Our murine model of mild traumatic brain injury (mTBI) has shown improved survival after Pseudomonas aeruginosa (Psd) challenge as compared to controls (tail trauma or sham injury). Previous work suggests an mTBI-specific involvement of the neuro-immune axis which augments the innate immune response, increasing survival. Additional factors for the enhanced mTBI survival were explored via microarray analysis of lungs harvested 48 hours post-trauma, the point prior to Psd challenge in our model. At 48 hours post-trauma, mTBI lungs have a number of upregulated ATP synthesis and mitochondrial gene sets. Increased available energy could prime the mTBI lungs, allowing an earlier and more robust response to Psd infection, possibly contributing to the increased mTBI survival. This is supported by increased neutrophil recruitment in the bronchoalveolar lavage of mTBI mice four hours after Psd instillation. Downregulated gene sets related to cellular connections suggest that neutrophils recruited to the lung have an easier extravasation pathway into the air space of mTBI lungs compared to control. Based on genetic and neutrophil recruitment data, it is possible that mTBI creates an energetically prepared and easily accessible lung better tailored for recruiting and allowing entry of neutrophils in response to an infection compared to control.

Gut microbiota has been shown to regulate the growth and development of the central and enteric nervous systems (CNS and ENS) after birth. There is ample evidence to suggest that intestinal bacteria can influence behavior of the host through both immune and immune-independent mechanisms. Gut-microbiota-regulated CNS structural changes are focused in the limbic system, at centres associated with memory, social and emotional behaviour. Several studies using germ-free (GF) and specific pathogen free (SPF) mice demonstrated microbial influence on behaviour development accompanied by neurochemical changes in the brain. Higher exploratory and lower anxiety-like behavior was found in GF mice compared to SPF mice with lower central expression of neurotrophins, such as nerve growth factor and BDNF. The mechanisms by which the microbiota influences behavior are unknown but could be immune-mediated, neural, or humoral in origin. In this study I investigated the role of immune system maturation on mouse behaviour after bacterial colonization. I showed that mono-colonization of GF mice with E. coli normalizes behaviour similar to colonization with complex microbiota (SPF and ASF) and the continuous presence of bacteria is not required to maintain this normal behaviour. I also showed that innate immunity through the MyD88/Ticam pathway is crucial for the development of normal behaviour and that multiple innate immunity and neuronal genes are involved in this process. Together these results suggest that bacterial colonization primes and matures the innate immunity and development of the central nervous system ultimately leading to normal behaviour. I believe that bacterial colonization at birth is not only important for the epithelial barrier function, gut homeostasis, and immune functions, but also for the development of normal behaviour. Altered immune priming during the postnatal period due to abnormal microbial colonization may have wider implications when considering psychiatric disorders in humans. / Thesis / Doctor of Philosophy (PhD)

Em artrópodes o sistema imune inato contribui para a adaptação de animais como os escorpiões à diferentes ambientes. Esse sistema é composto por mecanismos capazes de agir contra injúrias e a ação de microrganismos e entre esses mecanismos estão os peptídeos antimicrobianos (PAMs). O objetivo deste trabalho foi identificar PAMs presentes na hemolinfa de Tityus serrulatus. Para isso sua hemolinfa foi extraída e separados os hemócitos e plasma, em seguida fracionamos em 3 concentrações de acetonitrila em TFA 0,05% (05, 40 e 80%). Estas frações foram submetidas a uma cromatografia liquida de alta eficiência (CLAE) e os picos foram avaliados quanto a sua ação antimicrobiana e hemolítica. Foram identificadas 16 frações que apresentam atividade antimicrobiana. Uma das frações com atividade antimicrobiana, presente nos hemócitos apresentou similaridade com defensina descrita em carrapatos da espécie Ixodes scapularis. Essa fração possui aproximadamente 3486 Da, não apresenta atividade hemolítica e foi denominada como Serrulina. / In arthropods, its innate immune system contributes to the adaptation of animals like scorpions to different environments. This system consists of mechanisms that act avoiding injuries and against the action of microorganisms, among these mechanisms are antimicrobial peptides (AMPs). The aim of this study was to identify AMPs, present in the hemolymph of Tityus serrulatus. The hemolymph was extracted and then we separated hemocyte and plasma. The samples were fractionated in different concentrations of acetonitrile in TFA 0.05% (05, 40 and 80%). These fractions were subjected to high-performance liquid chromatography (HPLC) and the peaks obtained were evaluated for its antimicrobial and hemolytic action. We found sixteen fractions with antimicrobial activity. One of the fractions with antimicrobial activity, present in hemocytes, is similar with a defensin described in ticks, Ixodes scapularis. This fraction has about 3486 Da, has no hemolytic activity and was named as Serrulina.

