A Recommender System based on Idiotypic Artificial Immune Networks

The immune system is a complex biological system with a highly distributed, adaptive and self-organising nature. This paper presents an Artificial Immune System (AIS) that exploits some of these characteristics and is applied to the task of film recommendation by Collaborative Filtering (CF). Natural evolution and in particular the immune system have not been designed for classical optimisation. However, for this problem, we are not interested in finding a single optimum. Rather we intend to identify a sub-set of good matches on which recommendations can be based. It is our hypothesis that an AIS built on two central aspects of the biological immune system will be an ideal candidate to achieve this: Antigen-antibody interaction for matching and idiotypic antibody-antibody interaction for diversity. Computational results are presented in support of this conjecture and compared to those found by other CF techniques.

Artificial Immune Tissue using Self-Organizing Networks

As introduced by Bentley et al. (2005), artificial immune systems (AIS) are lacking tissue, which is present in one form or another in all living multi-cellular organisms. Some have argued that this concept in the context of AIS brings little novelty to the already saturated field of the immune inspired computational research. This article aims to show that such a component of an AIS has the potential to bring an advantage to a data processing algorithm in terms of data pre-processing, clustering and extraction of features desired by the immune inspired system. The proposed tissue algorithm is based on self-organizing networks, such as self-organizing maps (SOM) developed by Kohonen (1996) and an analogy of the so called Toll-Like Receptors (TLR) affecting the activation function of the clusters developed by the SOM.

A Recommender System based on the Immune Network

Abstract-The immune system is a complex biological system with a highly distributed, adaptive and self-organising nature. This paper presents an artificial immune system (AIS) that exploits some of these characteristics and is applied to the task of film recommendation by collaborative filtering (CF). Natural evolution and in particular the immune system have not been designed for classical optimisation. However, for this problem, we are not interested in finding a single optimum. Rather we intend to identify a sub-set of good matches on which recommendations can be based. It is our hypothesis that an AIS built on two central aspects of the biological immune system will be an ideal candidate to achieve this: Antigen - antibody interaction for matching and antibody - antibody interaction for diversity. Computational results are presented in support of this conjecture and compared to those found by other CF techniques.

A Recommender System based on Idiotypic Artificial Immune Networks

The immune system is a complex biological system with a highly distributed, adaptive and self-organising nature. This paper presents an Artificial Immune System (AIS) that exploits some of these characteristics and is applied to the task of film recommendation by Collaborative Filtering (CF). Natural evolution and in particular the immune system have not been designed for classical optimisation. However, for this problem, we are not interested in finding a single optimum. Rather we intend to identify a sub-set of good matches on which recommendations can be based. It is our hypothesis that an AIS built on two central aspects of the biological immune system will be an ideal candidate to achieve this: Antigen-antibody interaction for matching and idiotypic antibody-antibody interaction for diversity. Computational results are presented in support of this conjecture and compared to those found by other CF techniques.

Diet, microbes and gut immune responses in the pathogenesis of experimental type 1 diabetes

Type 1diabetes (T1D) is an autoimmune disease, which is influenced by a variety of environmental factors including diet and microbes. These factors affect the homeostasis and the immune system of the gut. This thesis explored the altered regulation of the immune system and the development of diabetes in non-obese diabetic (NOD) mice. Inflammation in the entire intestine of diabetes-prone NOD mice was studied using a novel ex-vivo imaging system of reactive oxygen and nitrogen species (RONS), in relation to two feeding regimens. In parallel, gut barrier integrity and intestinal T-cell activation were assessed. Extra-intestinal manifestations of inflammation and decreased barrier integrity were sought for by studying peritoneal leukocytes. In addition, the role of pectin and xylan as dietary factors involved in diabetes development in NOD mice was explored. NOD mice showed expression of RONS especially in the distal small intestine, which coincided with T-cell activation and increased permeability to macromolecules. The introduction of a casein hydrolysate (hydrolysed milk protein) diet reduced these phenomena, altered the gut microbiota and reduced the incidence of T1D. Extra-intestinally, macrophages appeared in large numbers in the peritoneum of NOD mice after weaning. Peritoneal macrophages (PM) expressed high levels of interleukin-1 receptor associated kinase M (IRAK-M), which was indicative of exposure to ligands of toll-like receptor 4 (TLR-4) such as bacterial lipopolysaccharide (LPS). Intraperitoneal LPS injections activated T cells in the pancreatic lymph nodes (PaLN) and thus, therefore potentially could activate islet-specific T cells. Addition of pectin and xylan to an otherwise diabetes-retarding semisynthetic diet affected microbial colonization of newly-weaned NOD mice, disturbed gut homeostasis and promoted diabetes development. These results help us to understand how diet and microbiota impact the regulation of the gut immune system in a way that might promote T1D in NOD mice.

