Samsum ant venom modulates the immune response and redox status at the acute toxic dose in vivo

Background:Ant venoms express surface molecules that participate in antigen presentation involving pro- and anti-inflammatory cytokines. This work aims to investigate the expression of MHC-II, CD80 and CD86 on the polymorphonuclear cells (PMNs) in rats injected with samsum ant venom (SAV).Methods:Rats were divided into three groups - control, SAV-treated (intraperitoneal route, 600 μg/kg), and SAV-treated (subcutaneous route, 600 μg/kg). After five doses, animals were euthanized and samples collected for analysis.Results:The subcutaneous SAV-trated rats presented decreased levels of glutathione with increased cholesterol and triglyceride levels. Intraperitoneal SAV-treated animals displayed significantly reduced concentrations of both IFN-γ and IL-17 in comparison with the control group. However, intraperitoneal and subcutaneous SAV-treated rats were able to upregulate the expressions of MHC-II, CD80 and CD86 on PMNs in comparison with the control respectively. The histological examination showed severe lymphocyte depletion in the splenic white pulp of the intraperitoneal SAV-injected rats.Conclusion:Stimulation of PMNs by SAV leads to upregulation of MHC-II, CD 80, and CD 86, which plays critical roles in antigen presentation and consequently proliferation of T-cells. Subcutaneous route was more efficient than intraperitoneal by elevating MHC-II, CD80 and CD86 expression, disturbing oxidative stability and increasing lipogram concentration.

O feto é um ser alogênico de sucesso / The fetus is a successful allogeneic being

O feto é um ser alogênico de sucesso. O feto é um aloenxerto natural bem tolerado pelo organismo materno. Vários fatores contribuem para a tolerância materna ao feto: 1. O útero é um local do corpo imunologicamente privilegiado, protegido por uma barreira tecidual não imunogênica; 2. A promoção de uma resposta imunossupressora local pela mãe: a. A molécula HLA-G do MHC de classe Ib, expressa nas células da placenta, impede que as células NK matem a placenta; b. A catabolização do aminoácido essencial triptofano pela placenta impede que as células T da mãe tenham acesso ao feto; c. A secreção das citocinas TGF-ß, IL-4 e IL-10, pelo epitélio uterino e trofoblasto, tende a suprimir as respostas das células T da mãe; d. A secreção das citocinas TGF-ß e IL-10, pelas células T reguladoras, também inibe as respostas de células T maternas.(AU)

The fetus is a successful allogeneic being. The fetus is a natural allograft well tolerated by the maternal organism. Several factors contribute to maternal fetal tolerance: 1. The uterus is an immunologically privileged body site, protected by a non-immunogenic tissue barrier. 2. Promoting a local immunosuppressive response by the mother: a. The MHC class Ib HLA-G molecule, expressed on placental cells, prevents NK cells from killing the placenta; b. The catabolization of the essential amino acid tryptophan by the placenta prevents the mother's T cells from accessing the fetus; c. Secretion of TGF-ß, IL-4 and IL-10 cytokines by the uterine and trophoblast epithelium tends to suppress the T-cell responses of the mother; d. Secretion of TGF-ß and IL-10 cytokines by regulatory T cells also inhibits maternal T cell responses.(AU)

Frequência dos alelos do sistema antígeno leucocitário humano em doadores e pacientes pré-transplante de medula óssea / Human leukocyte antigen alleles frequency in donors and pre-transplant patients from bone marrow

Introdução: O estudo da frequência dos alelos detectados nos doadores e pacientes previamente selecionados para o transplante de medula óssea permite estimar as reais chances de um paciente em lista de espera encontrar um doador com antígeno leucocitário humano (Human leucocite antigen; HLA) idêntico não relacionado, além de facilitar e direcionar o planejamento do crescimento do Registro Nacional deDoadores de Medula Óssea. Objetivo: Descrever e analisar afrequência dos alelos do sistema HLA de classe I (HLA-A, -B e -C) e classe II (HLA-DRB1 e -DQB1) de doadores e pacientespré-transplante de medula óssea, do Hospital de Câncer deBarretos. Material e Métodos: Um total de 98 amostras dedoadores e 106 amostras de pacientes foi selecionado comtipificações em alta resolução, no período de outubro de 2014a outubro de 2015. As amostras foram tipificadas para os lociHLA-A, -B, -C, -DR e -DQ. Resultados: O predomínio daraça branca reflete a composição étnica do Brasil. As doençasde base mais comuns que levaram o paciente ao transplanteforam a leucemia aguda linfóide (34%) e mieloide (29,2%).Os grupos alélicos mais frequentes nos registros foramA*02, A*24, A*03, A*01, B*35, B*44, C*07, DQB1*03,DQB1*05, DQB1*06, DRB1*01 e DRB1*13. Conclusão: Osresultados encontrados reforçam a importância de conhecero perfil demográfico e imunogenético das regiões do Brasil,contribuindo desta forma na redução do tempo de espera porum doador histocompatível