Fishes in the superorder Ostariophysi, including fathead minnows (Pimephales promelas), possess specialized epidermal club cells that contain an alarm substance. Damage to these cells, as would occur during a predator attack, causes the release of the alarm substance and can indicate the presence of actively foraging predators to nearby conspecifics. For nearly 70 years, research involving epidermal club cells has focused on the alarm substance and the role it plays in predator/prey interactions. However, recent studies have indicated that there may be a connection between epidermal club cells and the fish immune system. Fish increase investment in epidermal club cells upon exposure to skin penetrating pathogens and parasites. In this study I tested for differences in epidermal club cell investment by fathead minnows exposed to the immunosuppressive effects of the glucocorticoid hormone cortisol. In experiment 1, fathead minnows were exposed to either a single intraperitoneal injection of corn oil or no injection at all. The purpose of this experiment was to determine whether corn oil, the vehicle for cortisol injections in later experiments, had an effect on epidermal club cell density. The treatments had no effect on epidermal club cell size, cell area, or epidermal thickness. In experiment 2, skin extract was prepared from the skin of corn oil injected and non injected fathead minnows as in experiment 1 to determine whether corn oil had an effect on the epidermal club cell alarm substance concentration. The treatments showed no significant differences in observed anti-predator behaviour, including change in shelter use, dashing and freezing. In experiment 3, fathead minnows were exposed to either a single intraperitoneal injection of cortisol or corn oil. The purpose of this experiment was to determine whether cortisol, a known immunosuppressant, had an effect on epidermal club cell investment. Fathead minnows exposed to a single cortisol injection had significantly reduced respiratory burst activity of kidney phagocytes indicating that there was suppression of the innate immune system. Furthermore, cortisol treated fathead minnows showed significantly lower numbers of epidermal club cells. The treatments had no effect on individual epidermal club cell area, epidermal thickness and serum cortisol levels after 12 days. The results from this experiment suggest that pharmacological cortisol injections in fathead minnows have a suppressive effect on the fish innate immune system. Furthermore, the findings that cortisol induced immunosuppression also influences epidermal club cell investment provides support for the hypothesis that epidermal club cells may function as part of the fish immune system.

