An idiotypic immune network as a short-term learning architecture for mobile robots

A combined Short-Term Learning (STL) and Long-Term Learning (LTL) approach to solving mobile robot navigation problems is presented and tested in both real and simulated environments. The LTL consists of rapid simulations that use a Genetic Algorithm to derive diverse sets of behaviours. These sets are then transferred to an idiotypic Artificial Immune System (AIS), which forms the STL phase, and the system is said to be seeded. The combined LTL-STL approach is compared with using STL only, and with using a handdesigned controller. In addition, the STL phase is tested when the idiotypic mechanism is turned off. The results provide substantial evidence that the best option is the seeded idiotypic system, i.e. the architecture that merges LTL with an idiotypic AIS for the STL. They also show that structurally different environments can be used for the two phases without compromising transferability.

Cl��nica e cirurgia de animais de companhia

Este relat��rio foi realizado no ��mbito da conclus��o do mestrado integrado em medicina veterin��ria da Universidade de ��vora, encontrando-se dividido em duas partes. A primeira �� referente �� casu��stica acompanhada ao longo do est��gio curricular, decorrido no Hospital Veterin��rio do Restelo (HVR), com a dura����o de quatro meses, desde 03 de Agosto de 2015 a 06 de Dezembro de 2016, sob orienta����o da Doutora Sandra Branco e coorienta����o do Dr. Diogo Magno, subdiretor cl��nico do HVR. A segunda parte �� constitu��da por uma monografia subordinada ao tema ���Erliquiose Monoc��tica Canina���, seguida de um caso cl��nico acompanhado pelo autor no ��mbito do referido tema. A erliquiose monoc��tica canina (EMC) �� uma doen��a infeciosa transmitida por um vetor, o ixod��deo Riphicephalus sanguineus, cujos controlos qu��micos e ambientais s��o essenciais para reduzir a preval��ncia da doen��a. �� causada por uma bact��ria intracelular, Ehrlichia canis, que afeta o sistema imunit��rio dos c��es, manifestando diferentes fases de evolu����o e podendo apresentar formas aguda e cr��nica da doen��a. O tratamento de primeira escolha �� o uso da antibioterapia com tetraciclinas, dentre as quais a doxiciclina, para al��m do tratamento de suporte, como a fluidoterapia. O progn��stico �� vari��vel, dependendo da precocidade e efici��ncia da terap��utica institu��da; ABSTRACT: The present report, wrote to get the master degree in veterinary medicine area, on Universidade de ��vora, is divided up into two distinct parts. On one hand it describes the clinical situations��� roll, assisted through the experimental trainee, that took place on Hospital Veterin��rio do Restelo (HVR), for a period of four months, specifically since 3 august 2015 until 6 december 2015, and this trainee was led by Doctor Sandra Branco, and also the HVR���s clinical subdirector Dr. Diogo Magno. On other hand the second parts reveals a monograph titled ���ehrlichiosis monocytic canine��� (EMC), specifying a particular clinical case followed by the author. The EMC an infectious disease transmitted by a tick - Riphicephalus sanguineus ��� whose chemical controls and even the environmental ones are crucial to reduce the disease���s prevalence. The disease has an intracellular bacteria origin - Ehrlichia canis ��� responsability for the dog���s immune system infection, and it reveals different evolution phases and present acute or in some cases chronic forms. The treatment���s first step is to use an antibiotic with tetracycline that include doxycycline, and as a fluid���s therapy addition is use to do the supportive treatment. The diagnosis is variable so it depends on precocity evaluation and even on the therapeutics efficiencies.

Artificial immune systems

The human immune system has numerous properties that make it ripe for exploitation in the computational domain, such as robustness and fault tolerance, and many different algorithms, collectively termed Artificial Immune Systems (AIS), have been inspired by it. Two generations of AIS are currently in use, with the first generation relying on simplified immune models and the second generation utilising interdisciplinary collaboration to develop a deeper understanding of the immune system and hence produce more complex models. Both generations of algorithms have been successfully applied to a variety of problems, including anomaly detection, pattern recognition, optimisation and robotics. In this chapter an overview of AIS is presented, its evolution is discussed, and it is shown that the diversification of the field is linked to the diversity of the immune system itself, leading to a number of algorithms as opposed to one archetypal system. Two case studies are also presented to help provide insight into the mechanisms of AIS; these are the idiotypic network approach and the Dendritic Cell Algorithm.