Introduction: The study of allele frequencies detected in donors and patients previously selected for bone marrow transplantation allows us to estimate the real chances of a patient in the waiting list to find an Human leucocite antigen (HLA) identical unrelated donor. This also facilitates and drives the growth planning of the Brazilian Registry of planning Bone Marrow Transplantation (REDOME). Objective: Describe and analyze the frequency of HLA class I alleles (HLA-A*, -B* and ­C*) and class II alleles, genotypes, and haplotypes(HLA-DRB1* and -DQB1*) from donors and bone marrowpre-transplant patients. Material and Methods: A total of 98donor samples and 106 patient samples were selected withhigh resolution typing, from October 2014 to October 2015.Samples were typed for HLA-A, -B, -C, -DR and -DQ loci.Results: The predominance of the white race reflects theethnic composition of Brazil. The most common underlyingdiseases that led to transplantation patients were acutelymphoid leukemia (34%) and myeloid (29.2%). The mostfrequent allelic groups were A*02, A*24, A*03, A*01, B*35,B*44, C*07, DQB1*03, DQB1*05, DQB1*06, DRB1*01 andDRB1*13. Conclusion: The results reinforce the importanceof understanding the demographic and immunogenic profilefrom Brazilian Regions. This can contribute to the reduction ofwaiting time for a histocompatible donor.

Avaliação fenotípica e genotípica dos genes HLA LOCI (A*, B*, C*, DRB1* e DQB1*) dos doadores e pacientes pré-TMO do hospital de câncer de Barretos-SP / Phenotipic evaluation and genotypic genes HLA LOCI (A*, B*, C*, DRB1* and DQB1*) donor and patients in pre-BMT Barretos cancer hospital São Paulo state

Objetivo ­ Descrever e analisar a frequência dos alelos, genótipos e haplótipos HLA de classe I (HLA-A, -B e -C) e classe II (HLA-DRB1 e -DQB1) dos pacientes na fase pré-transplante de medula óssea, genotipados no laboratório de Imunogenética-HLA do Hospital de Câncer de Barretos. O estudo da frequência dos alelos detectados nos doadores e pacientes previamente selecionados para o transplante de medula óssea permite estimar as reais chances de um paciente em lista de espera encontrar um doador HLA idêntico não relacionado, além de facilitar e direcionar o planejamento do crescimento do Registro. Métodos ­ Os dados foram obtidos através da técnica de amplificação em cadeia de polimerase e para a genotipagem dos alelos dos genes A, B, C, DRB1 e DQB1 foi empregado o método de sequenciamento de nucleotídeos. Resultados ­ Entre outubro de 2014 a outubro de 2015 foram tratados 106 pacientes e 98 doadores de medula óssea cadastrados. As doenças de base mais comuns que levaram o paciente ao transplante foram as leucemias agudas linfóides (34%) e mielóides (29,2%). A caracterização imunogenética dos pacientes na fase pré-transplante de medula óssea mostrou um total de 19 alelos do loco A, 24 do loco B, 14 do loco C, 5 do loco DQ, 13 do loco DR; já nos dadores de medula óssea, 16 alelos do loco A, 25 do loco B, 13 do loco C, 5 do loco DQ e 12 do loco DR. Conclusão ­ Os grupos alélicos mais frequentes nos registros foram A*02, A*24, A*03, A*01, B*35, B*44, C*07, DQB1*03, DQB1*05, DQB1*06, DRB1*01 e DRB1*13. Apenas o conhecimento da frequência do tipo HLA específico do paciente na população não garante que ele encontre o doador compatível, é necessário também que o portador desse tipo HLA se encontre cadastrado no REDOME como doador voluntário.