Respiratory diseases are a major cause of human morbidity and mortality and are a leading cause of economic loss to livestock producers. The respiratory tract is constantly in contact with dust, bacteria, fungi, viruses and other pathogenic agents that are found in the air. Normally, the body has the ability to clear these foreign particles. However, physiological and environmental stresses can impair airway defense mechanisms resulting in establishment of pulmonary infections. The microbes and their products engage various receptors in the lung to activate epithelium, endothelium, macrophages, neutrophils and other cells. The activation of inflammatory cascade in the lung results in recruitment of neutrophils, damage to air-blood barrier and development of edema. Although there have been significant advances in our understanding of mechanisms of lung inflammation, there have been a lack of any significant advances in the development of new therapeutics to manage lung disease, which may suggest that our understanding of the inflammatory mechanisms is still incomplete. Pentraxin 3 (PTX3) is an innate immune protein which has been implicated in a diverse range of inflammatory processes, such as recruitment of cells and production of cytokines. PTX3 is an acute phase protein, with low or undetectable levels in the circulation of healthy humans and animals, and rapid, dramatic increase in inflammatory diseases. The expression and function of this protein has not been characterized in the lungs of domestic animal species. Because of potential implications of PTX3 in lung inflammation, I studied the expression of PTX3 in normal and inflamed lungs of calves, pigs, horses, foals and humans. Lungs from all of these species showed expression of PTX3 in airway epithelium, alveolar septa, vascular endothelium and inflammatory cells. Western blot performed on homogenates from normal and inflamed lungs from calves and pigs show an increased expression of PTX3 in inflamed lungs (P<0.05). Because protein function is influenced by its location in the cell, I clarified the subcellular expression of PTX3 with immuno-electron microscopy on normal and inflamed calf and horse lungs. PTX3 was localized on pulmonary intravascular macrophages, monocytes, neutrophils and, unexpectedly, platelets. PTX3 was also present in the nuclei of neutrophils, monocytes and pulmonary intravascular macrophages. Neutrophils are critical regulators of acute lung inflammation. Having observed PTX3 in neutrophils, I investigated the effect of E. coli lipopolysaccharide-induced activation on PTX3 in neutrophils in vitro. Neutrophils challenged with E. coli LPS were examined at 30, 60, 90 and 120 minutes after the treatment. Normal peripheral blood neutrophils showed PTX3 expression. Neutrophils activated with LPS appeared ruffled and showed loss of PTX3 expression at 30 minutes followed by recovery of the expression. Western blots performed on normal and activated neutrophil homogenates did not show any differences (P=0.05). Collectively, the data show PTX3 in normal and inflamed lungs across multiple species. PTX3 was also detected in normal and activated neutrophils. While the function of intriguing localization of PTX3 in the nuclei as well as in platelets is not known, the similarity of expression across the species suggest a role for PTX3 in lung inflammation.

Fishes in the superorder Ostariophysi, including fathead minnows (Pimephales promelas), possess specialized epidermal club cells that contain an alarm substance. Damage to these cells, as would occur during a predator attack, causes the release of the alarm substance and can indicate the presence of actively foraging predators to nearby conspecifics. For nearly 70 years, research involving epidermal club cells has focused on the alarm substance and the role it plays in predator/prey interactions. However, recent studies have indicated that there may be a connection between epidermal club cells and the fish immune system. Fish increase investment in epidermal club cells upon exposure to skin penetrating pathogens and parasites. In this study I tested for differences in epidermal club cell investment by fathead minnows exposed to the immunosuppressive effects of the glucocorticoid hormone cortisol. In experiment 1, fathead minnows were exposed to either a single intraperitoneal injection of corn oil or no injection at all. The purpose of this experiment was to determine whether corn oil, the vehicle for cortisol injections in later experiments, had an effect on epidermal club cell density. The treatments had no effect on epidermal club cell size, cell area, or epidermal thickness. In experiment 2, skin extract was prepared from the skin of corn oil injected and non injected fathead minnows as in experiment 1 to determine whether corn oil had an effect on the epidermal club cell alarm substance concentration. The treatments showed no significant differences in observed anti-predator behaviour, including change in shelter use, dashing and freezing. In experiment 3, fathead minnows were exposed to either a single intraperitoneal injection of cortisol or corn oil. The purpose of this experiment was to determine whether cortisol, a known immunosuppressant, had an effect on epidermal club cell investment. Fathead minnows exposed to a single cortisol injection had significantly reduced respiratory burst activity of kidney phagocytes indicating that there was suppression of the innate immune system. Furthermore, cortisol treated fathead minnows showed significantly lower numbers of epidermal club cells. The treatments had no effect on individual epidermal club cell area, epidermal thickness and serum cortisol levels after 12 days. The results from this experiment suggest that pharmacological cortisol injections in fathead minnows have a suppressive effect on the fish innate immune system. Furthermore, the findings that cortisol induced immunosuppression also influences epidermal club cell investment provides support for the hypothesis that epidermal club cells may function as part of the fish immune system.

