 200 mg/day daidzein treatment (P < 0.05 or P < 0.01). Moreover, 300 and 400 mg/day daidzein treatment markedly increased serum IL-2 (P < 0.01), while the levels of serum TP and ALB were not changed by any concentration of daidzein treatment (P > 0.05). Daidzein can enhance the immunocompetence of late lactation cows and strengthen cow resistance to heat stress. © 2013 Japanese Society of Animal Science.

Uncertainty and sensitivity analysis of the basic reproduction number of diphtheria: a case study of a Rohingya refugee camp in Bangladesh, November-December 2017.

PubMed

Matsuyama, Ryota; Akhmetzhanov, Andrei R; Endo, Akira; Lee, Hyojung; Yamaguchi, Takayuki; Tsuzuki, Shinya; Nishiura, Hiroshi

2018-01-01

A Rohingya refugee camp in Cox's Bazar, Bangladesh experienced a large-scale diphtheria epidemic in 2017. The background information of previously immune fraction among refugees cannot be explicitly estimated, and thus we conducted an uncertainty analysis of the basic reproduction number, R 0 . A renewal process model was devised to estimate the R 0 and ascertainment rate of cases, and loss of susceptible individuals was modeled as one minus the sum of initially immune fraction and the fraction naturally infected during the epidemic. To account for the uncertainty of initially immune fraction, we employed a Latin Hypercube sampling (LHS) method. R 0 ranged from 4.7 to 14.8 with the median estimate at 7.2. R 0 was positively correlated with ascertainment rates. Sensitivity analysis indicated that R 0 would become smaller with greater variance of the generation time. Estimated R 0 was broadly consistent with published estimate from endemic data, indicating that the vaccination coverage of 86% has to be satisfied to prevent the epidemic by means of mass vaccination. LHS was particularly useful in the setting of a refugee camp in which the background health status is poorly quantified.

Very Good Medicine: Indigenous Humor and Laughter

ERIC Educational Resources Information Center

Mala, Cynthia Lindquist

2016-01-01

Humor is not only instinctive and a basic human need, but it also is very good medicine. Laughter boosts the immune system, lowers blood pressure, reduces stress hormones, and is linked to healthy functioning organs. [This article was written with Mylo Redwater Smith.

Multiscale modeling of mucosal immune responses

PubMed Central

2015-01-01

Computational modeling techniques are playing increasingly important roles in advancing a systems-level mechanistic understanding of biological processes. Computer simulations guide and underpin experimental and clinical efforts. This study presents ENteric Immune Simulator (ENISI), a multiscale modeling tool for modeling the mucosal immune responses. ENISI's modeling environment can simulate in silico experiments from molecular signaling pathways to tissue level events such as tissue lesion formation. ENISI's architecture integrates multiple modeling technologies including ABM (agent-based modeling), ODE (ordinary differential equations), SDE (stochastic modeling equations), and PDE (partial differential equations). This paper focuses on the implementation and developmental challenges of ENISI. A multiscale model of mucosal immune responses during colonic inflammation, including CD4+ T cell differentiation and tissue level cell-cell interactions was developed to illustrate the capabilities, power and scope of ENISI MSM. Background Computational techniques are becoming increasingly powerful and modeling tools for biological systems are of greater needs. Biological systems are inherently multiscale, from molecules to tissues and from nano-seconds to a lifespan of several years or decades. ENISI MSM integrates multiple modeling technologies to understand immunological processes from signaling pathways within cells to lesion formation at the tissue level. This paper examines and summarizes the technical details of ENISI, from its initial version to its latest cutting-edge implementation. Implementation Object-oriented programming approach is adopted to develop a suite of tools based on ENISI. Multiple modeling technologies are integrated to visualize tissues, cells as well as proteins; furthermore, performance matching between the scales is addressed. Conclusion We used ENISI MSM for developing predictive multiscale models of the mucosal immune system during gut inflammation. Our modeling predictions dissect the mechanisms by which effector CD4+ T cell responses contribute to tissue damage in the gut mucosa following immune dysregulation. PMID:26329787

Multiscale modeling of mucosal immune responses.

PubMed

Mei, Yongguo; Abedi, Vida; Carbo, Adria; Zhang, Xiaoying; Lu, Pinyi; Philipson, Casandra; Hontecillas, Raquel; Hoops, Stefan; Liles, Nathan; Bassaganya-Riera, Josep

2015-01-01

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

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2010-02-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

Photodynamic therapy influence on anti-cancer immunity

NASA Astrophysics Data System (ADS)

Isaeva, O. G.; Osipov, V. A.

2009-10-01

The system of partial differential equations describing tumor-immune dynamics with angiogenesis taken into account is presented. For spatially homogeneous case, the steady state analysis of the model is carried out. The effects of single photodynamic impact are numerically simulated. In the case of strong immune response we found that the photodynamic therapy (PDT) gives rise to the substantial shrinkage of tumor size which is accompanied by the increase of IL-2 concentration. On the contrary, the photodynamic stimulation of weak immune response is shown to be insufficient to reduce the tumor. These findings indicate the important role of anti-cancer immune response in the long-term tumor control after PDT.

A stochastic spatial model of HIV dynamics with an asymmetric battle between the virus and the immune system

NASA Astrophysics Data System (ADS)

Lin, Hai; Shuai, J. W.

2010-04-01

A stochastic spatial model based on the Monte Carlo approach is developed to study the dynamics of human immunodeficiency virus (HIV) infection. We aim to propose a more detailed and realistic simulation frame by incorporating many important features of HIV dynamics, which include infections, replications and mutations of viruses, antigen recognitions, activations and proliferations of lymphocytes, and diffusions, encounters and interactions of virions and lymphocytes. Our model successfully reproduces the three-phase pattern observed in HIV infection, and the simulation results for the time distribution from infection to AIDS onset are also in good agreement with the clinical data. The interactions of viruses and the immune system in all the three phases are investigated. We assess the relative importance of various immune system components in the acute phase. The dynamics of how the two important factors, namely the viral diversity and the asymmetric battle between HIV and the immune system, result in AIDS are investigated in detail with the model.

[New simulation technologies in neurosurgery].

PubMed

Byvaltsev, V A; Belykh, E G; Konovalov, N A

2016-01-01

The article presents a literature review on the current state of simulation technologies in neurosurgery, a brief description of the basic technology and the classification of simulation models, and examples of simulation models and skills simulators used in neurosurgery. Basic models for the development of physical skills, the spectrum of available computer virtual simulators, and their main characteristics are described. It would be instructive to include microneurosurgical training and a cadaver course of neurosurgical approaches in neurosurgery training programs and to extend the use of three-dimensional imaging. Technologies for producing three-dimensional anatomical models and patient-specific computer simulators as well as improvement of tactile feedback systems and display quality of virtual models are promising areas. Continued professional education necessitates further research for assessing the validity and practical use of simulators and physical models.

A simulation for teaching the basic and clinical science of fluid therapy.

PubMed

Rawson, Richard E; Dispensa, Marilyn E; Goldstein, Richard E; Nicholson, Kimberley W; Vidal, Noni Korf

2009-09-01

The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical cases that, by nature, are diverse, change over time, and respond in unique ways to therapeutic interventions. We developed a dynamic model using STELLA software that simulates normal and abnormal fluid and electrolyte balance in the dog. Students interact, not with the underlying model, but with a user interface that provides sufficient data (skin turgor, chemistry panel, etc.) for the clinical assessment of patients and an opportunity for treatment. Students administer fluids and supplements, and the model responds in "real time," requiring regular reassessment and, potentially, adaptation of the treatment strategy. The level of success is determined by clinical outcome, including improvement, deterioration, or death. We expected that the simulated cases could be used to teach both the clinical and basic science of fluid therapy. The simulation provides exposure to a realistic clinical environment, and students tend to focus on this aspect of the simulation while, for the most part, ignoring an exploration of the underlying physiological basis for patient responses. We discuss how the instructor's expertise can provide sufficient support, feedback, and scaffolding so that students can extract maximum understanding of the basic science in the context of assessing and treating at the clinical level.

CD98 at the crossroads of adaptive immunity and cancer

PubMed Central

Cantor, Joseph M.; Ginsberg, Mark H.

2012-01-01

Adaptive immunity, a vertebrate specialization, adds memory and exquisite specificity to the basic innate immune responses present in invertebrates while conserving metabolic resources. In adaptive immunity, antigenic challenge requires extremely rapid proliferation of rare antigen-specific lymphocytes to produce large, clonally expanded effector populations that neutralize pathogens. Rapid proliferation and resulting clonal expansion are dependent on CD98, a protein whose well-conserved orthologs appear restricted to vertebrates. Thus, CD98 supports lymphocyte clonal expansion to enable protective adaptive immunity, an advantage that could account for the presence of CD98 in vertebrates. CD98 supports lymphocyte clonal expansion by amplifying integrin signals that enable proliferation and prevent apoptosis. These integrin-dependent signals can also provoke cancer development and invasion, anchorage-independence and the rapid proliferation of tumor cells. CD98 is highly expressed in many cancers and contributes to formation of tumors in experimental models. Strikingly, vertebrates, which possess highly conserved CD98 proteins, CD98-binding integrins and adaptive immunity, also display propensity towards invasive and metastatic tumors. In this Commentary, we review the roles of CD98 in lymphocyte biology and cancer. We suggest that the CD98 amplification of integrin signaling in adaptive immunity provides survival benefits to vertebrates, which, in turn, bear the price of increased susceptibility to cancer. PMID:22499670

The self and the nonself: immunorecognition and immunologic functions.

PubMed

del Guercio, P

1993-01-01

For almost a century self-nonself discrimination has been considered the driving force of the immune system and the dogma of self-tolerance (horror autotoxicus) the essential issue for understanding protective immunity and pathologic autoreactivity. This classical picture has been recently challenged by the discovery that the immune system is influenced by internal activation (amor autocognitus) and autoreactive clones are both present and activated in healthy individuals. Central to the concepts of reactivity and tolerance, in other terms, to physiology and pathology, is the analysis of structures involved in immunorecognition and as they contribute to the outcome of the immune response. The capacity of the immune system to recognize nonself structures and eventually react to them developed during evolution probably before the generation of clonally distributed antigen receptors. The high level of autoreactivity that characterizes the immune system seems to suggest that immunocompetent cells never learned to ignore the self, but rather that, sometime during evolution, they specialized in the function of self-identification, one of the most basic activities of all living cells. Autoimmune diseases would result from a pathologic deviation of a physiologic function, just as many other diseases do.

Basic leucine zipper domain transcription factors: the vanguards in plant immunity.

PubMed

Noman, Ali; Liu, Zhiqin; Aqeel, Muhammad; Zainab, Madiha; Khan, Muhammad Ifnan; Hussain, Ansar; Ashraf, Muhammad Furqan; Li, Xia; Weng, Yahong; He, Shuilin

2017-12-01

Regulation of spatio-temporal expression patterns of stress tolerance associated plant genes is an essential component of the stress responses. Eukaryotes assign a large amount of their genome to transcription with multiple transcription factors (TFs). Often, these transcription factors fit into outsized gene groups which, in several cases, exclusively belong to plants. Basic leucine zipper domain (bZIP) transcription factors regulate vital processes in plants and animals. In plants, bZIPs are implicated in numerous fundamental processes like seed development, energy balance, and responses to abiotic or biotic stresses. Systematic analysis of the information obtained over the last two decades disclosed a constitutive role of bZIPs against biotic stress. bZIP TFs are vital players in plant innate immunity due to their ability to regulate genes associated with PAMP-triggered immunity, effector-triggered immunity, and hormonal signaling networks. Expression analysis of studied bZIP genes suggests that exploration and functional characterization of novel bZIP TFs in planta is helpful in improving crop resistance against pathogens and environmental stresses. Our review focuses on major advancements in bZIP TFs and plant responses against different pathogens. The integration of genomics information with the functional studies provides new insights into the regulation of plant defense mechanisms and engineering crops with improved resistance to invading pathogens. Conclusively, succinct functions of bZIPs as positive or negative regulator mediate resistance to the plant pathogens and lay a foundation for understanding associated genes and TFs regulating different pathways. Moreover, bZIP TFs may offer a comprehensive transgenic gizmo for engineering disease resistance in plant breeding programs.

Vaccines Cold Chain Monitoring: A Cross Sectional Study at Three District In Indonesia

NASA Astrophysics Data System (ADS)

Saraswati, L. D.; Ginandjar, P.; Budiyono; Martini; Udiyono, A.; Kairul

2018-02-01

Vaccine cold chain is a procedure that is used to keep vaccines at a certain temperature. The aim was to describe the vaccine cold chain management of basic immunization program in health centers district. The study design descriptive observational. The samples was Health Centers (HCs); 12 HCs in Sarolangun Jambi Province, 16 HCs in Brebes Central Java Province, and 24 HCs in Temanggung Central Java Provice. Basic immunization vaccines were BCG, DPT-HB-HIB, Polio, and Measles. The results showed proportion of officers graduated from college in Sorolangun, Brebes, and Temanggung were 66.7%, 81.3%, and 52.0% respectively. Proportion of HC that did not have thermometer and fridge freeze was mostly found in Temanggung (52%) and in Sorolangun (91.7%). The heat-sensitive vaccines arranged near the evaporator mostly found in Temanggung (88%), while freeze-sensitive vaccines prepared away of the evaporator mostly in Brebes (100%). Freezer temperature recording chart is not available mostly found in Sorolangun and Brebes (50%), In Sorolangun 41.7% of the officers monitoring 2 times a day and mostly (91.7%) the refrigerator thermostat tape was not isolated. The officers did not perform daily maintenance (50%), weekly (66.7%), and montly (33.3%) mostly found in Sorolangun. From this study we can conclude there is no vaccine immunization program management in Sarolangun, Brebes, and Temanggung that managed according to Ministry of Health Regulations number 42/2013 on the Implementation of immunization. Improvement oversight, control over management of vaccine and management personal, also managing the temperature of the vaccine were recommended.

Health and Safety in Day Care.

ERIC Educational Resources Information Center

Sells, Clifford J.; Paeth, Susan

1987-01-01

Basic health and day care policies and procedures should be implemented and closely monitored with the help of a health consultant, particularly in terms of respiratory tract, enteric, skin, invasive bacterial, and multiple system infections; Acquired Immune Deficiency Syndrome; vaccine preventable diseases; and general safety procedures.…

Facts about Hib Disease. ARC Facts.

ERIC Educational Resources Information Center

Association for Retarded Citizens, Arlington, TX.

The fact sheet provides basic information about Hib Disease in young children, which may involve a bacterial meningitis causing mental retardation, hearing loss, partial blindness, speech disorders, partial paralysis, behavioral problems, or seizures. Stressed is prevention of Hib Disease through immunization. The question and answer format…

Review of the biological effects of weightlessness on the human endocrine system

NASA Technical Reports Server (NTRS)

Hughes-Fulford, M.

1993-01-01

Studies from space flights over the past two decades have demonstrated that there are basic physiological changes in humans during space flight. These changes include cephalad fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known but the general approach has been to investigate systemic and hormonal changes. However, data from the 1973-1974 Skylabs, Spacelab 3 (SL-3), Spacelab D-I (SL-DI), and now the new SLS-1 missions support a more basic biological response to microgravity that may occur at the tissue, cellular, and molecular level. This report summarizes ground-based and SLS-1 experiments that examined the mechanism of loss of red blood cell mass in humans, the loss of bone mass and lowered osteoblast growth under space flight conditions, and loss of immune function in microgravity.

Biological characters of bats in relation to natural reservoir of emerging viruses.

PubMed

Omatsu, Tsutomu; Watanabe, Shumpei; Akashi, Hiroomi; Yoshikawa, Yasuhiro

2007-09-01

Many investigators focused on bats (Chiroptera) for their specific character, i.e. echolocation system, phylogenic tree, food practice and unique reproduction. However, most of basic information about the vital functions related to anti-viral activity has been unclear. For evaluating some animals as a natural reservoir or host of infectious pathogens, it is necessary that not only their immune system but also their biology, the environment of their living, food habits and physiological features should be clarified and they should be analyzed from these multi-view points. The majority of current studies on infectious diseases have been conducted for the elucidation of viral virulence using experimental animals or viral gene function in vitro, but in a few case, researchers focused on wild animal itself. In this paper, we described basic information about bats as follows; genetic background, character of the immunological factors, histological character of immune organs, the physiological function and sensitivity of bat cells to viral infection.

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).

Novel Nipah virus immune-antagonism strategy revealed by experimental and computational study.

PubMed

Seto, Jeremy; Qiao, Liang; Guenzel, Carolin A; Xiao, Sa; Shaw, Megan L; Hayot, Fernand; Sealfon, Stuart C

2010-11-01

Nipah virus is an emerging pathogen that causes severe disease in humans. It expresses several antagonist proteins that subvert the immune response and that may contribute to its pathogenicity. Studies of its biology are difficult due to its high pathogenicity and requirement for biosafety level 4 containment. We integrated experimental and computational methods to elucidate the effects of Nipah virus immune antagonists. Individual Nipah virus immune antagonists (phosphoprotein and V and W proteins) were expressed from recombinant Newcastle disease viruses, and the responses of infected human monocyte-derived dendritic cells were determined. We developed an ordinary differential equation model of the infectious process that that produced results with a high degree of correlation with these experimental results. In order to simulate the effects of wild-type virus, the model was extended to incorporate published experimental data on the time trajectories of immune-antagonist production. These data showed that the RNA-editing mechanism utilized by the wild-type Nipah virus to produce immune antagonists leads to a delay in the production of the most effective immune antagonists, V and W. Model simulations indicated that this delay caused a disconnection between attenuation of the antiviral response and suppression of inflammation. While the antiviral cytokines were efficiently suppressed at early time points, some early inflammatory cytokine production occurred, which would be expected to increase vascular permeability and promote virus spread and pathogenesis. These results suggest that Nipah virus has evolved a unique immune-antagonist strategy that benefits from controlled expression of multiple antagonist proteins with various potencies.

Mathematical modeling the radiation effects on humoral immunity

NASA Astrophysics Data System (ADS)

Smirnova, O.

One of the biological processes affecting the carcinogenesis is a response of humoral immune system to an antigen of malignant cells. Humoral immunity involves the production of protein molecules, antibodies, which can specifically bind to a certain antigen. This body system is radiosensitive. Therefore when simulating the radiation carcinogenesis, it is important to take into account the radiation effects on humoral immunity. To this end, a model of humoral immune response in irradiated mammals is developed. It is based on conventional theories and experimental facts. The model represents a system of nonlinear differential equations whose variables are the concentrations of antigen-sensitive immuno-competent cells carrying surface receptors and their bone-marrow precursor cells, as well as the concentrations of antibody-producing cells, antibodies, and an antigen. The dose of acute exposure and the dose rate of chronic exposure are the variable parameters in our approach. The model quantitatively reproduces the dynamics of the humoral immune response to the T-independent antigen (capsular antigen of Pasteurella pestis) in nonirradiated mammals (CBA mice). The model simulates the processes of the damage and recovery of the system of humoral immunity after acute exposure and predicts an adaptation of this system to low-level long-term chronic irradiation. These results give evidence that the developed model, after the appropriate identification, can be incorporated into a model of radiation carcinogenesis in humans. Together with a model of cellular immunity, such joined model will give capability to estimate the risk of radiation carcinogenesis for cosmonauts and astronauts on long space missions such as a voyage to Mars or a lunar colony.

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.

Face, content, and construct validity of a novel portable ergonomic simulator for basic laparoscopic skills.

PubMed

Xiao, Dongjuan; Jakimowicz, Jack J; Albayrak, Armagan; Buzink, Sonja N; Botden, Sanne M B I; Goossens, Richard H M

2014-01-01

Laparoscopic skills can be improved effectively through laparoscopic simulation. The purpose of this study was to verify the face and content validity of a new portable Ergonomic Laparoscopic Skills simulator (Ergo-Lap simulator) and assess the construct validity of the Ergo-Lap simulator in 4 basic skills tasks. Four tasks were evaluated: 2 different translocation exercises (a basic bimanual exercise and a challenging single-handed exercise), an exercise involving tissue manipulation under tension, and a needle-handling exercise. Task performance was analyzed according to speed and accuracy. The participants rated the usability and didactic value of each task and the Ergo-Lap simulator along a 5-point Likert scale. Institutional academic medical center with its affiliated general surgery residency. Forty-six participants were allotted into 2 groups: a Novice group (n = 26, <10 clinical laparoscopic procedures) and an Experienced group (n = 20, >50 clinical laparoscopic procedures). The Experienced group completed all tasks in less time than the Novice group did (p < 0.001, Mann-Whitney U test). The Experienced group also completed tasks 1, 2, and 4 with fewer errors than the Novice group did (p < 0.05). Of the Novice participants, 96% considered that the present Ergo-Lap simulator could encourage more frequent practice of laparoscopic skills. In addition, 92% would like to purchase this simulator. All of the experienced participants confirmed that the Ergo-Lap simulator was easy to use and useful for practicing basic laparoscopic skills in an ergonomic manner. Most (95%) of these respondents would recommend this simulator to other surgical trainees. This Ergo-Lap simulator with multiple tasks was rated as a useful training tool that can distinguish between various levels of laparoscopic expertise. The Ergo-Lap simulator is also an inexpensive alternative, which surgical trainees could use to update their skills in the skills laboratory, at home, or in the office. Copyright © 2014 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Use of Multiple GPUs to Speedup the Execution of a Three-Dimensional Computational Model of the Innate Immune System

NASA Astrophysics Data System (ADS)

Xavier, M. P.; do Nascimento, T. M.; dos Santos, R. W.; Lobosco, M.

2014-03-01

The development of computational systems that mimics the physiological response of organs or even the entire body is a complex task. One of the issues that makes this task extremely complex is the huge computational resources needed to execute the simulations. For this reason, the use of parallel computing is mandatory. In this work, we focus on the simulation of temporal and spatial behaviour of some human innate immune system cells and molecules in a small three-dimensional section of a tissue. To perform this simulation, we use multiple Graphics Processing Units (GPUs) in a shared-memory environment. Despite of high initialization and communication costs imposed by the use of GPUs, the techniques used to implement the HIS simulator have shown to be very effective to achieve this purpose.

Clinical implications of basic science discoveries: nociceptive neurons as targets to control immunity--potential relevance for transplantation.

PubMed

Larregina, A T; Divito, S J; Morelli, A E

2015-06-01

Increasing evidence indicates the existence of a complex cross-regulation between the most important biosensors of the human body: The immune and nervous systems. Cytokines control body temperature and trigger autoimmune disorders in the central nervous system, whereas neuropeptides released in peripheral tissues and lymphoid organs modulate inflammatory (innate) and adaptive immune responses. Surprisingly, the effects of nerve fibers and the antidromic release of its pro-inflammatory neuropeptides on the leukocytes of the immune system that mediate graft rejection are practically unknown. In the transplantation field, such area of research remains practically unexplored. A recent study by Riol-Blanco et al has revealed new details on how nociceptive nerves regulate the pro-inflammatory function of leukocytes in peripheral tissues. Although the mechanism(s) by which neuroinflammation affects the immune response against the allograft remains unknown, recent data suggest that this new area of research is worth exploring for potential development of novel complementary therapies for prevention/treatment of graft rejection. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Autoimmunity in the Pathogenesis and Treatment of Keratoconjunctivitis Sicca

PubMed Central

Liu, Katy C.; Huynh, Kyle; Grubbs, Joseph; Davis, Richard M.

2014-01-01

Dry eye is a chronic corneal disease that impacts the quality of life of many older adults. keratoconjunctivitis sicca (KCS), a form of aqueous-deficient dry eye, is frequently associated with Sjögren’s syndrome and mechanisms of autoimmunity. For KCS and other forms of dry eye, current treatments are limited, with many medications providing only symptomatic relief rather than targeting the pathophysiology of disease. Here, we review proposed mechanisms in the pathogenesis of autoimmune-based KCS: genetic susceptibility and disruptions in antigen recognition, immune response, and immune regulation. By understanding the mechanisms of immune dysfunction through basic science and translational research, potential drug targets can be identified. Finally, we discuss current dry eye therapies as well as promising new treatment options and drug therapy targets. PMID:24395332

Missed Immunization Opportunities Among Children Under 5 Years Of Age Dwelling In Karachi City.

PubMed

Khaliq, Asif; Sayed, Sayeeda Amber; Hussaini, Syed Abdullah; Azam, Kiran; Qamar, Mehak

2017-01-01

Immunization is the safest and effective measure for preventing and eradicating various communicable diseases. A glaring immunization gap exists between developing and industrialized countries towards immunization, because the developing countries including Pakistan are still striving to provide basic immunization to their children. The purpose of this study was to access the prevalence and factors of missing immunization among under 5-year children of Karachi.. A cross sectional study was conducted from June 2015 to October 2015 among different outpatient clinics of Karachi. Parents who had child less than 5 year of age were approached by non-probability purposive sampling. Data was analysed by using Statistical Package of Social Sciences. There were around 59.09% (n=156) and 64.43% (n=165) parents who have correctly responded regarding the number of essential immunization visit during the first and second year of their child life respectively. About 28.12% (n=108) parents responded that they do not know about the name and number of missed doses of vaccines. 31.78% (n=122) parents responded that their children have missed either one or more than one doses of routine immunization vaccines. Of which 34.42% (n=42) children have missed more than one vaccine. Lack of knowledge regarding immunization schedule 28.68% (n=34), concern about vaccine side effects 21.31%, (n=26), child sickness 17.21% (n=21), and lack of trust about government 10.65%, (n=13) were the major barriers identified by parents for missed immunization opportunities. Parents have inadequate knowledge regarding routine immunization visits, immunization schedule and vaccine doses. The practices of parents for routine childhood immunization are also poor. Parents refuse to immunize their child because of lack of immunization visit knowledge and also because of their doubts regarding vaccine potency and side effects. A proper system of immunization promotion, advocacy and reminder systems with proper follow-up mechanism need to be developed by all healthcare centres.

Access to a simulator is not enough: the benefits of virtual reality training based on peer-group-derived benchmarks--a randomized controlled trial.

PubMed

von Websky, Martin W; Raptis, Dimitri A; Vitz, Martina; Rosenthal, Rachel; Clavien, P A; Hahnloser, Dieter

2013-11-01

Virtual reality (VR) simulators are widely used to familiarize surgical novices with laparoscopy, but VR training methods differ in efficacy. In the present trial, self-controlled basic VR training (SC-training) was tested against training based on peer-group-derived benchmarks (PGD-training). First, novice laparoscopic residents were randomized into a SC group (n = 34), and a group using PGD-benchmarks (n = 34) for basic laparoscopic training. After completing basic training, both groups performed 60 VR laparoscopic cholecystectomies for performance analysis. Primary endpoints were simulator metrics; secondary endpoints were program adherence, trainee motivation, and training efficacy. Altogether, 66 residents completed basic training, and 3,837 of 3,960 (96.8 %) cholecystectomies were available for analysis. Course adherence was good, with only two dropouts, both in the SC-group. The PGD-group spent more time and repetitions in basic training until the benchmarks were reached and subsequently showed better performance in the readout cholecystectomies: Median time (gallbladder extraction) showed significant differences of 520 s (IQR 354-738 s) in SC-training versus 390 s (IQR 278-536 s) in the PGD-group (p < 0.001) and 215 s (IQR 175-276 s) in experts, respectively. Path length of the right instrument also showed significant differences, again with the PGD-training group being more efficient. Basic VR laparoscopic training based on PGD benchmarks with external assessment is superior to SC training, resulting in higher trainee motivation and better performance in simulated laparoscopic cholecystectomies. We recommend such a basic course based on PGD benchmarks before advancing to more elaborate VR training.

Symposium on Biomedical Applications of Basic Research Held in Woods Hole, Massachusetts on 15 August 1988.

DTIC Science & Technology

1989-02-10

to the AIDS virus , in a presentation titled "Marine Invertebrate Immunity: The AIDS Cqnnectlon." Funding for "Biomedical Applications of Basic...ibl itY Codes iAv ~li anti/or Dist. Spoc al The February evening in 1975 after MV Islander hit the Gould are Alan G. Lunn, left, marine contractor...discovery 25 years ago in the mtnt, Dr. Kornberg pointed out. is that the AIDS virus is covea, they are abundant only where laboratory of Frederik B

Mastoidectomy performance assessment of virtual simulation training using final-product analysis.

PubMed

Andersen, Steven A W; Cayé-Thomasen, Per; Sørensen, Mads S

2015-02-01

The future development of integrated automatic assessment in temporal bone virtual surgical simulators calls for validation against currently established assessment tools. This study aimed to explore the relationship between mastoidectomy final-product performance assessment in virtual simulation and traditional dissection training. Prospective trial with blinding. A total of 34 novice residents performed a mastoidectomy on the Visible Ear Simulator and on a cadaveric temporal bone. Two blinded senior otologists assessed the final-product performance using a modified Welling scale. The simulator gathered basic metrics on time, steps, and volumes in relation to the on-screen tutorial and collisions with vital structures. Substantial inter-rater reliability (kappa = 0.77) for virtual simulation and moderate inter-rater reliability (kappa = 0.59) for dissection final-product assessment was found. The simulation and dissection performance scores had significant correlation (P = .014). None of the basic simulator metrics correlated significantly with the final-product score except for number of steps completed in the simulator. A modified version of a validated final-product performance assessment tool can be used to assess mastoidectomy on virtual temporal bones. Performance assessment of virtual mastoidectomy could potentially save the use of cadaveric temporal bones for more advanced training when a basic level of competency in simulation has been achieved. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Mathematical and Computational Modeling for Tumor Virotherapy with Mediated Immunity.

PubMed

Timalsina, Asim; Tian, Jianjun Paul; Wang, Jin

2017-08-01

We propose a new mathematical modeling framework based on partial differential equations to study tumor virotherapy with mediated immunity. The model incorporates both innate and adaptive immune responses and represents the complex interaction among tumor cells, oncolytic viruses, and immune systems on a domain with a moving boundary. Using carefully designed computational methods, we conduct extensive numerical simulation to the model. The results allow us to examine tumor development under a wide range of settings and provide insight into several important aspects of the virotherapy, including the dependence of the efficacy on a few key parameters and the delay in the adaptive immunity. Our findings also suggest possible ways to improve the virotherapy for tumor treatment.

Optometric Education's Challenge: AIDS in the Curriculum.

ERIC Educational Resources Information Center

Wilson, Roger J.

1988-01-01

A national survey of schools of optometry suggests that acquired immune deficiency syndrome (AIDS) needs to be more thoroughly addressed in some curricula. Suggestions are made for curriculum development in the areas of public health, basic coursework, immunology, clinical medicine, psychology, ocular manifestations, and contact lenses. (MSE)

Investigation of roughing machining simulation by using visual basic programming in NX CAM system

NASA Astrophysics Data System (ADS)

Hafiz Mohamad, Mohamad; Nafis Osman Zahid, Muhammed

2018-03-01

This paper outlines a simulation study to investigate the characteristic of roughing machining simulation in 4th axis milling processes by utilizing visual basic programming in NX CAM systems. The selection and optimization of cutting orientation in rough milling operation is critical in 4th axis machining. The main purpose of roughing operation is to approximately shape the machined parts into finished form by removing the bulk of material from workpieces. In this paper, the simulations are executed by manipulating a set of different cutting orientation to generate estimated volume removed from the machine parts. The cutting orientation with high volume removal is denoted as an optimum value and chosen to execute a roughing operation. In order to run the simulation, customized software is developed to assist the routines. Operations build-up instructions in NX CAM interface are translated into programming codes via advanced tool available in the Visual Basic Studio. The codes is customized and equipped with decision making tools to run and control the simulations. It permits the integration with any independent program files to execute specific operations. This paper aims to discuss about the simulation program and identifies optimum cutting orientations for roughing processes. The output of this study will broaden up the simulation routines performed in NX CAM systems.

Mitochondrial dysfunction as a trigger of innate immune responses and inflammation.

PubMed

West, A Phillip

2017-11-01

A growing literature indicates that mitochondria are key participants in innate immune pathways, functioning as both signaling platforms and contributing to effector responses. In addition to regulating antiviral signaling and antibacterial immunity, mitochondria are also important drivers of inflammation caused by sterile injury. Much research on mitochondrial control of immunity now centers on understanding how mitochondrial constituents released during cellular damage simulate the innate immune system. When mitochondrial integrity is compromised, mitochondrial damage-associated molecular patterns engage pattern recognition receptors, trigger inflammation, and promote pathology in an expanding list of diseases. Here, I review the emerging knowledge of mitochondrial dysfunction in innate immune responses and discuss how environmental exposures may induce mitochondrial damage to potentiate inflammation and human disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Chimera states in multi-strain epidemic models with temporary immunity

NASA Astrophysics Data System (ADS)

Bauer, Larissa; Bassett, Jason; Hövel, Philipp; Kyrychko, Yuliya N.; Blyuss, Konstantin B.

2017-11-01

We investigate a time-delayed epidemic model for multi-strain diseases with temporary immunity. In the absence of cross-immunity between strains, dynamics of each individual strain exhibit emergence and annihilation of limit cycles due to a Hopf bifurcation of the endemic equilibrium, and a saddle-node bifurcation of limit cycles depending on the time delay associated with duration of temporary immunity. Effects of all-to-all and non-local coupling topologies are systematically investigated by means of numerical simulations, and they suggest that cross-immunity is able to induce a diverse range of complex dynamical behaviors and synchronization patterns, including discrete traveling waves, solitary states, and amplitude chimeras. Interestingly, chimera states are observed for narrower cross-immunity kernels, which can have profound implications for understanding the dynamics of multi-strain diseases.

[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.

Group I p21-activated kinases: emerging roles in immune function and viral pathogenesis.

PubMed

Pacheco, Almudena; Chernoff, Jonathan

2010-01-01

Group I p21-activated kinases are a highly conserved three-member family of serine/threonine kinases that act as key effectors for the small GTPases Cdc42 and Rac. In man, these enzymes have been implicated in a wide range of biological processes and are beginning to draw the attention of the pharmaceutical industry as potential therapeutic targets in cancer and in inflammatory processes. In this review, we summarize basic properties of group I Paks and discuss recently uncovered roles for these kinases in immune function and in viral infection.

