Artificial immune systems applied to optimal capacitor placement in radial distribution networks

The capacitor placement problem for radial distribution networks aims to determine capacitor types, sizes, locations and control scheme. This is a combinatorial problem that can be formulated as a mixed integer nonlinear program. The paper presents an algorithm inspired in artificial immune systems and developed for this specific problem. A good performance was obtained through experimental tests applied to known systems. © 2006 IEEE.

Kaposi's sarcoma-associated herpesvirus latency-associated nuclear antigen 1 mimics Epstein-Barr virus EBNA1 immune evasion through central repeat domain effects on protein processing

Kaposi's sarcoma-associated herpesvirus (KSHV/human herpesvirus 8 [HHV8]) and Epstein-Barr virus (EBV/HHV4) are distantly related gammaherpesviruses causing tumors in humans. KSHV latency-associated nuclear antigen 1 (LANA1) is functionally similar to the EBV nuclear antigen-1 (EBNA1) protein expressed during viral latency, although they have no amino acid similarities. EBNA1 escapes cytotoxic lymphocyte (CTL) antigen processing by inhibiting its own proteosomal degradation and retarding its own synthesis to reduce defective ribosomal product processing. We show here that the LANA1 QED-rich central repeat (CR) region, particularly the CR2CR3 subdomain, also retards LANA1 synthesis and markedly enhances LANA1 stability in vitro and in vivo. LANA1 isoforms have half-lives greater than 24 h, and fusion of the LANA1 CR2CR3 domain to a destabilized heterologous protein markedly decreases protein turnover. Unlike EBNA1, the LANA1 CR2CR3 subdomain retards translation regardless of whether it is fused to the 5′ or 3′ end of a heterologous gene construct. Manipulation of sequence order, orientation, and composition of the CR2 and CR3 subdomains suggests that specific peptide sequences rather than RNA structures are responsible for synthesis retardation. Although mechanistic differences exist between LANA1 and EBNA1, the primary structures of both proteins have evolved to minimize provoking CTL immune responses. Simple strategies to eliminate these viral inhibitory regions may markedly improve vaccine effectiveness by maximizing CTL responses. Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Immune response to Mycobacterium bovis-an5 infection in genetically selected mice (selection IV-A)

Mice genetically selected for high (H) and low (L) antibody production (Selection IV-A) were used as murine experimental model. The aim of the present work was to evaluate the macrophagic activity and to characterize the immune response in Mycobacterium bovis-AN5 infected mice (3×10 7 bacteria). The response profile previously observed in such strains was not similar to that obtained during M. bovis infection; however, it corroborated works carried out using Selection I, which is very similar to Selection IV-A regarding infection by M. tuberculosis and Bacillus Calmette-Guérin (BCG). Considering bacterial recovery, LIV-A mice showed higher control of the infectious process in the lungs than in the spleen, whereas HIV-A mice presented more resistance in the spleen. With respect to macrophagic activity, hydrogen peroxide (H2O 2) was probably not involved in the infection control since there was an inhibition in the production of this metabolite. Nitric oxide (NO) and TNF-α production seemed to be important in the control of bacterial replication and varied according to the strain, period and organ. Evaluation of the antibody production indicated that the multi-specific effect commonly observed in these strains was not the same in the response to M. bovis. Antibody concentrations were higher in LIV-A than in HIV-A mice at the beginning of the infection, being similar afterwards. Such data were compared with delayed-type hypersensitivity (DTH), which was more intense in HIV-A than in LIV-A mice, indicating that antibody production is independent of the capability to trigger DTH reactions and that cellular and humoral responses to M. bovis antigens show a polygenic control and an independent quantitative genetic regulation. Differences were observed among organs and metabolites, suggesting that different mechanisms play an important role in this infection in natural heterogeneous populations, indicating that NO, TNF-α and Th1 cytokines are involved in the infection control.