System dynamics modelling of the processes involving the maintenance of the naive T cell repertoire

The study of immune system aging, i.e. immunosenescence, is a relatively new research topic. It deals with understanding the processes of immuno-degradation that indicate signs of functionality loss possibly leading to death. Even though it is not possible to prevent immunosenescence, there is great benefit in comprehending its causes, which may help to reverse some of the damage done and thus improve life expectancy. One of the main factors influencing the process of immunosenescence is the number and phenotypical variety of naive T cells in an individual. This work presents a review of immunosenescence, proposes system dynamics modelling of the processes involving the maintenance of the naive T cell repertoire and presents some preliminary results.

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.

D��terminer le r��le de C1orf106, un g��ne associ�� aux maladies inflammatoires de l���intestin

Les maladies inflammatoires de l���intestin (MIIs, [MIM 266600]) sont caract��ris��es par une inflammation chronique au niveau du tube gastro-intestinal. Les deux principales formes sont la maladie de Crohn (MC) et la colite ulc��reuse (CU). Les MIIs r��sulteraient d���un d��faut du syst��me immunitaire et de l�����pith��lium intestinal. Ce dernier forme une barri��re physique et biochimique qui s��pare notre syst��me immunitaire des microorganismes commensaux et pathog��nes de la microflore intestinale. Un d��faut dans la barri��re ��pith��liale intestinale pourrait donc mener �� une r��ponse immunitaire soutenue contre notre microflore intestinale. Les ��tudes d���association pang��nomiques (GWAS) ont permis d���identifier 201 r��gions de susceptibilit�� aux MIIs. Parmi celles-ci, la r��gion 1q32 associ��e �� la MC (p<2x10-11) et �� la CU (p<6x10-7) contient 4 g��nes, dont C1orf106, un g��ne codant pour une prot��ine de fonction inconnue. Le re-s��quen��age de la r��gion 1q32 a permis d���identifier une variante g��n��tique rare de C1orf106 (MAF��1%) associ��e aux MIIs (p=0,009), Y333F. Nous avons d��montr�� que la substitution de la tyr333 par une ph��nylalanine semble avoir un effet sur la stabilit�� prot��ique de C1orf106 tel que d��montr�� lors de l���inhibition de la synth��se prot��ique induite par le cycloheximide. Nous avons d��termin�� que C1orf106 est exprim�� dans le c��lon et l���intestin gr��le. De plus, son expression est augment��e lors de la diff��renciation des cellules ��pith��liales Caco-2 en ��pith��lium intestinal polaris��. Son profil d���expression correspond aux types cellulaires et tissulaires affect��s dans les MIIs. De plus, C1orf106 est partiellement co-localis��e avec le marqueur des jonctions serr��es, ZO-1. Toutefois, son marquage reproduit parfaitement celui du marqueur des jonctions adh��rentes, E-cadh��rine. Les jonctions serr��es et adh��rentes sont localis��es du c��t�� apical de la jonction intercellulaire et sont toutes deux impliqu��es dans l�����tablissement de la barri��re ��pith��liale. Nous avons donc test�� l���impact de C1orf106 sur la perm��abilit�� de l�����pith��lium intestinal. Nous avons observ�� une augmentation de la perm��abilit�� ��pith��liale chez un ��pith��lium intestinal form�� par des cellules Caco-2 sous-exprimant C1orf106. Nos r��sultats sugg��rent que C1orf106 pourrait ��tre le g��ne causal de la r��gion 1q32.