Exercise, exercise training, and the immune system. A compendium of research (1902-1991)

NASA Technical Reports Server (NTRS)

Hardesty, A. J.; Greenleaf, J. E.; Simonson, S.; Hu, A.; Jackson, C. G. R.

1993-01-01

This compendium includes abstracts and synopses of clinical observations and of more basic studies involving physiological mechanisms concerning interaction of physical exercise and the human immune system. If the author's abstract or summary was appropriate, it was included. In other cases, a more detailed synopsis of the paper was prepared under the subheadings 'Purpose,' 'Methods,' 'Results,' and 'Conclusions.' Author and subject indices are provided, plus a selected bibliography of related work or those papers received after the volume was being prepared for publication. This volume includes material published from 1902 through 1991.

Extraskeletal effects of vitamin D: facts, uncertainties, and controversies.

PubMed

Bouvard, Béatrice; Annweiler, Cédric; Sallé, Agnès; Beauchet, Olivier; Chappard, Daniel; Audran, Maurice; Legrand, Erick

2011-01-01

Vitamin D was long viewed as a hormone acting chiefly to regulate calcium-phosphate metabolism and bone mineralization. Over the last decade, however, basic science and clinical researchers have produced a bewildering amount of information on the extraskeletal effects of vitamin D. This article is a review of the clinical and biological actions of vitamin D including effects on the immune system, auto-immune diseases, infections, cancer, metabolic syndrome, fall risk, cognitive function, and muscle function. Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

The basic reproduction number (R0) of measles: a systematic review.

PubMed

Guerra, Fiona M; Bolotin, Shelly; Lim, Gillian; Heffernan, Jane; Deeks, Shelley L; Li, Ye; Crowcroft, Natasha S

2017-12-01

The basic reproduction number, R nought (R 0 ), is defined as the average number of secondary cases of an infectious disease arising from a typical case in a totally susceptible population, and can be estimated in populations if pre-existing immunity can be accounted for in the calculation. R 0 determines the herd immunity threshold and therefore the immunisation coverage required to achieve elimination of an infectious disease. As R 0 increases, higher immunisation coverage is required to achieve herd immunity. In July, 2010, a panel of experts convened by WHO concluded that measles can and should be eradicated. Despite the existence of an effective vaccine, regions have had varying success in measles control, in part because measles is one of the most contagious infections. For measles, R 0 is often cited to be 12-18, which means that each person with measles would, on average, infect 12-18 other people in a totally susceptible population. We did a systematic review to find studies reporting rigorous estimates and determinants of measles R 0 . Studies were included if they were a primary source of R 0 , addressed pre-existing immunity, and accounted for pre-existing immunity in their calculation of R 0 . A search of key databases was done in January, 2015, and repeated in November, 2016, and yielded 10 883 unique citations. After screening for relevancy and quality, 18 studies met inclusion criteria, providing 58 R 0 estimates. We calculated median measles R 0 values stratified by key covariates. We found that R 0 estimates vary more than the often cited range of 12-18. Our results highlight the importance of countries calculating R 0 using locally derived data or, if this is not possible, using parameter estimates from similar settings. Additional data and agreed review methods are needed to strengthen the evidence base for measles elimination modelling. Copyright © 2017 Elsevier Ltd. All rights reserved.

Studying longterm effects of micro gravity on basic immune functions - The development of an application based on the measuring of phagocytosis activity of Blue Mussel hemocytes

NASA Astrophysics Data System (ADS)

Unruh, Eckehardt

The immunsystem of astronauts exposed to microgravity is declining. Whether this effect is caused by microgravity or in combination with cosmic radiation is so far not clear. The immune system of vertebrates has several defence strategies but the basic immune response (Phagocytosis) is present as well in invertebrates. Phagocytotic cells are drawn by chemotaxis to the origin of an infection. By adhesion, ingestion and phagosome formation foreign particles, bacteria etc are transported inside of a cell were they are destroyed by native powerful biocides. Related to this biocide production is the formation of Reactive Oxygen Species (ROS). ROS can be measured by luminescence. The effects of microgravity will be simultaneously tested by exposure of phagocytotic hemocytes on orbit under microgravity, artificial gravity and, on ground under natural gravity. To address this purpose defined pools of Blue Mussel (Mytilus edulis) hemocytes will be launched frozen to the ISS. References for all batches will stay on ground. Shortly after arrival and then in three-month intervals batches of the same pool will be thawed and reconstituted. The phagocytosis related production of ROS will be stimulated with opsonized Zymosan. Luminescence will be measured and the data will be sent to ground. The experiment is scheduled for the Columbus Biolab early 2009. In preparation of this flight experiments the following procedures were investigated and the results will be presented: - a protocol for the cryoconservation and reconstituton of blue mussel hemocytes. - preliminary results of phagocytosis activity by reconstituted hemocytes after cryo-conservation and hemocytes without cryo-conservation treatment. The TRIPLELUX-B Experiment contributes to risk assessment concerning longterm immunotoxicity under space flight conditions. The immune system of invertebrates has not been studied so far in space. The choice of the phagocytes from invertebrates is justified by the claim to study the universal validity of innate immune responses.

Making evidence-based selections of influenza vaccines.

PubMed

Childress, Billy-Clyde; Montney, Joshua D; Albro, Elise A

2014-01-01

Years ago, intramuscular influenza vaccines were the only option for those who wanted to arm themselves against the flu. Today there are alternatives, including intradermal injections and intranasal sprays. In order to select the right influenza vaccine for their patients, pharmacists, and other healthcare professionals must have a basic understanding of the immune system. Influenza vaccines elicit different levels of immune response involving innate and adaptive immunity, which are critical to fighting infection. For the 2013-2014 flu season, there were 13 different formulations of influenza vaccines on the market with vast differences in indications, contraindications, and effectiveness. The CDC does not recommend one vaccine over another, but recommends that all patients be vaccinated against the flu. Preventing the spread of influenza is no simple task; however, the most recent evidence on influenza vaccines and sufficient knowledge of the immune system will allow pharmacists and other healthcare providers to better advocate for vaccines, determine which are most appropriate, and ensure their proper administration.

[Poliomyelitis--why we must continue to vaccinate!].

PubMed

Windorfer, A; Beyrer, K

2005-02-24

The eradication of polio--that is the worldwide elimination of the wild poliovirus--is now within reach. The current success of this international project is due largely to the rigorous immunization of the general population. Both live oral polio vaccine (OPV) and inactivated vaccine (IPV) administered by injection are applied, the pros and cons of each having to be weighed up. Since 1998, only the dead IPV vaccine has been recommended in Germany. It is essential that the acceptance of the need for immunization should not decline, and that the inoculation rate in countries in which polio has apparently been eliminated, should not fall below the critical threshold of about 85-80%. If in the future this figure is not reached, the population would be put at risk by the re-introduction of the polio virus into the country. Even when global elimination has been achieved, vaccination must be continued for several years. The recommended immunization schedule covers three vaccinations for basic immunization plus a booster vaccination in adolescence.

Eosinophils in mucosal immune responses

PubMed Central

Travers, J; Rothenberg, M E

2015-01-01

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

Seroprevalence of hepatitis A virus antibody in a population aged 0-30 years in Shanghai, China: implications for hepatitis A immunization.

PubMed

Zhu, Y; Yuan, Z; Zhao, Q; Chen, G; Xu, B

2013-03-01

This study aimed to determine current seroprevalence of hepatitis A virus (HAV) antibody in subjects aged 0-30 years in Shanghai. A total of 5515 subjects were recruited through random clustering sampling in 2009. Basic clinical and demographic information and records of HAV vaccination were acquired by questionnaire interviews and review of immunization records. Serum samples were collected and tested for anti-HAV IgM and total anti-HAV. The overall seroprevalence of total anti-HAV was 52·9%. Subjects aged 20-24 years had the lowest (34·4%) anti-HAV seropositivity and subjects aged 5-9 years had the highest (74·6%) positivity. Seroprevalence was significantly greater in subjects from suburban areas than in subjects from urban areas. Subjects who had HAV immunizations had significantly greater seropositivity for total anti-HAV. Previous hepatitis A immunization policies had a significant impact on the presence of anti-HAV seroprevalence in a population aged 0-30 years from Shanghai.

The Lake Tahoe Basin Land Use Simulation Model

USGS Publications Warehouse

Forney, William M.; Oldham, I. Benson

2011-01-01

This U.S. Geological Survey Open-File Report describes the final modeling product for the Tahoe Decision Support System project for the Lake Tahoe Basin funded by the Southern Nevada Public Land Management Act and the U.S. Geological Survey's Geographic Analysis and Monitoring Program. This research was conducted by the U.S. Geological Survey Western Geographic Science Center. The purpose of this report is to describe the basic elements of the novel Lake Tahoe Basin Land Use Simulation Model, publish samples of the data inputs, basic outputs of the model, and the details of the Python code. The results of this report include a basic description of the Land Use Simulation Model, descriptions and summary statistics of model inputs, two figures showing the graphical user interface from the web-based tool, samples of the two input files, seven tables of basic output results from the web-based tool and descriptions of their parameters, and the fully functional Python code.

Investigating AI with BASIC and Logo: Helping the Computer to Understand INPUTS.

ERIC Educational Resources Information Center

Mandell, Alan; Lucking, Robert

1988-01-01

Investigates using the microcomputer to develop a sentence parser to simulate intelligent conversation used in artificial intelligence applications. Compares the ability of LOGO and BASIC for this use. Lists and critiques several LOGO and BASIC parser programs. (MVL)

Intercellular Communication of Tumor Cells and Immune Cells after Exposure to Different Ionizing Radiation Qualities.

PubMed

Diegeler, Sebastian; Hellweg, Christine E

2017-01-01

Ionizing radiation can affect the immune system in many ways. Depending on the situation, the whole body or parts of the body can be acutely or chronically exposed to different radiation qualities. In tumor radiotherapy, a fractionated exposure of the tumor (and surrounding tissues) is applied to kill the tumor cells. Currently, mostly photons, and also electrons, neutrons, protons, and heavier particles such as carbon ions, are used in radiotherapy. Tumor elimination can be supported by an effective immune response. In recent years, much progress has been achieved in the understanding of basic interactions between the irradiated tumor and the immune system. Here, direct and indirect effects of radiation on immune cells have to be considered. Lymphocytes for example are known to be highly radiosensitive. One important factor in indirect interactions is the radiation-induced bystander effect which can be initiated in unexposed cells by expression of cytokines of the irradiated cells and by direct exchange of molecules via gap junctions. In this review, we summarize the current knowledge about the indirect effects observed after exposure to different radiation qualities. The different immune cell populations important for the tumor immune response are natural killer cells, dendritic cells, and CD8+ cytotoxic T-cells. In vitro and in vivo studies have revealed the modulation of their functions due to ionizing radiation exposure of tumor cells. After radiation exposure, cytokines are produced by exposed tumor and immune cells and a modulated expression profile has also been observed in bystander immune cells. Release of damage-associated molecular patterns by irradiated tumor cells is another factor in immune activation. In conclusion, both immune-activating and -suppressing effects can occur. Enhancing or inhibiting these effects, respectively, could contribute to modified tumor cell killing after radiotherapy.

Nucleic Acid Immunity.

PubMed

Hartmann, G

2017-01-01

Organisms throughout biology need to maintain the integrity of their genome. From bacteria to vertebrates, life has established sophisticated mechanisms to detect and eliminate foreign genetic material or to restrict its function and replication. Tremendous progress has been made in the understanding of these mechanisms which keep foreign or unwanted nucleic acids from viruses or phages in check. Mechanisms reach from restriction-modification systems and CRISPR/Cas in bacteria and archaea to RNA interference and immune sensing of nucleic acids, altogether integral parts of a system which is now appreciated as nucleic acid immunity. With inherited receptors and acquired sequence information, nucleic acid immunity comprises innate and adaptive components. Effector functions include diverse nuclease systems, intrinsic activities to directly restrict the function of foreign nucleic acids (e.g., PKR, ADAR1, IFIT1), and extrinsic pathways to alert the immune system and to elicit cytotoxic immune responses. These effects act in concert to restrict viral replication and to eliminate virus-infected cells. The principles of nucleic acid immunity are highly relevant for human disease. Besides its essential contribution to antiviral defense and restriction of endogenous retroelements, dysregulation of nucleic acid immunity can also lead to erroneous detection and response to self nucleic acids then causing sterile inflammation and autoimmunity. Even mechanisms of nucleic acid immunity which are not established in vertebrates are relevant for human disease when they are present in pathogens such as bacteria, parasites, or helminths or in pathogen-transmitting organisms such as insects. This review aims to provide an overview of the diverse mechanisms of nucleic acid immunity which mostly have been looked at separately in the past and to integrate them under the framework nucleic acid immunity as a basic principle of life, the understanding of which has great potential to advance medicine. © 2017 Elsevier Inc. All rights reserved.

An Application of the Patient-Oriented Problem-Solving (POPS) System.

ERIC Educational Resources Information Center

Chiodo, Gary T.; And Others

1991-01-01

The Patient-Oriented Problem-Solving System, a cooperative learning model, was implemented in a second year immunology course at the Oregon Health Sciences University School of Dentistry, to correlate basic and clinical sciences information about Acquired Immune Deficiency Syndrome. Student enthusiasm and learning were substantial. (MSE)

Integrating Artificial Immune, Neural and Endrocine Systems in Autonomous Sailing Robots

DTIC Science & Technology

2010-09-24

system - Development of an adaptive hormone system capable of changing operation and control of the neural network depending on changing enviromental ...and control of the neural network depending on changing enviromental conditions • First basic design of the MOOP and a simple neural-endocrine based

Negligence: What You Need To Know To Avoid Liability.

ERIC Educational Resources Information Center

Russo, Charles J.; Fericks, Donald J.

1996-01-01

To help educators understand their legal responsibilities when supervising students, this article reviews the elements of negligence (duty, breach, injury, and causation) an injured party must prove to hold an educator or school system legally accountable. The article also reviews basic defenses to negligence: immunity, comparative/contributory…

AIDS: Workplace Issues. INFO-LINE. Practical Guidelines for Training and Development Professionals. Issue 9208.

ERIC Educational Resources Information Center

American Society for Training and Development, Alexandria, VA.

Practical guidelines are presented for training and development professionals dealing with acquired immune deficiency syndrome (AIDS) in the workplace. The following topics are covered: AIDS in the workplace; AIDS basics, including information on the required corporate commitment and transmission of human immunodeficiency virus (HIV); employment…

Associating Changes in the Immune System with Clinical Diseases for Interpretation in Risk Assessment##

EPA Science Inventory

This overview is a revision to the unit originally published in 2004. While the basic tenants of immunotoxicity have not changed in the past 10 years, several publications have explored the application of immunotoxicological data to the risk assessment process. Therefore, the goa...

Clarifying Prescriptive Messages about HIV: The Case of Long-Term Mutually Monogamous Relationships.

ERIC Educational Resources Information Center

Parrillo, Anthony V.; Clark, Jeffrey K.

1995-01-01

Examines the appropriateness of using the word monogamy in acquired immune deficiency syndrome (AIDS) education, identifying basic concepts within prescriptive messages about human immunodeficiency virus (HIV); reviewing definitions, applications, and interpretations of monogamy in the literature; presenting a content analysis of sexuality and…

Performance factors in associative learning: assessment of the sometimes competing retrieval model.

PubMed

Witnauer, James E; Wojick, Brittany M; Polack, Cody W; Miller, Ralph R

2012-09-01

Previous simulations revealed that the sometimes competing retrieval model (SOCR; Stout & Miller, Psychological Review, 114, 759-783, 2007), which assumes local error reduction, can explain many cue interaction phenomena that elude traditional associative theories based on total error reduction. Here, we applied SOCR to a new set of Pavlovian phenomena. Simulations used a single set of fixed parameters to simulate each basic effect (e.g., blocking) and, for specific experiments using different procedures, used fitted parameters discovered through hill climbing. In simulation 1, SOCR was successfully applied to basic acquisition, including the overtraining effect, which is context dependent. In simulation 2, we applied SOCR to basic extinction and renewal. SOCR anticipated these effects with both fixed parameters and best-fitting parameters, although the renewal effects were weaker than those observed in some experiments. In simulation 3a, feature-negative training was simulated, including the often observed transition from second-order conditioning to conditioned inhibition. In simulation 3b, SOCR predicted the observation that conditioned inhibition after feature-negative and differential conditioning depends on intertrial interval. In simulation 3c, SOCR successfully predicted failure of conditioned inhibition to extinguish with presentations of the inhibitor alone under most circumstances. In simulation 4, cue competition, including blocking (4a), recovery from relative validity (4b), and unblocking (4c), was simulated. In simulation 5, SOCR correctly predicted that inhibitors gain more behavioral control than do excitors when they are trained in compound. Simulation 6 demonstrated that SOCR explains the slower acquisition observed following CS-weak shock pairings.

Psychosocial correlates of immune responsiveness and illness episodes in US Air Force Academy cadets undergoing basic cadet training

NASA Technical Reports Server (NTRS)

Lee, D. J.; Meehan, R. T.; Robinson, C.; Smith, M. L.; Mabry, T. R.

1995-01-01

This study examined psychosocial correlates of immune function and illness in 89 male first-year US Air Force Academy cadets. A psychosocial questionnaire was administered to cadets prior to their arrival at the academy and was readministered during cadet orientation and during the stressful environment of Basic Cadet Training (BCT). Immune responsiveness was analyzed by PHA-, PMA-, or anti-CD3-stimulated thymidine uptake in mononuclear leucocytes. Illness episodes were assessed via medical chart review and self-reported symptoms. There were significant increases in distress levels as cadets entered BCT. No psychosocial measure assessed prior to arrival at the academy predicted level of PHA-, PMA-, and anti-CD3-stimulated thymidine uptake or risk of illness. However, hostility levels reported during BCT predicted risk of illness in the four weeks following psychosocial assessment (odds ratio = 7.1; 95% confidence interval: 1.4-36.1). Elevated response to environmental stressors and lower well-being levels also predicted impending illness, but only in the cohort of cadets who had not contracted food poisoning prior to assessment during BCT (OR = 9.3, CI = 1.9-46.7; OR = 0.09, CI = 0.02-0.53). These results suggest that self-report measures of hostility, response to environmental stressors and well-being may be useful predictors of impending illness episodes in males encountering high stress environments.

Inhibition of allergic encephalomyelitis in marmosets by vaccination with recombinant vaccinia virus encoding for myelin basic protein.

PubMed

Genain, C P; Gritz, L; Joshi, N; Panicali, D; Davis, R L; Whitaker, J N; Letvin, N L; Hauser, S L

1997-11-01

A primary demyelinating form of experimental allergic encephalomyelitis (EAE) resembling human multiple sclerosis (MS) occurs in Callithrix jacchus marmosets following immunization with human white matter. Participation of a T-cell immune response against myelin basic protein (MBP) in this disease model is supported by observations of increased reactivity against MBP in PBMC and of adoptive transfer of an inflammatory form of EAE by MBP-reactive T-cells. To evaluate the effects of ectopic presentation of MBP on marmoset EAE, animals were vaccinated prior to induction of EAE by subcutaneous injection of attenuated strains of vaccinia virus genetically engineered to contain either the entire coding sequence for human MBP (vT15) or the equine herpes virus glycoprotein gH gene (vAbT249). Vaccination with vT15 was followed by transient cytoplasmic and surface membrane expression of MBP in circulating PBMC (15-45 days). The onset of clinical EAE after immunization (pi) was markedly delayed in vT15-vaccinated animals (37-97 days pi, n = 4) compared to vAbT249-vaccinated controls (14-18 days pi, n = 3). Proliferative responses against MBP but not against vaccinia antigens or phytohemagglutinin were suppressed in protected animals. Thus, development of attenuated live viruses carrying genes for myelin antigens could be useful for induction of immunologic tolerance and for modulation of autoimmune demyelination.

Effects of Simulated Microgravity on Functions of Neutrophil-like HL-60 Cells

NASA Astrophysics Data System (ADS)

Wang, Chengzhi; Li, Ning; Zhang, Chen; Sun, Shujin; Gao, Yuxin; Long, Mian

2015-11-01

Altered gravity, especially microgravity affects cellular functions of immune cells and can result in immune dysfunction for long-term, manned spaceflight and space exploration. The underlying mechanism, however, of sensing and responding to the gravity alteration is poorly understood. Here, a rotary cell culture system (RCCS) bioreactor was used to elucidate the effects of simulated microgravity on polymorphonuclear neutrophils (PMN)-like HL-60 cells. Alteration of cell morphology, up-regulation of (nitric oxide) NO production, enhancement of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemotactic protein 1 (MCP-1) secretion, and diversity of cellular adhesion molecule expression were observed for the cells cultured in RCCS, leading to the up-regulated inflammatory immune responses and host defense. It was also indicated that such alterations in biological responses of PMNs mediated the reduced rolling velocity and decreased adhesion of PMN-like HL-60 cells on endothelial cells under shear flow. This work furthers the understandings in the effects and mechanism of microgravity on PMN functions, which are potentially helpful for optimizing the countermeasures to immune suppression in the future long-term, manned spaceflight.

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

DOE PAGES

De Pillis, L. G.; Radunskaya, A.

2001-01-01

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

A Mathematical Tumor Model with Immune Resistance and Drug Therapy: An Optimal Control Approach

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

De Pillis, L. G.; Radunskaya, A.

We present a competition model of cancer tumor growth that includes both the immune system response and drug therapy. This is a four-population model that includes tumor cells, host cells, immune cells, and drug interaction. We analyze the stability of the drug-free equilibria with respect to the immune response in order to look for target basins of attraction. One of our goals was to simulate qualitatively the asynchronous tumor-drug interaction known as “Jeffs phenomenon.” The model we develop is successful in generating this asynchronous response behavior. Our other goal was to identify treatment protocols that could improve standard pulsed chemotherapymore » regimens. Using optimal control theory with constraints and numerical simulations, we obtain new therapy protocols that we then compare with traditional pulsed periodic treatment. The optimal control generated therapies produce larger oscillations in the tumor population over time. However, by the end of the treatment period, total tumor size is smaller than that achieved through traditional pulsed therapy, and the normal cell population suffers nearly no oscillations.« less

Implementing system simulation of C3 systems using autonomous objects

NASA Technical Reports Server (NTRS)

Rogers, Ralph V.

1987-01-01

The basis of all conflict recognition in simulation is a common frame of reference. Synchronous discrete-event simulation relies on the fixed points in time as the basic frame of reference. Asynchronous discrete-event simulation relies on fixed-points in the model space as the basic frame of reference. Neither approach provides sufficient support for autonomous objects. The use of a spatial template as a frame of reference is proposed to address these insufficiencies. The concept of a spatial template is defined and an implementation approach offered. Discussed are the uses of this approach to analyze the integration of sensor data associated with Command, Control, and Communication systems.

Development of a GA-Fuzzy-Immune PID Controller with Incomplete Derivation for Robot Dexterous Hand

PubMed Central

Liu, Xin-hua; Chen, Xiao-hu; Zheng, Xian-hua; Li, Sheng-peng; Wang, Zhong-bin

2014-01-01

In order to improve the performance of robot dexterous hand, a controller based on GA-fuzzy-immune PID was designed. The control system of a robot dexterous hand and mathematical model of an index finger were presented. Moreover, immune mechanism was applied to the controller design and an improved approach through integration of GA and fuzzy inference was proposed to realize parameters' optimization. Finally, a simulation example was provided and the designed controller was proved ideal. PMID:25097881

Antimicrobial peptide-like genes in Nasonia vitripennis: a genomic perspective

PubMed Central

2010-01-01

Background Antimicrobial peptides (AMPs) are an essential component of innate immunity which can rapidly respond to diverse microbial pathogens. Insects, as a rich source of AMPs, attract great attention of scientists in both understanding of the basic biology of the immune system and searching molecular templates for anti-infective drug design. Despite a large number of AMPs have been identified from different insect species, little information in terms of these peptides is available from parasitic insects. Results By using integrated computational approaches to systemically mining the Hymenopteran parasitic wasp Nasonia vitripennis genome, we establish the first AMP repertoire whose members exhibit extensive sequence and structural diversity and can be distinguished into multiple molecular types, including insect and fungal defensin-like peptides (DLPs) with the cysteine-stabilized α-helical and β-sheet (CSαβ) fold; Pro- or Gly-rich abaecins and hymenoptaecins; horseshoe crab tachystatin-type AMPs with the inhibitor cystine knot (ICK) fold; and a linear α-helical peptide. Inducible expression pattern of seven N. vitripennis AMP genes were verified, and two representative peptides were synthesized and functionally identified to be antibacterial. In comparison with Apis mellifera (Hymenoptera) and several non-Hymenopteran model insects, N. vitripennis has evolved a complex antimicrobial immune system with more genes and larger protein precursors. Three classical strategies that are likely responsible for the complexity increase have been recognized: 1) Gene duplication; 2) Exon duplication; and 3) Exon-shuffling. Conclusion The present study established the N. vitripennis peptidome associated with antimicrobial immunity by using a combined computational and experimental strategy. As the first AMP repertoire of a parasitic wasp, our results offer a basic platform for further studying the immunological and evolutionary significances of these newly discovered AMP-like genes in this class of insects. PMID:20302637

Reconstruction of an Immune Dynamic Model to Simulate the Contrasting Role of Auxin and Cytokinin in Plant Immunity.

PubMed

Kaltdorf, Martin; Dandekar, Thomas; Naseem, Muhammad

2017-01-01

In order to increase our understanding of biological dependencies in plant immune signaling pathways, the known interactions involved in plant immune networks are modeled. This allows computational analysis to predict the functions of growth related hormones in plant-pathogen interaction. The SQUAD (Standardized Qualitative Dynamical Systems) algorithm first determines stable system states in the network and then use them to compute continuous dynamical system states. Our reconstructed Boolean model encompassing hormone immune networks of Arabidopsis thaliana (Arabidopsis) and pathogenicity factors injected by model pathogen Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) can be exploited to determine the impact of growth hormones in plant immunity. We describe a detailed working protocol how to use the modified SQUAD-package by exemplifying the contrasting effects of auxin and cytokinins in shaping plant-pathogen interaction.

NOD-like receptor cooperativity in effector-triggered immunity.

PubMed

Griebel, Thomas; Maekawa, Takaki; Parker, Jane E

2014-11-01

Intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are basic elements of innate immunity in plants and animals. Whereas animal NLRs react to conserved microbe- or damage-associated molecular patterns, plant NLRs intercept the actions of diverse pathogen virulence factors (effectors). In this review, we discuss recent genetic and molecular evidence for functional NLR pairs, and discuss the significance of NLR self-association and heteromeric NLR assemblies in the triggering of downstream signaling pathways. We highlight the versatility and impact of cooperating NLR pairs that combine pathogen sensing with the initiation of defense signaling in both plant and animal immunity. We propose that different NLR receptor molecular configurations provide opportunities for fine-tuning resistance pathways and enhancing the host's pathogen recognition spectrum to keep pace with rapidly evolving microbial populations. Copyright © 2014. Published by Elsevier Ltd.

Adrenomedullin and endocrine control of immune cells during pregnancy.

PubMed

Matson, Brooke C; Caron, Kathleen M

2014-09-01

The immunology of pregnancy is complex and incompletely understood. Aberrant immune activity in the decidua and in the placenta is believed to play a role in diseases of pregnancy, such as infertility, miscarriage, fetal growth restriction and preeclampsia. Here, we briefly review the endocrine control of uterine natural killer cell populations and their functions by the peptide hormone adrenomedullin. Studies in genetic animal models have revealed the critical importance of adrenomedullin dosage at the maternal-fetal interface, with cells from both the maternal and fetal compartments contributing to essential aspects underlying appropriate uterine receptivity, implantation and vascular remodeling of spiral arteries. These basic insights into the crosstalk between the endocrine and immune systems within the maternal-fetal interface may ultimately translate to a better understanding of the functions and consequences of dysregulated adrenomedullin levels in clinically complicated pregnancies.

The overlooked "nonclassical" functions of major histocompatibility complex (MHC) class II antigens in immune and nonimmune cells.

PubMed

Altomonte, M; Pucillo, C; Maio, M

1999-06-01

Besides their "classical" antigenic peptide-presenting activity, major histocompatibility complex (MHC) class II antigens can activate different cellular functions in immune and nonimmune cells. However, this "nonclassical" role and its functional consequences are still substantially overlooked. In this review, we will focus on these alternative functional properties of MHC class II antigens, to reawaken attention to their present and foreseeable immunobiologic and pathogenetic implications. The main issues that will be addressed concern 1) the role of MHC class II molecules as basic components of exchangeable oligomeric protein complexes with intracellular signaling ability; 2) the nonclassical functions of MHC class II antigens in immune cells; 3) the pathogenetic role of MHC class II antigens in inflammatory/autoimmune and infectious disease; and 4) the functional role of MHC class II antigens in solid malignancies.

Immunity profile in breast cancer patients.

PubMed

Hrubisko, M; Sanislo, L; Zuzulova, M; Michalickova, J; Zeleznikova, T; Sedlak, J; Bella, V

2010-01-01

Despite the multifactorial pathogenesis of malignant transformation, it is assumed that deficiency in some immune mechanisms plays a considerable role in its development. Chronically activated immune cells exert tumour-promoting effects directly by influencing the proliferation and survival of neoplastic cells, as well as by indirect modulation of neoplastic microenvironments in favour of tumour progression. We refer to results of two separate investigations that aim to monitor the immune functions in patients with breast cancer. In the first investigation, we compare the picture of basic cellular immunity profile of patients in early stage of breast cancer with those suffering from advanced disease; in the second one, we compare the production of Th1-cytokines in patients in different stages of breast cancer and atopic healthy controls. We recognized that the totals of T-lymphocytes and T-helpers were lower and the expression of HLADR on T-lymphocytes were higher in patients with advanced disease; the expression of IL-2 and LFN-gamma by T-lymphocytes was decreased in metastatic breast cancer patients, however IL-2 production was increased in patients in early stage of disease. We conclude that the role of immune system in cancer development is ambivalent as it may be not only protective, but also harmful (Tab. 1, Fig. 3, Ref. 22). Full Text (Free, PDF) www.bmj.sk.

Triactome: neuro-immune-adipose interactions. Implication in vascular biology.

PubMed

Chaldakov, George Nikov; Fiore, Marco; Ghenev, Peter I; Beltowski, Jerzy; Ranćić, Gorana; Tunçel, Neşe; Aloe, Luigi

2014-01-01

Understanding how the precise interactions of nerves, immune cells, and adipose tissue account for cardiovascular and metabolic biology is a central aim of biomedical research at present. A long standing paradigm holds that the vascular wall is composed of three concentric tissue coats (tunicae): intima, media, and adventitia. However, large- and medium-sized arteries, where usually atherosclerotic lesions develop, are consistently surrounded by periadventitial adipose tissue (PAAT), we recently designated tunica adiposa (in brief, adiposa like intima, media, and adventitia). Today, atherosclerosis is considered an immune-mediated inflammatory disease featured by endothelial dysfunction/intimal thickening, medial atrophy, and adventitial lesions associated with adipose dysfunction, whereas hypertension is characterized by hyperinnervation-associated medial thickening due to smooth muscle cell hypertrophy/hyperplasia. PAAT expansion is associated with increased infiltration of immune cells, both adipocytes and immunocytes secreting pro-inflammatory and anti-inflammatory (metabotrophic) signaling proteins collectively dubbed adipokines. However, the role of vascular nerves and their interactions with immune cells and paracrine adipose tissue is not yet evaluated in such an integrated way. The present review attempts to briefly highlight the findings in basic and translational sciences in this area focusing on neuro-immune-adipose interactions, herein referred to as triactome. Triactome-targeted pharmacology may provide a novel therapeutic approach in cardiovascular disease.

Molecular Dynamics Simulation and Statistics Analysis Reveals the Defense Response Mechanism in Plants

NASA Astrophysics Data System (ADS)

Liu, Zhichao; Zhao, Yunjie; Zeng, Chen; Computational Biophysics Lab Team

As the main protein of the bacterial flagella, flagellin plays an important role in perception and defense response. The newly discovered locus, FLS2, is ubiquitously expressed. FLS2 encodes a putative receptor kinase and shares many homologies with some plant resistance genes and even with some components of immune system of mammals and insects. In Arabidopsis, FLS2 perception is achieved by the recognition of epitope flg22, which induces FLS2 heteromerization with BAK1 and finally the plant immunity. Here we use both analytical methods such as Direct Coupling Analysis (DCA) and Molecular Dynamics (MD) Simulations to get a better understanding of the defense mechanism of FLS2. This may facilitate a redesign of flg22 or de-novo design for desired specificity and potency to extend the immune properties of FLS2 to other important crops and vegetables.

Virtual reality training for endoscopic surgery: voluntary or obligatory?

PubMed

van Dongen, K W; van der Wal, W A; Rinkes, I H M Borel; Schijven, M P; Broeders, I A M J

2008-03-01

Virtual reality (VR) simulators have been developed to train basic endoscopic surgical skills outside of the operating room. An important issue is how to create optimal conditions for integration of these types of simulators into the surgical training curriculum. The willingness of surgical residents to train these skills on a voluntary basis was surveyed. Twenty-one surgical residents were given unrestricted access to a VR simulator for a period of four months. After this period, a competitive element was introduced to enhance individual training time spent on the simulator. The overall end-scores for individual residents were announced periodically to the full surgical department, and the winner was awarded a prize. In the first four months of study, only two of the 21 residents (10%) trained on the simulator, for a total time span of 163 minutes. After introducing the competitive element the number of trainees increased to seven residents (33%). The amount of training time spent on the simulator increased to 738 minutes. Free unlimited access to a VR simulator for training basic endoscopic skills, without any form of obligation or assessment, did not motivate surgical residents to use the simulator. Introducing a competitive element for enhancing training time had only a marginal effect. The acquisition of expensive devices to train basic psychomotor skills for endoscopic surgery is probably only effective when it is an integrated and mandatory part of the surgical curriculum.