Genetic vaccine for tuberculosis (pVAXhsp65) primes neonate mice for a strong immune response at the adult stage

Background: Vaccination of neonates is generally difficult due to the immaturity of the immune system and consequent higher susceptibility to tolerance induction. Genetic immunization has been described as an alternative to trigger a stronger immune response in neonates, including significant Th1 polarization. In this investigation we analysed the potential use of a genetic vaccine containing the heat shock protein (hsp65) from Mycobacterium leprae (pVAXhsp65) against tuberculosis (TB) in neonate mice. Aspects as antigen production, genomic integration and immunogenicity were evaluated. Methods: Hsp65 message and genomic integration were evaluated by RT-PCR and Southern blot, respectively. Immunogenicity of pVAXhsp65 alone or combined with BCG was analysed by specific induction of antibodies and cytokines, both quantified by ELISA. Results: This DNA vaccine was transcribed by muscular cells of neonate mice without integration into the cellular genome. Even though this vaccine was not strongly immunogenic when entirely administered (three doses) during early animal's life, it was not tolerogenic. In addition, pVAXhsp65 and BCG were equally able to prime newborn mice for a strong and mixed immune response (Th1 + Th2) to pVAXhsp65 boosters administered later, at the adult life. Conclusion: These results suggest that pVAXhsp65 can be safely used as a priming stimulus in neonate animals in prime-boost similar strategies to control TB. However, priming with BCG or pVAXhsp65, directed the ensuing immune response triggered by an heterologous or homologous booster, to a mixed Th1/Th2 pattern of response. Measures as introduction of IL-12 or GM-CSF genes in the vaccine construct or even IL-4 neutralization, are probably required to increase the priming towards Th1 polarization to ensure control of tuberculosis infection. © 2007 Pelizon et al; licensee BioMed Central Ltd.

Citotoxicity and immune response induced by organopalladium(II) compounds in mice bearing Ehrlich ascites tumour

Cyclometallated palladium(II) complexes are reactive inorganic compounds employed in several biological studies because of their antitumour potential and interaction with immune system. In the present study, the immune and citotoxic response induced by two organopalladated complexes: [{Pd(N,C-dmba)} 2(μ-NCS) 2] (1), [Pd(C-dmba)(NCS)(dppp)] (2) [dmba = N,N′-dimethylbenzylamine, dppp = 1,3-bis(diphenylphosphino)propane] and cisplatin (cis-DDP), as standard, were investigated in mice bearing Ehrlich ascites tumour. The mice were divided into five groups and inoculated with the compounds (1) or (2) or cisplatin, or only vehicle or phosphate-buffered saline (PBS). Many parameters were evaluated, such as tumour cell percentage in the peritoneal exsudate, levels of seric nitric oxide (NO) and tumour necrosis factor-alpha (TNF-α) and increase in life span. Analysis of all data revealed, for compound (2), an activity similar to that presented by cisplatin, resulting in increased life span, lower levels of seric TNF-α and increase in NO production. ©2007 Sociedade Brasileira de Química.

A malware detection system inspired on the human immune system

Malicious programs (malware) can cause severe damage on computer systems and data. The mechanism that the human immune system uses to detect and protect from organisms that threaten the human body is efficient and can be adapted to detect malware attacks. In this paper we propose a system to perform malware distributed collection, analysis and detection, this last inspired by the human immune system. After collecting malware samples from Internet, they are dynamically analyzed so as to provide execution traces at the operating system level and network flows that are used to create a behavioral model and to generate a detection signature. Those signatures serve as input to a malware detector, acting as the antibodies in the antigen detection process. This allows us to understand the malware attack and aids in the infection removal procedures. © 2012 Springer-Verlag.

Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2 -/- animals. The results showed that TLR-2-/- animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2-/-. The absence of TLR-2 led to lower production of the cytokines TNF, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii. Copyright © Informa Healthcare USA, Inc.

Reduced in vitro immune response on titania nanotube arrays compared to titanium surface

Material surfaces that provide biomimetic cues, such as nanoscale architectures, have been shown to alter cell/biomaterial interactions. Recent studies have identified titania nanotube arrays as strong candidates for use in interfaces on implantable devices due to their ability to elicit improved cellular functionality. However, limited information exists regarding the immune response of nanotube arrays. Thus, in this study, we have investigated the short- and long-term immune cell reaction of titania nanotube arrays. Whole blood lysate (containing leukocytes, thrombocytes and trace amounts of erythrocytes), isolated from human blood, were cultured on titania nanotube arrays and biomedical grade titanium (as a control) for 2 hours and 2 and 7 days. In order to determine the in vitro immune response on titania nanotube arrays, immune cell functionality was evaluated by cellular viability, adhesion, proliferation, morphology, cytokine/chemokine expression, with and without lipopolysaccharide (LPS), and nitric oxide release. The results presented in this study indicate a decrease in short- and long-term monocyte, macrophage and neutrophil functionality on titania nanotube arrays as compared to the control substrate. This work shows a reduced stimulation of the immune response on titania nanotube arrays, identifying this specific nanoarchitecture as a potentially optimal interface for implantable biomedical devices. © 2013 The Royal Society of Chemistry.