Polycystic ovary syndrome as a proinflammatory state:the role of adipokines

Background: Polycystic Ovary Syndrome (PCOS) is a complex heterogeneous disorder and the most common endocrinopathy amongst women of reproductive age. It is characterized by androgen excess, chronic anovulation and an altered cardiometabolic profile. PCOS is linked to impaired adipose tissue (AT) physiology and women with this disorder present with greater risk for insulin resistance (IR), hyperinsulinemia, central adiposity, nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) than matched for age and body mass index (BMI) women without PCOS. Hyperandrogenaemia appears to be driving adipocyte hypertrophy observed in PCOS under the influence of a hyperinsulinaemic state. Changes in the function of adipocytes have an impact on the secretion of adipokines, adipose tissue-derived proinflammatory factors promoting susceptibility to low grade inflammation. Methods: In this article, we review the existing knowledge on the interplay between hyperandrogenaemia, insulin resistance, impaired adipocyte biology, adipokines and chronic low-grade inflammation in PCOS. Results: In PCOS, more than one mechanisms have been suggested in the development of a chronic low-grade inflammation state with the most prevalent being that of a direct effect of the immune system on adipose tissue functions as previously reported in obese women without PCOS. Despite the lack of conclusive evidence regarding a direct mechanism linking hyperandrogenaemia to pro-inflammation in PCOS, there have been recent findings indicating that hyperandrogenaemia might be involved in chronic inflammation by exerting an effect on adipocytes morphology and attributes. Conclusion: Increasing evidence suggests that there is an important connection and interaction between proinflammatory pathways, hyperinsulinemia, androgen excess and adipose tissue hypertrophy and, dysfunction in PCOS. While lifestyle changes and individualized prescription of insulin-sensitizing drugs are common in managing PCOS, further studies are warranted to eventually identify an adipokine that could serve as an indirect marker of adipocyte dysfunction in PCOS, used as a reliable and pathognomic sign of metabolic alteration in this syndrome.

D��terminer le r��le de C1orf106, un g��ne associ�� aux maladies inflammatoires de l���intestin

Les maladies inflammatoires de l���intestin (MIIs, [MIM 266600]) sont caract��ris��es par une inflammation chronique au niveau du tube gastro-intestinal. Les deux principales formes sont la maladie de Crohn (MC) et la colite ulc��reuse (CU). Les MIIs r��sulteraient d���un d��faut du syst��me immunitaire et de l�����pith��lium intestinal. Ce dernier forme une barri��re physique et biochimique qui s��pare notre syst��me immunitaire des microorganismes commensaux et pathog��nes de la microflore intestinale. Un d��faut dans la barri��re ��pith��liale intestinale pourrait donc mener �� une r��ponse immunitaire soutenue contre notre microflore intestinale. Les ��tudes d���association pang��nomiques (GWAS) ont permis d���identifier 201 r��gions de susceptibilit�� aux MIIs. Parmi celles-ci, la r��gion 1q32 associ��e �� la MC (p<2x10-11) et �� la CU (p<6x10-7) contient 4 g��nes, dont C1orf106, un g��ne codant pour une prot��ine de fonction inconnue. Le re-s��quen��age de la r��gion 1q32 a permis d���identifier une variante g��n��tique rare de C1orf106 (MAF��1%) associ��e aux MIIs (p=0,009), Y333F. Nous avons d��montr�� que la substitution de la tyr333 par une ph��nylalanine semble avoir un effet sur la stabilit�� prot��ique de C1orf106 tel que d��montr�� lors de l���inhibition de la synth��se prot��ique induite par le cycloheximide. Nous avons d��termin�� que C1orf106 est exprim�� dans le c��lon et l���intestin gr��le. De plus, son expression est augment��e lors de la diff��renciation des cellules ��pith��liales Caco-2 en ��pith��lium intestinal polaris��. Son profil d���expression correspond aux types cellulaires et tissulaires affect��s dans les MIIs. De plus, C1orf106 est partiellement co-localis��e avec le marqueur des jonctions serr��es, ZO-1. Toutefois, son marquage reproduit parfaitement celui du marqueur des jonctions adh��rentes, E-cadh��rine. Les jonctions serr��es et adh��rentes sont localis��es du c��t�� apical de la jonction intercellulaire et sont toutes deux impliqu��es dans l�����tablissement de la barri��re ��pith��liale. Nous avons donc test�� l���impact de C1orf106 sur la perm��abilit�� de l�����pith��lium intestinal. Nous avons observ�� une augmentation de la perm��abilit�� ��pith��liale chez un ��pith��lium intestinal form�� par des cellules Caco-2 sous-exprimant C1orf106. Nos r��sultats sugg��rent que C1orf106 pourrait ��tre le g��ne causal de la r��gion 1q32.