Variability simulations with a steady, linearized primitive equations model

NASA Technical Reports Server (NTRS)

Kinter, J. L., III; Nigam, S.

1985-01-01

Solutions of the steady, primitive equations on a sphere, linearized about a zonally symmetric basic state are computed for the purpose of simulating monthly mean variability in the troposphere. The basic states are observed, winter monthly mean, zonal means of zontal and meridional velocities, temperatures and surface pressures computed from the 15 year NMC time series. A least squares fit to a series of Legendre polynomials is used to compute the basic states between 20 H and the equator, and the hemispheres are assumed symmetric. The model is spectral in the zonal direction, and centered differences are employed in the meridional and vertical directions. Since the model is steady and linear, the solution is obtained by inversion of a block, pente-diagonal matrix. The model simulates the climatology of the GFDL nine level, spectral general circulation model quite closely, particularly in middle latitudes above the boundary layer. This experiment is an extension of that simulation to examine variability of the steady, linear solution.

Mathematical modeling of tumor-induced immunosuppression by myeloid-derived suppressor cells: Implications for therapeutic targeting strategies.

PubMed

Shariatpanahi, Seyed Peyman; Shariatpanahi, Seyed Pooya; Madjidzadeh, Keivan; Hassan, Moustapha; Abedi-Valugerdi, Manuchehr

2018-04-07

Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs. We also provide simulation models that evaluate or predict the effects of anti-MDSC drugs (e.g., l-arginine and 5-Fluorouracil (5-FU)) on the tumor growth and the restoration of anti-tumor immunity. The simulated results obtained using our model were in good agreement with the corresponding experimental findings on the expansion of splenic MDSCs, immunosuppressive effects of these cells at the tumor site and effectiveness of l-arginine and 5-FU on the re-establishment of antitumor immunity. Regarding this latter issue, our predictive simulation results demonstrated that intermittent therapy with low-dose 5-FU alone could eradicate the tumors irrespective of their origins and types. Furthermore, at the time of tumor eradication, the number of CTLs prevailed over that of cancer cells and the number of splenic MDSCs returned to the normal levels. Finally, our predictive simulation results also showed that the addition of l-arginine supplementation to the intermittent 5-FU therapy reduced the time of the tumor eradication and the number of iterations for 5-FU treatment. Thus, the present mathematical model provides important implications for designing new therapeutic strategies that aim to restore antitumor immunity by targeting MDSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inferring the Impact of Regulatory Mechanisms that Underpin CD8+ T Cell Control of B16 Tumor Growth In vivo Using Mechanistic Models and Simulation.

PubMed

Klinke, David J; Wang, Qing

2016-01-01

A major barrier for broadening the efficacy of immunotherapies for cancer is identifying key mechanisms that limit the efficacy of tumor infiltrating lymphocytes. Yet, identifying these mechanisms using human samples and mouse models for cancer remains a challenge. While interactions between cancer and the immune system are dynamic and non-linear, identifying the relative roles that biological components play in regulating anti-tumor immunity commonly relies on human intuition alone, which can be limited by cognitive biases. To assist natural intuition, modeling and simulation play an emerging role in identifying therapeutic mechanisms. To illustrate the approach, we developed a multi-scale mechanistic model to describe the control of tumor growth by a primary response of CD8+ T cells against defined tumor antigens using the B16 C57Bl/6 mouse model for malignant melanoma. The mechanistic model was calibrated to data obtained following adenovirus-based immunization and validated to data obtained following adoptive transfer of transgenic CD8+ T cells. More importantly, we use simulation to test whether the postulated network topology, that is the modeled biological components and their associated interactions, is sufficient to capture the observed anti-tumor immune response. Given the available data, the simulation results also provided a statistical basis for quantifying the relative importance of different mechanisms that underpin CD8+ T cell control of B16F10 growth. By identifying conditions where the postulated network topology is incomplete, we illustrate how this approach can be used as part of an iterative design-build-test cycle to expand the predictive power of the model.

[Development of Markov models for economics evaluation of strategies on hepatitis B vaccination and population-based antiviral treatment in China].

PubMed

Yang, P C; Zhang, S X; Sun, P P; Cai, Y L; Lin, Y; Zou, Y H

2017-07-10

Objective: To construct the Markov models to reflect the reality of prevention and treatment interventions against hepatitis B virus (HBV) infection, simulate the natural history of HBV infection in different age groups and provide evidence for the economics evaluations of hepatitis B vaccination and population-based antiviral treatment in China. Methods: According to the theory and techniques of Markov chain, the Markov models of Chinese HBV epidemic were developed based on the national data and related literature both at home and abroad, including the settings of Markov model states, allowable transitions and initial and transition probabilities. The model construction, operation and verification were conducted by using software TreeAge Pro 2015. Results: Several types of Markov models were constructed to describe the disease progression of HBV infection in neonatal period, perinatal period or adulthood, the progression of chronic hepatitis B after antiviral therapy, hepatitis B prevention and control in adults, chronic hepatitis B antiviral treatment and the natural progression of chronic hepatitis B in general population. The model for the newborn was fundamental which included ten states, i.e . susceptiblity to HBV, HBsAg clearance, immune tolerance, immune clearance, low replication, HBeAg negative CHB, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma (HCC) and death. The susceptible state to HBV was excluded in the perinatal period model, and the immune tolerance state was excluded in the adulthood model. The model for general population only included two states, survive and death. Among the 5 types of models, there were 9 initial states assigned with initial probabilities, and 27 states for transition probabilities. The results of model verifications showed that the probability curves were basically consistent with the situation of HBV epidemic in China. Conclusion: The Markov models developed can be used in economics evaluation of hepatitis B vaccination and treatment for the elimination of HBV infection in China though the structures and parameters in the model have uncertainty with dynamic natures.

Advances in asthma, allergy and immunology series 2004: basic and clinical immunology.

PubMed

Chinen, Javier; Shearer, William T

2004-08-01

This review highlights some of the most significant advances in basic and clinical immunology that were published from August 2002 to December 2003, focusing on manuscripts that appeared in the Journal. Articles selected were those considered most relevant to Journal readers. With regard to basic immunology, this report includes articles describing FcepsilonRI expression in mucosal Langerhans cells and type II dendritic cells, mechanisms of TH1 and TH2 regulation, the role of Foxp3 in the development of CD4+CD25+ regulatory T cells, and the increasing importance of Toll receptors in immunity. Articles related to clinical immunology that were selected include the first report of lymphocyte subsets values from a large cohort of normal children; the description of new genetic defects in primary immunodeficiencies; a description of the complications of gene therapy for X-linked severe combined immunodeficiency; a report of 79 patients with hyper-IgM syndrome; a report of the mechanism of action and complications of intravenous immunoglobulin; a report of new approaches for immunotherapy; and an article on advances in HIV infection and management, including a report of defensins, small molecules with anti-HIV properties. Also summarized is an article that studied the immune system during a prolonged stay in the Antarctic, a model for human studies on the effect of environmental conditions similar to space expeditions.

A Novel Energy-Efficient Multi-Sensor Fusion Wake-Up Control Strategy Based on a Biomimetic Infectious-Immune Mechanism for Target Tracking.

PubMed

Zhou, Jie; Liang, Yan; Shen, Qiang; Feng, Xiaoxue; Pan, Quan

2018-04-18

A biomimetic distributed infection-immunity model (BDIIM), inspired by the immune mechanism of an infected organism, is proposed in order to achieve a high-efficiency wake-up control strategy based on multi-sensor fusion for target tracking. The resultant BDIIM consists of six sub-processes reflecting the infection-immunity mechanism: occurrence probabilities of direct-infection (DI) and cross-infection (CI), immunity/immune-deficiency of DI and CI, pathogen amount of DI and CI, immune cell production, immune memory, and pathogen accumulation under immunity state. Furthermore, a corresponding relationship between the BDIIM and sensor wake-up control is established to form the collaborative wake-up method. Finally, joint surveillance and target tracking are formulated in the simulation, in which we show that the energy cost and position tracking error are reduced to 50.8% and 78.9%, respectively. Effectiveness of the proposed BDIIM algorithm is shown, and this model is expected to have a significant role in guiding the performance improvement of multi-sensor networks.

Structure-based design of ligands for protein basic domains: Application to the HIV-1 Tat protein

NASA Astrophysics Data System (ADS)

Filikov, Anton V.; James, Thomas L.

1998-05-01

A methodology has been developed for designing ligands to bind a flexible basic protein domain where the structure of the domain is essentially known. It is based on an empirical binding free energy function developed for highly charged complexes and on Monte Carlo simulations in internal coordinates with both the ligand and the receptor being flexible. HIV-1 encodes a transactivating regulatory protein called Tat. Binding of the basic domain of Tat to TAR RNA is required for efficient transcription of the viral genome. The structure of a biologically active peptide containing the Tat basic RNA-binding domain is available from NMR studies. The goal of the current project is to design a ligand which will bind to that basic domain and potentially inhibit the TAR-Tat interaction. The basic domain contains six arginine and two lysine residues. Our strategy was to design a ligand for arginine first and then a superligand for the basic domain by joining arginine ligands with a linker. Several possible arginine ligands were obtained by searching the Available Chemicals Directory with DOCK 3.5 software. Phytic acid, which can potentially bind multiple arginines, was chosen as a building block for the superligand. Calorimetric binding studies of several compounds to methylguanidine and Arg-/Lys-containing peptides were performed. The data were used to develop an empirical binding free energy function for prediction of affinity of the ligands for the Tat basic domain. Modeling of the conformations of the complexes with both the superligand and the basic domain being flexible has been carried out via Biased Probability Monte Carlo (BPMC) simulations in internal coordinates (ICM 2.6 suite of programs). The simulations used parameters to ensure correct folding, i.e., consistent with the experimental NMR structure of a 25-residue Tat peptide, from a random starting conformation. Superligands for the basic domain were designed by joining together two molecules of phytic acid with peptidic and peptidomimetic linkers. The linkers were refined by varying the length and side chains of the linking residues, carrying out BPMC simulations, and evaluation of the binding free energy for the best energy conformation. The dissociation constant of the best ligand designed is estimated to be in the low- to mid-nanomolar range.

How Does the Macula Protect Itself from Oxidative Stress?

PubMed Central

Handa, James T.

2012-01-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. PMID:22503691

How does the macula protect itself from oxidative stress?

PubMed

Handa, James T

2012-08-01

Oxidative stress has been hypothesized to contribute to the development of age-related macular degeneration (AMD), the most common cause of blindness in the United States. At present, there is no treatment for early disease. Reactive oxygen species (ROS) play a physiological role in the retinal pigment epithelium (RPE), a key cell type in this disease, but with excessive ROS, oxidative damage or excessive innate immune system activation can result. The RPE has developed a robust antioxidant system driven by the transcription factor Nrf2. Impaired Nrf2 signaling can lead to oxidative damage or activate the innate immune response, both of which can lead to RPE apoptosis, a defining change in AMD. Several mouse models simulating environmental stressors or targeting specific antioxidant enzymes such as superoxide dismutase or Nrf2, have simulated some of the features of AMD. While ROS are short-lived, oxidatively damaged molecules termed oxidation specific epitopes (OSEs), can be long-lived and a source of chronic stress that activates the innate immune system through pattern recognition receptors (PRRs). The macula accumulates a number of OSEs including carboxyethylpyrrole, malondialdehyde, 4-hydroxynonenal, and advanced glycation endproducts, as well as their respective neutralizing PRRs. Excessive accumulation of OSEs results in pathologic immune activation. For example, mice immunized with the carboxyethylpyrrole develop cardinal features of AMD. Regulating ROS in the RPE by modulating antioxidant systems or neutralizing OSEs through an appropriate innate immune response are potential modalities to treat or prevent early AMD. Copyright © 2012 Elsevier Ltd. All rights reserved.

Proteflazid® and local immunity in diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections.

PubMed

Kaminsky, Vjacheslav; Chernyshov, Viktor; Grynevych, Oleksandr; Benyuk, Vasil; Kornatskaya, Alla; Shalko, Miroslava; Usevich, Igor; Revenko, Oleg; Shepetko, Maxim; Solomakha, Ludmila

2017-03-21

Reporting of clinical trials results for Proteflazid® in the drug formulation suppositories and vaginal swabs soaked in the solution of the drug to the local immunity of the female reproductive tract. The aim of study was to examine the state of local immunity in the reproductive tract of women with sexually transmitted diseases caused by human papillomavirus, herpes viruses (Type 1, 2) and mixed infection (herpes viruses + chlamydia). The trials involved 216 women with viral sexually transmitted diseases: Cervical Dysplasia associated with papillomavirus infection (HPV) (Group 1); Herpes genitalis type 1 (HSV- 1) and type 2 (HSV-1) (Group 2); mixed infection - HSV-1, HSV-2 and chlamydia (Group 3). Treatment results have confirmed that Proteflazid® contributes to sustainable performance improvement of basic factors of local immunity - sIgA, lysozyme and complement component C3 in the cervical mucus for all three groups of women. Proteflazid® enhances level of local immunity markers (sIgA, lysozyme, C3 complement component) and improves their ratios. Also it intensifies anticontagious activity of mucosal protection and female reproductive system as whole, during treatment diseases caused by human papillomavirus, herpesvirus and mixed urogenital infections (herpesvirus and chlamydia).

Parainflammation, chronic inflammation and age-related macular degeneration

PubMed Central

Chen, Mei; Xu, Heping

2016-01-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune privileged tissue due to its unique anatomical and physiological properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate immune system, particularly microglia and the complement system, undergo low levels of activation (para-inflammation). In many cases, this para-inflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration (AMD), this para-inflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal para-inflammation include genetic predisposition, environmental risk factors and old age. Dysregulated para-inflammation (chronic inflammation) in AMD damages the blood retina barrier (BRB), resulting in the breach of retinal immune privilege leading to the development of retinal lesions. This review discusses the basic principles of retinal innate immune responses to endogenous chronic insults in normal aging and in AMD, and explores the difference between beneficial para-inflammation and the detrimental chronic inflammation in the context of AMD. PMID:26292978

Immune cell functions in pancreatic cancer.

PubMed

Plate, J M; Harris, J E

2000-01-01

Pancreatic cancer kills nearly 29,000 people in the United States annually-as many people as are diagnosed with the disease. Chemotherapeutic treatment is ineffective in halting progression of the disease. Yet, specific immunity to pancreatic tumor cells in subjects with pancreatic cancer has been demonstrated repeatedly during the last 24 years. Attempts to expand and enhance tumor-specific immunity with biotherapy, however, have not met with success. The question remains, "Why can't specific immunity regulate pancreatic cancer growth?" The idea that tumor cells have evolved protective mechanisms against immunity was raised years ago and has recently been revisited by a number of research laboratories. In pancreatic cancer, soluble factors produced by and for the protection of the tumor environment have been detected and are often distributed to the victim's circulatory system where they may effect a more generalized immunosuppression. Yet the nature of these soluble factors remains controversial, since some also serve as tumor antigens that are recognized by the same T cells that may become inactivated by them. Unless the problem of tumor-derived immunosuppressive products is addressed directly through basic and translational research studies, successful biotherapeutic treatment for pancreatic cancer may not be forthcoming.

What Controls the Acute Viral Infection Following Yellow Fever Vaccination?

PubMed

Moore, James; Ahmed, Hasan; Jia, Jonathan; Akondy, Rama; Ahmed, Rafi; Antia, Rustom

2018-01-01

Does target cell depletion, innate immunity, or adaptive immunity play the dominant role in controlling primary acute viral infections? Why do some individuals have higher peak virus titers than others? Answering these questions is a basic problem in immunology and can be particularly difficult in humans due to limited data, heterogeneity in responses in different individuals, and limited ability for experimental manipulation. We address these questions for infections following vaccination with the live attenuated yellow fever virus (YFV-17D) by analyzing viral load data from 80 volunteers. Using a mixed effects modeling approach, we find that target cell depletion models do not fit the data as well as innate or adaptive immunity models. Examination of the fits of the innate and adaptive immunity models to the data allows us to select a minimal model that gives improved fits by widely used model selection criteria (AICc and BIC) and explains why it is hard to distinguish between the innate and adaptive immunity models. We then ask why some individuals have over 1000-fold higher virus titers than others and find that most of the variation arises from differences in the initial/maximum growth rate of the virus in different individuals.

Teaching basic lung isolation skills on human anatomy simulator: attainment and retention of lung isolation skills.

PubMed

Latif, Rana K; VanHorne, Edgar M; Kandadai, Sunitha Kanchi; Bautista, Alexander F; Neamtu, Aurel; Wadhwa, Anupama; Carter, Mary B; Ziegler, Craig H; Memon, Mohammed Faisal; Akça, Ozan

2016-01-20

Lung isolation skills, such as correct insertion of double lumen endobronchial tube and bronchial blocker, are essential in anesthesia training; however, how to teach novices these skills is underexplored. Our aims were to determine (1) if novices can be trained to a basic proficiency level of lung isolation skills, (2) whether video-didactic and simulation-based trainings are comparable in teaching lung isolation basic skills, and (3) whether novice learners' lung isolation skills decay over time without practice. First, five board certified anesthesiologist with experience of more than 100 successful lung isolations were tested on Human Airway Anatomy Simulator (HAAS) to establish Expert proficiency skill level. Thirty senior medical students, who were naive to bronchoscopy and lung isolation techniques (Novice) were randomized to video-didactic and simulation-based trainings to learn lung isolation skills. Before and after training, Novices' performances were scored for correct placement using pass/fail scoring and a 5-point Global Rating Scale (GRS); and time of insertion was recorded. Fourteen novices were retested 2 months later to assess skill decay. Experts' and novices' double lumen endobronchial tube and bronchial blocker passing rates showed similar success rates after training (P >0.99). There were no differences between the video-didactic and simulation-based methods. Novices' time of insertion decayed within 2 months without practice. Novices could be trained to basic skill proficiency level of lung isolation. Video-didactic and simulation-based methods we utilized were found equally successful in training novices for lung isolation skills. Acquired skills partially decayed without practice.

A practical 3D printed simulator for endoscopic endonasal transsphenoidal surgery to improve basic operational skills.

PubMed

Wen, Guodao; Cong, ZiXiang; Liu, KaiDong; Tang, Chao; Zhong, Chunyu; Li, Liwen; Dai, XuJie; Ma, Chiyuan

2016-06-01

We aimed to present a practical three-dimensional (3D) printed simulator to comprehensively and effectively accelerate the learning curve of endoscopic endonasal transsphenoidal surgery (EETS). The 3D printed simulator consists of three parts: (1) skull frame, (2) the nasal passage and the nasal alar of the face, and (3) a modified sella turcica. We aimed to improve three basic operational skills of surgeons: drilling, curetting, and aspirating. Eighteen neurosurgeons and five post-graduates were recruited and consented for the training. For trainees, (1) as the training progressed, the scores increased gradually, (2) a significant increase in the average scores was observed in the tenth training compared to the first training, and (3) there is a significant decrease in trainee variability in the shortening of the gap. The 18 neurosurgeons were divided into three groups: experts, assistants, and observers. For all three basic operations, (1) the average score of experts was obviously higher than that of the assistants, observers, and trainees' tenth training and (2) the average scores of assistants and observers were obviously higher than that of trainees' first training. A significant high in the average score between the assistants and the observers was seen for aspirating, but not for drilling or curetting. For curetting and aspirating, the tenth training average score of trainees was obviously higher than that of assistants and observers. This 3D printed simulator allows different endoscopic basic operations to be simulated and improves the EETS techniques of surgeons. We believed it to be a practical, simple, and low-cost simulator.

Monte Carlo Computer Simulation of a Rainbow.

ERIC Educational Resources Information Center

Olson, Donald; And Others

1990-01-01

Discusses making a computer-simulated rainbow using principles of physics, such as reflection and refraction. Provides BASIC program for the simulation. Appends a program illustrating the effects of dispersion of the colors. (YP)

AIDS and Child Care: A Booklet for Child Care Workers, Management Committees and Parents.

ERIC Educational Resources Information Center

Fricke, Caroline; Glasson, Mark

This booklet provides Australians with basic information about the Acquired Immune Deficiency Syndrome (AIDS). Contents cover the definiton of AIDS, ways the disease is transmitted, Human Immunodeficiency Virus (HIV) antibody testing for adults and children, variations among children infected with HIV, information that HIV is not transmitted…

Are School Districts Immune to a Weak Economy? Don't Believe It!

ERIC Educational Resources Information Center

Horner, Jeffrey

2009-01-01

Why should school districts worry about today's down economy? After all, the vast majority of their income comes from state legislatures and local property taxes, with some additional funding from the federal government. This funding is unaffected by downturns in sales, the stock market, and other basic economic indicators. School business…

An Unforgiving Enemy: AIDS. Student Reader and Teacher's Guide.

ERIC Educational Resources Information Center

Adult Education Services, Johnstown, PA.

These adult basic education instructional materials on the prevention of Acquired Immune Deficiency Syndrome (AIDS) include a student reader and a teacher's guide. The student reader contains six chapters. Chapter 1 introduces two characters--Ricco and Francis--and focuses on the definition of AIDS, the three stages of the disease, the cause, and…

Bypassing An Open-Circuit Power Cell

NASA Technical Reports Server (NTRS)

Wannemacher, Harry E.

1994-01-01

Collection of bypass circuits enables battery consisting series string of cells to continue to function when one of its cells fails in open-circuit (high-resistance) condition. Basic idea simply to shunt current around defective cell to prevent open circuit from turning off battery altogether. Bypass circuits dissipate little power and are nearly immune to false activation.

Mommy, Daddy--What's AIDS?

ERIC Educational Resources Information Center

National Association of Pediatric Nurse Associates and Practitioners, Cherry Hill, NJ.

This brochure is designed to help parents answer the questions that their children may ask them about Acquired Immune Deficiency Syndrome (AIDS) and the Human Immuno Deficiency Virus (HIV), the virus that causes AIDS. It provides basic information about AIDS and HIV, as well as sources for further information, such as the National AIDS Hotline. It…

Impact of oral rehydration and selected public health interventions on reduction of mortality from childhood diarrhoeal diseases in Mexico.

PubMed Central

Gutiérrez, G.; Tapia-Conyer, R.; Guiscafré, H.; Reyes, H.; Martínez, H.; Kumate, J.

1996-01-01

Reported are the results of an analysis of mortality trends from diarrhoeal diseases among under-5-year-olds in Mexico between 1978 and 1993 in relation to the impact of education, basic sanitation, and selected medical care practices. The study period was divided into three stages; the first pre-dated the widespread application of oral rehydration therapy (ORT); the second, covered the implementation of a nationwide programme promoting ORT; and the third included additional measures, such as immunization and improvements in basic sanitation. Mortality rates decreased progressively, at an average of 1.8% per year in the first stage, 6.4% in the second, and 17.8% in the third. The importance of literacy campaigns for women and the promotion of ORT was confirmed. Both of these measures reduced mortality; however, a greater reduction resulted from a massive immunization campaign against measles and improvements in sanitation (expansion of the drainage and piped water systems, improved water chlorination procedure, and effective prohibition of the use of sanitary sewage for vegetable irrigation). PMID:8706235

Highlights of the advances in basic immunology in 2011.

PubMed

Liu, Juan; Liu, Shuxun; Cao, Xuetao

2012-05-01

In this review, we summarize the major fundamental advances in immunological research reported in 2011. The highlights focus on the improved understanding of key questions in basic immunology, including the initiation and activation of innate responses as well as mechanisms for the development and function of various T-cell subsets. The research includes the identification of novel cytosolic RNA and DNA sensors as well as the identification of the novel regulators of the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway. Moreover, remarkable advances have been made in the developmental and functional properties of innate lymphoid cells (ILCs). Helper T cells and regulatory T (Treg) cells play indispensable roles in orchestrating adaptive immunity. There have been exciting discoveries regarding the regulatory mechanisms of the development of distinct T-cell subsets, particularly Th17 cells and Treg cells. The emerging roles of microRNAs (miRNAs) in T cell immunity are discussed, as is the recent identification of a novel T-cell subset referred to as follicular regulatory T (TFR) cells.

Highlights of the advances in basic immunology in 2011

PubMed Central

Liu, Juan; Liu, Shuxun; Cao, Xuetao

2012-01-01

In this review, we summarize the major fundamental advances in immunological research reported in 2011. The highlights focus on the improved understanding of key questions in basic immunology, including the initiation and activation of innate responses as well as mechanisms for the development and function of various T-cell subsets. The research includes the identification of novel cytosolic RNA and DNA sensors as well as the identification of the novel regulators of the Toll-like receptor (TLR) and retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) signaling pathway. Moreover, remarkable advances have been made in the developmental and functional properties of innate lymphoid cells (ILCs). Helper T cells and regulatory T (Treg) cells play indispensable roles in orchestrating adaptive immunity. There have been exciting discoveries regarding the regulatory mechanisms of the development of distinct T-cell subsets, particularly Th17 cells and Treg cells. The emerging roles of microRNAs (miRNAs) in T cell immunity are discussed, as is the recent identification of a novel T-cell subset referred to as follicular regulatory T (TFR) cells. PMID:22522654

Virtual reality based surgery simulation for endoscopic gynaecology.

PubMed

Székely, G; Bajka, M; Brechbühler, C; Dual, J; Enzler, R; Haller, U; Hug, J; Hutter, R; Ironmonger, N; Kauer, M; Meier, V; Niederer, P; Rhomberg, A; Schmid, P; Schweitzer, G; Thaler, M; Vuskovic, V; Tröster, G

1999-01-01

Virtual reality (VR) based surgical simulator systems offer very elegant possibilities to both enrich and enhance traditional education in endoscopic surgery. However, while a wide range of VR simulator systems have been proposed and realized in the past few years, most of these systems are far from able to provide a reasonably realistic surgical environment. We explore the basic approaches to the current limits of realism and ultimately seek to extend these based on our description and analysis of the most important components of a VR-based endoscopic simulator. The feasibility of the proposed techniques is demonstrated on a first modular prototype system implementing the basic algorithms for VR-training in gynaecologic laparoscopy.

Simulation research of the tire Basic Relaxation Model in conditions of the wheel cornering angle oscillations

NASA Astrophysics Data System (ADS)

Luty, W.

2016-09-01

- A description of the tire Basic Relaxation Model (BRM) is presented in this paper. Simulation research of the tire BRM model in conditions of oscillatory changes of the wheel cornering angle were performed. During the simulation tests the courses of changes in the value of lateral reaction force, transmitted by the wheel, as a response to the sinusoidal changes in the value of the wheel cornering angle have been presented. There have been compared the simulation results obtained for the model of tire-road interaction in two modes: including and not including the BRM. The simulation results allowed to verify prepared BRM and also to determine the influence of the tire relaxation process on the tire behavior in conditions of dynamic changes of the wheel cornering angle.

Studying the Effect of Radiation in the Context of Deep Space Travel

NASA Technical Reports Server (NTRS)

Bhattacharya, Sharmila; Gilbert, Rachel R.; Lo, Rachel

2017-01-01

While it has been shown that decades of astronauts and cosmonauts can suffer from illnesses both during and after spaceflight, the underlying causes are still poorly understood, due in part to the fact that there are so many variables to consider when investigating the human immune system in a complex environment. Invertebrates have become popular models for studying human disease because they are cheap, highly amenable to experimental manipulation, and have innate immune systems with a high genetic similarity to humans. Fruit flies (Drosophila melanogaster) have been shown to experience a dramatic shift in immune gene expression following spaceflight, but are still able to fight off infections when exposed to bacteria. However, the common bacterial pathogen Serratia marcescens was shown to become more lethal to fruit flies after being cultured in space, suggesting that not only do we need to consider host changes in susceptibility, but also changes in the pathogen itself after spaceflight conditions. Being able to simulate spaceflight conditions in a controlled environment on the ground gives us the ability to not only evaluate the effects of microgravity on the host immune system, but also how the microorganisms that cause immune disorders are being affected by these drastic environmental shifts. In this study, I use a ground-based simulated microgravity environment to examine the genetic changes associated with increased S. marcescens virulence in order to understand how microgravity is affecting this pathogen, as well as how these genetic changes influence and interact with the host immune system. This study will provide us with more directed approaches to studying the effects of spaceflight on human beings, with the ultimate goal of being able to counteract immune dysfunction in future space exploration.

Relative stress corrosion susceptibilities of alloys 690 and 600 in simulated boiling water reactor environments

NASA Astrophysics Data System (ADS)

Page, R. A.; McMinn, A.

1986-05-01

The relative susceptibilities of alloys 600 and 690 to intergranular stress corrosion cracking (IGSCC) in pure water and a simulated resin intrusion environment at 288 °C were evaluated. A combination of creviced and noncreviced slow-strain-rate, and precracked fracture mechanics tests were employed in the evaluation. Susceptibility was determined as a function of dissolved oxygen content, degree of sensitization, and crevice condition. The results indicated that alloy 600 was susceptible to various degrees of IGSCC in oxygen containing pure water when creviced, and immune to IGSCC when uncreviced. Alloy 690 was immune to IGSCC under all pure water conditions examined. Alloy 600 and alloy 690 were both susceptible to cracking in the simulated resin intrusion environment. Alloy 690, however, exhibited the greatest resistance to SCC of the two alloys.

The role of the plasma membrane H+-ATPase in plant-microbe interactions.

PubMed

Elmore, James Mitch; Coaker, Gitta

2011-05-01

Plasma membrane (PM) H+-ATPases are the primary pumps responsible for the establishment of cellular membrane potential in plants. In addition to regulating basic aspects of plant cell function, these enzymes contribute to signaling events in response to diverse environmental stimuli. Here, we focus on the roles of the PM H+-ATPase during plant-pathogen interactions. PM H+-ATPases are dynamically regulated during plant immune responses and recent quantitative proteomics studies suggest complex spatial and temporal modulation of PM H+-ATPase activity during early pathogen recognition events. Additional data indicate that PM H+-ATPases cooperate with the plant immune signaling protein RIN4 to regulate stomatal apertures during bacterial invasion of leaf tissue. Furthermore, pathogens have evolved mechanisms to manipulate PM H+-ATPase activity during infection. Thus, these ubiquitous plant enzymes contribute to plant immune responses and are targeted by pathogens to increase plant susceptibility.

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

Steven Larson MD

This project funded since 1986 serves as a core project for cancer research throughout MSKCC, producing key radiotracers as well as basic knowledge about thel physics of radiation decay and imaging, for nuclear medicine applications to cancer diagnosis and therapy. In recent years this research application has broadened to include experiments intended to lead to an improved understanding of cancer biology and into the discovery and testing of new cancer drugs. Advances in immune based radiotargeting form the basis for this project. Both antibody and cellular based immune targeting methods have been explored. The multi-step targeting methodologies (MST) developed bymore » NeoRex (Seattle,Washington), have been adapted for use with positron emitting isotopes and PET allowing the quantification and optimization of targeted delivery. In addition, novel methods for radiolabeling immune T-cells with PET tracers have advanced our ability to track these cells of prolonged period of time.« less

Current Efforts and Future Prospects in the Development of Live Mycobacteria as Vaccines

PubMed Central

Porcelli, Steven A.; Ng, Tony W.; Saavedra-Avila, Noemi A; Kennedy, Steven C.; Carreno, Leandro J.

2016-01-01

Summary The development of more effective vaccines against Mycobacterium tuberculosis (Mtb) remains a major goal in the effort to reduce the enormous global burden of disease caused by this pathogen. Whole-cell vaccines based on live mycobacteria with attenuated virulence represent an appealing approach, providing broad antigen exposure and intrinsic adjuvant properties to prime durable immune responses. However, designing vaccine strains with an optimal balance between attenuation and immunogenicity has proven to be extremely challenging. Recent basic and clinical research efforts have broadened our understanding of Mtb pathogenesis and created numerous new vaccine candidates that are designed to overcome different aspects of immune evasion by Mtb. In this review, we provide an overview of current efforts to create improved vaccines against tuberculosis based on modifications of live attenuated mycobacteria. In addition, we discuss the use of such vaccine strains as vectors for stimulating protective immunity against other infectious diseases and cancers. PMID:26366616

Basic science for the clinician 53: mast cells.

PubMed

Sigal, Leonard H

2011-10-01

Mast cells stand at the interface between the innate immune system and the acquired (adaptive) immune response, serving as sentinels detecting invaders and directing a concerted and coordinated response. Mast cells reside immediately under body surfaces and within lymph nodes, near blood vessels and nerves, perfectly situated to for early detection and defense. They secrete a wide array of prostanoids, cytokines, chemokines, and other proteins mediators and modifiers of a variety of immune and inflammatory functions and bear surface markers suggesting broad functions, including as antigen-presenting cells. Although usually not given their due in medical school lectures, there is great likelihood that mast cells will be implicated in the pathogenesis of rheumatoid arthritis, scleroderma, multiple sclerosis, and perhaps cancer. Thus, better insights into mast cell functions and mast cell-derived effector molecules should command our attention as we move forward in better understanding disease immunopathogenesis and directed intelligent therapeutics development.

Immune heterogeneity in neuroinflammation: dendritic cells in the brain.

PubMed

Colton, Carol A

2013-03-01

Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72

PubMed Central

Asea, Alexzander

2007-01-01

Heat shock proteins exert their beneficial effects via basically two modes of action depending on their relative location within the host. Intracellular heat shock proteins found within cells serve a cytoprotective role by chaperoning naïve, misfolded and/or denatured proteins in response to stressful stimuli by a process known as the stress response. However, stressful stimuli also induce the release of intracellular heat shock proteins into the extracellular milieu and circulation. The extracellular heat shock protein proteins serve a cytostimulatory role by initiating immune responses designed to fend off microbial infection and destroy neoplastic transformed cells. This review will briefly cover recent advances into elucidating the mechanism(s) by which stress induces the release of heat shock proteins into the circulation, how it initiates immune responses and suggest the possible biological significance of circulating Hsp to the host. PMID:17502920

Initiation of the Immune Response by Extracellular Hsp72: Chaperokine Activity of Hsp72.