Do Atopobium vaginae, Megasphaera sp. and Leptotrichia sp. change the local innate immune response and sialidase activity in bacterial vaginosis?

Objectives: To investigate if the participation of Atopobium vaginae, Megasphaera sp. and Leptotrichia sp. in the bacterial community of bacterial vaginosis (BV) is associated with distinct patterns of this condition. Methods: In this cross-sectional controlled study, 205 women with BV and 205 women with normal flora were included. Vaginal rinsing samples were obtained for measuring the levels of pro-inflammatory cytokines and bacterial sialidases. Real-time PCR was used to quantify the BV-associated bacteria and to estimate the total bacterial load using the 16S rRNA. Principal component analysis (PCA) using the measured parameters was performed to compare the BV samples with lower and higher loads of the species of interest. Results: Higher bacterial load (p<0.001), levels of interleukin 1-β (p<0.001) and sialidase activity (p<0.001) were associated with BV. Women with BV and higher relative loads of A vaginae, Megasphaera sp. and Leptotrichia sp. presented increased sialidase activity, but unchanged cytokine levels. PCA analysis did not indicate a different pattern of BV according to the loads of A vaginae, Megasphaera sp. and Leptotrichia sp. Conclusions: Greater participation of A vaginae, Megasphaera sp. and Leptotrichia sp. in vaginal bacterial community did not indicate a less severe form of BV; moreover, it was associated with increased sialidase activity.

Analysis of the risk factors related to the immune humoral anti-Anaplasma marginale in dairy cattle

Anaplasma marginale is the most prevalent pathogen of cattle transmitted by ticks in the world. This study aimed to evaluate the risk factors for anaplasmosis in dairy cattle. Fifty dairy cattle from the herd of Empresa de Pesquisa Agropecuaria do Estado do Rio de Janeiro were selected by proportional stratified sampling. The risk factors evaluated were: physiological state, race pattern, number of lactations, milk production, infestation by Rhipicephalus microplus and animal density. Antibody activity against A. marginale was determined using the indirect enzyme-linked immunosorbent assay. The percentual values of seroprevalence for A. marginale were submitted to X2 test, and the level of minimum significance, to keep a factor in the model of logistic regression, was fixated in 5%. It was observed that pregnancy and lactation influenced significantly (p<0.05) in the seropositivity of the animals. Bos indicus animals had 5.21 times more chances of being seropositive than B. taurus animals. Primiparous female had 88% more chances of being seropositive than pluriparous female. Animals with high milk production were 63% more positive than low production animals. When infested by ticks the animals had 39% more chance of being seropositive to A. marginale. Bos indicus animals presented 5.21 times more chance of being seropositive than B. taurus animals. Primiparous females presented 88% more chance of being seropositive than the pluriparous ones. High milk production animals were 63% more positive than the low production ones. When infested by ticks the animals had 39% more chance of being seropositive to A. marginale. High density grazing provided for the animals 3.2 times more chances of being seropositive than low density ones. The herd was classified as erratic to A. marginale, even being placed in a steady enzootic area.

Humoral antibody immune response of newcastle disease vaccination in lovebirds (Agapornis roseicollis)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Humoral and cell-mediated immune responses to different doses of attenuated vaccine against avian infectious bronchitis virus

The antibody and cellular immune responses against infectious bronchitis virus (IBV) were evaluated at mucosal sites of chickens after immunization with various doses of an attenuated vaccine at 1 day of age. The correlation of these immune responses with protection of tracheal tissues was evaluated after experimental infection of these birds. Significantly reduced tracheal pathologic effects, measured according to ciliostasis and histology lesions, and reduced viral load were observed only in the full-dose vaccinated group at 5 days post-infection (dpi), while incomplete protection was observed for the subdose vaccinated groups. Moreover, birds of vaccinated groups, especially with full dose, developed higher levels of lachrymal IBV-specific IgG and IgA and increased the expression of cell-mediated immunity (CMI) genes, such as gamma interferon (IFNγ), CD8+ T cell marker, and granzyme homolog A more rapidly. In addition, these humoral and cellular immune responses evaluated at mucosal sites correlated significantly with tracheal protection against homologous IBV challenge in a vaccine dose-dependent manner. The results indicate that IgG, IgA and CD8+ T cell responses developed at mucosal sites after IBV vaccination of day-old chicks, could be taken as good correlates of protection against this virus. © 2013, Mary Ann Liebert, Inc.