Made available in DSpace on 2014-06-11T19:30:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-10-26Bitstream added on 2014-06-13T20:21:11Z : No. of bitstreams: 1 abreu_js_dr_jabo.pdf: 580857 bytes, checksum: 7cd4b8b96649d30421df9e3fae023302 (MD5) / Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) / O sistema imune é dividido em duas partes que se complementam: o sistema imune inato (não específico) e o adquirido (específico). O sistema imune inato é considerado como a primeira linha de defesa e inclui barreiras físicas (pele e muco) e componentes celulares e moleculares (macrófagos, células killer e fatores solúveis de imunidade, como lisozima, proteínas do sistema complemento, peptídeos antimicrobianos, entre outros). No processo de criação, o sistema imune dos peixes pode ser prejudicado por vários fatores, mas efeitos benéficos podem ser observados com o uso de substâncias conhecidas como imunoestimulantes. Dentre os imunoestimulantes estudados, os glicanos vêm sendo amplamente utilizados como importantes indutores de mecanismos não específicos de defesa. Em algumas espécies de peixes tropicais, como o pacu (Piaractus mesopotamicus) e matrinxã (Brycon amazonicus), estudos observaram o papel da vitamina C como imunoestimulante avaliando a hematologia dos peixes como indicador das alterações imunológicas. O número de leucócitos e de trombócitos é considerado importante indicador de seu estado de saúde. Entretanto, não são conhecidos estudos que avaliem outros parâmetros imunológicos bem como os efeitos do glicano nas respostas imunológicas inatas de peixes tropicais. O pacu, por ser uma espécie onívora, de fácil cultivo e adaptada a ampla variedade de alimentos, tem grande importância na piscicultura brasileira e por esta razão foi escolhido como modelo experimental nesta pesquisa. O objetivo deste trabalho foi testar, inicialmente, técnicas para avaliação de alguns mecanismos inatos de defesa (atividade respiratória de leucócitos e concentração e atividade de lisozima) nesta 37 espécie tropical, cujos resultados são apresentados no capítulo 2 desta tese. Este estudo registrou essas respostas imunes inatas no pacu... / The immune system is divided in two parts that complement each other: the specific and non-specific immune system. The non-specific immune system is the primary defence line and includes natural barriers (skin and mucus) and cellular and molecular components (macrophages, natural killer cells, immune soluble factors, like lysozyme, complement, antimicrobials peptides, among others). In all farming, the immune system of fish may be damaged by many factors, but the benefic effects may be observed using immunostimulants. It has been of common knowledge that glucans are the most known of them and are being used like nonspecific defence mechanisms stimulants. In some tropical fish species, such as pacu (Piaractus mesopotamicus) and matrinxã (Brycon amazonicus), studies evaluated vitamin C effect as immunostimulant, considerating the fish hematology as immune alterations indicator. The leucocytes and trombocytes number is considerated an important health indicator. However, there are no studies evaluating different immune parameters and the glucan effect in innate immune response of tropical fish. The pacu is an omnivore specie of great importance to Brazilian fish farming. For this reason, it was chosen as experimental model in this research. The aim of this work was to test some techniques for evaluation of some defence innate mechanisms (burst oxidative and lysozyme) in this tropical specie, whose results are showed in chapter 2 of this work. This research recorded these immune responses of pacu and established adequate methodologies for its determination. After, this study evaluated the effect of glucan, administered to intraperitoneal injection and incorporated in the diet, in stimulation of some immune systems components of pacu. Besides, it was also verified 39 the stress responses after the capture of pacu fed with diets supplemented with glucan ...(Complete abstract, click electronic access below)