PubMed

Asea, Alexzander

2006-08-01

Heat shock proteins exert their beneficial effects via basically two modes of action depending on their relative location within the host. Intracellular heat shock proteins found within cells serve a cytoprotective role by chaperoning naïve, misfolded and/or denatured proteins in response to stressful stimuli by a process known as the stress response. However, stressful stimuli also induce the release of intracellular heat shock proteins into the extracellular milieu and circulation. The extracellular heat shock protein proteins serve a cytostimulatory role by initiating immune responses designed to fend off microbial infection and destroy neoplastic transformed cells. This review will briefly cover recent advances into elucidating the mechanism(s) by which stress induces the release of heat shock proteins into the circulation, how it initiates immune responses and suggest the possible biological significance of circulating Hsp to the host.

The unresponsiveness of the immune system of the rat to hypergravity

NASA Technical Reports Server (NTRS)

Scibetta, S. M.; Caren, L. D.; Oyama, J.

1984-01-01

The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

Evaluation of mucoadhesive carrier adjuvant: toward an oral anthrax vaccine.

PubMed

Mangal, Sharad; Pawar, Dilip; Agrawal, Udita; Jain, Arvind K; Vyas, Suresh P

2014-02-01

The aim of present study was to evaluate the potential of mucoadhesive alginate-coated chitosan microparticles (A-CHMp) for oral vaccine against anthrax. The zeta potential of A-CHMp was -29.7 mV, and alginate coating could prevent the burst release of antigen in simulated gastric fluid. The results indicated that A-CHMp was mucoadhesive in nature and transported it to the peyer's patch upon oral delivery. The immunization studies indicated that A-CHMp resulted in the induction of potent systemic and mucosal immune responses, whereas alum-adjuvanted rPA could induce only systemic immune response. Thus, A-CHMp represents a promising acid carrier adjuvant for oral immunization against anthrax.

Pitting Behavior of L415 Pipeline Steel in Simulated Leaching Liquid Environment

NASA Astrophysics Data System (ADS)

Wan, H. X.; Yang, X. J.; Liu, Z. Y.; Song, D. D.; Du, C. W.; Li, X. G.

2017-02-01

The corrosion behavior and laws of the west-east gas pressure pipeline of L415 steel were studied in simulated leaching liquid. The failure of the L415 steel during the pressure testing process was investigated using electrochemical polarization, electrochemical impedance spectroscopy, and immersion test. The corrosion rate of the L415 steel increased with ion concentration in the leaching liquid. This rate reached about 0.8 mm a-1 and belonged to the severe corrosion grade. Pitting corrosion was observed in various simulated solutions with different aggressive species concentrations. The original ion concentration in the leaching liquid (1×) is the key factor influencing pitting initiation and development. Pitting showed easy nucleation, and its growth rate was relatively slow, in the basic simulating solution of the leach liquid (i.e., the ion content is compactable to the real condition in the rust on the inner steel pipe surface). Pitting was also highly sensitive and easily grew in the solution with doubled ion concentration in the basic simulating solution (2×). A uniform corrosion, instead of pitting, mainly occurred when the ion concentration was up to 10× of the basic solution.

A Simulation for Teaching the Basic and Clinical Science of Fluid Therapy

ERIC Educational Resources Information Center

Rawson, Richard E.; Dispensa, Marilyn E.; Goldstein, Richard E.; Nicholson, Kimberley W.; Vidal, Noni Korf

2009-01-01

The course "Management of Fluid and Electrolyte Disorders" is an applied physiology course taught using lectures and paper-based cases. The course approaches fluid therapy from both basic science and clinical perspectives. While paper cases provide a basis for application of basic science concepts, they lack key components of genuine clinical…

Immunization of ducks for type C botulism.

PubMed

Martinez, R; Wobeser, G

1999-10-01

A single subcutaneous immunization with a vaccine used for protecting ranch mink (Mustela vison) against type C botulism reduced morbidity and mortality in mallard (Anas platyrhynchos) and northern pintail (Anas acuta) ducks challenged with approximately 4.5 x 10(4) and 2.25 x 10(4) mouse lethal doses (MLD50), respectively, of botulinum toxin at 10 and 15 days post-immunization (pi). There was no significant protection at 5 days pi. Protection persisted in mallards for 90 days pi. To simulate use of vaccine as a part of treatment of sick birds in the field, mallards were exposed to toxin and, when clinical signs were evident, each bird was treated by intraperitoneal injection of type C botulinum antitoxin and one-half of the birds were immunized. Immunization had no significant effect on recovery from intoxication. At 10 days posttreatment, all birds were challenged with toxin. Clinical signs and mortality were significantly less frequent among immunized birds than among non-immunized birds after the second exposure. Immunization might be useful as part of the treatment regimen in botulism outbreaks.

Evaluation of Sintering Behaviors of Saprolitic Nickeliferous Laterite Based on Quaternary Basicity

NASA Astrophysics Data System (ADS)

Luo, Jun; Li, Guanghui; Rao, Mingjun; Zhang, Yuanbo; Peng, Zhiwei; Zhi, Qian; Jiang, Tao

2015-09-01

The sintering behaviors of saprolitic nickeliferous laterite with various quaternary basicities [(CaO + MgO)/(SiO2 + Al2O3) mass ratio] in a reductive atmosphere are investigated by simulative sintering and validated by sintering pot tests. The simulative sintering results show that the generation of diopside (CaMgSi2O6) with low melting point is the key reason for the decrease in characteristic fusion temperatures when the quaternary basicity increases from 0.5 to 0.8-1.0. Continuous increase of basicity leads to transformation of diopside (CaMgSi2O6) into akermanite (Ca2MgSi2O7), which adversely increases the characteristic fusion temperatures. These findings are confirmed by the sinter pot tests, which demonstrate that the sintering indexes including vertical sintering velocity (VSV), yield ( Y), and productivity ( P), can be improved by optimizing quaternary basicity. At basicity of 1.0, the VSV, Y, P, and ISO tumbling index reach 49.2 mm/min, 80.5%, 1.0 t/(h m2), and 66.5%, respectively.

Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry Modelling Under Saturated Absorption

NASA Astrophysics Data System (ADS)

Dupré, Patrick

2015-06-01

The Noise-Immune Cavity-Enhanced Optical Heterodyne Molecular Spectrometry (NICE-OHMS) is a modern technique renowned for its ultimate sensitivity, because it combines long equivalent absorption length provided by a high finesse cavity, and a detection theoretically limited by the sole photon-shot-noise. One fallout of the high finesse is the possibility to accumulating strong intracavity electromagnetic fields (EMF). Under this condition, molecular transitions can be easy saturated giving rise to the usual Lamb dips (or hole burning). However, the unusual shape of the basically trichromatic EMF (due to the RF lateral sidebands) induces nonlinear couplings, i.e., new crossover transitions. An analytical methodology will be presented to calculate spectra provided by NICE-OHMS experiments. It is based on the solutions of the equations of motion of an open two-blocked-level system performed in the frequency-domain (optically thin medium). Knowing the transition dipole moment, the NICE-OHMS signals (``absorption-like'' and ``dispersion-like'') can be simulated by integration over the Doppler shifts and by paying attention to the molecular Zeeman sublevels and to the EMF polarization The approach has been validated by discussion experimental data obtained on two transitions of {C2H2} in the near-infrared under moderated saturation. One of the applications of the saturated absorption is to be able to simultaneously determine the transition intensity and the density number while only one these 2 quantities can only be assessed in nonlinear absorption. J. Opt. Soc. Am. B 32, 838 (2015) Optics Express 16, 14689 (2008)

Local and systemic tumor immune dynamics

NASA Astrophysics Data System (ADS)

Enderling, Heiko

Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

A short history of research on immunity to infectious diseases in fish.

PubMed

Van Muiswinkel, Willem B; Nakao, Miki

2014-04-01

This review describes the history of research on immunity to infectious diseases of fish in the period between 1965 and today. Special attention is paid to those studies, which are dealing with the interaction between immune system and invading pathogens in bony fish. Moreover, additional biographic information will be provided of people involved. In the 1960s and 1970s the focus of most studies was on humoral (Ig, B-cell) responses. Thorough studies on specific cellular (T-cell) responses and innate immunity (lectins, lysozyme, interferon, phagocytic cells) became available later. In the period between 1980 and today an overwhelming amount of data on regulation (e.g. cell cooperation, cytokines) and cell surface receptors (e.g. T-cell receptor; MHC) was published. It became also clear, that innate responses were often interacting with the acquired immune responses. Fish turned out to be vertebrates like all others with a sophisticated immune system showing specificity and memory. These basic data on the immune system could be applied in vaccination or in selection of disease resistant fish. Successful vaccines against bacterial diseases became available in the 1970s and 1980s. Effective anti-viral vaccines appeared from the 1980s onwards. There is no doubt, that Fish Immunology has become a flourishing science by the end of the 20th century and has contributed to our understanding of fish diseases as well as the success of aquaculture. Copyright © 2013 Elsevier Ltd. All rights reserved.

A basic mathematical model of the immune response

NASA Astrophysics Data System (ADS)

Mayer, H.; Zaenker, K. S.; an der Heiden, U.

1995-03-01

Interaction of the immune system with a target population of, e.g., bacteria, viruses, antigens, or tumor cells must be considered as a dynamic process. We describe this process by a system of two ordinary differential equations. Although the model is strongly idealized it demonstrates how the combination of a few proposed nonlinear interaction rules between the immune system and its targets are able to generate a considerable variety of different kinds of immune responses, many of which are observed both experimentally and clinically. In particular, solutions of the model equations correspond to states described by immunologists as ``virgin state,'' ``immune state'' and ``state of tolerance.'' The model successfully replicates the so-called primary and secondary response. Moreover, it predicts the existence of a threshold level for the amount of pathogen germs or of transplanted tumor cells below which the host is able to eliminate the infectious organism or to reject the tumor graft. We also find a long time coexistence of targets and immune competent cells including damped and undamped oscillations of both. Plausibly the model explains that if the number of transformed cells or pathogens exeeds definable values (poor antigenicity, high reproduction rate) the immune system fails to keep the disease under control. On the other hand, the model predicts apparently paradoxical situations including an increased chance of target survival despite enhanced immune activity or therapeutically achieved target reduction. A further obviously paradoxical behavior consists of a positive effect for the patient up to a complete cure by adding an additional target challenge where the benefit of the additional targets depends strongly on the time point and on their amount. Under periodically pulsed stimulation the model may show a chaotic time behavior of both target growth and immune response.

More than Fever: Thermoregulatory Responses to Immunological Stimulation and Consequences of Thermoregulatory Strategy on Innate Immunity in Gopher Tortoises (Gopherus polyphemus).

PubMed

Goessling, Jeffrey M; Guyer, Craig; Mendonça, Mary T

Organisms possess a range of thermoregulatory strategies that may vary in response to sickness, thereby driving important life-history consequences. Because the immune system is vital to maintaining organism function, understanding the suite of immune responses to infection indicates basic costs and benefits of physiological strategies. Here, we assessed consequences of thermoregulation and seasonality on immune function in both immunologically stimulated and nonstimulated gopher tortoises (Gopherus polyphemus). An ectothermic vertebrate was used as an experimental model because the effects of thermoregulation on immunity remain understudied and are of increasing importance in light of anthropogenic alterations to thermal environments. We found that G. polyphemus increased body temperature (T b ) at 1 h after injection with lipopolysaccharide (LPS) when compared with saline controls (P = 0.04), consistent with behavioral fever. LPS increased plasma bactericidal ability (BA; P = 0.006), reduced plasma iron concentration (P = 0.041), and increased heterophil∶lymphocyte ratios (P < 0.001). In nonstimulated animals, thermoregulatory strategy had a strong effect on innate immunity, which demonstrated that individuals have the ability to facultatively adjust immune function when infection burden is low; this relationship was not present in LPS-injected animals, which suggested that animals stimulated with LPS maximize bactericidal ability independently of temperature. Seasonal acclimation state did not influence responses to LPS, although baseline plasma iron was significantly lower in animals acclimated to winter. These results support that a trade-off exists between immunity and other conflicting physiological interests. Moreover, these results clearly demonstrate the ability of individuals to modulate immune function as a direct result of thermoregulatory decisions.

Conceptual Hierarchies in a Flat Attractor Network

PubMed Central

O’Connor, Christopher M.; Cree, George S.; McRae, Ken

2009-01-01

The structure of people’s conceptual knowledge of concrete nouns has traditionally been viewed as hierarchical (Collins & Quillian, 1969). For example, superordinate concepts (vegetable) are assumed to reside at a higher level than basic-level concepts (carrot). A feature-based attractor network with a single layer of semantic features developed representations of both basic-level and superordinate concepts. No hierarchical structure was built into the network. In Experiment and Simulation 1, the graded structure of categories (typicality ratings) is accounted for by the flat attractor-network. Experiment and Simulation 2 show that, as with basic-level concepts, such a network predicts feature verification latencies for superordinate concepts (vegetable ). In Experiment and Simulation 3, counterintuitive results regarding the temporal dynamics of similarity in semantic priming are explained by the model. By treating both types of concepts the same in terms of representation, learning, and computations, the model provides new insights into semantic memory. PMID:19543434

Effects of space flight conditions on the function of the immune system and catecholamine production simulated in a rodent model of hindlimb unloading

NASA Technical Reports Server (NTRS)

Aviles, Hernan; Belay, Tesfaye; Vance, Monique; Sonnenfeld, Gerald

2005-01-01

The rodent model of hindlimb unloading has been successfully used to simulate some of the effects of space flight conditions. Previous studies have indicated that mice exposed to hindlimb-unloading conditions have decreased resistance to infections compared to restrained and normally housed control mice. OBJECTIVE: The purpose of this study was to clarify the mechanisms involved in resistance to infection in this model by examining the effects of hindlimb unloading on the function of the immune system and its impact on the production of catecholamines. METHODS: Female Swiss Webster mice were hindlimb-unloaded during 48 h and the function of the immune system was assessed in spleen and peritoneal cells immediately after this period. In addition, the kinetics of catecholamine production was measured throughout the hindlimb-unloading period. RESULTS: The function of the immune system was significantly suppressed in the hindlimb-unloaded group compared to restrained and normally housed control mice. Levels of catecholamines were increased in the hindlimb-unloaded group and peaked at 12 h following the commencement of unloading. CONCLUSION: These results suggest that physiological responses of mice are altered early after hindlimb unloading and that catecholamines may play a critical role in the modulation of the immune system. These changes may affect the ability of mice to resist infections. Copyright (c) 2005 S. Karger AG, Basel.

A two-scale model for correlation between B cell VDJ usage in zebrafish

NASA Astrophysics Data System (ADS)

Pan, Keyao; Deem, Michael

2011-03-01

The zebrafish (Danio rerio) is one of the model animals for study of immunology. The dynamics of the adaptive immune system in zebrafish is similar to that in higher animals. In this work, we built a two-scale model to simulate the dynamics of B cells in primary and secondary immune reactions in zebrafish and to explain the reported correlation between VDJ usage of B cell repertoires in distinct zebrafish. The first scale of the model consists of a generalized NK model to simulate the B cell maturation process in the 10-day primary immune response. The second scale uses a delay ordinary differential equation system to model the immune responses in the 6-month lifespan of zebrafish. The generalized NK model shows that mature B cells specific to one antigen mostly possess a single VDJ recombination. The probability that mature B cells in two zebrafish have the same VDJ recombination increases with the B cell population size or the B cell selection intensity and decreases with the B cell hypermutation rate. The ODE model shows a distribution of correlation in the VDJ usage of the B cell repertoires in two six-month-old zebrafish that is highly similar to that from experiment. This work presents a simple theory to explain the experimentally observed correlation in VDJ usage of distinct zebrafish B cell repertoires after an immune response.

Structural and functional features of central nervous system lymphatics

PubMed Central

Louveau, Antoine; Smirnov, Igor; Keyes, Timothy J.; Eccles, Jacob D.; Rouhani, Sherin J.; Peske, J. David; Derecki, Noel C.; Castle, David; Mandell, James W.; Kevin, S. Lee; Harris, Tajie H.; Kipnis, Jonathan

2015-01-01

One of the characteristics of the CNS is the lack of a classical lymphatic drainage system. Although it is now accepted that the CNS undergoes constant immune surveillance that takes place within the meningeal compartment1–3, the mechanisms governing the entrance and exit of immune cells from the CNS remain poorly understood4–6. In searching for T cell gateways into and out of the meninges, we discovered functional lymphatic vessels lining the dural sinuses. These structures express all of the molecular hallmarks of lymphatic endothelial cells, are able to carry both fluid and immune cells from the CSF, and are connected to the deep cervical lymph nodes. The unique location of these vessels may have impeded their discovery to date, thereby contributing to the long-held concept of the absence of lymphatic vasculature in the CNS. The discovery of the CNS lymphatic system may call for a reassessment of basic assumptions in neuroimmunology and shed new light on the etiology of neuroinflammatory and neurodegenerative diseases associated with immune system dysfunction. PMID:26030524

Immune deficiency in mouse models for inherited peripheral neuropathies leads to improved myelin maintenance.

PubMed

Schmid, C D; Stienekemeier, M; Oehen, S; Bootz, F; Zielasek, J; Gold, R; Toyka, K V; Schachner, M; Martini, R

2000-01-15

The adhesive cell surface molecule P(0) is the most abundant glycoprotein in peripheral nerve myelin and fulfills pivotal functions during myelin formation and maintenance. Mutations in the corresponding gene cause hereditary demyelinating neuropathies. In mice heterozygously deficient in P(0) (P(0)(+/-) mice), an established animal model for a subtype of hereditary neuropathies, T-lymphocytes are present in the demyelinating nerves. To monitor the possible involvement of the immune system in myelin pathology, we cross-bred P(0)(+/-) mice with null mutants for the recombination activating gene 1 (RAG-1) or with mice deficient in the T-cell receptor alpha-subunit. We found that in P(0)(+/-) mice myelin degeneration and impairment of nerve conduction properties is less severe when the immune system is deficient. Moreover, isolated T-lymphocytes from P(0)(+/-) mice show enhanced reactivity to myelin components of the peripheral nerve, such as P(0), P(2), and myelin basic protein. We hypothesize that autoreactive immune cells can significantly foster the demyelinating phenotype of mice with a primarily genetically based peripheral neuropathy.

Cognitive simulators for medical education and training.

PubMed

Kahol, Kanav; Vankipuram, Mithra; Smith, Marshall L

2009-08-01

Simulators for honing procedural skills (such as surgical skills and central venous catheter placement) have proven to be valuable tools for medical educators and students. While such simulations represent an effective paradigm in surgical education, there is an opportunity to add a layer of cognitive exercises to these basic simulations that can facilitate robust skill learning in residents. This paper describes a controlled methodology, inspired by neuropsychological assessment tasks and embodied cognition, to develop cognitive simulators for laparoscopic surgery. These simulators provide psychomotor skill training and offer the additional challenge of accomplishing cognitive tasks in realistic environments. A generic framework for design, development and evaluation of such simulators is described. The presented framework is generalizable and can be applied to different task domains. It is independent of the types of sensors, simulation environment and feedback mechanisms that the simulators use. A proof of concept of the framework is provided through developing a simulator that includes cognitive variations to a basic psychomotor task. The results of two pilot studies are presented that show the validity of the methodology in providing an effective evaluation and learning environments for surgeons.

Basic life support: evaluation of learning using simulation and immediate feedback devices1.

PubMed

Tobase, Lucia; Peres, Heloisa Helena Ciqueto; Tomazini, Edenir Aparecida Sartorelli; Teodoro, Simone Valentim; Ramos, Meire Bruna; Polastri, Thatiane Facholi

2017-10-30

to evaluate students' learning in an online course on basic life support with immediate feedback devices, during a simulation of care during cardiorespiratory arrest. a quasi-experimental study, using a before-and-after design. An online course on basic life support was developed and administered to participants, as an educational intervention. Theoretical learning was evaluated by means of a pre- and post-test and, to verify the practice, simulation with immediate feedback devices was used. there were 62 participants, 87% female, 90% in the first and second year of college, with a mean age of 21.47 (standard deviation 2.39). With a 95% confidence level, the mean scores in the pre-test were 6.4 (standard deviation 1.61), and 9.3 in the post-test (standard deviation 0.82, p <0.001); in practice, 9.1 (standard deviation 0.95) with performance equivalent to basic cardiopulmonary resuscitation, according to the feedback device; 43.7 (standard deviation 26.86) mean duration of the compression cycle by second of 20.5 (standard deviation 9.47); number of compressions 167.2 (standard deviation 57.06); depth of compressions of 48.1 millimeter (standard deviation 10.49); volume of ventilation 742.7 (standard deviation 301.12); flow fraction percentage of 40.3 (standard deviation 10.03). the online course contributed to learning of basic life support. In view of the need for technological innovations in teaching and systematization of cardiopulmonary resuscitation, simulation and feedback devices are resources that favor learning and performance awareness in performing the maneuvers.

Is Colombia reaching the goals on infant immunization coverage? A quantitative survey from 80 municipalities.

PubMed

Narváez, Javier; Osorio, May Bibiana; Castañeda-Orjuela, Carlos; Alvis Zakzuk, Nelson; Cediel, Natalia; Chocontá-Piraquive, Luz Ángela; de La Hoz-Restrepo, Fernando

2017-03-13

This study aimed to evaluate the coverage of the Colombian Expanded Program on Immunization among children less than 6years old, to evaluate the timeliness of immunization, to assess the coverage of newly introduced vaccines, and to identify factors associated with lack of immunization. We conducted a cross-sectional survey in 80 municipalities of Colombia, using a two-stage cluster random sampling. We attempted to contact all children less than 6years old living in the sampled blocks, and asked their caregivers to provide immunization record cards. We also collected basic sociodemographic information. We reached 81% of the attempted household contacts, identifying 18,232 children; of them, 14,805 (83%) had an immunization record card. Coverage for traditional vaccines was above 90%: BCG (tuberculosis) 95.7% (95%CI: 95.1-96.4), pentavalent vaccine 93.3% (92.4-94.3), MMR (measles, mumps, rubella) initial dose 94.5% (93.5-95.6); but it was lower for recently introduced vaccines: rotavirus 80% (77.8-82.1), influenza 48.4% (45.9-50.8). Results for timely vaccination were not equally successful: pentavalent vaccine 44.2% (41.4-47.1), MMR initial dose 71.2% (68.9-73.4). Mother's education was significantly associated with higher immunization odds. Older age, a greater number of siblings, low socioeconomic status, and not having health insurance were significantly associated with lower immunization odds. There was significant heterogeneity in immunization rates by municipality across the country. Although absolute immunization coverage for traditional vaccines met the goal of 90% for the 80 municipalities combined, disparities in coverage across municipalities, delayed immunization, and decline of coverage with age, are common problems in Colombia that may result in reduced protection. Newly introduced vaccines require additional efforts to reach the goal. These results highlight the association of health inequities with low immunization coverage and delayed immunization. Identification of vulnerable populations and their missed opportunities for vaccination may help to improve the reach of immunization programs. Copyright © 2017 Elsevier Ltd. All rights reserved.

AIDS Education Curriculum Guide. Grades 7-10. Bulletin 1827, 1988.

ERIC Educational Resources Information Center

Louisiana State Dept. of Education, Baton Rouge.

This curriculum guide on acquired immune deficiency syndrome (AIDS) was developed for students at the junior high school level. There are five major sections: (1) introduction, an overview of AIDS; (2) an overview of the history of AIDS; (3) basic immunology; (4) the effects of AIDS on the host; and (5) prevention of AIDS. The appendices include…

The State of the World's Children 1985: A Report by United Nations Children's Fund (UNICEF).

ERIC Educational Resources Information Center

Early Child Development and Care, 1985

1985-01-01

Reports four basic strategies of the current child survival revolution in the world: use of oral rehydration therapy (ORT) for preventing and treating diarrheal dehydration (the biggest single killer of children in the modern world), growth monitoring to prevent child malnutrition, breast-feeding, and immunization to provide protection against six…

Higher Education and the Transmission of Educational Values in Today's Society.

ERIC Educational Resources Information Center

Escobar-Ortloff, Luz; Ortloff, Warren G.

Education has traditionally been the primary method of passing on a society's culture and the values it considers to be important. Higher education institutions have not been immune to the crises in the transmission of values. Typically, in higher education basic intellectual values and virtues are mostly left for students to pick up through…

The biology of human immunodeficiency virus infection.

PubMed

Kotler, Donald P

2004-08-01

The aim of this article is to review the basic biology of infection with HIV-1 and the development of the acquired immunodeficiency syndrome. The discussion will include epidemiology, general description of the retroviruses, pathogenesis of the immune deficiency, clinical consequences, treatment, and treatment outcomes. Aspects of the infection that affect protein and energy balance will be identified.

Th1/Th2 Cytokines: An Easy Model to Study Gene Expression in Immune Cells

ERIC Educational Resources Information Center

Moran, Jose M.; Gonzalez-Polo, Rosa A.; Soler, German; Fuentes, Jose M.

2006-01-01

This report describes a laboratory exercise that was incorporated into a Cell Biology and Molecular Biology advanced course. The exercise was made for a class size with eight students and was designed to reinforce the understanding of basic molecular biology techniques. Students used the techniques of reverse transcription and arginase activity…

An active-learning laboratory on immunizations.

PubMed

Donohoe, Krista L; Mawyer, Tonya M; Stevens, J Tyler; Morgan, Laura A; Harpe, Spencer E

2012-12-12

To implement and evaluate an active-learning laboratory activity to teach pharmacy students about influenza, pneumococcal, and shingles vaccines. The laboratory session was divided into 6 immunization stations: 3 stations on influenza including a pediatrics station, and 1 station each for pneumococcal, shingles, and anaphylaxis. Although 118 of 123 (95.9%) students had completed an immunization training certificate prior to attending the laboratory, the average score on a pre-assessment to measure immunization knowledge and confidence was 56%. The post-assessment score was 87.4%. Students' confidence improved by 18.7% to 51.2% in each of the 5 areas assessed. Most respondents rated the activity overall as good or excellent on a post-activity evaluation. An active-learning approach to teaching immunizations allowed students to gain knowledge in simulated real-world experiences and reinforced key concepts on influenza, pneumococcal, and shingles vaccines.

The most common friend first immunization

NASA Astrophysics Data System (ADS)

Nian, Fu-Zhong; Hu, Cha-Sheng

2016-12-01

In this paper, a standard susceptible-infected-recovered-susceptible(SIRS) epidemic model based on the Watts-Strogatz (WS) small-world network model and the Barabsi-Albert (BA) scale-free network model is established, and a new immunization scheme — “the most common friend first immunization” is proposed, in which the most common friend’s node is described as being the first immune on the second layer protection of complex networks. The propagation situations of three different immunization schemes — random immunization, high-risk immunization, and the most common friend first immunization are studied. At the same time, the dynamic behaviors are also studied on the WS small-world and the BA scale-free network. Moreover, the analytic and simulated results indicate that the immune effect of the most common friend first immunization is better than random immunization, but slightly worse than high-risk immunization. However, high-risk immunization still has some limitations. For example, it is difficult to accurately define who a direct neighbor in the life is. Compared with the traditional immunization strategies having some shortcomings, the most common friend first immunization is effective, and it is nicely consistent with the actual situation. Project supported by the National Natural Science Foundation of China (Grant No. 61263019), the Program for International Science and Technology Cooperation Projects of Gansu Province, China (Grant No. 144WCGA166), and the Program for Longyuan Young Innovation Talents and the Doctoral Foundation of Lanzhou University of Technology, China.

Active and Cooperative Learning Using Web-Based Simulations.

ERIC Educational Resources Information Center

Schmidt, Stephen J.

2003-01-01

Cites advantages of using computers and the World Wide Web in classroom simulations. Provides a sample simulation that teaches the basic economic principles of trade, investment, and public goods in the context of U.S. economic history. (JEH)

The Clinical Value, Principle, and Basic Practical Technique of Mindfulness Intervention.

PubMed

Zou, Tao; Wu, Chenghan; Fan, Xiaoduo

2016-06-25

Mindfulness intervention is a psychotherapy based on the Buddhist practice of meditation, combining the theories and methodology of contemporary psychology. The empirical research in recent years has indicated that mindfulness intervention yields favorable results including reduction of depression relapse, alleviation of the symptoms of depression and anxiety, reduction of substance abuse, relief of pain, blood pressure management, enhancement of immunity, and improvement of sleep. Currently, mindfulness therapy has become the mainstream of psychotherapy in the realm of European and American psychotherapy. The fields of psychology and psychotherapy in China have also begun to introduce mindfulness intervention in recent years. However, there is a lack of relevant practice and research in the field of clinical mental health. This article will briefly introduce the concept of mindfulness, the basic mechanism of the intervention, and the basic skills and guidelines in clinical practice.

Basic guidelines to introduce electric circuit simulation software in a general physics course

NASA Astrophysics Data System (ADS)

Moya, A. A.

2018-05-01

The introduction of electric circuit simulation software for undergraduate students in a general physics course is proposed in order to contribute to the constructive learning of electric circuit theory. This work focuses on the lab exercises based on dc, transient and ac analysis in electric circuits found in introductory physics courses, and shows how students can use the simulation software to do simple activities associated with a lab exercise itself and with related topics. By introducing electric circuit simulation programs in a general physics course as a brief activitiy complementing lab exercise, students develop basic skills in using simulation software, improve their knowledge on the topology of electric circuits and perceive that the technology contributes to their learning, all without reducing the time spent on the actual content of the course.

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

Fedorka, K. M.; Copeland, E. K.; Winterhalter, W. E.

To improve thermoregulation in colder environments, insects are expected to darken their cuticles with melanin via the phenoloxidase cascade, a phenomenon predicted by the thermal melanin hypothesis. However, the phenoloxidase cascade also plays a significant role in insect immunity, leading to the additional hypothesis that the thermal environment indirectly shapes immune function via direct selection on cuticle color. Support for the latter hypothesis comes from the cricket Allonemobius socius, where cuticle darkness and immune-related phenoloxidase activity increase with latitude. However, thermal environments vary seasonally as well as geographically, suggesting that seasonal plasticity in immunity may also exist. Although seasonal fluctuationsmore » in vertebrate immune function are common (because of flux in breeding or resource abundance), seasonality in invertebrate immunity has not been widely explored. We addressed this possibility by rearing crickets in simulated summer and fall environments and assayed their cuticle color and immune function. Prior to estimating immunity, crickets were placed in a common environment to minimize metabolic rate differences. Individuals reared under fall-like conditions exhibited darker cuticles, greater phenoloxidase activity and greater resistance to the bacteria Serratia marcescens. These data support the hypothesis that changes in the thermal environment modify cuticle color, which indirectly shapes immune investment through pleiotropy. This hypothesis may represent a widespread mechanism governing immunity in numerous systems, considering that most insects operate in seasonally and geographically variable thermal environments.« less

Improved targeted immunization strategies based on two rounds of selection

NASA Astrophysics Data System (ADS)

Xia, Ling-Ling; Song, Yu-Rong; Li, Chan-Chan; Jiang, Guo-Ping

2018-04-01

In the case of high degree targeted immunization where the number of vaccine is limited, when more than one node associated with the same degree meets the requirement of high degree centrality, how can we choose a certain number of nodes from those nodes, so that the number of immunized nodes will not exceed the limit? In this paper, we introduce a new idea derived from the selection process of second-round exam to solve this problem and then propose three improved targeted immunization strategies. In these proposed strategies, the immunized nodes are selected through two rounds of selection, where we increase the quotas of first-round selection according the evaluation criterion of degree centrality and then consider another characteristic parameter of node, such as node's clustering coefficient, betweenness and closeness, to help choose targeted nodes in the second-round selection. To validate the effectiveness of the proposed strategies, we compare them with the degree immunizations including the high degree targeted and the high degree adaptive immunizations using two metrics: the size of the largest connected component of immunized network and the number of infected nodes. Simulation results demonstrate that the proposed strategies based on two rounds of sorting are effective for heterogeneous networks and their immunization effects are better than that of the degree immunizations.

Estimating the Lineage Dynamics of Human Influenza B Viruses.

PubMed

Nyirenda, Mayumbo; Omori, Ryosuke; Tessmer, Heidi L; Arimura, Hiroki; Ito, Kimihito

2016-01-01

The prediction of the lineage dynamics of influenza B viruses for the next season is one of the largest obstacles for constructing an appropriate influenza trivalent vaccine. Seasonal fluctuation of transmissibility and epidemiological interference between the two major influenza B lineages make the lineage dynamics complicated. Here we construct a parsimonious model describing the lineage dynamics while taking into account seasonal fluctuation of transmissibility and epidemiological interference. Using this model we estimated the epidemiological and evolutional parameters with the time-series data of the lineage specific isolates in Japan from the 2010-2011 season to the 2014-2015 season. The basic reproduction number is similar between Victoria and Yamagata, with a minimum value during one year as 0.82 (95% highest posterior density (HPD): 0.77-0.87) for the Yamagata and 0.83 (95% HPD: 0.74-0.92) for Victoria, the amplitude of seasonal variation of the basic reproduction number is 0.77 (95% HPD:0.66-0.87) for Yamagata and 1.05 (95% HPD: 0.89-1.02) for Victoria. The duration for which the acquired immunity is effective against infection by the Yamagata lineage is shorter than the acquired immunity for Victoria, 424.1days (95% HPD:317.4-561.5days). The reduction rate of susceptibility due to immune cross-reaction is 0.51 (95% HPD: 0.084-0.92) for the immunity obtained from the infection with Yamagata against the infection with Victoria and 0.62 (95% HPD: 0.42-0.80) for the immunity obtained from the infection with Victoria against the infection with Yamagata. Using estimated parameters, we predicted the dominant lineage in 2015-2016 season. The accuracy of this prediction is 68.8% if the emergence timings of the two lineages are known and 61.4% if the emergence timings are unknown. Estimated seasonal variation of the lineage specific reproduction number can narrow down the range of emergence timing, with an accuracy of 64.6% if the emergence times are assumed to be the time at which the estimated reproduction number exceeds one.