Phenotypic and metabolic aspects of prostatic epithelial cells in aged gerbils after antisteroidal therapy: Turnover in the state of chromatin condensation and androgen-independent cell replacement

The gerbil is a rodent considered a good model for studies of prostatic morphophysiology under different experimental conditions. Studies involving castration and steroidal blockers of aged gerbils showed that the glandular epithelium persists after long-term therapy, preventing the organ atrophy. Thus, the objective of this study was to evaluate the phenotypic characteristics and behavior of prostatic epithelial cells that remained after different periods of hormone ablation in aged gerbils. The identification of elements that influenced the survival of this cell type was performed by morphometric, nuclear phenotypes, ultrastructural and immune histochemical analysis. The most significant responses to treatment, by analyzing morphometric features, were observed during the first three time points (day 1, day 3, and day 7), after which there appeared to be an adjustment of the gland to the hormone ablation. All treatments led to changes in the state of chromatin condensation, DNA methylation pattern and phenotypic changes indicated cell senescence. Additionally, an increase in the basal cells seemed to guarantee self-renewal properties to the epithelium. These data indicate that changes occur at many levels, including gene expression and nuclear architecture in the epithelial cells, when aging and steroidal blockade are associated. These aspects are important when considering castration-resistant prostate cancer, a malignant tumor posing difficult therapeutic intervention. © 2013 Elsevier GmbH. All rights reserved.

Broiler breeder feeding programs and trace minerals on maternal antibody transfer and broiler humoral immune response

Breeder feed restriction may negatively affect broiler progeny immunity. Sources of trace minerals (TM) with higher bioavailability in breeder diets have been reported to enhance humoral and cellular immunity in broiler progeny. An experiment was conducted to examine the effects of breeder feeding programs and TM dietary sources on maternal antibody transfer and humoral immune response of progeny to a live vaccine against Newcastle disease virus (NDV). Cobb 500 breeders were fed according to 2 feed allocation programs, sigmoid late fast and sigmoid late slow, from 14 to 29 wk of age. From 56 to 62 wk of age, breeders were fed with either inorganic TM or an organic source (OTM) to replace 30% of Cu, Zn, and Mn. Progeny broilers were vaccinated intraocularly with La Sota NDV vaccine at 7 d of age. Blood samples were collected at hatching, 4, and 14 d postvaccination. Serum antibody levels against NDV were assessed by ELISA and cytokine expression by real time PCR. At hatching, late slow breeder progeny fed diets with 30% OTM had higher antibody titers as compared with progeny of breeders fed 100% inorganic TM. Similar results were observed 2 wk postvaccination. Breeder feeding programs and TM sources affected the expression level of IL-4 in NDV vaccinated broiler progeny. It was concluded that breeder feeding programs influenced humoral immune response to NDV vaccine in the broiler progeny, and 30% OTM may increase these responses. © 2013 Poultry Science Association, Inc.

Salivary epithelial cells as model to study immune response against cutaneous pathogens

The human skin not only provides passive protection as a physical barrier against external injury, but also mediates active surveillance via epidermal cell surface receptors that recognize and respond to potential invaders. Primary keratinocytes and immortalized cell lines, the commonly used sources to investigate immune responses of cutaneous epithelium are often difficult to obtain and/or potentially exhibit changes in cellular genetic make-up. Here we investigated the possibility of using salivary epithelial cells (SEC) to evaluate the host response to cutaneous microbes. Elevated secretion of IFN-γ and IL-12 was observed in the SEC stimulated with Staphylococcus aureus, a transient pathogen of the skin, as mono species biofilm as compared to SEC stimulated with a commensal microbe, the Staphylococcus epidermidis. Co-culture of the SEC with both microbes as dual species biofilm elicited maximum cytokine response. Stimulation with S. aureus alone but not with S. epidermidis alone induced maximum toll-like receptor-2 (TLR-2) expression in the SEC. Exposure to dual species biofilm induced a sustained upregulation of TLR-2 in the SEC for up to an hour. The data support novel application of the SEC as efficient biospecimen that may be used to investigate personalized response to cutaneous microflora. © 2013 Wiley Periodicals, Inc.