Impact of exercise on innate immunity in multiple sclerosis progression and symptomatology

Multiple Sclerosis (MS), an idiopathic progressive immune-mediated neurological disorder of the central nervous system (CNS), is characterized by recurrent episodes of inflammatory demyelination and consequent axonal deterioration. It accounts for functional deterioration and lasting disability among young adults. A body of literature demonstrates that physical activity counteracts fatigue and depression and may improve overall quality of life in MS patients. Furthermore, much data indicates that exercise ameliorates chronic neuroinflammation and its related pathologies by tipping cytokine profiles toward an anti-inflammatory signature. Recent data has focused on the direct impact of exercise training on the innate immune system by targeting toll-like receptors (TLRs), signaling pattern recognition receptors that govern the innate immune response, shedding light on the physiological role of TLRs in health and disease. Indeed, TLRs continue to emerge as players in the neuroinflammatory processes underpinning MS. This review will highlight evidence that physical activity and exercise are potential immunomodulatory therapies, targeting innate signaling mechanism(s) to modulate MS symptom development and progression.

The role of inflammation in vascular function and pregnancy outcome in the pregnant stroke prone spontaneously hypertensive rat

During pregnancy, the maternal cardiovascular system undergoes major adaptation. One of these changes is a 40-50 % increase in circulating blood volume which requires a systemic remodelling of the vasculature in order to regulate maternal blood pressure and maximise blood supply to the developing placenta and fetus. These changes are broadly conserved between humans and rats making them an appropriate pre-clinical model in which to study the underlying mechanisms of pregnancy-dependent cardiovascular remodelling. Whilst women are normally protected against cardiovascular disease; pregnancy marks a period of time where women are susceptible to cardiovascular complications. Cardiovascular disease is the leading cause of maternal mortality in the United Kingdom; in particular hypertensive conditions are among the most common complications of pregnancy. One of the main underlying pathologies of these pregnancy complications is thought to be a failure of the maternal cardiovascular system to adapt. The remodelling of the uterine arteries, which directly supply the maternal-fetal interface, is paramount to a healthy pregnancy. Failure of the uterine arteries to remodel sufficiently can result in a number of obstetric complications such as preeclampsia, fetal growth restriction and spontaneous pregnancy loss. At present, it is poorly understood whether this deficient vascular response is due to a predisposition from existing maternal cardiovascular risk factors, the physiological changes that occur during pregnancy or a combination of both. Previous work in our group employed the stroke prone spontaneously hypertensive rat (SHRSP) as a model to investigate pregnancy-dependent remodelling of the uterine arteries. The SHRSP develops hypertension from 6 weeks of age and can be contrasted with the control strain, the Wistar Kyoto (WKY) rat. The phenotype of the SHRSP is therefore reflective of the clinical situation of maternal chronic hypertension during pregnancy. We showed that the SHRSP exhibited a deficient uterine artery remodelling response with respect to both structure and function accompanied by a reduction in litter size relative to the WKY at gestational day (GD) 18. A previous intervention study using nifedipine in the SHRSP achieved successful blood pressure reduction from 6 weeks of age and throughout pregnancy; however uterine artery remodelling and litter size at GD18 was not improved. We concluded that the abnormal uterine artery remodelling present in the SHRSP was independent of chronic hypertension. From these findings, we hypothesised that the SHRSP could be a novel model of spontaneously deficient uterine artery remodelling in response to pregnancy which was underpinned by other as yet unidentified cardiovascular risk factors. In Chapter 1 of this thesis, I have characterised the maternal, placental and fetal phenotype in pregnant (GD18) SHRSP and WKY. The pregnant SHRSP exhibit features of left ventricular hypertrophy in response to pregnancy and altered expression of maternal plasma biomarkers which have been previously associated with hypertension in human pregnancy. I developed a protocol for accurate dissection of the rat uteroplacental unit using qPCR probes specific