History of Primary Immunodeficiency Diseases in Iran

PubMed Central

Aghamohammadi, Asghar; Moin, Mostafa; Rezaei, Nima

2010-01-01

Pediatric immunology came into sight in the second half of 20th century, when pediatricians and basic immunologists began to give attention to diagnosis and treatment of children with primary immunodeficiency diseases (PIDs). Understanding the genetic and mechanistic basis of PIDs provides unique insight into the functioning of the immune system. By progress in basic and clinical immunology, many infrastructural organizations and academic centers have been established in many countries worldwide to focus on training and research on the immune system and related disorders. Along with progress in basic and clinical immunology in the world, pediatric immunology had a good progress in Iran during the last 33-year period. Now, patients with PIDs can benefit from multidisciplinary comprehensive care, which is provided by clinical immunologists in collaboration with other specialists. Patients with history of recurrent and/or chronic infections suggestive of PIDs are evaluated by standard and research-based testing and receive appropriate treatment. The progress in PIDs can be described in three periods. Development of training program for clinical fellowship in allergy and immunology, multidisciplinary and international collaborative projects, primary immunodeficiency diseases textbooks, meetings on immunodeficiency disorders, improvement in diagnosis and treatment, and construction of Iranian primary immunodeficiency association, Students' research group for immunodeficiencies, Iranian primary immunodeficiency registry, and the immunological societies and centers were the main activities on PIDs during these years. In this article, we review the growth of modern pediatric immunology and PIDs status in Iran. PMID:23056678

A cellular automata model of SARS epidemic spreading

NASA Astrophysics Data System (ADS)

Xu, Tian; Zhang, Peipei; Su, Beibei; Jiang, Yumai; He, Da-Ren

2004-03-01

We suggest a cellular automata model for a simulation on the process of SARS spreading in Beijing. Suppose a number of people are located in a two-dimensional lattice, in which a certain portion belongs to immune and others belong to acceptive. In every time step each of the acceptive people may become ill with a certain probability if one of his 8 neighbors is a SARS patient. At same time all the people have another possibility to change their positions. Each patient will recover or die after different number of days. A recovered patient becomes immune. The numerical simulation by this model leads to the results, which are in a good agreement with the practical statistical data.

Multi-Agent Simulations of the Immune Response to Hiv during the Acute Stage of Infection

NASA Astrophysics Data System (ADS)

Walshe, R.; Ruskin, H. J.; Callaghan, A.

Results of multi-agent based simulations of the immune response to HIV during the acute phase of infection are presented here. The model successfully recreates the viral dynamics associated with the acute phase of infection, i.e., a rapid rise in viral load followed by a sharp decline to what is often referred to as a "set point", a result of T-cell response and emergence of HIV neutralizing antibodies. The results indicate that sufficient T Killer cell response is the key factor in controlling viral growth during this phase with antibody levels of critical importance only in the absence of a sufficient T Killer response.

How regulatory T cells work

PubMed Central

Vignali, Dario A. A.; Collison, Lauren W.; Workman, Creg J.

2009-01-01

Regulatory T (Treg) cells are essential for maintaining peripheral tolerance, preventing autoimmune diseases and limiting chronic inflammatory diseases. However, they also limit beneficial responses by suppressing sterilizing immunity and limiting anti-tumour immunity. Given that Treg cells can have both beneficial and deleterious effects, there is considerable interest in determining their mechanisms of action. In this Review, we discuss the basic mechanisms used by Treg cells to mediate suppression, and discuss whether one or many of these mechanisms are likely to be crucial for Treg-cell function. In addition, we present the hypothesis that effector T cells may not be ‘innocent’ parties in this suppressive process and might in fact potentiate Treg-cell function. PMID:18566595

Impact of the Tumor Microenvironment on Tumor-Infiltrating Lymphocytes: Focus on Breast Cancer

PubMed Central

Cohen, Ivan J; Blasberg, Ronald

2017-01-01

Immunotherapy is revolutionizing cancer care across disciplines. The original success of immune checkpoint blockade in melanoma has already been translated to Food and Drug Administration–approved therapies in a number of other cancers, and a large number of clinical trials are underway in many other disease types, including breast cancer. Here, we review the basic requirements for a successful antitumor immune response, with a focus on the metabolic and physical barriers encountered by lymphocytes entering breast tumors. We also review recent clinical trials of immunotherapy in breast cancer and provide a number of interesting questions that will need to be answered for successful breast cancer immunotherapy. PMID:28979132

Toll-like receptor signaling: a perspective to develop vaccine against leishmaniasis.

PubMed

Singh, Rakesh K; Srivastava, Ankita; Singh, Nisha

2012-09-06

The toll-like receptors (TLRs) are the sentinel factor of the innate immunity, which are essential for host defense. These receptors detect the presence of conserved molecular patterns of potentially pathogenic microorganisms and contribute in both, cellular as well as humoral immune responses. Leishmania is an intracellular pathogen that silently invades host immune system. After phagocytosis, it divides and proliferates in the harmful environment of host macrophages by down-regulating its vital effector functions. In leishmaniasis, the outcome of the infection basically relies on the skewed balance between Th1/Th2 immune responses. Lots of work have been done and on progress but still characterization of either preventive or prophylactic candidate antigen/s is far from satisfactory. How does Leishmania regulate host innate immune system? Still it is unanswered. TLRs play very important role during inflammatory process of various diseases such as cancer, bacterial and viral infections but TLR signaling is comparatively less explained in leishmanial infection. In the context to Th1/Th2 dichotomy, identification of leishmanial antigens that modulate toll-like receptor signaling will certainly help in the development of future vaccine. This review will initially describe global properties of TLRs, and later will discuss their role in the pathogenesis of leishmaniasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Current understanding of interactions between nanoparticles and the immune system

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

Dobrovolskaia, Marina A., E-mail: marina@mail.nih.

2016-05-15

The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guidemore » safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.« less

Parainflammation, chronic inflammation, and age-related macular degeneration.

PubMed

Chen, Mei; Xu, Heping

2015-11-01

Inflammation is an adaptive response of the immune system to noxious insults to maintain homeostasis and restore functionality. The retina is considered an immune-privileged tissue as a result of its unique anatomic and physiologic properties. During aging, the retina suffers from a low-grade chronic oxidative insult, which sustains for decades and increases in level with advancing age. As a result, the retinal innate-immune system, particularly microglia and the complement system, undergoes low levels of activation (parainflammation). In many cases, this parainflammatory response can maintain homeostasis in the healthy aging eye. However, in patients with age-related macular degeneration, this parainflammatory response becomes dysregulated and contributes to macular damage. Factors contributing to the dysregulation of age-related retinal parainflammation include genetic predisposition, environmental risk factors, and old age. Dysregulated parainflammation (chronic inflammation) in age-related macular degeneration damages the blood retina barrier, resulting in the breach of retinal-immune privilege, leading to the development of retinal lesions. This review discusses the basic principles of retinal innate-immune responses to endogenous chronic insults in normal aging and in age-related macular degeneration and explores the difference between beneficial parainflammation and the detrimental chronic inflammation in the context of age-related macular degeneration. © Society for Leukocyte Biology.

Hypogammaglobulinemia factitia- Munchausen syndrome masquerading as common variable immune deficiency

PubMed Central

2013-01-01

Background We describe the first case of a patient with factitious disorder who closely simulated a primary immune deficiency disorder – Common Variable Immune Deficiency (CVID), by surreptitiously ingesting non-steroidal anti-inflammatory agents. Case description He was treated with several expensive and potentially dangerous drugs before the diagnosis was established through collateral information. In retrospect he did not meet the proposed new criteria for CVID. These criteria may prove useful in distinguishing cases of CVID from secondary hypogammaglobulinemia. Conclusion It is imperative clinicians recognise patients with factitious disorder at the earliest opportunity to prevent iatrogenic morbidity and mortality. PMID:24341706

The application of immune genetic algorithm in main steam temperature of PID control of BP network

NASA Astrophysics Data System (ADS)

Li, Han; Zhen-yu, Zhang

In order to overcome the uncertainties, large delay, large inertia and nonlinear property of the main steam temperature controlled object in the power plant, a neural network intelligent PID control system based on immune genetic algorithm and BP neural network is designed. Using the immune genetic algorithm global search optimization ability and good convergence, optimize the weights of the neural network, meanwhile adjusting PID parameters using BP network. The simulation result shows that the system is superior to conventional PID control system in the control of quality and robustness.

Reviews, Software.

ERIC Educational Resources Information Center

Science Teacher, 1988

1988-01-01

Reviews two software programs for Apple series computers. Includes "Orbital Mech," a basic planetary orbital simulation for the Macintosh, and "START: Stimulus and Response Tools for Experiments in Memory, Learning, Cognition, and Perception," a program that demonstrates basic psychological principles and experiments. (CW)

Box- or Virtual-Reality Trainer: Which Tool Results in Better Transfer of Laparoscopic Basic Skills?-A Prospective Randomized Trial.

PubMed

Brinkmann, Christian; Fritz, Mathias; Pankratius, Ulrich; Bahde, Ralf; Neumann, Philipp; Schlueter, Steffen; Senninger, Norbert; Rijcken, Emile

Simulation training improves laparoscopic performance. Laparoscopic basic skills can be learned in simulators as box- or virtual-reality (VR) trainers. However, there is no clear recommendation for either box or VR trainers as the most appropriate tool for the transfer of acquired laparoscopic basic skills into a surgical procedure. Both training tools were compared, using validated and well-established curricula in the acquirement of basic skills, in a prospective randomized trial in a 5-day structured laparoscopic training course. Participants completed either a box- or VR-trainer curriculum and then applied the learned skills performing an ex situ laparoscopic cholecystectomy on a pig liver. The performance was recorded on video and evaluated offline by 4 blinded observers using the Global Operative Assessment of Laparoscopic Skills (GOALS) score. Learning curves of the various exercises included in the training course were compared and the improvement in each exercise was analyzed. Surgical Skills Lab of the Department of General and Visceral Surgery, University Hospital Muenster. Surgical novices without prior surgical experience (medical students, n = 36). Posttraining evaluation showed significant improvement compared with baseline in both groups, indicating acquisition of laparoscopic basic skills. Learning curves showed almost the same progression with no significant differences. In simulated laparoscopic cholecystectomy, total GOALS score was significantly higher for the box-trained group than the VR-trained group (box: 15.31 ± 3.61 vs. VR: 12.92 ± 3.06; p = 0.039; Hedge׳s g* = 0.699), indicating higher technical skill levels. Despite both systems having advantages and disadvantages, they can both be used for simulation training for laparoscopic skills. In the setting with 2 structured, validated and almost identical curricula, the box-trained group appears to be superior in the better transfer of basic skills into an experimental but structured surgical procedure. Copyright © 2017 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Immune checkpoint inhibitor-related myocarditis.

PubMed

Tajiri, Kazuko; Aonuma, Kazutaka; Sekine, Ikuo

2018-01-01

Immune checkpoint inhibitors have demonstrated significant clinical benefit in many cancers. The clinical benefit afforded by these treatments can be accompanied by a unique and distinct spectrum of adverse events. Recently, several fatal cases of immune checkpoint inhibitor-related myocarditis were reported. Although its frequency is comparatively lower than that of other immune-related adverse events, myocarditis can lead to circulatory collapse and lethal ventricular arrhythmia. Immune checkpoints, cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1), play important roles in establishing peripheral tolerance to the heart. Evidence from studies using genetically engineered mouse models suggests that CTLA-4 signaling terminates proliferation and promotes anergy during the primary response to cardiac self-peptide recognition. PD-1 signaling restrains autoreactive T cells that enter the peripheral tissues and recognize cardiac-peptide, maintaining them in an anergic state. Patients affected by immune checkpoint inhibitor-related myocarditis often experience rapid onset of profound hemodynamic compromise progressing to cardiogenic shock. Early diagnosis is mandatory to address specific therapy and correct the timing of circulatory support. However, the diagnosis of myocarditis is challenging due to the heterogeneity of clinical presentations. Owing to its early onset, nonspecific symptomatology and fulminant progression, especially when these drugs are used in combination, oncologists should be vigilant for immune checkpoint inhibitor-related myocarditis. With many questions yet to be answered, from basic immune biology to clinical management, future research should aim to optimize the use of these drugs by identifying predictive biomarkers of either a response to therapy or the risks of myocarditis development. © The Author 2017. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

European consensus on a competency-based virtual reality training program for basic endoscopic surgical psychomotor skills.

PubMed

van Dongen, Koen W; Ahlberg, Gunnar; Bonavina, Luigi; Carter, Fiona J; Grantcharov, Teodor P; Hyltander, Anders; Schijven, Marlies P; Stefani, Alessandro; van der Zee, David C; Broeders, Ivo A M J

2011-01-01

Virtual reality (VR) simulators have been demonstrated to improve basic psychomotor skills in endoscopic surgery. The exercise configuration settings used for validation in studies published so far are default settings or are based on the personal choice of the tutors. The purpose of this study was to establish consensus on exercise configurations and on a validated training program for a virtual reality simulator, based on the experience of international experts to set criterion levels to construct a proficiency-based training program. A consensus meeting was held with eight European teams, all extensively experienced in using the VR simulator. Construct validity of the training program was tested by 20 experts and 60 novices. The data were analyzed by using the t test for equality of means. Consensus was achieved on training designs, exercise configuration, and examination. Almost all exercises (7/8) showed construct validity. In total, 50 of 94 parameters (53%) showed significant difference. A European, multicenter, validated, training program was constructed according to the general consensus of a large international team with extended experience in virtual reality simulation. Therefore, a proficiency-based training program can be offered to training centers that use this simulator for training in basic psychomotor skills in endoscopic surgery.

Computerized Clinical Simulations.

ERIC Educational Resources Information Center

Reinecker, Lynn

1985-01-01

Describes technique involved in designing a clinical simulation problem for the allied health field of respiratory therapy; discusses the structure, content, and scoring categories of the simulation; and provides a sample program which illustrates a programming technique in BASIC, including a program listing and a sample flowchart. (MBR)

Transmission probabilities and durations of immunity for three pathogenic group B Streptococcus serotypes

PubMed Central

Percha, Bethany; Newman, M. E. J.; Foxman, Betsy

2012-01-01

Group B Streptococcus (GBS) remains a major cause of neonatal sepsis and is an emerging cause of invasive bacterial infections. The 9 known serotypes vary in virulence, and there is little cross-immunity. Key parameters for planning an effective vaccination strategy, such as average length of immunity and transmission probabilities by serotype, are unknown. We simulated GBS spread in a population using a computational model with parameters derived from studies of GBS sexual transmission in a college dormitory. Here we provide estimates of the duration of immunity relative to the transmission probabilities for the 3 GBS serotypes most associated with invasive disease: Ia, III, and V. We also place upper limits on the durations of immunity for serotype Ia (570 days), III (1125 days) and V (260 days). Better transmission estimates are required to establish the epidemiological parameters of GBS infection and determine the best vaccination strategies to prevent GBS disease. PMID:21605704

Simulation of Behavioral Variations in the Submission of Student Financial Statements: Effects on BEOG Costs. Stage I Draft Final Report for the Study of Program Management Procedures in the Campus-Based and Basic Grant Programs. (Volume IV).

ERIC Educational Resources Information Center

Ellis, Richard

Volume IV of a study of program management procedures in the campus-based and Basic Educational Opportunity Grant (BEOG) programs deals with a set of simulated modifications in the statements made by BEOG applicants about their financial circumstances. Various kinds of misrepresentation of income, assets, and other factors are postulated, and the…

Modeling Systems-Level Regulation of Host Immune Responses

PubMed Central

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

2007-01-01

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

A Search for Cosmic String Loops Using GADGET-2 Cosmological N-Body Simulator

NASA Astrophysics Data System (ADS)

Braverman, William; Cousins, Bryce; Jia, Hewei

2018-01-01

Cosmic string loops are an extremely elusive hypothetical entity that have eluded the grasp of physicists and astronomers since their existence was postulated in the 1970’s. Finding evidence of their existence could be the first empirical evidence of string theory.Simulating their basic motion in a cold dark matter background using GADGET-2 allows us to predict where they may cluster during large scale structure formation (if they cluster at all). Here, we present our progress in placing cosmic strings into GADGET-2 with their basic equations of motion to lay a ground work for more complex simulations to find where these strings cluster. Ultimately, these simulations could lay a groundwork as to where future microlensing and gravitational wave observatories should look for cosmic strings.

Quality Improvement With Discrete Event Simulation: A Primer for Radiologists.

PubMed

Booker, Michael T; O'Connell, Ryan J; Desai, Bhushan; Duddalwar, Vinay A

2016-04-01

The application of simulation software in health care has transformed quality and process improvement. Specifically, software based on discrete-event simulation (DES) has shown the ability to improve radiology workflows and systems. Nevertheless, despite the successful application of DES in the medical literature, the power and value of simulation remains underutilized. For this reason, the basics of DES modeling are introduced, with specific attention to medical imaging. In an effort to provide readers with the tools necessary to begin their own DES analyses, the practical steps of choosing a software package and building a basic radiology model are discussed. In addition, three radiology system examples are presented, with accompanying DES models that assist in analysis and decision making. Through these simulations, we provide readers with an understanding of the theory, requirements, and benefits of implementing DES in their own radiology practices. Copyright © 2016 American College of Radiology. All rights reserved.

Inorganic nanoparticles and the immune system: detection, selective activation and tolerance

NASA Astrophysics Data System (ADS)

Bastús, Neus G.; Sánchez-Tilló, Ester; Pujals, Silvia; Comenge, Joan; Giralt, Ernest; Celada, Antonio; Lloberas, Jorge; Puntes, Victor F.

2012-03-01

The immune system is the responsible for body integrity and prevention of external invasion. On one side, nanoparticles are no triggers that the immune system is prepared to detect, on the other side it is known that foreign bodies, not only bacteria, viruses and parasites, but also inorganic matter, can cause various pathologies such as silicosis, asbestosis or inflammatory reactions. Therefore, nanoparticles entering the body, after interaction with proteins, will be either recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression responses. The nature of these interactions seems to be dictated not specially by the composition of the material but by modifications of NP coating (composition, surface charge and structure). Herein, we explore the use of gold nanoparticles as substrates to carry multifunctional ligands to manipulate the immune system in a controlled manner, from undetection to immunostimulation. Murine bone marrow macrophages can be activated with artificial nanometric objects consisting of a gold nanoparticle functionalized with peptides. In the presence of some conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines were induced. The biochemical type of response depended on the type of conjugated peptide and was correlated with the degree of ordering in the peptide coating. These findings help to illustrate the basic requirements involved in medical NP conjugate design to either activate the immune system or hide from it, in order to reach their targets before being removed by phagocytes. Additionally, it opens up the possibility to modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens.

A statistical mechanics approach to autopoietic immune networks

NASA Astrophysics Data System (ADS)

Barra, Adriano; Agliari, Elena

2010-07-01

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

Aircraft Electronics Maintenance Training Simulator. Curriculum Outlines.

ERIC Educational Resources Information Center

Blackhawk Technical Coll., Janesville, WI.

Instructional materials are provided for nine courses in an aircraft electronics maintenance training program. Courses are as follows: aviation basic electricity, direct current and alternating current electronics, basic avionic installations, analog electronics, digital electronics, microcomputer electronics, radio communications, aircraft…

A fuzzy MICMAC analysis for improving supply chain performance of basic vaccines in developing countries.

PubMed

Chandra, Dheeraj; Kumar, Dinesh

2018-03-01

In recent years, demand to improve child immunization coverage globally, and the development of the latest vaccines and technology has made the vaccine market very complex. The rise in such complexities often gives birth to numerous issues in the vaccine supply chain, which are the primary cause of its poor performance. Figuring out the cause of the performance problem can help you decide how to address it. The goal of the present study is to identify and analyze important issues in the supply chain of basic vaccines required for child immunization in the developing countries. Twenty-five key issues as various factors of the vaccine supply chain have been presented in this paper. Fuzzy MICMAC analysis has been carried out to classify the factors based on their driving and dependence power and to develop a hierarchy based model. Further, the findings have been discussed with the field experts to identify the critical factors. Three factors: better demand forecast, communication between the supply chain members, and proper planning and scheduling have been identified as the critical factors of vaccine supply chain. These factors should be given special care to improve vaccine supply chain performance.

Causes and consequences of coagulation activation in sepsis: an evolutionary medicine perspective.

PubMed

Fiusa, Maiara Marx Luz; Carvalho-Filho, Marco Antonio; Annichino-Bizzacchi, Joyce M; De Paula, Erich V

2015-05-06

Coagulation and innate immunity have been linked together for at least 450 million years of evolution. Sepsis, one of the world's leading causes of death, is probably the condition in which this evolutionary link is more evident. However, the biological and the clinical relevance of this association have only recently gained the attention of the scientific community. During sepsis, the host response to a pathogen is invariably associated with coagulation activation. For several years, coagulation activation has been solely regarded as a mechanism of tissue damage, a concept that led to several clinical trials of anticoagulant agents for sepsis. More recently, this paradigm has been challenged by the failure of these clinical trials, and by a growing bulk of evidence supporting the concept that coagulation activation is beneficial for pathogen clearance. In this article we discuss recent basic and clinical data that point to a more balanced view of the detrimental and beneficial consequences of coagulation activation in sepsis. Reappraisal of the association between coagulation and immune activation from an evolutionary medicine perspective offers a unique opportunity to gain new insights about the pathogenesis of sepsis, paving the way to more successful approaches in both basic and clinical research in this field.

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.

Basic biology and role of interleukin-17 in immunity and inflammation

PubMed Central

Zenobia, Camille; Hajishengallis, George

2014-01-01

Interleukin-17 (IL-17, also known as IL-17A) is a key cytokine that links T cell activation to neutrophil mobilization and activation. As such, IL-17 can mediate protective innate immunity to pathogens or contribute to the pathogenesis of inflammatory diseases, such as psoriasis and rheumatoid arthritis. This review summarizes the basic biology of IL-17 and discusses its emerging role in periodontal disease. The current burden of evidence from human and animal model studies suggests that the net effect of IL-17 signaling promotes disease development. In addition to promoting neutrophilic inflammation, IL-17 has potent pro-osteoclastogenic effects that are likely to contribute to the pathogenesis of periodontitis, rheumatoid arthritis, and other diseases involving bone immunopathology. Systemic treatments with anti-IL-17 biologics have shown promising results in clinical trials for psoriasis and rheumatoid arthritis, although their impact on the highly prevalent periodontal disease has not been investigated or reported. Future clinical trials, preferably using locally administered IL-17 blockers, are required to conclusively implicate IL-17 in periodontitis and, more importantly, to establish an effective adjunctive treatment for this oral inflammatory disease. PMID:26252407

Contributions of basic immunology to human health.

PubMed

Albright, J F; Oppenheim, J J

1991-03-01

The sixth symposium in the series "Contemporary Topics in Immunology" was held in New Orleans on June 3, 1990, at the joint meeting of The American Association of Immunologists and the American Society of Biochemistry and Molecular Biology. The symposium was sponsored jointly by The American Association of Immunologists, the Clinical Immunology Society, and and the National Institute of Allergy and Infectious Diseases, and was titled "The Contributions of Basic Immunology to Human Health." Five speakers, whose research has clear relevance to the treatment and prevention of major human diseases, discussed topics of great current interest: hematopoietic stem cells, cell adhesion and lymphocyte homing; the complexities of autoimmunity and approaches to diverting or depressing autoaggressive immunity; structure and functions of the interferons and the construction of designer and chimeric interferons; the varied functions of transforming growth factors and molecular events that regulate the synthesis of TGF beta; and the roles of cytokines in the expression of human immunodeficiency virus and the prospects for controlling HIV infections by regulating selected cytokines. This symposium will be remembered for the exceptional clarity with which each speaker illustrated how fundamental knowledge in immunology fuels advances in the treatment and prevention of those human disorders that involve the immune system.

Optimization of HAART with genetic algorithms and agent-based models of HIV infection.

PubMed

Castiglione, F; Pappalardo, F; Bernaschi, M; Motta, S

2007-12-15

Highly Active AntiRetroviral Therapies (HAART) can prolong life significantly to people infected by HIV since, although unable to eradicate the virus, they are quite effective in maintaining control of the infection. However, since HAART have several undesirable side effects, it is considered useful to suspend the therapy according to a suitable schedule of Structured Therapeutic Interruptions (STI). In the present article we describe an application of genetic algorithms (GA) aimed at finding the optimal schedule for a HAART simulated with an agent-based model (ABM) of the immune system that reproduces the most significant features of the response of an organism to the HIV-1 infection. The genetic algorithm helps in finding an optimal therapeutic schedule that maximizes immune restoration, minimizes the viral count and, through appropriate interruptions of the therapy, minimizes the dose of drug administered to the simulated patient. To validate the efficacy of the therapy that the genetic algorithm indicates as optimal, we ran simulations of opportunistic diseases and found that the selected therapy shows the best survival curve among the different simulated control groups. A version of the C-ImmSim simulator is available at http://www.iac.cnr.it/~filippo/c-ImmSim.html

Promoting tissue regeneration by modulating the immune system.

PubMed

Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

2017-04-15

The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support existing regenerative strategies or could be an alternative to using stem cells and growth factors. The first part of this review we highlight key immune mechanisms involved in the tissue healing process and marks them as potential target for designing regenerative strategies. In the second part, we discuss various approaches using biomaterials and drug delivery systems that aim at modulating the components of the immune system to promote tissue regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keeping It All Going-Complement Meets Metabolism.

PubMed

Kolev, Martin; Kemper, Claudia

2017-01-01

The complement system is an evolutionary old and crucial component of innate immunity, which is key to the detection and removal of invading pathogens. It was initially discovered as a liver-derived sentinel system circulating in serum, the lymph, and interstitial fluids that mediate the opsonization and lytic killing of bacteria, fungi, and viruses and the initiation of the general inflammatory responses. Although work performed specifically in the last five decades identified complement also as a critical instructor of adaptive immunity-indicating that complement's function is likely broader than initially anticipated-the dominant opinion among researchers and clinicians was that the key complement functions were in principle defined. However, there is now a growing realization that complement activity goes well beyond "classic" immune functions and that this system is also required for normal (neuronal) development and activity and general cell and tissue integrity and homeostasis. Furthermore, the recent discovery that complement activation is not confined to the extracellular space but occurs within cells led to the surprising understanding that complement is involved in the regulation of basic processes of the cell, particularly those of metabolic nature-mostly via novel crosstalks between complement and intracellular sensor, and effector, pathways that had been overlooked because of their spatial separation. These paradigm shifts in the field led to a renaissance in complement research and provide new platforms to now better understand the molecular pathways underlying the wide-reaching effects of complement functions in immunity and beyond. In this review, we will cover the current knowledge about complement's emerging relationship with the cellular metabolism machinery with a focus on the functional differences between serum-circulating versus intracellularly active complement during normal cell survival and induction of effector functions. We will also discuss how taking a closer look into the evolution of key complement components not only made the functional connection between complement and metabolism rather "predictable" but how it may also give clues for the discovery of additional roles for complement in basic cellular processes.

Modelling the Immune Response to Cancer: An Individual-Based Approach Accounting for the Difference in Movement Between Inactive and Activated T Cells.

PubMed

Macfarlane, Fiona R; Lorenzi, Tommaso; Chaplain, Mark A J

2018-06-01

A growing body of experimental evidence indicates that immune cells move in an unrestricted search pattern if they are in the pre-activated state, whilst they tend to stay within a more restricted area upon activation induced by the presence of tumour antigens. This change in movement is not often considered in the existing mathematical models of the interactions between immune cells and cancer cells. With the aim to fill such a gap in the existing literature, in this work we present a spatially structured individual-based model of tumour-immune competition that takes explicitly into account the difference in movement between inactive and activated immune cells. In our model, a Lévy walk is used to capture the movement of inactive immune cells, whereas Brownian motion is used to describe the movement of antigen-activated immune cells. The effects of activation of immune cells, the proliferation of cancer cells and the immune destruction of cancer cells are also modelled. We illustrate the ability of our model to reproduce qualitatively the spatial trajectories of immune cells observed in experimental data of single-cell tracking. Computational simulations of our model further clarify the conditions for the onset of a successful immune action against cancer cells and may suggest possible targets to improve the efficacy of cancer immunotherapy. Overall, our theoretical work highlights the importance of taking into account spatial interactions when modelling the immune response to cancer cells.

Reevaluation of epidemiological data demonstrates that it is consistent with cross-immunity among human papillomavirus types.

PubMed

Durham, David P; Poolman, Eric M; Ibuka, Yoko; Townsend, Jeffrey P; Galvani, Alison P

2012-10-01

The degree of cross-immunity between human papillomavirus (HPV) types is fundamental both to the epidemiological dynamics of HPV and to the impact of HPV vaccination. Epidemiological data on HPV infections has been repeatedly interpreted as inconsistent with cross-immunity. We reevaluate the epidemiological data using a model to determine the odds ratios of multiple to single infections expected in the presence or absence of cross-immunity. We simulate a virtual longitudinal survey to determine the effect cross-immunity has on the prevalence of multiple infections. We calibrate our model to epidemiological data and estimate the extent of type replacement following vaccination against specific HPV types. We find that cross-immunity can produce odds ratios of infection comparable with epidemiological observations. We show that the sample sizes underlying existing surveys have been insufficient to identify even intense cross-immunity. We also find that the removal of HPV type 16, type 18, and types 6 and 11 would increase the prevalence of nontargeted types by 50%, 29%, and 183%, respectively. Cross-immunity between HPV types is consistent with epidemiological data, contrary to previous interpretations. Cross-immunity may cause significant type replacement following vaccination, and therefore should be considered in future vaccine studies and epidemiological models.

A new strategy based on SmRho protein loaded chitosan nanoparticles as a candidate oral vaccine against schistosomiasis.

PubMed

Oliveira, Carolina R; Rezende, Cíntia M F; Silva, Marina R; Pêgo, Ana Paula; Borges, Olga; Goes, Alfredo M

2012-01-01

Schistosomiasis is one of the most important neglected tropical diseases and an effective control is unlikely in the absence of improved sanitation and vaccination. A new approach of oral vaccination with alginate coated chitosan nanoparticles appears interesting because their great stability and the ease of target accessibility, besides of chitosan and alginate immunostimulatory properties. Here we propose a candidate vaccine based on the combination of chitosan-based nanoparticles containing the antigen SmRho and coated with sodium alginate. Our results showed an efficient performance of protein loading of nanoparticles before and after coating with alginate. Characterization of the resulting nanoparticles reported a size around 430 nm and a negative zeta potential. In vitro release studies of protein showed great stability of coated nanoparticles in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). Further in vivo studies was performed with different formulations of chitosan nanoparticles and it showed that oral immunization was not able to induce high levels of antibodies, otherwise intramuscular immunization induced high levels of both subtypes IgG1 and IgG2a SmRho specific antibodies. Mice immunized with nanoparticles associated to CpG showed significant modulation of granuloma reaction. Mice from all groups immunized orally with nanoparticles presented significant levels of protection against infection challenge with S. mansoni worms, suggesting an important role of chitosan in inducing a protective immune response. Finally, mice immunized with nanoparticles associated with the antigen SmRho plus CpG had 38% of the granuloma area reduced and also presented 48% of protection against of S. mansoni infection. Taken together, this results support this new strategy as an efficient delivery system and a potential vaccine against schistosomiasis.

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans.

PubMed

Cuesta, Marc; Boudreau, Philippe; Dubeau-Laramée, Geneviève; Cermakian, Nicolas; Boivin, Diane B

2016-03-15

Recent research unveiled a circadian regulation of the immune system in rodents, yet little is known about rhythms of immune functions in humans and how they are affected by circadian disruption. In this study, we assessed rhythms of cytokine secretion by immune cells and tested their response to simulated night shifts. PBMCs were collected from nine participants kept in constant posture over 24 h under a day-oriented schedule (baseline) and after 3 d under a night-oriented schedule. Monocytes and T lymphocytes were stimulated with LPS and PHA, respectively. At baseline, a bimodal rhythmic secretion was detected for IL-1β, IL-6, and TNF-α: a night peak was primarily due to a higher responsiveness of monocytes, and a day peak was partly due to a higher proportion of monocytes. A rhythmic release was also observed for IL-2 and IFN-γ, with a nighttime peak due to a higher cell count and responsiveness of T lymphocytes. Following night shifts, with the exception of IL-2, cytokine secretion was still rhythmic but with peak levels phase advanced by 4.5-6 h, whereas the rhythm in monocyte and T lymphocyte numbers was not shifted. This suggests distinct mechanisms of regulation between responsiveness to stimuli and cell numbers of the human immune system. Under a night-oriented schedule, only cytokine release was partly shifted in response to the change in the sleep-wake cycle. This led to a desynchronization of rhythmic immune parameters, which might contribute to the increased risk for infection, autoimmune diseases, cardiovascular and metabolic disorders, and cancer reported in shift workers. Copyright © 2016 by The American Association of Immunologists, Inc.