An immune inspired Network Intrusion Detection System utilising correlation

Network Intrusion Detection Systems (NIDS) are computer systems which monitor a network with the aim of discerning malicious from benign activity on that network. While a wide range of approaches have met varying levels of success, most IDSs rely on having access to a database of known attack signatures which are written by security experts. Nowadays, in order to solve problems with false positive alerts, correlation algorithms are used to add additional structure to sequences of IDS alerts. However, such techniques are of no help in discovering novel attacks or variations of known attacks, something the human immune system (HIS) is capable of doing in its own specialised domain. This paper presents a novel immune algorithm for application to the IDS problem. The goal is to discover packets containing novel variations of attacks covered by an existing signature base.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.

Immune Response In Thyroid Cancer: Widening The Boundaries.

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

Immune cells and oxidative stress in the endotoxin tolerance mouse model

Sepsis is a systemic inflammatory response that can lead to tissue damage and death. In order to increase our understanding of sepsis, experimental models are needed that produce relevant immune and inflammatory responses during a septic event. We describe a lipopolysaccharide tolerance mouse model to characterize the cellular and molecular alterations of immune cells during sepsis. The model presents a typical lipopolysaccharide tolerance pattern in which tolerance is related to decreased production and secretion of cytokines after a subsequent exposure to a lethal dose of lipopolysaccharide. The initial lipopolysaccharide exposure also altered the expression patterns of cytokines and was followed by an 8- and a 1.5-fold increase in the T helper 1 and 2 cell subpopulations. Behavioral data indicate a decrease in spontaneous activity and an increase in body temperature following exposure to lipopolysaccharide. In contrast, tolerant animals maintained production of reactive oxygen species and nitric oxide when terminally challenged by cecal ligation and puncture (CLP). Survival study after CLP showed protection in tolerant compared to naive animals. Spleen mass increased in tolerant animals followed by increases of B lymphocytes and subpopulation Th1 cells. An increase in the number of stem cells was found in spleen and bone marrow. We also showed that administration of spleen or bone marrow cells from tolerant to naive animals transfers the acquired resistance status. In conclusion, lipopolysaccharide tolerance is a natural reprogramming of the immune system that increases the number of immune cells, particularly T helper 1 cells, and does not reduce oxidative stress.

Modulation of peritoneal macrophage activity by the saturation state of the fatty acid moiety of phosphatidylcholine

To determine the effects of saturated and unsaturated fatty acids in phosphatidylcholine (PC) on macrophage activity, peritoneal lavage cells were cultured in the presence of phosphatidylcholine rich in saturated or unsaturated fatty acids (sat PC and unsat PC, respectively), both used at concentrations of 32 and 64 µM. The treatment of peritoneal macrophages with 64 µM unsat PC increased the production of hydrogen peroxide by 48.3% compared to control (148.3 ± 16.3 vs 100.0 ± 1.8%, N = 15), and both doses of unsat PC increased adhesion capacity by nearly 50%. Moreover, 64 µM unsat PC decreased neutral red uptake by lysosomes by 32.5% compared to the untreated group (67.5 ± 6.8 vs 100.0 ± 5.5%, N = 15), while both 32 and 64 µM unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 ± 2.6 vs 19.4 ± 2.5 µM) and 46.4% (10.4 ± 3.1 vs 19.4 ± 2.5 µM), respectively. Unsat PC did not affect anion production in non-stimulated cells or phagocytosis of unopsonized zymosan particles. A different result pattern was obtained for macrophages treated with sat PC. Phorbol 12-miristate 13-acetate-elicited superoxide production and neutral red uptake were decreased by nearly 25% by 32 and 64 µM sat PC, respectively. Sat PC did not affect nitric oxide or hydrogen peroxide production, adhesion capacity or zymosan phagocytosis. Thus, PC modifies macrophage activity, but this effect depends on cell activation state, fatty acid saturation and esterification to PC molecule and PC concentration. Taken together, these results indicate that the fatty acid moiety of PC modulates macrophage activity and, consequently, is likely to affect immune system regulation in vivo.

The effects of nitric oxide on the immune response during giardiasis

Nitric oxide (NO) is a free radical synthesized from L-arginine by different isoforms NO-synthases. NO possesses multiple and complex biological functions. NO is an important mediator of homeostasis, and changes in its generation or actions can contribute or not to pathological states. The knowledge of effects of NO has been not only important to our understanding of immune response, but also to new tools for research and treatment of various diseases. Knowing the importance of NO as inflammatory mediator in diverse infectious diseases, we decided to develop a revision that shows the participation/effect of this mediator in immune response induced against Giardia spp. Several studies already demonstrated the participation of NO with microbicidal and microbiostatic activity in giardiasis. On the other hand, some works report that Giardia spp. inhibit NO production by consuming the intermediate metabolite arginine. In fact, studies in vitro showed that G. lamblia infection of human intestinal epithelial cells had reduced NO production. This occurs due to limited offer of the crucial substrate arginine (essential aminoacid for NO production), consequently reducing NO production. Therefore, the balance between giardial arginine consumption and epithelial NO production could contribute to the variability of the duration and severity of infections by this ubiquitous parasite.