Orientador: Elisabeth Criscuolo Urbinati / Banca: Cleni Mara Marzocchi Machado / Banca: Luis Henrique Montrezor / Banca: João Batista Kochenborger Fernandes / Banca: Flávio Ruas de Moraes / Resumo: O sistema imune é dividido em duas partes que se complementam: o sistema imune inato (não específico) e o adquirido (específico). O sistema imune inato é considerado como a primeira linha de defesa e inclui barreiras físicas (pele e muco) e componentes celulares e moleculares (macrófagos, células killer e fatores solúveis de imunidade, como lisozima, proteínas do sistema complemento, peptídeos antimicrobianos, entre outros). No processo de criação, o sistema imune dos peixes pode ser prejudicado por vários fatores, mas efeitos benéficos podem ser observados com o uso de substâncias conhecidas como imunoestimulantes. Dentre os imunoestimulantes estudados, os glicanos vêm sendo amplamente utilizados como importantes indutores de mecanismos não específicos de defesa. Em algumas espécies de peixes tropicais, como o pacu (Piaractus mesopotamicus) e matrinxã (Brycon amazonicus), estudos observaram o papel da vitamina C como imunoestimulante avaliando a hematologia dos peixes como indicador das alterações imunológicas. O número de leucócitos e de trombócitos é considerado importante indicador de seu estado de saúde. Entretanto, não são conhecidos estudos que avaliem outros parâmetros imunológicos bem como os efeitos do glicano nas respostas imunológicas inatas de peixes tropicais. O pacu, por ser uma espécie onívora, de fácil cultivo e adaptada a ampla variedade de alimentos, tem grande importância na piscicultura brasileira e por esta razão foi escolhido como modelo experimental nesta pesquisa. O objetivo deste trabalho foi testar, inicialmente, técnicas para avaliação de alguns mecanismos inatos de defesa (atividade respiratória de leucócitos e concentração e atividade de lisozima) nesta 37 espécie tropical, cujos resultados são apresentados no capítulo 2 desta tese. Este estudo registrou essas respostas imunes inatas no pacu ...(Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The immune system is divided in two parts that complement each other: the specific and non-specific immune system. The non-specific immune system is the primary defence line and includes natural barriers (skin and mucus) and cellular and molecular components (macrophages, natural killer cells, immune soluble factors, like lysozyme, complement, antimicrobials peptides, among others). In all farming, the immune system of fish may be damaged by many factors, but the benefic effects may be observed using immunostimulants. It has been of common knowledge that glucans are the most known of them and are being used like nonspecific defence mechanisms stimulants. In some tropical fish species, such as pacu (Piaractus mesopotamicus) and matrinxã (Brycon amazonicus), studies evaluated vitamin C effect as immunostimulant, considerating the fish hematology as immune alterations indicator. The leucocytes and trombocytes number is considerated an important health indicator. However, there are no studies evaluating different immune parameters and the glucan effect in innate immune response of tropical fish. The pacu is an omnivore specie of great importance to Brazilian fish farming. For this reason, it was chosen as experimental model in this research. The aim of this work was to test some techniques for evaluation of some defence innate mechanisms (burst oxidative and lysozyme) in this tropical specie, whose results are showed in chapter 2 of this work. This research recorded these immune responses of pacu and established adequate methodologies for its determination. After, this study evaluated the effect of glucan, administered to intraperitoneal injection and incorporated in the diet, in stimulation of some immune systems components of pacu. Besides, it was also verified 39 the stress responses after the capture of pacu fed with diets supplemented with glucan ...(Complete abstract, click electronic access below) / Doutor

Les troubles bipolaires (TB) sont des troubles chroniques, multifactoriels et multi-systémiques avec une morbidité, mortalité et fardeau socio-économique très élevée. Mieux comprendre le fond génétique et les facteurs environnementaux déclencheurs permettra d'améliorer le diagnostic et la prise en charge thérapeutique. La dysimmunité semble être parallèle à l'apparition, la progression ainsi qu'au développement de comorbidités psychiatriques et somatiques. L'inflammation chronique et l'activation de la microglie sont des mécanismes liant potentiellement l'infection et le stress pendant l'enfance avec la survenue d'un TB, en particulier la plus sévère forme d'apparition précoce. Les variants génétiques des récepteurs de reconnaissance de motifs moléculaires, première ligne de défense