Are fish immune systems really affected by parasites? an immunoecological study of common carp (Cyprinus carpio)

PubMed Central

2011-01-01

Background The basic function of the immune system is to protect an organism against infection in order to minimize the fitness costs of being infected. According to life-history theory, energy resources are in a trade-off between the costly demands of immunity and other physiological demands. Concerning fish, both physiology and immunity are influenced by seasonal changes (i.e. temporal variation) associated to the changes of abiotic factors (such as primarily water temperature) and interactions with pathogens and parasites. In this study, we investigated the potential associations between the physiology and immunocompetence of common carp (Cyprinus carpio) collected during five different periods of a given year. Our sampling included the periods with temporal variability and thus, it presented a different level in exposure to parasites. We analyzed which of two factors, seasonality or parasitism, had the strongest impact on changes in fish physiology and immunity. Results We found that seasonal changes play a key role in affecting the analyzed measurements of physiology, immunity and parasitism. The correlation analysis revealed the relationships between the measures of overall host physiology, immunity and parasite load when temporal variability effect was removed. When analyzing separately parasite groups with different life-strategies, we found that fish with a worse condition status were infected more by monogeneans, representing the most abundant parasite group. The high infection by cestodes seems to activate the phagocytes. A weak relationship was found between spleen size and abundance of trematodes when taking into account seasonal changes. Conclusions Even if no direct trade-off between the measures of host immunity and physiology was confirmed when taking into account the seasonality, it seems that seasonal variability affects host immunity and physiology through energy allocation in a trade-off between life important functions, especially reproduction and fish condition. Host immunity measures were not found to be in a trade-off with the investigated physiological traits or functions, but we confirmed the immunosuppressive role of 11-ketotestosterone on fish immunity measured by complement activity. We suggest that the different parasite life-strategies influence different aspects of host physiology and activate the different immunity pathways. PMID:21708010

Modelling and Simulation of the Dynamics of the Antigen-Specific T Cell Response Using Variable Structure Control Theory.

PubMed

Anelone, Anet J N; Spurgeon, Sarah K

2016-01-01

Experimental and mathematical studies in immunology have revealed that the dynamics of the programmed T cell response to vigorous infection can be conveniently modelled using a sigmoidal or a discontinuous immune response function. This paper hypothesizes strong synergies between this existing work and the dynamical behaviour of engineering systems with a variable structure control (VSC) law. These findings motivate the interpretation of the immune system as a variable structure control system. It is shown that dynamical properties as well as conditions to analytically assess the transition from health to disease can be developed for the specific T cell response from the theory of variable structure control. In particular, it is shown that the robustness properties of the specific T cell response as observed in experiments can be explained analytically using a VSC perspective. Further, the predictive capacity of the VSC framework to determine the T cell help required to overcome chronic Lymphocytic Choriomeningitis Virus (LCMV) infection is demonstrated. The findings demonstrate that studying the immune system using variable structure control theory provides a new framework for evaluating immunological dynamics and experimental observations. A modelling and simulation tool results with predictive capacity to determine how to modify the immune response to achieve healthy outcomes which may have application in drug development and vaccine design.

The Effect of Simulated Flash-Heat Pasteurization on Immune Components of Human Milk.

PubMed

Daniels, Brodie; Schmidt, Stefan; King, Tracy; Israel-Ballard, Kiersten; Amundson Mansen, Kimberly; Coutsoudis, Anna

2017-02-22

A pasteurization temperature monitoring system has been designed using FoneAstra, a cellphone-based networked sensing system, to monitor simulated flash-heat (FH) pasteurization. This study compared the effect of the FoneAstra FH (F-FH) method with the Sterifeed Holder method currently used by human milk banks on human milk immune components (immunoglobulin A (IgA), lactoferrin activity, lysozyme activity, interleukin (IL)-8 and IL-10). Donor milk samples ( N = 50) were obtained from a human milk bank, and pasteurized. Concentrations of IgA, IL-8, IL-10, lysozyme activity and lactoferrin activity were compared to their controls using the Student's t -test. Both methods demonstrated no destruction of interleukins. While the Holder method retained all lysozyme activity, the F-FH method only retained 78.4% activity ( p < 0.0001), and both methods showed a decrease in lactoferrin activity (71.1% Holder vs. 38.6% F-FH; p < 0.0001) and a decrease in the retention of total IgA (78.9% Holder vs. 25.2% F-FH; p < 0.0001). Despite increased destruction of immune components compared to Holder pasteurization, the benefits of F-FH in terms of its low cost, feasibility, safety and retention of immune components make it a valuable resource in low-income countries for pasteurizing human milk, potentially saving infants' lives.

Structure and expression of the attacin genes in Hyalophora cecropia.

PubMed

Sun, S C; Lindström, I; Lee, J Y; Faye, I

1991-02-26

To study the regulation of the immune genes in insects, we have cloned and sequenced the attacin gene locus of the giant silk moth Hyalophora cecropia. The locus contains one acidic and one basic attacin gene as well as two pseudogenes, which are remnants of basic attacin genes. A small insertion element was found within the locus. The two functional attacin genes are transcribed in opposite directions and have two introns inserted at homologous positions. A common sequence, GGGGATTCCT, is found at nucleotide position -48 in the acidic gene and at nucleotide position -58 in the basic gene. Interestingly, this decanucleotide is similar to the consensus of the NF-k B-binding site. Expression studies revealed that both attacins are strongly induced by phorbol 12-myristate 13-acetate, lipopolysaccharide and bacteria. However, only the acidic attacin gene showed a clear response to injury.

Network-level reproduction number and extinction threshold for vector-borne diseases.

PubMed

Xue, Ling; Scoglio, Caterina

2015-06-01

The basic reproduction number of deterministic models is an essential quantity to predict whether an epidemic will spread or not. Thresholds for disease extinction contribute crucial knowledge of disease control, elimination, and mitigation of infectious diseases. Relationships between basic reproduction numbers of two deterministic network-based ordinary differential equation vector-host models, and extinction thresholds of corresponding stochastic continuous-time Markov chain models are derived under some assumptions. Numerical simulation results for malaria and Rift Valley fever transmission on heterogeneous networks are in agreement with analytical results without any assumptions, reinforcing that the relationships may always exist and proposing a mathematical problem for proving existence of the relationships in general. Moreover, numerical simulations show that the basic reproduction number does not monotonically increase or decrease with the extinction threshold. Consistent trends of extinction probability observed through numerical simulations provide novel insights into mitigation strategies to increase the disease extinction probability. Research findings may improve understandings of thresholds for disease persistence in order to control vector-borne diseases.

The first invertebrate NFIL3 transcription factor with role in immune defense identified from the Hong Kong oyster, Crassostrea hongkongensis.

PubMed

Li, Jun; Zhang, Yang; Zhang, Yuehuan; Mao, Fan; Xiang, Zhiming; Xiao, Shu; Ma, Haitao; Yu, Ziniu

2017-11-01

NFIL3 (nuclear factor interleukin 3-regulated) is a basic leucine zipper type transcription factor that mediates a variety of immune responses in vertebrates. However, the sequence information and function of NFIL3 homologs in invertebrates, especially mollusks, remains unknown. In the present study, the first NFIL3 homolog was identified in a marine mollusk, Crassostrea hongkongensis (designated as ChNFIL3), followed by its functional characterization. The full-length cDNA of ChNFIL3 is 2221 bp and consists of an open reading frame (ORF) of 1536 bp that encodes a polypeptide of 551 amino acids. Simple Modular Architecture Research Tool (SMART) analysis indicated that ChNFIL3 has two basic leucin zipper domains, similar to the other known NFIL3 family proteins. Tissue distribution analysis of NFIL3 in this mollusk revealed high expression in digestive glands and hemocytes. A significant induction in the mRNA level of ChNFIL3 was observed following bacterial stimulation. ChNFIL3 was found to be localized in the nucleus and over expression of ChNIFL3 led to upregulation of transcriptional activity of an NF-κB reporter gene in HEK 293T cells, indicating its role in innate immunity. Furthermore, addition of exogenous recombinant ChNFIL3 proteins resulted in enhanced mRNA level of hemocyte interleukin 17 in vitro. In conclusion, our findings revealed that NFIL3 in molluscs, plays a conserved role in host defense, similar to its mammalian homolog. Copyright © 2017 Elsevier Ltd. All rights reserved.

How do immune cells support and shape the brain in health, disease, and aging?

PubMed

Schwartz, Michal; Kipnis, Jonathan; Rivest, Serge; Prat, Alexandre

2013-11-06

For decades, several axioms have prevailed with respect to the relationships between the CNS and circulating immune cells. Specifically, immune cell entry was largely considered to be pathological or to mark the beginning of pathology within the brain. Moreover, local inflammation associated with neurodegenerative diseases such Alzheimer's disease or amyotrophic lateral sclerosis, were considered similar in their etiology to inflammatory diseases, such as remitting relapsing-multiple sclerosis. The ensuing confusion reflected a lack of awareness that the etiology of the disease as well as the origin of the immune cells determines the nature of the inflammatory response, and that inflammation resolution is an active cellular process. The last two decades have seen a revolution in these prevailing dogmas, with a significant contribution made by the authors. Microglia and infiltrating monocyte-derived macrophages are now known to be functionally distinct and of separate origin. Innate and adaptive immune cells are now known to have protective/healing properties in the CNS, as long as their activity is regulated, and their recruitment is well controlled; their role is appreciated in maintenance of brain plasticity in health, aging, and chronic neurodevelopmental and neurodegenerative diseases. Moreover, it is now understood that the barriers of the brain are not uniform in their interactions with the circulating immune cells. The implications of these new findings to the basic understanding of CNS repair processes, brain aging, and a wide spectrum of CNS disorders, including acute injuries, Rett syndrome, Alzheimer's disease, and multiple sclerosis, will be discussed.

Mathematical modeling provides kinetic details of the human immune response to vaccination

PubMed Central

Le, Dustin; Miller, Joseph D.; Ganusov, Vitaly V.

2015-01-01

With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data. PMID:25621280

Mathematical modeling provides kinetic details of the human immune response to vaccination.

PubMed

Le, Dustin; Miller, Joseph D; Ganusov, Vitaly V

2014-01-01

With major advances in experimental techniques to track antigen-specific immune responses many basic questions on the kinetics of virus-specific immunity in humans remain unanswered. To gain insights into kinetics of T and B cell responses in human volunteers we combined mathematical models and experimental data from recent studies employing vaccines against yellow fever and smallpox. Yellow fever virus-specific CD8 T cell population expanded slowly with the average doubling time of 2 days peaking 2.5 weeks post immunization. Interestingly, we found that the peak of the yellow fever-specific CD8 T cell response was determined by the rate of T cell proliferation and not by the precursor frequency of antigen-specific cells as has been suggested in several studies in mice. We also found that while the frequency of virus-specific T cells increased slowly, the slow increase could still accurately explain clearance of yellow fever virus in the blood. Our additional mathematical model described well the kinetics of virus-specific antibody-secreting cell and antibody response to vaccinia virus in vaccinated individuals suggesting that most of antibodies in 3 months post immunization were derived from the population of circulating antibody-secreting cells. Taken together, our analysis provided novel insights into mechanisms by which live vaccines induce immunity to viral infections and highlighted challenges of applying methods of mathematical modeling to the current, state-of-the-art yet limited immunological data.

Development of a Rotary Wing Unmanned Aerial Vehicle (UAV) Simulation Model

DTIC Science & Technology

2014-03-01

Features Language URL Autopilot: DIY UAV - 2 DOF proportional controller - Kalman filtering C http://autopilot.sour ceforge.net Paperazzi - 3 DOF...proprtional controller - Basic navigation OCaml http://paparazzi.ena c.fr JSBSim - Basic control system blockset - Sample autopilot

Preliminary basic performance analysis of the Cedar multiprocessor memory system

NASA Technical Reports Server (NTRS)

Gallivan, K.; Jalby, W.; Turner, S.; Veidenbaum, A.; Wijshoff, H.

1991-01-01

Some preliminary basic results on the performance of the Cedar multiprocessor memory system are presented. Empirical results are presented and used to calibrate a memory system simulator which is then used to discuss the scalability of the system.

Modelling a stochastic HIV model with logistic target cell growth and nonlinear immune response function

NASA Astrophysics Data System (ADS)

Wang, Yan; Jiang, Daqing; Alsaedi, Ahmed; Hayat, Tasawar

2018-07-01

A stochastic HIV viral model with both logistic target cell growth and nonlinear immune response function is formulated to investigate the effect of white noise on each population. The existence of the global solution is verified. By employing a novel combination of Lyapunov functions, we obtain the existence of the unique stationary distribution for small white noises. We also derive the extinction of the virus for large white noises. Numerical simulations are performed to highlight the effect of white noises on model dynamic behaviour under the realistic parameters. It is found that the small intensities of white noises can keep the irregular blips of HIV virus and CTL immune response, while the larger ones force the virus infection and immune response to lose efficacy.

Instrument Motion Metrics for Laparoscopic Skills Assessment in Virtual Reality and Augmented Reality.

PubMed

Fransson, Boel A; Chen, Chi-Ya; Noyes, Julie A; Ragle, Claude A

2016-11-01

To determine the construct and concurrent validity of instrument motion metrics for laparoscopic skills assessment in virtual reality and augmented reality simulators. Evaluation study. Veterinarian students (novice, n = 14) and veterinarians (experienced, n = 11) with no or variable laparoscopic experience. Participants' minimally invasive surgery (MIS) experience was determined by hospital records of MIS procedures performed in the Teaching Hospital. Basic laparoscopic skills were assessed by 5 tasks using a physical box trainer. Each participant completed 2 tasks for assessments in each type of simulator (virtual reality: bowel handling and cutting; augmented reality: object positioning and a pericardial window model). Motion metrics such as instrument path length, angle or drift, and economy of motion of each simulator were recorded. None of the motion metrics in a virtual reality simulator showed correlation with experience, or to the basic laparoscopic skills score. All metrics in augmented reality were significantly correlated with experience (time, instrument path, and economy of movement), except for the hand dominance metric. The basic laparoscopic skills score was correlated to all performance metrics in augmented reality. The augmented reality motion metrics differed between American College of Veterinary Surgeons diplomates and residents, whereas basic laparoscopic skills score and virtual reality metrics did not. Our results provide construct validity and concurrent validity for motion analysis metrics for an augmented reality system, whereas a virtual reality system was validated only for the time score. © Copyright 2016 by The American College of Veterinary Surgeons.

NVU dynamics. I. Geodesic motion on the constant-potential-energy hypersurface.

PubMed

Ingebrigtsen, Trond S; Toxvaerd, Søren; Heilmann, Ole J; Schrøder, Thomas B; Dyre, Jeppe C

2011-09-14

An algorithm is derived for computer simulation of geodesics on the constant-potential-energy hypersurface of a system of N classical particles. First, a basic time-reversible geodesic algorithm is derived by discretizing the geodesic stationarity condition and implementing the constant-potential-energy constraint via standard Lagrangian multipliers. The basic NVU algorithm is tested by single-precision computer simulations of the Lennard-Jones liquid. Excellent numerical stability is obtained if the force cutoff is smoothed and the two initial configurations have identical potential energy within machine precision. Nevertheless, just as for NVE algorithms, stabilizers are needed for very long runs in order to compensate for the accumulation of numerical errors that eventually lead to "entropic drift" of the potential energy towards higher values. A modification of the basic NVU algorithm is introduced that ensures potential-energy and step-length conservation; center-of-mass drift is also eliminated. Analytical arguments confirmed by simulations demonstrate that the modified NVU algorithm is absolutely stable. Finally, we present simulations showing that the NVU algorithm and the standard leap-frog NVE algorithm have identical radial distribution functions for the Lennard-Jones liquid. © 2011 American Institute of Physics

Advanced Simulation in Undergraduate Pilot Training: Systems Integration. Final Report (February 1972-March 1975).

ERIC Educational Resources Information Center

Larson, D. F.; Terry, C.

The Advanced Simulator for Undergraduate Pilot Training (ASUPT) was designed to investigate the role of simulation in the future Undergraduate Pilot Training (UPT) program. The problem addressed in this report was one of integrating two unlike components into one synchronized system. These two components were the Basic T-37 Simulators and their…

Health benefits and health claims of probiotics: bridging science and marketing.

PubMed

Rijkers, Ger T; de Vos, Willem M; Brummer, Robert-Jan; Morelli, Lorenzo; Corthier, Gerard; Marteau, Philippe

2011-11-01

Health claims for probiotics are evaluated by the Panel on Dietetic Products, Nutrition and Allergies of the European Food Safety Authority. Despite a substantial amount of basic and clinical research on the beneficial effects of probiotics, all of the evaluated claim applications thus far have received a negative opinion. With the restrictions on the use of clinical endpoints, validated biomarkers for gut health and immune health in relation to reduction in disease risk are needed. Clear-cut criteria for design as well as evaluation of future studies are needed. An open dialogue between basic and clinical scientists, regulatory authorities, food and nutrition industry, and consumers could bridge the gap between science and marketing of probiotics.

Autoimmune polyglandular syndromes: interplay between the immune and the endocrine systems leading to a diverse set of clinical diseases and new insights into immune regulation.

PubMed

Lebovitz, Harold E

2013-06-01

During the last 50 years, three major classes of autoimmune polyglandular syndromes (APSs) have been defined, and their characteristics and heritability have been delineated. Simultaneously, studies of the immunologic bases of these syndromes provided fundamental information in understanding immune regulation. Genetic analyses of patients and their families with APS type 1 (autoimmune polyendocrinopathy candidiasis, ectodermal dystrophy) identified the autoimmune regulator (AIRE) gene, which drives the expression of peripheral tissue-specific antigens in thymic cells and is critical in the development of self-tolerance. Mutations in this gene cause APS type 1. In contrast, studies in APS type 2 have been instrumental in understanding the role of human leukocyte antigen type II and related molecules in the pathogenesis of polygenetic autoimmune diseases such as type 1A diabetes. Immune dysfunction polyendocrinopathy, enteropathy, X-linked syndrome, which is caused by mutations in the forkhead box P3 gene, has been a model for studying regulatory T cell biology. The APSs epitomize the synergies that the merger of clinical and basic science can achieve. This is the environment that George Eisenbarth was able to create at the Barbara Davis Center for Diabetes.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

PubMed

Cao, Nan; Li, Wanyan; Li, Bingxin; Tian, Yunbo; Xu, Danning

2017-12-01

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese. © 2017 Japanese Society of Animal Science.

Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides

PubMed Central

Jia, Haibo; Halilou, Amadou I.; Hu, Liang; Cai, Wenqian; Liu, Jing; Huang, Bo

2011-01-01

Heat shock protein 10 (Hsp10) in eukaryotes, originally identified as a mitochondrial chaperone, now is also known to be present in cytosol, cell surface, extracellular space and peripheral blood. Functionally besides participating in mitochondrial protein folding in association with Hsp60, Hsp10 appears to be related to pregnancy, cancer and autoimmune inhibition. Hsp10 can be released to peripheral blood at very early time point of pregnancy and given another name called early pregnancy factor (EPF), which seems to play a critical role in developing a pregnant niche. In malignant disorders, Hsp10 is usually abnormally expressed in the cytosol of malignant cells and further released to extracellular space, resulting in tumor-promoting effect from various aspects. Furthermore, distinct from other heat shock protein members, whose soluble form is recognized as danger signal by immune cells and triggers immune responses, Hsp10 after release, however, is designed to be an inhibitory signal by limiting immune response. This review discusses how Hsp10 participates in various physiological and pathological processes from basic protein molecule folding to pregnancy, cancer and autoimmune diseases, and emphasizes how important the location is for the function exertion of a molecule. PMID:21969171

Direct Delivery of Antigens to Dendritic Cells via Antibodies Specific for Endocytic Receptors as a Promising Strategy for Future Therapies

PubMed Central

Lehmann, Christian H. K.; Heger, Lukas; Heidkamp, Gordon F.; Baranska, Anna; Lühr, Jennifer J.; Hoffmann, Alana; Dudziak, Diana

2016-01-01

Dendritic cells (DCs) are the most potent professional antigen presenting cells and are therefore indispensable for the control of immunity. The technique of antibody mediated antigen targeting to DC subsets has been the basis of intense research for more than a decade. Many murine studies have utilized this approach of antigen delivery to various kinds of endocytic receptors of DCs both in vitro and in vivo. Today, it is widely accepted that different DC subsets are important for the induction of select immune responses. Nevertheless, many questions still remain to be answered, such as the actual influence of the targeted receptor on the initiation of the immune response to the delivered antigen. Further efforts to better understand the induction of antigen-specific immune responses will support the transfer of this knowledge into novel treatment strategies for human diseases. In this review, we will discuss the state-of-the-art aspects of the basic principles of antibody mediated antigen targeting approaches. A table will also provide a broad overview of the latest studies using antigen targeting including addressed DC subset, targeted receptors, outcome, and applied coupling techniques. PMID:27043640

Emerging concepts and future challenges in innate lymphoid cell biology

PubMed Central

Artis, David

2016-01-01

Innate lymphoid cells (ILCs) are innate immune cells that are ubiquitously distributed in lymphoid and nonlymphoid tissues and enriched at mucosal and barrier surfaces. Three major ILC subsets are recognized in mice and humans. Each of these subsets interacts with innate and adaptive immune cells and integrates cues from the epithelium, the microbiota, and pathogens to regulate inflammation, immunity, tissue repair, and metabolic homeostasis. Although intense study has elucidated many aspects of ILC development, phenotype, and function, numerous challenges remain in the field of ILC biology. In particular, recent work has highlighted key new questions regarding how these cells communicate with their environment and other cell types during health and disease. This review summarizes new findings in this rapidly developing field that showcase the critical role ILCs play in directing immune responses through their ability to interact with a variety of hematopoietic and nonhematopoietic cells. In addition, we define remaining challenges and emerging questions facing the field. Finally, this review discusses the potential application of basic studies of ILC biology to the development of new treatments for human patients with inflammatory and infectious diseases in which ILCs play a role. PMID:27811053

The Immune Landscape of Non-Small Cell Lung Cancer: Utility of Cytologic and Histologic Samples Obtained Through Minimally Invasive Pulmonary Procedures.

PubMed

Beattie, Jason; Yarmus, Lonny; Wahidi, Momen M; Rivera, M Patricia; Gilbert, Christopher; Maldonado, Fabien; Czarnecka, Kasia; Argento, Angela; Chen, Alexander; Herth, Felix; Sterman, Daniel H

2018-05-14

The success of immune checkpoint inhibitors and the discovery of useful biomarkers to predict response to these agents is shifting much of the focus of personalized care for non-small cell lung cancer towards harnessing the immune response. With further advancement, more effective immunotherapy options will emerge along with more useful biomarkers. Paradoxically, minimally invasive small biopsy and cytology specimens have become the primary method for diagnosis of patients with advanced disease, as well for initial diagnosis and staging in earlier stage disease. For the benefit of these patients, we will continue to learn how to do more with less. In this perspective, we review aspects of immunobiology that underlie the current state of the art of existing and emerging immunologic biomarkers that hold potential to enhance the care of patients with non-small cell lung cancer. We address practical considerations for acquiring patient samples that accurately reflect disease immune status. We also propose a paradigm shift wherein the most important sample types that need to be proven in pioneering basic science and translation work and subsequent clinical trials are the specimens most often obtained clinically.

Immunotherapeutic potential of CpG oligodeoxynucleotides in veterinary species.

PubMed

Manuja, Anju; Manuja, Balvinder K; Kaushik, Jyoti; Singha, Harisankar; Singh, Raj Kumar

2013-10-01

Innate immunity plays a critical role in host defense against infectious diseases by discriminating between self and infectious non-self. The recognition of infectious non-self involves germ-line encoded pattern recognition receptors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs). The PAMPs are the components of pathogenic microbes which include not only the cell wall constituents but also the unmethylated 2'-deoxy-ribo-cytosine-phosphate-guanosine (CpG) motifs. These CpG motifs present within bacterial and viral DNA are recognized by toll-like receptor 9 (TLR9), and signaling by this receptor triggers a proinflammatory cytokine response which, in turn, influences both innate and adaptive immune responses. The activation of TLR9 with synthetic CpG oligodeoxynucleotides (ODNs) induces powerful Th1-like immune responses. It has been shown to provide protection against infectious diseases, allergy and cancer in laboratory animal models and some domestic animal species. With better understanding of the basic biology and immune mechanisms, it would be possible to exploit the potential of CpG motifs for animal welfare. The research developments in the area of CpG and TLR9 and the potential applications in animal health have been reviewed in this article.

Atezolizumab for the treatment of non-small cell lung cancer.

PubMed

Santini, Fernando C; Rudin, Charles M

2017-09-01

The immune system can restrain or promote cancer development and growth. Antibodies targeting immune checkpoints have revolutionized cancer treatment. Among the best responses have been in non-small cell lung cancer (NSCLC) which is largely caused by chronic exposure to carcinogens; associated with high neoantigen creation and sensitization to immune recognition. Atezolizumab was the first approved antibody that targets the PD-1 ligand (PD-L1). Areas covered: This drug profile article covers the basics of the cancer-immunity cycle and reviews some aspects of innate and adaptive immunology. We discuss the discovery of PD-L1 and PD-L2 while highlight the potential differences in targeting PD-L1 versus PD-1. In addition, we briefly summarized the available pre-clinical and clinical data of atezolizumab use in NSCLC. A special section covers the challenges of PD-L1 immunohistochemistry assay. Expert commentary: PD-1:PD-L1 blockade has taken the lead in the immunotherapeutics field and represents the backbone of developing combination immunotherapies. Atezolizumab represents a step forward in the treatment of advanced NSCLC, nonetheless PD1:PD-L1 blockade in early-stage lung cancer is still a matter of debate.

10 CFR 431.17 - Determination of efficiency.

Code of Federal Regulations, 2014 CFR

2014-01-01

... characteristics of that basic model, and (ii) Based on engineering or statistical analysis, computer simulation or... simulation or modeling, and other analytic evaluation of performance data on which the AEDM is based... applied. (iii) If requested by the Department, the manufacturer shall conduct simulations to predict the...

10 CFR 431.17 - Determination of efficiency.

Code of Federal Regulations, 2012 CFR

2012-01-01

... characteristics of that basic model, and (ii) Based on engineering or statistical analysis, computer simulation or... simulation or modeling, and other analytic evaluation of performance data on which the AEDM is based... applied. (iii) If requested by the Department, the manufacturer shall conduct simulations to predict the...

Structural basis for dsRNA recognition and interferon antagonism by Ebola VP35

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

Leung, Daisy W.; Prins, Kathleen C.; Borek, Dominika M.

2010-03-12

Ebola viral protein 35 (VP35), encoded by the highly pathogenic Ebola virus, facilitates host immune evasion by antagonizing antiviral signaling pathways, including those initiated by RIG-I-like receptors. Here we report the crystal structure of the Ebola VP35 interferon inhibitory domain (IID) bound to short double-stranded RNA (dsRNA), which together with in vivo results reveals how VP35-dsRNA interactions contribute to immune evasion. Conserved basic residues in VP35 IID recognize the dsRNA backbone, whereas the dsRNA blunt ends are 'end-capped' by a pocket of hydrophobic residues that mimic RIG-I-like receptor recognition of blunt-end dsRNA. Residues critical for RNA binding are also importantmore » for interferon inhibition in vivo but not for viral polymerase cofactor function of VP35. These results suggest that simultaneous recognition of dsRNA backbone and blunt ends provides a mechanism by which Ebola VP35 antagonizes host dsRNA sensors and immune responses.« less

The immune response of hemocytes of the insect Oncopeltus fasciatus against the flagellate Phytomonas serpens.

PubMed

Alves e Silva, Thiago L; Vasconcellos, Luiz R C; Lopes, Angela H; Souto-Padrón, Thaïs

2013-01-01

The genus Phytomonas includes parasites that are etiological agents of important plant diseases, especially in Central and South America. These parasites are transmitted to plants via the bite of an infected phytophagous hemipteran. Despite the economic impact of these parasites, many basic questions regarding the genus Phytomonas remain unanswered, such as the mechanism by which the parasites cope with the immune response of the insect vector. In this report, using a model of systemic infection, we describe the function of Oncopeltus fasciatus hemocytes in the immune response towards the tomato parasite Phytomonas serpens. Hemocytes respond to infection by trapping parasites in nodular structures and phagocytizing the parasites. In electron microscopy of hemocytes, parasites were located inside vacuoles, which appear fused with lysosomes. The parasites reached the O. fasciatus salivary glands at least six hours post-infection. After 72 hours post-infection, many parasites were attached to the salivary gland outer surface. Thus, the cellular responses did not kill all the parasites.

The Immune Response of Hemocytes of the Insect Oncopeltus fasciatus against the Flagellate Phytomonas serpens

PubMed Central

Alves e Silva, Thiago L.; Vasconcellos, Luiz R. C.

2013-01-01

The genus Phytomonas includes parasites that are etiological agents of important plant diseases, especially in Central and South America. These parasites are transmitted to plants via the bite of an infected phytophagous hemipteran. Despite the economic impact of these parasites, many basic questions regarding the genus Phytomonas remain unanswered, such as the mechanism by which the parasites cope with the immune response of the insect vector. In this report, using a model of systemic infection, we describe the function of Oncopeltus fasciatus hemocytes in the immune response towards the tomato parasite Phytomonas serpens. Hemocytes respond to infection by trapping parasites in nodular structures and phagocytizing the parasites. In electron microscopy of hemocytes, parasites were located inside vacuoles, which appear fused with lysosomes. The parasites reached the O. fasciatus salivary glands at least six hours post-infection. After 72 hours post-infection, many parasites were attached to the salivary gland outer surface. Thus, the cellular responses did not kill all the parasites. PMID:24015207

Aryl hydrocarbon receptor and intestinal immunity.

PubMed

Lamas, Bruno; Natividad, Jane M; Sokol, Harry

2018-04-07

Aryl hydrocarbon receptor (AhR) is a member of the basic helix-loop-helix-(bHLH) superfamily of transcription factors, which are associated with cellular responses to environmental stimuli, such as xenobiotics and oxygen levels. Unlike other members of bHLH, AhR is the only bHLH transcription factor that is known to be ligand activated. Early AhR studies focused on understanding the role of AhR in mediating the toxicity and carcinogenesis properties of the prototypic ligand 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In recent years, however, it has become apparent that, in addition to its toxicological involvement, AhR is highly receptive to a wide array of endogenous and exogenous ligands, and that its activation leads to a myriad of key host physiological functions. In this study, we review the current understanding of the functions of AhR in the mucosal immune system with a focus on its role in intestinal barrier function and intestinal immune cells, as well as in intestinal homeostasis.

Gene Transfer into Rat Brain Using Adenoviral Vectors

PubMed Central

Puntel, Mariana; Kroeger, Kurt M.; Sanderson, Nicholas S.R.; Thomas, Clare E.; Castro, Maria G.; Lowenstein, Pedro R.

2010-01-01

Viral vector–mediated gene delivery is an attractive procedure for introducing genes into the brain, both for purposes of basic neuroscience research and to develop gene therapy for neurological diseases. Replication-defective adenoviruses possess many features which make them ideal vectors for this purpose—efficiently transducing terminally differentiated cells such as neurons and glial cells, resulting in high levels of transgene expression in vivo. Also, in the absence of anti-adenovirus immunity, these vectors can sustain very long-term transgene expression within the brain parenchyma. This unit provides protocols for the stereotactic injection of adenoviral vectors into the brain, followed by protocols to detect transgene expression or infiltrates of immune cells by immunocytochemistry or immunofluorescence. ELISPOT and neutralizing antibody assay methodologies are provided to quantitate the levels of cellular and humoral immune responses against adenoviruses. Quantitation of adenoviral vector genomes within the rat brain using qPCR is also described. Curr. Protoc. Neurosci. 50:4.24.1–4.24.49. © 2010 by John Wiley & Sons, Inc. PMID:20066657

Mechanisms by which pesticides affect insect immunity.

PubMed

James, R R; Xu, J

2012-02-01

The current state of knowledge regarding the effect of pesticides on insect immunity is reviewed here. A basic understanding of these interactions is needed for several reasons, including to improve methods for controlling pest insects in agricultural settings, for controlling insect vectors of human diseases, and for reducing mortality in beneficial insects. Bees are particularly vulnerable to sublethal pesticide exposures because they gather nectar and pollen, concentrating environmental toxins in their nests in the process. Pesticides do have effects on immunity. Organophosphates and some botanicals have been found to impact hemocyte number, differentiation, and thus affect phagocytosis. The phenoloxidase cascade and malanization have also been shown to be affected by several insecticides. Many synthetic insecticides increase oxidative stress, and this could have severe impacts on the production of some antimicrobial peptides in insects, but research is needed to determine the actual effects. Pesticides can also affect grooming behaviors, rendering insects more susceptible to disease. Despite laboratory data documenting pesticide/pathogen interactions, little field data is available at the population level. Published by Elsevier Inc.

Topics in this issue: cancer testes antigens, immune checkpoints, inflammation associated with ischemia-reperfusion and integrin targeting.

PubMed

Bot, Adrian; Chiriva-Internati, Maurizio

2012-10-01

This issue of the International Reviews of Immunology is dedicated to several topics: cancer immunotherapy, and basic and translational aspects of immunity. Two reviews, one focused on breast and the other on lung cancer, highlight the need to redefine the cancer testes antigens (CTAs) as novel information regarding their expression profile and biological role emerges. Two other reviews showcase pivotal molecules that keep in check immunity at two different levels: the transcription factor autoimmune regulator (AIRE) important to negative selection of the T-cell repertoire, and CD22 that limits the antigen-initiated B-cell response. Two other articles focus on the debated role of Toll-like receptors (TLRs) and inflammation in general, in ischemia-reperfusion lesions that follow cardiovascular disorders and stroke. Last but not the least, this issue hosts a review that discusses the role and translational potential of the α4 integrin for the treatment of inflammatory bowel disease (IBD).

Mucosal vaccination--an old but still vital strategy.

PubMed

Długońska, Henryka; Grzybowski, Marcin

2012-01-01

The basic premise of vaccinology is to achieve strong protective immunity against defined infectious agents by a vaccine mimicking the effects of natural primary exposure to a pathogen. Because an exposure of humans and animals to microbes occurs mostly through mucosal surfaces, targeting the mucosa seems a rational and efficient vaccination strategy. Many experimental and clinical data confirmed that mucosal immunization offers many advantages over widely used in human and veterinary medicine subcutaneous or intramuscular immunization. In the present article selected aspects regarding mucosal vaccination are discussed. The structure and function of mucosa-associated lymphoid tissue (MALT), comprised of four main mucosal compartments forming a structural and functional unity as well as pivotal cellular MALT components (dendritic and M cells) were briefly characterized. Particular attention was focused on the mode of simple but efficacious delivery of vaccine antigens to mucosal surfaces. A few trials to generate potential mucosal vaccines against toxoplasmosis introduced by nasal or oral routes to experimental animals are also presented.