for each layer. This allowed me to make an accurate and specific statement about gene expression in the SHRSP GD18 placenta; where oxidative stress related gene markers were increased in the vascular compartments. The majority of SHRSP placenta presented at GD18 with a blackened ring which encircled the tissue. Further investigation of the placenta using western blot for caspase 3 cleavage determined that this was likely due to increased cell death in the SHRSP placenta. The SHRSP also presented with a loss of one particular placental cell type at GD18: the glycogen cells. These cells could have been the target of cell death in the SHRSP placenta or were utilised early in pregnancy as a source of energy due to the deficient uterine artery blood supply. Blastocyst implantation was not altered but resorption rate was increased between SHRSP and WKY; indicating that the reduction in litter size in the SHRSP was primarily due to late (>GD14) pregnancy loss. Fetal growth was not restricted in SHRSP which led to the conclusion that SHRSP sacrifice part of their litter to deliver a smaller number of healthier pups. Activation of the immune system is a common pathway that has been implicated in the development of both hypertension and adverse pregnancy outcome. In Chapter 2, I proposed that this may be a mechanism of interest in SHRSP pregnancy and measured the pro-inflammatory cytokine, TNF��, as a marker of inflammation in pregnant SHRSP and WKY and in the placentas from these animals. TNF�� was up-regulated in maternal plasma and urine from the GD18 SHRSP. In addition, TNF�� release was increased from the GD18 SHRSP placenta as was the expression of the pro-inflammatory TNF�� receptor 1 (Tnfr1). In order to investigate whether this excess TNF�� was detrimental to SHRSP pregnancy, a vehicle-controlled intervention study using etanercept (a monoclonal antibody which works as a TNF�� antagonist) was carried out. Etanercept treatment at GD0, 6, 12 and 18 resulted in an improvement in pregnancy outcome in the SHRSP with an increased litter size and reduced resorption rate. Furthermore, there was an improved uterine artery function in GD18 SHRSP treated with etanercept which was associated with an improved uterine artery blood flow over the course of gestation. In Chapter 3, I sought to identify the source of this detrimental excess of TNF�� by designing a panel for maternal leukocytes in the blood and placenta at GD18. A population of CD3- CD161+ cells, which are defined as rat natural killer (NK) cells, were increased in number in the SHRSP. Intracellular flow cytometry also identified this cell type as a source of excess TNF�� in blood and placenta from pregnant SHRSP. I then went on to evaluate the effects of etanercept treatment on these CD3- CD161+ cells and showed that etanercept reduced the expression of CD161 and the cytotoxic molecule, granzyme B, in the NK cells. Thus, etanercept limits the cytotoxicity and potential damaging effect of these NK cells in the SHRSP placenta. Analysing the urinary peptidome has clinical potential to identify novel pathways involved with disease and/or to develop biomarker panels to aid and stratify diagnosis. In Chapter 4, I utilised the SHRSP as a pre-clinical model to identify novel urinary peptides associated with hypertensive pregnancy. Firstly, a characterisation study was carried out in the kidney of the WKY and SHRSP. Urine samples from WKY and SHRSP taken at pre-pregnancy, mid-pregnancy (GD12) and late pregnancy (GD18) were used in the peptidomic screen. In order to capture peptides which were markers of hypertensive pregnancy from the urinary peptidomic data, I focussed on those that were only changed in a strain dependent manner at GD12 and 18 and not pre-pregnancy. Peptide fragments from the uromodulin protein were identified from this analysis to be increased in pregnant SHRSP relative to pregnant WKY. This increase in uromodulin was validated at the SHRSP kidney level using qPCR. Uromodulin has previously been identified to be a candidate molecule involved in systemic arterial hypertension but not in hypertensive pregnancy thus is a promising target for further study. In summary, we have characterised the SHRSP as the first model of maternal chronic hypertension during pregnancy and identified that inflammation mediated by TNF�� and NK cells plays a key role in the pathology. The evidence presented in this thesis establishes the SHRSP as a pre-clinical model for pregnancy research and can be continued into clinical studies in pregnant women with chronic hypertension which remains an area of unmet research need.

HIV-1 infection: back and forth between virus and host.