immunitaire, pourraient participer à la résilience/vulnérabilité aux facteurs de risque environnementaux tôt au cours de la vie. Nous avons exploré cette possibilité en analysant les associations génétiques entre des acteurs centraux de la réponse immunitaire innée, TLR2, TLR4 et NOD2 et les TB, en testant aussi l'hétérogénéité entre les sous-groupes d'apparition précoce et tardive. Étant donné que l'activation de ces voies augmente la production d'oxyde nitrique (NO) et en vue de son rôle dans l'inflammation, le stress oxydatif et la neurotransmission ainsi que son dysfonctionnement dans les TB et suicide, nous avons analysé simultanément des variants génétiques des trois isoformes de NO-synthase (NOS) chez les patients avec antécédents de conduites suicidaires. Nous avons trouvé que les génotypes TLR4 rs1927914 AA et rs11536891 TT sont significativement plus fréquents chez les patients tandis que l'allèle NOD2 rs2066842 T est significativement plus fréquent chez les témoins suggérant une vulnérabilité génétique à l'exposition aux pathogènes dans les TB. En plus, l'association avec TLR4 est restreinte au sous-groupe à début précoce et le génotype TLR2 rs3804099 TT est significativement plus fréquent chez les patients à début précoce qu'à début tardif, confortant l'hypothèse que les facteurs génétiques ont un poids plus important dans les TB d'apparition précoce. Des associations entre NOS1, NOS2 et NOS3 et TB n'ont pas été observées mais NOS3 rs1799983 T à l'état homozygote a été associé aux tentatives de suicide violentes, chez les patients à début précoce, apportant une preuve supplémentaire de l'implication de variants de NOS3 (endothéliale) dans les conduites suicidaires. En étudiant l'effet de l'interaction entre les variants génétiques de TLR2/TLR4 et les antécédents d'abus dans l'enfance mesurées par le Childhood Trauma Questionnaire (CTQ) sur l'âge de début des TB, nous avons observé un effet combiné du génotype TLR2 rs3804099 T avec antécédents d'abus sexuels sur la détermination d'un âge plus précoce d'apparition des TB. Les effets de l'abus sexuel dans l'enfance sur l'âge d'apparition des TB peuvent être accrus chez les porteurs du génotype TLR2 rs3804099 TT potentiellement médié par des voies liés aux réponses inflammatoires. Nos résultats sont en faveur d'un modèle « multiple-hit » dans lequel une vulnérabilité génétique liée au système immunitaire contribuerait à des réponses anormales aux infections périnatales baissant le seuil pour les effets adverses des stress ultérieurs. La confirmation de ces données par réplication dans des cohortes indépendantes est nécessaire. La caractérisation de la sévérité de la maladie, des phénotypes immunitaires et du type, intensité, fréquence et moment de survenue des stress doivent être prévues dans les futures études. Le développement de modèles animaux pourra aussi permettre de mieux comprendre les mécanismes impliqués à travers la manipulation expérimentale de la génétique et des conditions environnementales. Ces approches pourraient permettre l'identification de biomarqueurs et de signes cliniques prodromiques bien que des nouvelles stratégies de prévention et des cibles thérapeutiques. / Bipolar disorders (BD) are chronic, multisystem and multifactorial disorders with significant lifetime morbidity, mortality and socioeconomic burden. Understanding its genetic background and triggering environmental factors should improve diagnosis and therapeutic management. Immune dysregulation seems to parallel its onset and progression as well as the development of psychiatric and other medical comorbidities. Chronic low-grade inflammation and microglia activation are thought to be important mechanisms linking infection and childhood trauma with BD, in particular the more severe early-onset subform. Genetic variations in pattern-recognition receptors, the first line of immune defence, may thus participate in one's resilience/vulnerability to environmental exposures, particularly early in life. We explored that possibility by investigating genetic associations between central players of innate immune protection, TLR2, TLR4 and NOD2 and BD, taking into account the potential genetic heterogeneity between the early- and late-onset subgroups. Given that the activation of these pathways increases the production of nitric oxide (NO), a potent innate immune effector, by immune cells and taking into consideration the role of NO in oxidative stress and neurotransmission