Objective assessment of gynecologic laparoscopic skills using the LapSimGyn virtual reality simulator.

PubMed

Larsen, C R; Grantcharov, T; Aggarwal, R; Tully, A; Sørensen, J L; Dalsgaard, T; Ottesen, B

2006-09-01

Safe realistic training and unbiased quantitative assessment of technical skills are required for laparoscopy. Virtual reality (VR) simulators may be useful tools for training and assessing basic and advanced surgical skills and procedures. This study aimed to investigate the construct validity of the LapSimGyn VR simulator, and to determine the learning curves of gynecologists with different levels of experience. For this study, 32 gynecologic trainees and consultants (juniors or seniors) were allocated into three groups: novices (0 advanced laparoscopic procedures), intermediate level (>20 and <60 procedures), and experts (>100 procedures). All performed 10 sets of simulations consisting of three basic skill tasks and an ectopic pregnancy program. The simulations were carried out on 3 days within a maximum period of 2 weeks. Assessment of skills was based on time, economy of movement, and error parameters measured by the simulator. The data showed that expert gynecologists performed significantly and consistently better than intermediate and novice gynecologists. The learning curves differed significantly between the groups, showing that experts start at a higher level and more rapidly reach the plateau of their learning curve than do intermediate and novice groups of surgeons. The LapSimGyn VR simulator package demonstrates construct validity on both the basic skills module and the procedural gynecologic module for ectopic pregnancy. Learning curves can be obtained, but to reach the maximum performance for the more complex tasks, 10 repetitions do not seem sufficient at the given task level and settings. LapSimGyn also seems to be flexible and widely accepted by the users.

Epidemic spreading and global stability of an SIS model with an infective vector on complex networks

NASA Astrophysics Data System (ADS)

Kang, Huiyan; Fu, Xinchu

2015-10-01

In this paper, we present a new SIS model with delay on scale-free networks. The model is suitable to describe some epidemics which are not only transmitted by a vector but also spread between individuals by direct contacts. In view of the biological relevance and real spreading process, we introduce a delay to denote average incubation period of disease in a vector. By mathematical analysis, we obtain the epidemic threshold and prove the global stability of equilibria. The simulation shows the delay will effect the epidemic spreading. Finally, we investigate and compare two major immunization strategies, uniform immunization and targeted immunization.

Artificial Immune Algorithm for Subtask Industrial Robot Scheduling in Cloud Manufacturing

NASA Astrophysics Data System (ADS)

Suma, T.; Murugesan, R.

2018-04-01

The current generation of manufacturing industry requires an intelligent scheduling model to achieve an effective utilization of distributed manufacturing resources, which motivated us to work on an Artificial Immune Algorithm for subtask robot scheduling in cloud manufacturing. This scheduling model enables a collaborative work between the industrial robots in different manufacturing centers. This paper discussed two optimizing objectives which includes minimizing the cost and load balance of industrial robots through scheduling. To solve these scheduling problems, we used the algorithm based on Artificial Immune system. The parameters are simulated with MATLAB and the results compared with the existing algorithms. The result shows better performance than existing.

Evaluation of outbreak response immunization in the control of pertussis using agent-based modeling.

PubMed

Doroshenko, Alexander; Qian, Weicheng; Osgood, Nathaniel D

2016-01-01

Pertussis control remains a challenge due to recently observed effects of waning immunity to acellular vaccine and suboptimal vaccine coverage. Multiple outbreaks have been reported in different ages worldwide. For certain outbreaks, public health authorities can launch an outbreak response immunization (ORI) campaign to control pertussis spread. We investigated effects of an outbreak response immunization targeting young adolescents in averting pertussis cases. We developed an agent-based model for pertussis transmission representing disease mechanism, waning immunity, vaccination schedule and pathogen transmission in a spatially-explicit 500,000-person contact network representing a typical Canadian Public Health district. Parameters were derived from literature and calibration. We used published cumulative incidence and dose-specific vaccine coverage to calibrate the model's epidemiological curves. We endogenized outbreak response by defining thresholds to trigger simulated immunization campaigns in the 10-14 age group offering 80% coverage. We ran paired simulations with and without outbreak response immunization and included those resulting in a single ORI within a 10-year span. We calculated the number of cases averted attributable to outbreak immunization campaign in all ages, in the 10-14 age group and in infants. The count of cases averted were tested using Mann-Whitney U test to determine statistical significance. Numbers needed to vaccinate during immunization campaign to prevent a single case in respective age groups were derived from the model. We varied adult vaccine coverage, waning immunity parameters, immunization campaign eligibility and tested stronger vaccination boosting effect in sensitivity analyses. 189 qualified paired-runs were analyzed. On average, ORI was triggered every 26 years. On a per-run basis, there were an average of 124, 243 and 429 pertussis cases averted across all age groups within 1, 3 and 10 years of a campaign, respectively. During the same time periods, 53, 96, and 163 cases were averted in the 10-14 age group, and 6, 11, 20 in infants under 1 (p < 0.001, all groups). Numbers needed to vaccinate ranged from 49 to 221, from 130 to 519 and from 1,031 to 4,903 for all ages, the 10-14 age group and for infants, respectively. Most sensitivity analyses resulted in minimal impact on a number of cases averted. Our model generated 30 years of longitudinal data to evaluate effects of outbreak response immunization in a controlled study. Immunization campaign implemented as an outbreak response measure among adolescents may confer benefits across all ages accruing over a 10-year period. Our inference is dependent on having an outbreak of significant magnitude affecting predominantly the selected age and achieving a comprehensive vaccine coverage during the campaign. Economic evaluations and comparisons with other control measures can add to conclusions generated by our work.

CRISPR/Cas9 Immune System as a Tool for Genome Engineering.

PubMed

Hryhorowicz, Magdalena; Lipiński, Daniel; Zeyland, Joanna; Słomski, Ryszard

2017-06-01

CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) adaptive immune systems constitute a bacterial defence against invading nucleic acids derived from bacteriophages or plasmids. This prokaryotic system was adapted in molecular biology and became one of the most powerful and versatile platforms for genome engineering. CRISPR/Cas9 is a simple and rapid tool which enables the efficient modification of endogenous genes in various species and cell types. Moreover, a modified version of the CRISPR/Cas9 system with transcriptional repressors or activators allows robust transcription repression or activation of target genes. The simplicity of CRISPR/Cas9 has resulted in the widespread use of this technology in many fields, including basic research, biotechnology and biomedicine.

The potential of mesenchymal stromal cells as a novel cellular therapy for multiple sclerosis

PubMed Central

Auletta, Jeffery J; Bartholomew, Amelia M; Maziarz, Richard T; Deans, Robert J; Miller, Robert H; Lazarus, Hillard M; Cohen, Jeffrey A

2012-01-01

Multiple sclerosis (MS) is an inflammatory neurodegenerative disease of the CNS for which only partially effective therapies exist. Intense research defining the underlying immune pathophysiology is advancing both the understanding of MS as well as revealing potential targets for disease intervention. Mesenchymal stromal cell (MSC) therapy has the potential to modulate aberrant immune responses causing demyelination and axonal injury associated with MS, as well as to repair and restore damaged CNS tissue and cells. This article reviews the pathophysiology underlying MS, as well as providing a cutting-edge perspective into the field of MSC therapy based upon the experience of authors intrinsically involved in MS and MSC basic and translational science research. PMID:22642335

Exploiting Uptake of Nanoparticles by Phagocytes for Cancer Treatment.

PubMed

Sheen, Mee Rie; Fiering, Steven

2017-01-01

Many cancers including ovarian, pancreatic, colon, liver, and stomach cancers are largely confined to the peritoneal cavity. Peritoneal tumors are directly accessible by intraperitoneal injections. Previously we demonstrated that intraperitoneal injection of nanoparticles and subsequent ingestion by tumor-associated phagocytes can be used to either directly impact tumors or stimulate antitumor immune responses. Here we outline methods to specifically utilize iron oxide nanoparticles with the ID8-Defb29/Vegf-A murine ovarian cancer model and discuss the tendency of phagocytes to ingest nanoparticles and the potential of phagocytes to carry nanoparticles to tumors resulting in direct killing of tumor cells or stimulate antitumor immune responses in peritoneal cancers. This basic approach can be modified as needed for different types of tumors and nanoparticles.

Simulation of Mission Phases

NASA Technical Reports Server (NTRS)

Carlstrom, Nicholas Mercury

2016-01-01

This position with the Simulation and Graphics Branch (ER7) at Johnson Space Center (JSC) provided an introduction to vehicle hardware, mission planning, and simulation design. ER7 supports engineering analysis and flight crew training by providing high-fidelity, real-time graphical simulations in the Systems Engineering Simulator (SES) lab. The primary project assigned by NASA mentor and SES lab manager, Meghan Daley, was to develop a graphical simulation of the rendezvous, proximity operations, and docking (RPOD) phases of flight. The simulation is to include a generic crew/cargo transportation vehicle and a target object in low-Earth orbit (LEO). Various capsule, winged, and lifting body vehicles as well as historical RPOD methods were evaluated during the project analysis phase. JSC core mission to support the International Space Station (ISS), Commercial Crew Program (CCP), and Human Space Flight (HSF) influenced the project specifications. The simulation is characterized as a 30 meter +V Bar and/or -R Bar approach to the target object's docking station. The ISS was selected as the target object and the international Low Impact Docking System (iLIDS) was selected as the docking mechanism. The location of the target object's docking station corresponds with the RPOD methods identified. The simulation design focuses on Guidance, Navigation, and Control (GNC) system architecture models with station keeping and telemetry data processing capabilities. The optical and inertial sensors, reaction control system thrusters, and the docking mechanism selected were based on CCP vehicle manufacturer's current and proposed technologies. A significant amount of independent study and tutorial completion was required for this project. Multiple primary source materials were accessed using the NASA Technical Report Server (NTRS) and reference textbooks were borrowed from the JSC Main Library and International Space Station Library. The Trick Simulation Environment and User Training Materials version 2013.0 release was used to complete the Trick tutorial. Multiple network privilege and repository permission requests were required in order to access previous simulation models. The project was also an introduction to computer programming and the Linux operating system. Basic C++ and Python syntax was used during the completion of the Trick tutorial. Trick's engineering analysis and Monte Carlo simulation capabilities were observed and basic space mission planning procedures were applied in the conceptual design phase. Multiple professional development opportunities were completed in addition to project duties during this internship through the System for Administration, Training, and Education Resources for NASA (SATERN). Topics include: JSC Risk Management Workshop, CCP Risk Management, Basic Radiation Safety Training, X-Ray Radiation Safety, Basic Laser Safety, JSC Export Control, ISS RISE Ambassador, Basic SharePoint 2013, Space Nutrition and Biochemistry, and JSC Personal Protective Equipment. Additionally, this internship afforded the opportunity for formal project presentation and public speaking practice. This was my first experience at a NASA center. After completing this internship I have a much clearer understanding of certain aspects of the agency's processes and procedures, as well as a deeper appreciation from spaceflight simulation design and testing. I will continue to improve my technical skills so that I may have another opportunity to return to NASA and Johnson Space Center.

Organ-on-a-chip: development and clinical prospects toward toxicity assessment with an emphasis on bone marrow.

PubMed

Kim, Jeehye; Lee, Hanna; Selimović, Šeila; Gauvin, Robert; Bae, Hojae

2015-05-01

Conventional approaches for toxicity evaluation of drugs and chemicals, such as animal tests, can be impractical due to the large experimental scale and the immunological differences between species. Organ-on-a-chip models have recently been recognized as a prominent alternative to conventional toxicity tests aiming to simulate the human in vivo physiology. This review focuses on the organ-on-a-chip applications for high-throughput screening of candidate drugs against toxicity, with a particular emphasis on bone-marrow-on-a-chip. Studies in which organ-on-a-chip models have been developed and utilized to maximize the efficiency and predictability in toxicity assessment are introduced. The potential of these devices to replace tests of acute systemic toxicity in animals, and the challenges that are inherent in simulating the human immune system are also discussed. As a promising approach to overcome the limitations, we further focus on an in-depth analysis of the development of bone-marrow-on-a-chip that is capable of simulating human immune responses against external stimuli due to the key roles of marrow in immune systems with hematopoietic activities. Owing to the complex interactions between hematopoietic stem cells and marrow microenvironments, precise control of both biochemical and physical niches that are critical in maintenance of hematopoiesis remains a key challenge. Thus, recently developed bone-marrow-on-a-chip models support immunogenicity and immunotoxicity testing in long-term cultivation with repeated antigen stimulation. In this review, we provide an overview of clinical studies that have been carried out on bone marrow transplants in patients with immune-related diseases and future aspects of clinical and pharmaceutical application of bone-marrow-on-a-chip.

49 CFR 236.923 - Task analysis and basic requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... classroom, simulator, computer-based, hands-on, or other formally structured training and testing, except... for Processor-Based Signal and Train Control Systems § 236.923 Task analysis and basic requirements...) Based on a formal task analysis, identify the installation, maintenance, repair, modification...

Agent-based modeling: Methods and techniques for simulating human systems

PubMed Central

Bonabeau, Eric

2002-01-01

Agent-based modeling is a powerful simulation modeling technique that has seen a number of applications in the last few years, including applications to real-world business problems. After the basic principles of agent-based simulation are briefly introduced, its four areas of application are discussed by using real-world applications: flow simulation, organizational simulation, market simulation, and diffusion simulation. For each category, one or several business applications are described and analyzed. PMID:12011407

Mosquito population dynamics from cellular automata-based simulation

NASA Astrophysics Data System (ADS)

Syafarina, Inna; Sadikin, Rifki; Nuraini, Nuning

2016-02-01

In this paper we present an innovative model for simulating mosquito-vector population dynamics. The simulation consist of two stages: demography and dispersal dynamics. For demography simulation, we follow the existing model for modeling a mosquito life cycles. Moreover, we use cellular automata-based model for simulating dispersal of the vector. In simulation, each individual vector is able to move to other grid based on a random walk. Our model is also capable to represent immunity factor for each grid. We simulate the model to evaluate its correctness. Based on the simulations, we can conclude that our model is correct. However, our model need to be improved to find a realistic parameters to match real data.

Antibody-supervised deep learning for quantification of tumor-infiltrating immune cells in hematoxylin and eosin stained breast cancer samples.

PubMed

Turkki, Riku; Linder, Nina; Kovanen, Panu E; Pellinen, Teijo; Lundin, Johan

2016-01-01

Immune cell infiltration in tumor is an emerging prognostic biomarker in breast cancer. The gold standard for quantification of immune cells in tissue sections is visual assessment through a microscope, which is subjective and semi-quantitative. In this study, we propose and evaluate an approach based on antibody-guided annotation and deep learning to quantify immune cell-rich areas in hematoxylin and eosin (H&E) stained samples. Consecutive sections of formalin-fixed parafin-embedded samples obtained from the primary tumor of twenty breast cancer patients were cut and stained with H&E and the pan-leukocyte CD45 antibody. The stained slides were digitally scanned, and a training set of immune cell-rich and cell-poor tissue regions was annotated in H&E whole-slide images using the CD45-expression as a guide. In analysis, the images were divided into small homogenous regions, superpixels, from which features were extracted using a pretrained convolutional neural network (CNN) and classified with a support of vector machine. The CNN approach was compared to texture-based classification and to visual assessments performed by two pathologists. In a set of 123,442 labeled superpixels, the CNN approach achieved an F-score of 0.94 (range: 0.92-0.94) in discrimination of immune cell-rich and cell-poor regions, as compared to an F-score of 0.88 (range: 0.87-0.89) obtained with the texture-based classification. When compared to visual assessment of 200 images, an agreement of 90% (κ = 0.79) to quantify immune infiltration with the CNN approach was achieved while the inter-observer agreement between pathologists was 90% (κ = 0.78). Our findings indicate that deep learning can be applied to quantify immune cell infiltration in breast cancer samples using a basic morphology staining only. A good discrimination of immune cell-rich areas was achieved, well in concordance with both leukocyte antigen expression and pathologists' visual assessment.

A cost effective small hospital in Bangladesh: what it can mean for emergency obstetric care.

PubMed

McCord, C; Chowdhury, Q

2003-04-01

Mortality has improved dramatically in most of South Asia as a consequence of modest economic improvement, better nutrition and a combination of health education, immunization, family planning and home treatment of certain common diseases, especially diarrhea and respiratory infections. However, death rates are still much higher than in parts of the world with fully developed health services and residual mortality is largely due to conditions which require very basic hospital services such as surgery for complications of pregnancy, infections and trauma, transfusion, intravenous fluids, oxygen and intensive antibiotics. All of these can be made available in very simple and unsophisticated hospital facilities. It has generally been assumed that the cost of such facilities would be high, and cost effectiveness much less than that of preventive, educational and home care programs. In 1995, our 50 bed hospital in rural Bangladesh had a cost per patient-day of 525 Bangladesh Takas (US dollars 13.15) and a cost per capita for the population served of 25 Takas (US dollars 0.62) per year. Every month 180 patients were admitted, one-third with clearly life-threatening or disabling conditions which could be successfully treated in such a facility. We adapted the Disability Adjusted Life Year (DALY) method of cost effectiveness analysis to calculate the DALYs (years of disability-free life) preserved for individual patients during a 3-month period, using what we considered to be very conservative estimates of the threat to life and the efficacy of treatment. The total cost of all hospital activities over the 3 months was divided by the sum of the DALYS for those patients who were successfully treated for clearly life threatening or disabling conditions, to give a cost per DALY of 437 Takas (US dollars 10.93). This compares favorably with estimates by others of a cost per DALY of US dollars 30 for measles immunization, 20 for acute lower respiratory infection detection and home treatment, or 2 for tetanus immunization of pregnant women. Sixty-two percent of the DALYS saved came from emergency obstetric care (EmOC) related activities. We conclude that cost effective basic hospital service can be added to immunization, family planning and other basic health services now available in countries like Bangladesh with a very low increase in total cost and that the benefits which would accrue, particularly for maternal and perinatal mortality, would be great.

Achieving Remission in Gulf War Illness: A Simulation-Based Approach to Treatment Design.

PubMed

Craddock, Travis J A; Del Rosario, Ryan R; Rice, Mark; Zysman, Joel P; Fletcher, Mary Ann; Klimas, Nancy G; Broderick, Gordon

2015-01-01

Gulf War Illness (GWI) is a chronic multi-symptom disorder affecting up to one-third of the 700,000 returning veterans of the 1991 Persian Gulf War and for which there is no known cure. GWI symptoms span several of the body's principal regulatory systems and include debilitating fatigue, severe musculoskeletal pain, cognitive and neurological problems. Using computational models, our group reported previously that GWI might be perpetuated at least in part by natural homeostatic regulation of the neuroendocrine-immune network. In this work, we attempt to harness these regulatory dynamics to identify treatment courses that might produce lasting remission. Towards this we apply a combinatorial optimization scheme to the Monte Carlo simulation of a discrete ternary logic model that represents combined hypothalamic-pituitary-adrenal (HPA), gonadal (HPG), and immune system regulation in males. In this work we found that no single intervention target allowed a robust return to normal homeostatic control. All combined interventions leading to a predicted remission involved an initial inhibition of Th1 inflammatory cytokines (Th1Cyt) followed by a subsequent inhibition of glucocorticoid receptor function (GR). These first two intervention events alone ended in stable and lasting return to the normal regulatory control in 40% of the simulated cases. Applying a second cycle of this combined treatment improved this predicted remission rate to 2 out of 3 simulated subjects (63%). These results suggest that in a complex illness such as GWI, a multi-tiered intervention strategy that formally accounts for regulatory dynamics may be required to reset neuroendocrine-immune homeostasis and support extended remission.

Virtual reality-based assessment of basic laparoscopic skills using the Leap Motion controller.

PubMed

Lahanas, Vasileios; Loukas, Constantinos; Georgiou, Konstantinos; Lababidi, Hani; Al-Jaroudi, Dania

2017-12-01

The majority of the current surgical simulators employ specialized sensory equipment for instrument tracking. The Leap Motion controller is a new device able to track linear objects with sub-millimeter accuracy. The aim of this study was to investigate the potential of a virtual reality (VR) simulator for assessment of basic laparoscopic skills, based on the low-cost Leap Motion controller. A simple interface was constructed to simulate the insertion point of the instruments into the abdominal cavity. The controller provided information about the position and orientation of the instruments. Custom tools were constructed to simulate the laparoscopic setup. Three basic VR tasks were developed: camera navigation (CN), instrument navigation (IN), and bimanual operation (BO). The experiments were carried out in two simulation centers: MPLSC (Athens, Greece) and CRESENT (Riyadh, Kingdom of Saudi Arabia). Two groups of surgeons (28 experts and 21 novices) participated in the study by performing the VR tasks. Skills assessment metrics included time, pathlength, and two task-specific errors. The face validity of the training scenarios was also investigated via a questionnaire completed by the participants. Expert surgeons significantly outperformed novices in all assessment metrics for IN and BO (p < 0.05). For CN, a significant difference was found in one error metric (p < 0.05). The greatest difference between the performances of the two groups occurred for BO. Qualitative analysis of the instrument trajectory revealed that experts performed more delicate movements compared to novices. Subjects' ratings on the feedback questionnaire highlighted the training value of the system. This study provides evidence regarding the potential use of the Leap Motion controller for assessment of basic laparoscopic skills. The proposed system allowed the evaluation of dexterity of the hand movements. Future work will involve comparison studies with validated simulators and development of advanced training scenarios on current Leap Motion controller.

Evaluation of Medical Students' Attitudes and Performance of Basic Surgery Skills in a Training Program Using Fresh Human skin, Excised During Body Contouring Surgeries.

PubMed

Rothenberger, Jens; Seyed Jafari, Seyed Morteza; Schnabel, Kai P; Tschumi, Christian; Angermeier, Sarina; Shafighi, Maziar

2015-01-01

Learning surgical skills in the operating room may be a challenge for medical students. Therefore, more approaches using simulation to enable students to develop their practical skills are required. We hypothesized that (1) there would be a need for additional surgical training for medical students in the pre-final year, and (2) our basic surgery skills training program using fresh human skin would improve medical students' surgical skills. We conducted a preliminary survey of medical students to clarify the need for further training in basic surgery procedures. A new approach using simulation to teach surgical skills on human skin was set up. The procedural skills of 15 randomly selected students were assessed in the operating room before and after participation in the simulation, using Objective Structured Assessment of Technical Skills. Furthermore, subjective assessment was performed based on students' self-evaluation. The data were analyzed using SPSS, version 21 (SPSS, Inc., Chicago, IL). The study took place at the Inselspital, Bern University Hospital. A total of 186 pre-final-year medical students were enrolled into the preliminary survey; 15 randomly selected medical students participated in the basic surgical skills training course on the fresh human skin operating room. The preliminary survey revealed the need for a surgical skills curriculum. The simulation approach we developed showed significant (p < 0.001) improvement for all 12 surgical skills, with mean cumulative precourse and postcourse values of 31.25 ± 5.013 and 45.38 ± 3.557, respectively. The self-evaluation contained positive feedback as well. Simulation of surgery using human tissue samples could help medical students become more proficient in handling surgical instruments before stepping into a real surgical situation. We suggest further studies evaluating our proposed teaching method and the possibility of integrating this simulation approach into the medical school curriculum. Copyright © 2015 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.

Robotic surgery basic skills training: Evaluation of a pilot multidisciplinary simulation-based curriculum

PubMed Central

Foell, Kirsten; Finelli, Antonio; Yasufuku, Kazuhiro; Bernardini, Marcus Q.; Waddell, Thomas K.; Pace, Kenneth T.; Honey, R. John D.’A.; Lee, Jason Y.

2013-01-01

Purpose: Simulation-based training improves clinical skills, while minimizing the impact of the educational process on patient care. We present results of a pilot multidisciplinary, simulation-based robotic surgery basic skills training curriculum (BSTC) for robotic novices. Methods: A 4-week, simulation-based, robotic surgery BSTC was offered to the Departments of Surgery and Obstetrics & Gynecology (ObGyn) at the University of Toronto. The course consisted of various instructional strategies: didactic lecture, self-directed online-training modules, introductory hands-on training with the da Vinci robot (dVR) (Intuitive Surgical Inc., Sunnyvale, CA), and dedicated training on the da Vinci Skills Simulator (Intuitive Surgical Inc., Sunnyvale, CA) (dVSS). A third of trainees participated in competency-based dVSS training, all others engaged in traditional time-based training. Pre- and post-course skill testing was conducted on the dVR using 2 standardized skill tasks: ring transfer (RT) and needle passing (NP). Retention of skills was assessed at 5 months post-BSTC. Results: A total of 37 participants completed training. The mean task completion time and number of errors improved significantly post-course on both RT (180.6 vs. 107.4 sec, p < 0.01 and 3.5 vs. 1.3 sec, p < 0.01, respectively) and NP (197.1 vs. 154.1 sec, p < 0.01 and 4.5 vs. 1.8 sec, p = 0.04, respectively) tasks. No significant difference in performance was seen between specialties. Competency-based training was associated with significantly better post-course performance. The dVSS demonstrated excellent face validity. Conclusions: The implementation of a pilot multidisciplinary, simulation-based robotic surgery BSTC revealed significantly improved basic robotic skills among novice trainees, regardless of specialty or level of training. Competency-based training was associated with significantly better acquisition of basic robotic skills. PMID:24381662

Initial laparoscopic basic skills training shortens the learning curve of laparoscopic suturing and is cost-effective.

PubMed

Stefanidis, Dimitrios; Hope, William W; Korndorffer, James R; Markley, Sarah; Scott, Daniel J

2010-04-01

Laparoscopic suturing is an advanced skill that is difficult to acquire. Simulator-based skills curricula have been developed that have been shown to transfer to the operating room. Currently available skills curricula need to be optimized. We hypothesized that mastering basic laparoscopic skills first would shorten the learning curve of a more complex laparoscopic task and reduce resource requirements for the Fundamentals of Laparoscopic Surgery suturing curriculum. Medical students (n = 20) with no previous simulator experience were enrolled in an IRB-approved protocol, pretested on the Fundamentals of Laparoscopic Surgery suturing model, and randomized into 2 groups. Group I (n = 10) trained (unsupervised) until proficiency levels were achieved on 5 basic tasks; Group II (n = 10) received no basic training. Both groups then trained (supervised) on the Fundamentals of Laparoscopic Surgery suturing model until previously reported proficiency levels were achieved. Two weeks later, they were retested to evaluate their retention scores, training parameters, instruction requirements, and cost between groups using t-test. Baseline characteristics and performance were similar for both groups, and 9 of 10 subjects in each group achieved the proficiency levels. The initial performance on the simulator was better for Group I after basic skills training, and their suturing learning curve was shorter compared with Group II. In addition, Group I required less active instruction. Overall time required to finish the curriculum was similar for both groups; but the Group I training strategy cost less, with a savings of $148 per trainee. Teaching novices basic laparoscopic skills before a more complex laparoscopic task produces substantial cost savings. Additional studies are needed to assess the impact of such integrated curricula on ultimate educational benefit. Copyright (c) 2010 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Simulations in Foreign Languages.

ERIC Educational Resources Information Center

Nebraska State Dept. of Education, Lincoln. Div. of Instructional Services.

The purpose of this publication is to define minimal competencies for foreign language classes. The term "simulation" refers to role playing. The simulations are stated in terms of practical communication performance objectives. The intent is to have the student direct his learning in the basic skills toward an immediate objective rather than a…

The Use of Simulation Models in Teaching Geomorphology and Hydrology.

ERIC Educational Resources Information Center

Kirkby, Mike; Naden, Pam

1988-01-01

Learning about the physical environment from computer simulation models is discussed in terms of three stages: exploration, experimentation, and calibration. Discusses the effective use of models and presents two computer simulations written in BBC BASIC, STORFLO (for catchment hydrology) and SLOPEK (for hillslope evolution). (Author/GEA)

Using a Population-Ecology Simulation in College Courses.

ERIC Educational Resources Information Center

Hinze, Kenneth E.

1984-01-01

Describes instructional use of a microcomputer version of the WORLD2 global population-ecology simulation. Reactions of students and instructors are discussed and a WORLD2 simulation assignment is appended. The BASIC version used by the author runs on Apple II, DOS 3.3, with 80 column board. (MBR)

Using a Commercial Simulator to Teach Sorption Separations

ERIC Educational Resources Information Center

Wankat, Phillip C.

2006-01-01

The commercial simulator Aspen Chromatography was used in the computer laboratory of a dual-level course. The lab assignments used a cookbook approach to teach basic simulator operation and open-ended exploration to understand adsorption. The students learned theory better than in previous years despite having less lecture time. Students agreed…

Rethinking History with Simulations.

ERIC Educational Resources Information Center

Corbeil, Pierre

1988-01-01

Suggests that simulations and new technologies present new ways to look at historical questions. Discusses approaches from basic board game simulations to the use of artificial intelligence. States that educators must accept new technologies as instructional tools and that the concept of history must be modified to work with these tools. (GEA)

"Does AIDS Hurt?": Educating Young Children about AIDS. Suggestions for Parents, Teachers, and Other Care Providers of Children to Age 10.

ERIC Educational Resources Information Center

Quackenbush, Marcia; Villarreal, Sylvia

This document gives parents, teachers, and others basic information and suggested guidelines for teaching children aged 10 and younger about Acquired Immune Deficiency Syndrome (AIDS). These topics concerning AIDS and young children are discussed: (1) talking with young children about AIDS; (2) things to keep in mind when talking with children,…

Nonvolatile GaAs Random-Access Memory

NASA Technical Reports Server (NTRS)

Katti, Romney R.; Stadler, Henry L.; Wu, Jiin-Chuan

1994-01-01

Proposed random-access integrated-circuit electronic memory offers nonvolatile magnetic storage. Bits stored magnetically and read out with Hall-effect sensors. Advantages include short reading and writing times and high degree of immunity to both single-event upsets and permanent damage by ionizing radiation. Use of same basic material for both transistors and sensors simplifies fabrication process, with consequent benefits in increased yield and reduced cost.

Regulatory T cells in atherosclerosis: critical immune regulatory function and therapeutic potential.

PubMed

Spitz, Charlotte; Winkels, Holger; Bürger, Christina; Weber, Christian; Lutgens, Esther; Hansson, Göran K; Gerdes, Norbert

2016-03-01

Atherosclerosis is a chronic inflammatory disease that is mediated by innate and adaptive immune responses. The disease is characterized by sub-endothelial accumulation and modification of lipids in the artery wall triggering an inflammatory reaction which promotes lesion progression and eventual plaque rupture, thrombus formation, and the respective clinical sequelae such as myocardial infarction or stroke. During the past decade, T-cell-mediated immune responses, especially control of pro-inflammatory signals by regulatory T cells (Tregs), have increasingly attracted the interest of experimental and clinical researchers. By suppression of T cell proliferation and secretion of anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-β, Tregs exert their atheroprotective properties. Atherosclerosis-prone, hyperlipidemic mice harbor systemically less Tregs compared to wild-type mice, suggesting an imbalance of immune cells which affects local and systemic inflammatory and potentially metabolic processes leading to atherogenesis. Restoring or increasing Treg frequency and enhancing their suppressive capacity by various modulations may pose a promising approach for treating inflammatory conditions such as cardiovascular diseases. In this review, we briefly summarize the immunological basics of atherosclerosis and introduce the role and contribution of different subsets of T cells. We then discuss experimental data and current knowledge pertaining to Tregs in atherosclerosis and perspectives on manipulating the adaptive immune system to alleviate atherosclerosis and cardiovascular disease.

Helminth Infection and Type 1 Diabetes

PubMed Central

Zaccone, Paola; Hall, Samuel W.

2012-01-01

The increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our co-evolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation. PMID:23804266

Louis pasteur, the father of immunology?

PubMed

Smith, Kendall A

2012-01-01

Louis Pasteur is traditionally considered as the progenitor of modern immunology because of his studies in the late nineteenth century that popularized the germ theory of disease, and that introduced the hope that all infectious diseases could be prevented by prophylactic vaccination, as well as also treated by therapeutic vaccination, if applied soon enough after infection. However, Pasteur was working at the dawn of the appreciation of the microbial world, at a time when the notion of such a thing as an immune system did not exist, certainly not as we know it today, more than 130 years later. Accordingly, why was Pasteur such a genius as to discern how the immune system functions to protect us against invasion by the microbial world when no one had even made the distinction between fungi, bacteria, or viruses, and no one had formulated any theories of immunity. A careful reading of Pasteur's presentations to the Academy of Sciences reveals that Pasteur was entirely mistaken as to how immunity occurs, in that he reasoned, as a good microbiologist would, that appropriately attenuated microbes would deplete the host of vital trace nutrients absolutely required for their viability and growth, and not an active response on the part of the host. Even so, he focused attention on immunity, preparing the ground for others who followed. This review chronicles Pasteur's remarkable metamorphosis from organic chemist to microbiologist to immunologist, and from basic science to medicine.

Interaction of microbial agents with the immune system during infectious disease.

PubMed

Frøland, S S

1984-01-01

Research during the last years has revealed a considerable complexity of the immune system. It is clear that immunological reactions depend on extensive and only partly clarified interactions between a number of different cell types (e.g. B lymphocytes, plasma cells, T cell subpopulations, cytotoxic K and NK cells, monocytic cells, neutrophilic and eosinophilic granulocytes) and their molecular products (e.g. immunoglobulins, lymphokines and interleukins). These components further interact with the complement system, as well as with immunologically nonspecific components like acute phase proteins (e.g. C-reactive protein) and with other pathophysiological phenomena occurring during infections, e.g. the fever response. The application of these observations from basic and experimental immunology to the investigation of antimicrobial immune reactions is still only in its beginning, but has already resulted in new concepts of clinical value for the understanding of infectious diseases. The present paper briefly describes certain aspects of the immune response to infections with various microbial agents, with particular emphasis on reactions of clinical importance. In addition to B and T cell reactions, possible antimicrobial functions of K cells and NK cells are discussed, and the possible importance in infectious disease of various T cell subpopulations, particularly T suppressor cells, is discussed. Lastly, various escape mechanisms are mentioned whereby certain microbial agents may evade elimination by the immune response of the host.