Depressão, antidepressivos e sistema imune: um novo olhar sobre um velho problema

CONTEXTO: A hipótese monoaminérgica da depressão não responde a uma série de questões, tais como "quais as causas dos distúrbios monoaminérgicos?" e "como explicar uma taxa de 30% de refratariedade aos antidepressivos?". Sendo assim, outras teorias têm sido propostas, entre elas, aquelas que enfocam as participações dos sistemas imune e endócrino. OBJETIVOS: Analisar criticamente o papel do sistema de resposta imunoinflamatória na depressão e discutir a interação dos antidepressivos com esse sistema, tanto do ponto de vista básico como clínico. MÉTODOS: Realizou-se pesquisa bibliográfica utilizando-se as bases de dados MedLine e SciELO. RESULTADOS: Pacientes vítimas de estresse crônico e depressão apresentam ativação das respostas imunoinflamatórias e do eixo hipotálamo-hipófise-adrenal, os quais, direta ou indiretamente, influenciam a neurotransmissão. Nesse sentido, a utilização de antidepressivos não apenas aumenta a disponibilidade de neurotransmissores na fenda sináptica, mas também induz mudança do padrão de resposta imune Th1 - pró-inflamatório - para o Th2, que é antiinflamatório. Além disso, sabe-se que pacientes não responsivos aos antidepressivos possuem o sistema imuneinflamatório mais ativo. No entanto, há uma série de dados controversos na literatura, havendo indícios de um perfil imune diferente de acordo com o tipo de depressão. CONCLUSÕES: A compreensão de aspectos neuroimunes presentes na depressão poderia contribuir para um melhor entendimento das bases biológicas desse transtorno e, possivelmente, para novas perspectivas na busca de uma terapêutica mais efetiva.

Impact of Periodontitis on the Diabetes-Related Inflammatory Status

Wide-ranging activation of the innate immune system causing chronic low-grade inflammation is closely involved not only in the pathogenesis of type 2 diabetes mellitus and its complications, through an ongoing cytokine-induced acute-phase response, but also in the pathogenesis of periodontal diseases, whereby cytokines play a central role in the host's response to the periodontal biofilm. Although there is extensive knowledge about the pathways through which diabetes affects periodontal status, less is known about the impact of periodontal diseases on the diabetes-related inflammatory state. This review attempts to explain the immunobiological connection between periodontal diseases and type 2 diabetes mellitus, exploring the mechanisms through which periodontal infection can contribute to the low-grade general inflammation associated with diabetes (thus aggravating insulin resistance) and discussing the impact of periodontal treatment on glycemic control in people living with both diabetes and periodontal disease.

Prostaglandin E(2)-loaded microspheres as strategy to inhibit phagocytosis and modulate inflammatory mediators release

PGE(2), an arachidonic acid metabolite produced by various type of cells regulates a broad range of physiological activities in the endocrine, cardiovascular, gastrointestinal, and immune systems, and is involved in maintaining the local homeostasis. In the immune system, PGE(2) is mainly produced by APCs and it can suppress the Th1-mediated immune responses. The aim of this study was to develop PGE(2)-loaded biodegradable MS that prolong and sustain the in vivo release of this mediator. An o/w emulsion solvent extraction-evaporation method was chosen to prepare the MS. We determined their diameters, evaluated the in vitro release of PGE(2), using enzyme immunoassay and MS uptake by peritoneal macrophages. To assess the preservation of biological activities of this mediator, we determined the effect of PGE(2) released from MS on LPS-induced TNF-alpha release by murine peritoneal macrophages. We also analyzed the effect of encapsulated PGE(2) on inflammatory mediators release from HUVECs. Finally, we studied the effect of PGE(2) released from biodegradable MS in sepsis animal model. The use of this formulation can provide an alternative strategy for treating infections, by modulating or inhibiting inflammatory responses, especially when they constitute an exacerbated profile. (C) 2008 Elsevier B.V. All rights reserved.

Melatonin enhances pro-inflammatory cytokine levels and protects against Chagas disease

Pro-inflammatory and modulatory cytokines have an essential role in host defense against human and murine Trypanosoma cruzi infection. Control of T. cruzi parasitism during the acute phase of infection is considered to be critically dependent on direct macrophage activation by cytokines. Melatonin has been proposed to regulate the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. The aims of this work were to evaluate in rats, the influences of exogenous melatonin treatment on T. cruzi-infected host`s immune responses. With this in mind, several immunological parameters were analyzed, including tumor necrosis factor-alpha, gamma-interferon, interleukin-12, nitric oxide (NO) and macrophage count. The melatonin therapy was provided in one of two different treatment regimens, that is, either beginning 7 days prior to infection or concomitant with the infection. Both treatments triggered an up-regulation of the immune response, with the concomitant treatment being more effective; in this case all cytokines studied, with exception of NO, displayed enhanced concentrations and there was a higher number of peritoneal macrophages, which displayed reduced concentrations under melatonin therapy. We conclude that melatonin plays a pivotal role in up-regulating the Th1 immune response thus controlling parasite replication.