as well as its dysfunction in both BD and suicide, we simultaneously analysed variants of the three isoforms of nitric oxide synthase (NOS) genes with suicidal behaviour in BD. We found TLR4 rs1927914 AA and rs11536891 TT genotypes to be significantly more prevalent in patients than in controls. We also found that NOD2 rs2066842 T allele carrier state may confer some protection against BD as it was more prevalent in controls. These results suggest a genetic vulnerability to pathogen exposure in BD. We also found that the referred association with TLR4 was restricted to the early-onset subgroup and that a TLR2 genotype (rs3804099 TT) was significantly more prevalent in early- than in late-onset patients comforting the hypothesis that genetic factors are of greater importance in early-onset BD. While associations between NOS1, NOS2 and NOS3 with BD were not observed, NOS3 rs1799983 T in homozygous state was associated with violent suicide attempts, seemingly restricted to the early-onset BD bringing further evidence for the potential involvement of endothelial NOS genetic variants in the susceptibility to suicidal behaviour. By investigating the effect of potential interaction between TLR2 and TLR4 and childhood abuses as measured by the Childhood Trauma Questionnaire (CTQ) on the age at onset of BD, we observed a combined effect of TLR2 rs3804099 TT genotype and childhood sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve. The effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways.Altogether the present results comfort a multiple-hit model in which immune-related genetic susceptibility contributes to abnormal responses to perinatal infectious insults establishing a lower threshold for subsequent stress-triggered events. Confirmation by replication in independent BD cohorts is warranted. Characteristics of illness severity, immune phenotypes and detailed annotation of type, intensity, frequency and time of stress exposure should be documented in future studies involving large cohorts. Additionally, the development of animal models in conformity with the presented model would facilitate better understanding of the precise mechanisms involved by allowing specific manipulation of genetic and environmental conditions. These approaches may allow the identification of both biological and clinical prodromal manifestations and consequently lead to preventive strategies and novel therapeutic targets.

Em artrópodes o sistema imune inato contribui para a adaptação de animais como os escorpiões à diferentes ambientes. Esse sistema é composto por mecanismos capazes de agir contra injúrias e a ação de microrganismos e entre esses mecanismos estão os peptídeos antimicrobianos (PAMs). O objetivo deste trabalho foi identificar PAMs presentes na hemolinfa de Tityus serrulatus. Para isso sua hemolinfa foi extraída e separados os hemócitos e plasma, em seguida fracionamos em 3 concentrações de acetonitrila em TFA 0,05% (05, 40 e 80%). Estas frações foram submetidas a uma cromatografia liquida de alta eficiência (CLAE) e os picos foram avaliados quanto a sua ação antimicrobiana e hemolítica. Foram identificadas 16 frações que apresentam atividade antimicrobiana. Uma das frações com atividade antimicrobiana, presente nos hemócitos apresentou similaridade com defensina descrita em carrapatos da espécie Ixodes scapularis. Essa fração possui aproximadamente 3486 Da, não apresenta atividade hemolítica e foi denominada como Serrulina. / In arthropods, its innate immune system contributes to the adaptation of animals like scorpions to different environments. This system consists of mechanisms that act avoiding injuries and against the action of microorganisms, among these mechanisms are antimicrobial peptides (AMPs). The aim of this study was to identify AMPs, present in the hemolymph of Tityus serrulatus. The hemolymph was extracted and then we separated hemocyte and plasma. The samples were fractionated in different concentrations of acetonitrile in TFA 0.05% (05, 40 and 80%). These fractions were subjected to high-performance liquid chromatography (HPLC) and the peaks obtained were evaluated for its antimicrobial and hemolytic action. We found sixteen fractions with antimicrobial activity. One of the fractions with antimicrobial activity, present in hemocytes, is similar with a defensin described in ticks, Ixodes scapularis. This fraction has about 3486 Da, has no hemolytic activity and was named as Serrulina.