Estimating the critical immunity threshold for preventing hepatitis A outbreaks in men who have sex with men.

PubMed

Regan, D G; Wood, J G; Benevent, C; Ali, H; Smith, L Watchirs; Robertson, P W; Ferson, M J; Fairley, C K; Donovan, B; Law, M G

2016-05-01

Several outbreaks of hepatitis A in men who have sex with men (MSM) were reported in the 1980s and 1990s in Australia and other countries. An effective hepatitis A virus (HAV) vaccine has been available in Australia since 1994 and is recommended for high-risk groups including MSM. No outbreaks of hepatitis A in Australian MSM have been reported since 1996. In this study, we aimed to estimate HAV transmissibility in MSM populations in order to inform targets for vaccine coverage in such populations. We used mathematical models of HAV transmission in a MSM population to estimate the basic reproduction number (R 0) and the probability of an HAV epidemic occurring as a function of the immune proportion. We estimated a plausible range for R 0 of 1·71-3·67 for HAV in MSM and that sustained epidemics cannot occur once the proportion immune to HAV is greater than ~70%. To our knowledge this is the first estimate of R 0 and the critical population immunity threshold for HAV transmission in MSM. As HAV is no longer endemic in Australia or in most other developed countries, vaccination is the only means of maintaining population immunity >70%. Our findings provide impetus to promote HAV vaccination in high-risk groups such as MSM.

Jet fuel-induced immunotoxicity.

PubMed

Harris, D T; Sakiestewa, D; Titone, D; Robledo, R F; Young, R S; Witten, M

2000-09-01

Chronic exposure to jet fuel has been shown to cause human liver dysfunction, emotional dysfunction, abnormal electroencephalograms, shortened attention spans, and to decrease sensorimotor speed (3-5). Exposure to potential environmental toxicants such as jet fuel may have significant effects on host systems beyond those readily visible (e.g., physiology, cardiology, respiratory, etc.), e.g., the immune system. Significant changes in immune function, even if short-lived, may have serious consequences for the exposed host that may impinge affect susceptibility to infectious agents. Major alterations in immune function that are long lasting may result in an increased likelihood of development and/or progression of cancer, as well as autoimmune diseases. In the current study mice were exposed 1 h/day for 7 days to a 1000-mg/m3 concentration of aerosolized jet fuel obtained from various sources (JP-8, JP-8+100 and Jet A1) and of differing compositions to simulate occupational exposures. Twenty-four hours after the last exposure the mice were analyzed for effects on the immune system. It was observed that exposure to all jet fuel sources examined had detrimental effects on the immune system. Decreases in viable immune cell numbers and immune organ weights were found. Jet fuel exposure resulted in differential losses of immune cell populations in the thymus. Further, jet fuel exposure resulted in significantly decreased immune function, as analyzed by mitogenesis assays. Suppressed immune function could not be overcome by the addition of exogenous growth factors known to stimulate immune function. Thus, short-term, low-concentration exposure of mice to aerosolized jet fuel, regardless of source or composition, caused significant deleterious effects on the immune system.

Modelling Risk to US Military Populations from Stopping Blanket Mandatory Polio Vaccination.

PubMed

Burgess, Colleen; Burgess, Andrew; McMullen, Kellie

2017-01-01

Transmission of polio poses a threat to military forces when deploying to regions where such viruses are endemic. US-born soldiers generally enter service with immunity resulting from childhood immunization against polio; moreover, new recruits are routinely vaccinated with inactivated poliovirus vaccine (IPV), supplemented based upon deployment circumstances. Given residual protection from childhood vaccination, risk-based vaccination may sufficiently protect troops from polio transmission. This analysis employed a mathematical system for polio transmission within military populations interacting with locals in a polio-endemic region to evaluate changes in vaccination policy. Removal of blanket immunization had no effect on simulated polio incidence among deployed military populations when risk-based immunization was employed; however, when these individuals reintegrated with their base populations, risk of transmission to nondeployed personnel increased by 19%. In the absence of both blanket- and risk-based immunization, transmission to nondeployed populations increased by 25%. The overall number of new infections among nondeployed populations was negligible for both scenarios due to high childhood immunization rates, partial protection against transmission conferred by IPV, and low global disease incidence levels. Risk-based immunization driven by deployment to polio-endemic regions is sufficient to prevent transmission among both deployed and nondeployed US military populations.

The use of TEE simulation in teaching basic echocardiography skills to senior anesthesiology residents.

PubMed

Jelacic, Srdjan; Bowdle, Andrew; Togashi, Kei; VonHomeyer, Peter

2013-08-01

The authors evaluated the educational benefits of using a first-generation HeartWorks simulator to teach senior anesthesiology residents basic echocardiography skills. Prospective observational study. A single academic medical center (teaching hospital). Thirty-seven senior (fourth-year) anesthesiology residents participated in this study. Groups of 3 senior anesthesiology residents participated in a single 3-hour tutorial in the simulation laboratory in the authors' institution during their cardiothoracic anesthesiology rotation. A cardiothoracic anesthesiology faculty member demonstrated the use of the transesophageal echocardiography (TEE) simulator and instructed the residents on obtaining standard TEE views of normal anatomy. Prior to the laboratory session, the residents took an online multiple-choice pretest with 25 questions related to safety, probe manipulation, clinical application, and pathology, which was accompanied by echo images of normal cardiac anatomy and video clips of pathology. Three to four weeks after the TEE tutorial, the residents completed an online post-test and evaluation of the teaching session. There was a statistically significant increase in knowledge of normal echocardiographic anatomy (p = 0.04), with an average improvement in normal echocardiographic anatomy scores of 15%. Virtual reality TEE simulation technology was endorsed strongly by residents, produced a statistically significant improvement in knowledge of normal echocardiographic anatomy, and could be effective for teaching basic echocardiography to anesthesiology residents. Copyright © 2013 Elsevier Inc. All rights reserved.

Topical application of green and white tea extracts provides protection from solar-simulated ultraviolet light in human skin.

PubMed

Camouse, Melissa M; Domingo, Diana Santo; Swain, Freddie R; Conrad, Edward P; Matsui, Mary S; Maes, Daniel; Declercq, Lieve; Cooper, Kevin D; Stevens, Seth R; Baron, Elma D

2009-06-01

Tea polyphenols have been found to exert beneficial effects on the skin via their antioxidant properties. We sought to determine whether topical application of green tea or white tea extracts would prevent simulated solar radiation-induced oxidative damages to DNA and Langerhans cells that may lead to immune suppression and carcinogenesis. Skin samples were analysed from volunteers or skin explants treated with white tea or green tea after UV irradiation. In another group of patients, the in vivo immune protective effects of green and white tea were evaluated using contact hypersensitivity to dinitrochlorobenzene. Topical application of green and white tea offered protection against detrimental effects of UV on cutaneous immunity. Such protection is not because of direct UV absorption or sunscreen effects as both products showed a sun protection factor of 1. There was no significant difference in the levels of protection afforded by the two agents. Hence, both green tea and white tea are potential photoprotective agents that may be used in conjunction with established methods of sun protection.

How do scientists respond to anomalies? Different strategies used in basic and applied science.

PubMed

Trickett, Susan Bell; Trafton, J Gregory; Schunn, Christian D

2009-10-01

We conducted two in vivo studies to explore how scientists respond to anomalies. Based on prior research, we identify three candidate strategies: mental simulation, mental manipulation of an image, and comparison between images. In Study 1, we compared experts in basic and applied domains (physics and meteorology). We found that the basic scientists used mental simulation to resolve an anomaly, whereas applied science practitioners mentally manipulated the image. In Study 2, we compared novice and expert meteorologists. We found that unlike experts, novices used comparison to address anomalies. We discuss the nature of expertise in the two kinds of science, the relationship between the type of science and the task performed, and the relationship of the strategies investigated to scientific creativity. Copyright © 2009 Cognitive Science Society, Inc.

Geometric Distribution-Based Readers Scheduling Optimization Algorithm Using Artificial Immune System.

PubMed

Duan, Litian; Wang, Zizhong John; Duan, Fu

2016-11-16

In the multiple-reader environment (MRE) of radio frequency identification (RFID) system, multiple readers are often scheduled to interrogate the randomized tags via operating at different time slots or frequency channels to decrease the signal interferences. Based on this, a Geometric Distribution-based Multiple-reader Scheduling Optimization Algorithm using Artificial Immune System (GD-MRSOA-AIS) is proposed to fairly and optimally schedule the readers operating from the viewpoint of resource allocations. GD-MRSOA-AIS is composed of two parts, where a geometric distribution function combined with the fairness consideration is first introduced to generate the feasible scheduling schemes for reader operation. After that, artificial immune system (including immune clone, immune mutation and immune suppression) quickly optimize these feasible ones as the optimal scheduling scheme to ensure that readers are fairly operating with larger effective interrogation range and lower interferences. Compared with the state-of-the-art algorithm, the simulation results indicate that GD-MRSOA-AIS could efficiently schedules the multiple readers operating with a fairer resource allocation scheme, performing in larger effective interrogation range.

Web-based e-learning and virtual lab of human-artificial immune system.

PubMed

Gong, Tao; Ding, Yongsheng; Xiong, Qin

2014-05-01

Human immune system is as important in keeping the body healthy as the brain in supporting the intelligence. However, the traditional models of the human immune system are built on the mathematics equations, which are not easy for students to understand. To help the students to understand the immune systems, a web-based e-learning approach with virtual lab is designed for the intelligent system control course by using new intelligent educational technology. Comparing the traditional graduate educational model within the classroom, the web-based e-learning with the virtual lab shows the higher inspiration in guiding the graduate students to think independently and innovatively, as the students said. It has been found that this web-based immune e-learning system with the online virtual lab is useful for teaching the graduate students to understand the immune systems in an easier way and design their simulations more creatively and cooperatively. The teaching practice shows that the optimum web-based e-learning system can be used to increase the learning effectiveness of the students.

Geometric Distribution-Based Readers Scheduling Optimization Algorithm Using Artificial Immune System

PubMed Central

Duan, Litian; Wang, Zizhong John; Duan, Fu

2016-01-01

In the multiple-reader environment (MRE) of radio frequency identification (RFID) system, multiple readers are often scheduled to interrogate the randomized tags via operating at different time slots or frequency channels to decrease the signal interferences. Based on this, a Geometric Distribution-based Multiple-reader Scheduling Optimization Algorithm using Artificial Immune System (GD-MRSOA-AIS) is proposed to fairly and optimally schedule the readers operating from the viewpoint of resource allocations. GD-MRSOA-AIS is composed of two parts, where a geometric distribution function combined with the fairness consideration is first introduced to generate the feasible scheduling schemes for reader operation. After that, artificial immune system (including immune clone, immune mutation and immune suppression) quickly optimize these feasible ones as the optimal scheduling scheme to ensure that readers are fairly operating with larger effective interrogation range and lower interferences. Compared with the state-of-the-art algorithm, the simulation results indicate that GD-MRSOA-AIS could efficiently schedules the multiple readers operating with a fairer resource allocation scheme, performing in larger effective interrogation range. PMID:27854342

A Rutherford Scattering Simulation with Microcomputer Graphics.

ERIC Educational Resources Information Center

Calle, Carlos I.; Wright, Lavonia F.

1989-01-01

Lists a program for a simulation of Rutherford's gold foil experiment in BASIC for both Apple II and IBM compatible computers. Compares Rutherford's model of the atom with Thompson's plum pudding model of the atom. (MVL)

Halley's Comet and Beyond.

ERIC Educational Resources Information Center

Sneider, Cary; DeVore, Edna

1986-01-01

Reviews software packages under these headings: (1) simulations of experiments; (2) space flight simulators; (3) planetariums; (4) space adventure games; and (5) drill and practice packages (designed for testing purposes or for helping students learn basic astronomy vocabulary). (JN)

Testing the World with Simulations.

ERIC Educational Resources Information Center

Roberts, Nancy

1983-01-01

Explains the three main concepts of the system dynamics approach to model building (dynamics, feedback, and systems) and the basic steps to problem solving by simulation applicable to all educational levels. Some DYNAMO commands are briefly described. (EAO)

Ontogenetic profile of innate immune related genes and their tissue-specific expression in brown trout, Salmo trutta (Linnaeus, 1758).

PubMed

Cecchini, Stefano; Paciolla, Mariateresa; Biffali, Elio; Borra, Marco; Ursini, Matilde V; Lioi, Maria B

2013-09-01

The innate immune system is a fundamental defense weapon of fish, especially during early stages of development when acquired immunity is still far from being completely developed. The present study aims at looking into ontogeny of innate immune system in the brown trout, Salmo trutta, using RT-PCR based approach. Total RNA extracted from unfertilized and fertilized eggs and hatchlings at 0, 1 h and 1, 2, 3, 4, 5, 6, 7 weeks post-fertilization was subjected to RT-PCR using self-designed primers to amplify some innate immune relevant genes (TNF-α, IL-1β, TGF-β and lysozyme c-type). The constitutive expression of β-actin was detected in all developmental stages. IL-1β and TNF-α transcripts were detected from 4 week post-fertilization onwards, whereas TGF-β transcript was detected only from 7 week post-fertilization onwards. Lysozyme c-type transcript was detected early from unfertilized egg stage onwards. Similarly, tissues such as muscle, ovary, heart, brain, gill, testis, liver, intestine, spleen, skin, posterior kidney, anterior kidney and blood collected from adult brown trout were subjected to detection of all selected genes by RT-PCR. TNF-α and lysozyme c-type transcripts were expressed in all tissues. IL-1β and TGF-β transcripts were expressed in all tissues except for the brain and liver, respectively. Taken together, our results show a spatial-temporal expression of some key innate immune-related genes, improving the basic knowledge of the function of innate immune system at early stage of brown trout. Copyright © 2013 Elsevier Ltd. All rights reserved.

Sustained and transient oscillations and chaos induced by delayed antiviral immune response in an immunosuppressive infection model.

PubMed

Shu, Hongying; Wang, Lin; Watmough, James

2014-01-01

Sustained and transient oscillations are frequently observed in clinical data for immune responses in viral infections such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus. To account for these oscillations, we incorporate the time lag needed for the expansion of immune cells into an immunosuppressive infection model. It is shown that the delayed antiviral immune response can induce sustained periodic oscillations, transient oscillations and even sustained aperiodic oscillations (chaos). Both local and global Hopf bifurcation theorems are applied to show the existence of periodic solutions, which are illustrated by bifurcation diagrams and numerical simulations. Two types of bistability are shown to be possible: (i) a stable equilibrium can coexist with another stable equilibrium, and (ii) a stable equilibrium can coexist with a stable periodic solution.

Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration.

PubMed

Jain, Sanyog; Harde, Harshad; Indulkar, Anura; Agrawal, Ashish Kumar

2014-02-01

The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher (P<0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization. This team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization. © 2014.

Bandwidth turbulence control based on flow community structure in the Internet

NASA Astrophysics Data System (ADS)

Wu, Xiaoyu; Gu, Rentao; Ji, Yuefeng

2016-10-01

Bursty flows vary rapidly in short period of time, and cause fierce bandwidth turbulence in the Internet. In this letter, we model the flow bandwidth turbulence process by constructing a flow interaction network (FIN network), with nodes representing flows and edges denoting bandwidth interactions among them. To restrain the bandwidth turbulence in FIN networks, an immune control strategy based on flow community structure is proposed. Flows in community boundary positions are immunized to cut off the inter-community turbulence spreading. By applying this control strategy in the first- and the second-level flow communities separately, 97.2% flows can effectively avoid bandwidth variations by immunizing 21% flows, and the average bandwidth variation degree reaches near zero. To achieve a similar result, about 70%-90% immune flows are needed with targeted control strategy based on flow degrees and random control strategy. Moreover, simulation results showed that the control effect of the proposed strategy improves significantly if the immune flow number is relatively smaller in each control step.

Effects of small increases in corticosterone levels on morphology, immune function, and feather development.

PubMed

Butler, Michael W; Leppert, Lynda L; Dufty, Alfred M

2010-01-01

Stressors encountered during avian development may affect an individual's phenotype, including immunocompetence, growth, and feather quality. We examined effects of simulated chronic low-level stress on American kestrel (Falco sparverius) nestlings. Continuous release of corticosterone, a hormone involved in the stress response, can model chronic stress in birds. We implanted 13-d-old males with either corticosterone-filled implants or shams and measured their growth, immune function, and feather coloration. We found no significant differences between groups at the end of the weeklong exposure period in morphometrics (mass, tarsus, wing length, and asymmetry), immunocompetence (cutaneous immunity, heterophil/lymphocyte ratio, and humoral immunity), or feather coloration. One week subsequent to implant removal, however, differences were detected. Sham-implanted birds had significantly longer wings and a reduced level of cutaneous immune function compared with those of birds given corticosterone-filled implants. Therefore, increases of only 2 ng/mL in basal corticosterone titer can have small but measurable effects on subsequent avian development.

Diagnostic Accuracy Comparison of Artificial Immune Algorithms for Primary Headaches.

PubMed

Çelik, Ufuk; Yurtay, Nilüfer; Koç, Emine Rabia; Tepe, Nermin; Güllüoğlu, Halil; Ertaş, Mustafa

2015-01-01

The present study evaluated the diagnostic accuracy of immune system algorithms with the aim of classifying the primary types of headache that are not related to any organic etiology. They are divided into four types: migraine, tension, cluster, and other primary headaches. After we took this main objective into consideration, three different neurologists were required to fill in the medical records of 850 patients into our web-based expert system hosted on our project web site. In the evaluation process, Artificial Immune Systems (AIS) were used as the classification algorithms. The AIS are classification algorithms that are inspired by the biological immune system mechanism that involves significant and distinct capabilities. These algorithms simulate the specialties of the immune system such as discrimination, learning, and the memorizing process in order to be used for classification, optimization, or pattern recognition. According to the results, the accuracy level of the classifier used in this study reached a success continuum ranging from 95% to 99%, except for the inconvenient one that yielded 71% accuracy.

Balancing selection on immunity genes: review of the current literature and new analysis in Drosophila melanogaster.

PubMed

Croze, Myriam; Živković, Daniel; Stephan, Wolfgang; Hutter, Stephan

2016-08-01

Balancing selection has been widely assumed to be an important evolutionary force, yet even today little is known about its abundance and its impact on the patterns of genetic diversity. Several studies have shown examples of balancing selection in humans, plants or parasites, and many genes under balancing selection are involved in immunity. It has been proposed that host-parasite coevolution is one of the main forces driving immune genes to evolve under balancing selection. In this paper, we review the literature on balancing selection on immunity genes in several organisms, including Drosophila. Furthermore, we performed a genome scan for balancing selection in an African population of Drosophila melanogaster using coalescent simulations of a demographic model with and without selection. We find very few genes under balancing selection and only one novel candidate gene related to immunity. Finally, we discuss the possible causes of the low number of genes under balancing selection. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Session RPE and salivary immune-endocrine responses to simulated and official basketball matches in elite young male athletes.

PubMed

Moreira, A; Crewther, B; Freitas, C G; Arruda, A F S; Costa, E C; Aoki, M S

2012-12-01

The present study compared the ratings of perceived exertion (RPE) and immune-endocrine (IgA and cortisol) responses to simulated training matches (TM) and official matches (OM) in elite young male basketball players (N.=10). Saliva samples were collected from each player before and after three TM and two OM and subsequently tested for cortisol and IgA concentrations by immunoassay. The perceived intensity of each match was rated using a RPE scale (CR-10). The training match and official match data were pooled to provide an aggregate value for each setting. The session RPE scores from the OM were significantly (P<0.05) greater than the simulated TM. Pre- and postcortisol concentrations assessed during the OM were also found to be significantly higher than the TM (P<0.05). No significant changes in salivary IgA concentrations were observed across either the simulated or official match settings. In summary, the OM induced greater RPE and salivary cortisol responses than the simulated TM, probably due to the additional stressors associated with real competition. The data also suggests that acute changes in cortisol concentrations do not play a role in the regulation of salivary IgA under the current testing conditions.

Teaching Reinforcement of Stochastic Behavior Using Monte Carlo Simulation.

ERIC Educational Resources Information Center

Fox, William P.; And Others

1996-01-01

Explains a proposed block of instruction that would give students in industrial engineering, operations research, systems engineering, and applied mathematics the basic understanding required to begin more advanced courses in simulation theory or applications. (DDR)

Microprocessor Simulation: A Training Technique.

ERIC Educational Resources Information Center

Oscarson, David J.

1982-01-01

Describes the design and application of a microprocessor simulation using BASIC for formal training of technicians and managers and as a management tool. Illustrates the utility of the modular approach for the instruction and practice of decision-making techniques. (SK)

Construct and concurrent validity of a Nintendo Wii video game made for training basic laparoscopic skills.

PubMed

Jalink, M B; Goris, J; Heineman, E; Pierie, J P E N; ten Cate Hoedemaker, H O

2014-02-01

Virtual reality (VR) laparoscopic simulators have been around for more than 10 years and have proven to be cost- and time-effective in laparoscopic skills training. However, most simulators are, in our experience, considered less interesting by residents and are often poorly accessible. Consequently, these devices are rarely used in actual training. In an effort to make a low-cost and more attractive simulator, a custom-made Nintendo Wii game was developed. This game could ultimately be used to train the same basic skills as VR laparoscopic simulators ought to. Before such a video game can be implemented into a surgical training program, it has to be validated according to international standards. The main goal of this study was to test construct and concurrent validity of the controls of a prototype of the game. In this study, the basic laparoscopic skills of experts (surgeons, urologists, and gynecologists, n = 15) were compared to those of complete novices (internists, n = 15) using the Wii Laparoscopy (construct validity). Scores were also compared to the Fundamentals of Laparoscopy (FLS) Peg Transfer test, an already established assessment method for measuring basic laparoscopic skills (concurrent validity). Results showed that experts were 111 % faster (P = 0.001) on the Wii Laparoscopy task than novices. Also, scores of the FLS Peg Transfer test and the Wii Laparoscopy showed a significant, high correlation (r = 0.812, P < 0.001). The prototype setup of the Wii Laparoscopy possesses solid construct and concurrent validity.

Evaluating the Effects of Stressors on Immune Function during Simulated Dives in Marine Mammals

DTIC Science & Technology

2014-09-30

Physiology and Stressors on Immune Cell Function in a Deep Diving Monodontid and Three Shallow Diving Phocid Species. PhD Dissertation, University...Research Permit No. 14245). Blood samples were initially processed in the field and shipped back to Mystic Aquarium in LN dry shippers for hormone...of damage from inflammatory processes . Values were returned to control levels suggesting the effects of a dive are not long lasting. That results for

Observation of backscattering-immune chiral electromagnetic modes without time reversal breaking.

PubMed

Chen, Wen-Jie; Hang, Zhi Hong; Dong, Jian-Wen; Xiao, Xiao; Wang, He-Zhou; Chan, C T

2011-07-08

A strategy is proposed to realize robust transport in a time reversal invariant photonic system. Using numerical simulation and a microwave experiment, we demonstrate that a chiral guided mode in the channel of a three-dimensional dielectric layer-by-layer photonic crystal is immune to the scattering of a square patch of metal or dielectric inserted to block the channel. The chirality based robust transport can be realized in nonmagnetic dielectric materials without any external field.

Biomarkers to Assess Possible Biological Effects on Reproductive Potential, Immune Function, and Energetic Fitness of Bottlenose Dolphins Exposed to Sounds Consistent with Naval Sonars

DTIC Science & Technology

2012-09-30

Reproductive Potential, Immune Function, and Energetic Fitness of Bottlenose Dolphins Exposed to Sounds Consistent with Naval Sonars Dana L. Wetzel...biomarkers to examine whether significant sublethal responses to sonar-type sounds occur in bottlenose dolphins exposed to such sounds. The...investigate samples collected from trained dolphins before exposure to simulated mid-frequency sonar signals, immediately after exposure, and one week post

Assessment of CFD Estimation of Aerodynamic Characteristics of Basic Reusable Rocket Configurations

NASA Astrophysics Data System (ADS)

Fujimoto, Keiichiro; Fujii, Kozo

Flow-fields around the basic SSTO-rocket configurations are numerically simulated by the Reynolds-averaged Navier-Stokes (RANS) computations. Simulations of the Apollo-like configuration is first carried out, where the results are compared with NASA experiments and the prediction ability of the RANS simulation is discussed. The angle of attack of the freestream ranges from 0° to 180° and the freestream Mach number ranges from 0.7 to 2.0. Computed aerodynamic coefficients for the Apollo-like configuration agree well with the experiments under a wide range of flow conditions. The flow simulations around the slender Apollo-type configuration are carried out next and the results are compared with the experiments. Computed aerodynamic coefficients also agree well with the experiments. Flow-fields are dominated by the three-dimensional massively separated flow, which should be captured for accurate aerodynamic prediction. Grid refinement effects on the computed aerodynamic coefficients are investigated comprehensively.

Modeling a maintenance simulation of the geosynchronous platform

NASA Technical Reports Server (NTRS)

Kleiner, A. F., Jr.

1980-01-01

A modeling technique used to conduct a simulation study comparing various maintenance routines for a space platform is dicussed. A system model is described and illustrated, the basic concepts of a simulation pass are detailed, and sections on failures and maintenance are included. The operation of the system across time is best modeled by a discrete event approach with two basic events - failure and maintenance of the system. Each overall simulation run consists of introducing a particular model of the physical system, together with a maintenance policy, demand function, and mission lifetime. The system is then run through many passes, each pass corresponding to one mission and the model is re-initialized before each pass. Statistics are compiled at the end of each pass and after the last pass a report is printed. Items of interest typically include the time to first maintenance, total number of maintenance trips for each pass, average capability of the system, etc.

Distributed delays in a hybrid model of tumor-immune system interplay.

PubMed

Caravagna, Giulio; Graudenzi, Alex; d'Onofrio, Alberto

2013-02-01

A tumor is kinetically characterized by the presence of multiple spatio-temporal scales in which its cells interplay with, for instance, endothelial cells or Immune system effectors, exchanging various chemical signals. By its nature, tumor growth is an ideal object of hybrid modeling where discrete stochastic processes model low-numbers entities, and mean-field equations model abundant chemical signals. Thus, we follow this approach to model tumor cells, effector cells and Interleukin-2, in order to capture the Immune surveillance effect. We here present a hybrid model with a generic delay kernel accounting that, due to many complex phenomena such as chemical transportation and cellular differentiation, the tumor-induced recruitment of effectors exhibits a lag period. This model is a Stochastic Hybrid Automata and its semantics is a Piecewise Deterministic Markov process where a two-dimensional stochastic process is interlinked to a multi-dimensional mean-field system. We instantiate the model with two well-known weak and strong delay kernels and perform simulations by using an algorithm to generate trajectories of this process. Via simulations and parametric sensitivity analysis techniques we (i) relate tumor mass growth with the two kernels, we (ii) measure the strength of the Immune surveillance in terms of probability distribution of the eradication times, and (iii) we prove, in the oscillatory regime, the existence of a stochastic bifurcation resulting in delay-induced tumor eradication.

The impact of vaccine failure rate on epidemic dynamics in responsive networks.

PubMed

Liang, Yu-Hao; Juang, Jonq

2015-04-01

An SIS model based on the microscopic Markov-chain approximation is considered in this paper. It is assumed that the individual vaccination behavior depends on the contact awareness, local and global information of an epidemic. To better simulate the real situation, the vaccine failure rate is also taken into consideration. Our main conclusions are given in the following. First, we show that if the vaccine failure rate α is zero, then the epidemic eventually dies out regardless of what the network structure is or how large the effective spreading rate and the immunization response rates of an epidemic are. Second, we show that for any positive α, there exists a positive epidemic threshold depending on an adjusted network structure, which is only determined by the structure of the original network, the positive vaccine failure rate and the immunization response rate for contact awareness. Moreover, the epidemic threshold increases with respect to the strength of the immunization response rate for contact awareness. Finally, if the vaccine failure rate and the immunization response rate for contact awareness are positive, then there exists a critical vaccine failure rate αc > 0 so that the disease free equilibrium (DFE) is stable (resp., unstable) if α < αc (resp., α > αc). Numerical simulations to see the effectiveness of our theoretical results are also provided.

Determining the optimal vaccine vial size in developing countries: a Monte Carlo simulation approach.

PubMed

Dhamodharan, Aswin; Proano, Ruben A

2012-09-01

Outreach immunization services, in which health workers immunize children in their own communities, are indispensable to improve vaccine coverage in rural areas of developing countries. One of the challenges faced by these services is how to reduce high levels of vaccine wastage. In particular, the open vial wastage (OVW) that result from the vaccine doses remaining in a vial after a time for safe use -since opening the vial- has elapsed. This wastage is highly dependent on the choice of vial size and the expected number of participants for which the outreach session is planned (i.e., session size). The use single-dose vials results in zero OVW, but it increases the vaccine purchase, transportation, and holding costs per dose as compared to those resulting from using larger vial sizes. The OVW also decreases when more people are immunized in a session. However, controlling the actual number of people that show to an outreach session in rural areas of developing countries highly depends on factors that are out of control of the immunization planners. This paper integrates a binary integer-programming model to a Monte Carlo simulation method to determine the choice of vial size and the optimal reordering point level to implement an (nQ, r, T) lot-sizing policy that provides the best tradeoff between procurement costs and wastage.

The Effect of Simulated Flash-Heat Pasteurization on Immune Components of Human Milk

PubMed Central

Daniels, Brodie; Schmidt, Stefan; King, Tracy; Israel-Ballard, Kiersten; Amundson Mansen, Kimberly; Coutsoudis, Anna

2017-01-01

A pasteurization temperature monitoring system has been designed using FoneAstra, a cellphone-based networked sensing system, to monitor simulated flash-heat (FH) pasteurization. This study compared the effect of the FoneAstra FH (F-FH) method with the Sterifeed Holder method currently used by human milk banks on human milk immune components (immunoglobulin A (IgA), lactoferrin activity, lysozyme activity, interleukin (IL)-8 and IL-10). Donor milk samples (N = 50) were obtained from a human milk bank, and pasteurized. Concentrations of IgA, IL-8, IL-10, lysozyme activity and lactoferrin activity were compared to their controls using the Student’s t-test. Both methods demonstrated no destruction of interleukins. While the Holder method retained all lysozyme activity, the F-FH method only retained 78.4% activity (p < 0.0001), and both methods showed a decrease in lactoferrin activity (71.1% Holder vs. 38.6% F-FH; p < 0.0001) and a decrease in the retention of total IgA (78.9% Holder vs. 25.2% F-FH; p < 0.0001). Despite increased destruction of immune components compared to Holder pasteurization, the benefits of F-FH in terms of its low cost, feasibility, safety and retention of immune components make it a valuable resource in low-income countries for pasteurizing human milk, potentially saving infants’ lives. PMID:28241418

[Mechanism of action of intravesical BCG. Biological bases and clinical applicability.

PubMed

Carballido, Joaquín A; Rodríguez Monsalve, María

2018-05-01

The therapeutic approaches developed around immune system modulation find the therapeutic contribution of intravesical Bacillus Calmette Guerin (BCG) for transitional cell bladder cancer an unquestionable example as a proof of concept of antitumor immunotherapy since more than 30 years ago. Intravesical immunotherapy for urothelial carcinomas is considered with periodic intravesical instillations schedules, and the one with longer historic development and wider diffusion is BCG in the form of suspension. BCG is a unique strain obtained from Mycobacterium bovis at the end of the first third of the XX century and represents the historically most successful immunotherapeutic modality of all tumors with a high level body of evidence. Currently, we even see an unpredictable development potential of this therapeutic modality based on immunomodulation related with activation or suppression of T lymphocytes by blocking the immune system checkpoints. This option is at this time a decisive step in the treatment of chemotherapy refractory metastatic urothelial carcinoma. Over the last years, there have been advances in the intimate mechanism of action of intravesical BCG, but there are many open questions that will only be answered from complex basic and translational research platforms. The objective of this review article is to try to translate the basic mechanisms currently implicated in the different phases of antitumor response of BCG in its routine use in clinical practice. Also, to analyze the future lines already active under clinical research with and without implications of the mechanisms of action of BCG. We describe the role of interactions basally established between urothelial tumor cells and cellular and molecular elements of the immune system of the patients with ulterior antitumor effector capacity. After intravesical BCG therapy and its interaction, we describe the various phases of its mechanism of action, namely fixation, internalization and triggering of the lytic cytotoxic antitumor response, and its integration in the current intravesical treatment regimens The implication of all these mechanisms in the varied capacity of clinical response observed in patients, reviewing the current status of knowledge of BCG mechanisms of action, leads unavoidably to the search of better clinical efficacy through eventual immune response markers and to set the approach to the knowledge of the individual reactivity of the immune system of each patient as a determinant factor to be able to adopt adjusted therapeutic patterns.

United States Air Force Training Line Simulator. Final Report.

ERIC Educational Resources Information Center

Nauta, Franz; Pierce, Michael B.

This report describes the technical aspects and potential applications of a computer-based model simulating the flow of airmen through basic training and entry-level technical training. The objective of the simulation is to assess the impacts of alternative recruit classification and training policies under a wide variety of assumptions regarding…

The Utah State Public School Finance Simulator

ERIC Educational Resources Information Center

Steffensen, Robert G.

1973-01-01

Reports on a simulator that shows the effect of proposed changes to school finance laws by legislatures on school administration. The simulator produces a report that (1) defines the basic units used to determine the dollar amounts to be disbursed to each local school district, (2) shows local school district disbursement amounts by program, and…

Advanced Computer Image Generation Techniques Exploiting Perceptual Characteristics. Final Report.

ERIC Educational Resources Information Center

Stenger, Anthony J.; And Others

This study suggests and identifies computer image generation (CIG) algorithms for visual simulation that improve the training effectiveness of CIG simulators and identifies areas of basic research in visual perception that are significant for improving CIG technology. The first phase of the project entailed observing three existing CIG simulators.…