The main obstacles to HIV-1 eradication are linked to the viral ability to evade immune system and establish a reservoir where virus is transcriptionally latent but able to replicate. IFN action and Restriction Factors (RFs) expression, dominant proteins that target multiple steps of the HIV-1 lifecycle, represent an early line of defence Because of their interplay with viral replication, we would like to study the relationship between RFs and the viral amount in latently infected cells.The first part of this project investigates the expression levels variations of a selected group of RFs (APOBEC3G, BST2, TRIM5��, MX2, SAMHD1, SERINC3/5, IFI16 and STING) in HIV-1 patients during the course of infection before and after ART administration by using Real Time qPCR. The second part of this study deals with the role of IFN�� and IFN��, and their role in the immune system disfunction that has been described during chronic inflammation associated to cancer, viral infection such as HIV-1, and autoimmune-disease. Immune Check Point proteins (ICPs) are a group of inhibitory receptors expressed on the cellular surface of immune cells and trigger immunosuppressive signaling pathways leading to T-cell exhaustion and the expression of immune checkpoint molecules (PD-1, PD-L1, TIGIT, LILRB2). The major aim of this project is to assess the clinical meaning of ICPs expression in HIV-1 chronically infected patients to better characterized their involvement in immune system disfunction.

Fractalkine (cx3cl1) Is Involved In The Early Activation Of Hypothalamic Inflammation In Experimental Obesity.

Hypothalamic inflammation is a common feature of experimental obesity. Dietary fats are important triggers of this process, inducing the activation of toll-like receptor-4 (TLR4) signaling and endoplasmic reticulum stress. Microglia cells, which are the cellular components of the innate immune system in the brain, are expected to play a role in the early activation of diet-induced hypothalamic inflammation. Here, we use bone marrow transplants to generate mice chimeras that express a functional TLR4 in the entire body except in bone marrow-derived cells or only in bone marrow-derived cells. We show that a functional TLR4 in bone marrow-derived cells is required for the complete expression of the diet-induced obese phenotype and for the perpetuation of inflammation in the hypothalamus. In an obesity-prone mouse strain, the chemokine CX3CL1 (fractalkine) is rapidly induced in the neurons of the hypothalamus after the introduction of a high-fat diet. The inhibition of hypothalamic fractalkine reduces diet-induced hypothalamic inflammation and the recruitment of bone marrow-derived monocytic cells to the hypothalamus; in addition, this inhibition reduces obesity and protects against diet-induced glucose intolerance. Thus, fractalkine is an important player in the early induction of diet-induced hypothalamic inflammation, and its inhibition impairs the induction of the obese and glucose intolerance phenotypes.

The Role Of The Inflammatory Microenvironment In Thyroid Carcinogenesis.

Immune responses against thyroid carcinomas have long been demonstrated and associations between inflammatory microenvironment and thyroid carcinomas repeatedly reported. This scenario has prompted scientists throughout the world to unveil how the inflammatory microenvironment is established in thyroid tumors and what is its influence on the outcome of patients with thyroid carcinoma. Many studies have reported the role of evasion from the immune system in tumor progression and reinforced the weakness of the innate immune response toward thyroid cancer spread in advanced stages. Translational studies have provided evidence that an increased density of tumor-associated macrophages in poorly differentiated thyroid carcinoma (DTC) is associated with an aggressive phenotype at diagnosis and decreased cancer-related survival, whereas well-DTC microenvironment enriched with macrophages is correlated with improved disease-free survival. It is possible that these different results are related to different microenvironments. Several studies have provided evidence that patients whose tumors are not infiltrated by lymphocytes present a high recurrence rate, suggesting that the presence of lymphocytes in the tumor microenvironment may favor the prognosis of patients with thyroid carcinoma. However, the effect of lymphocytes and other immune cells on patient outcome seems to result from complex interactions between the tumor and immune system, and the molecular pattern of cytokines and chemokines helps to explain the involvement of the immune system in thyroid tumor progression. The inflammatory microenvironment may help to characterize aggressive tumors and to identify patients who would benefit from a more invasive approach, probably sparing the vast majority of patients with an indolent disease from unnecessary procedures.

Monitoramento de par��metros imunol��gicos em atletas adolescentes de basquetebol durante e ap��s a temporada esportiva= : Monitoring of immunological parameters in adolescent basketball athletes during and after a sports season

Universidade Estadual de Campinas . Faculdade de Educa����o F��sica

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 ��M. The treatment of peritoneal macrophages with 64 ��M 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 ��M 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 ��M unsat PC decreased the production of lipopolysaccharide-elicited nitric oxide by 30.4% (13.5 �� 2.6 vs 19.4 �� 2.5 ��M) and 46.4% (10.4 �� 3.1 vs 19.4 �� 2.5 ��M), 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 ��M 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.