Objective ­ Describe and analyze the frequency of the alleles, genotypes, and haplotypes HLA class I (HLA-A*, -B* and ­C*) and class II (HLA-DRB1* and -DQB1*) of patients in the bone marrow before transplantation phase genotyped in laboratory of ImmunogeneticsHLA Barretos Cancer Hospital. The study detected the frequency of alleles in patients and donors selected for bone marrow transplantation allows to estimate the real chances of a patient on the waiting list to find an unrelated HLA-identical donor, and to facilitate and direct the Brazilian Registry of planning Bone Marrow Transplantation (REDOME). Methods ­ The data were obtained by amplification using polymerase chain, and for genotyping the alleles of the genes A, B, C, DRB1 and DQB1 was employed nucleotide sequencing method. Results ­ From October 2014 to October 2015 were treated 106 patients and 98 donors registered bone marrow. The most common underlying diseases that led to transplantation patients were acute lymphoid leukemias (34%) and myeloid (29.2%). Immunogenetics characterization of patients in the bone marrow pre-transplant phase showed a total of 19 alleles at the A loci, 24 in B loci, 14in C loci, 5 in DQB1 loci and 13 in DRB1 loci; already in the bone marrow donors, 16 alleles at the A loci, 25 in B loci, 13 in C loci, 5 in DQB1 loci and 12 in DRB1 loci. Conclusion ­ The most frequent allelic groups were A*02, A*24, A*03, A*01, B*35, B*44, C*07, DQB1*03, DQB1*05, DQB1*06, DRB1*01 and DRB1*13. Knowledge of the frequency of HLA genes patients are not enough to find a compatible donor, it is necessary that the record contains the donor available

Avaliação da qualidade do sono em estudantes de Biomedicina / Sleep quality assessment in Biomedicine students

Objetivo ­ Avaliar a qualidade de sono e a sonolência diurna excessiva nos alunos de Biomedicina da Universidade Paulista ­ Sorocaba, comparando-as entre os alunos dos períodos diurno e noturno, além de identificar o cronotipo desses alunos. Métodos ­ Submeter 100 estudantes, de ambos os gêneros, com idade entre 18 e 52 anos, ao questionário de Qualidade de Sono de Pittsburgh (PSQI), à Escala de Sonolência de Epworth (ESE) e ao Questionário de Matutinidade/Vespertinidade. Resultados ­ Verificou-se que 61,5% dos alunos da manhã apresentaram má qualidade de sono, 51,3% sonolência diurna excessiva e 61,5% cronotipo indiferente; enquanto, 65,6% dos alunos da noite apresentavam má qualidade de sono, 57,4% sonolência diurna excessiva e 72,1% cronotipo indiferente. Conclusão ­ A má qualidade de sono foi mais frequente no período noturno, porém, mais relevante no período diurno. Ambos os períodos indicaram relevante prevalência de sonolência diurna excessiva, sem apresentar, contudo, uma preferência por um turno específico para realizarem suas atividades, o que foi observado por meio da maior frequência do cronotipo indiferente.

Objective ­ To evaluate the sleep quality and the presence of excessive daytime sleepiness in Biomedicine students from Universidade Paulista ­ Sorocaba; 2) to compare the results obtained from students enrolled in different periods of day or night; 3) to identify the best period of performance from these students. Methods ­ A hundred students from both genders, aged over 18 years, filled three questionnaires: Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS) and Questionnaire morningness/eveningness. Afterward, all the data was analyzed and presented accordingly. Results ­ It was found that 61.5% of the morning students presented poor sleep, 51.3% excessive daytime sleepiness, and 61.5% indifferent chronotype; while 65.6% of night's students presented poor sleep, 57.4% excessive daytime sleepiness, and 72.1% indifferent chronotype. Conclusions ­ Poor sleep was more frequent among night's students. In contrast, the worst quality of sleep was more relevant among morning's student. Students in both periods presented excessive daytime sleepiness and indifferent chronotype.

Actualidad y perspectivas del HLA en el trasplante renal / Actual situation and perspectives of HLA typing in renal transplant

La introducción de la compatibilidad en los antígenos leucocitarios humanos (HLA) en la selección de los injertos para trasplante renal ha mejorado la sobrevida y el pronóstico del órgano trasplantado, a corto y largo plazo. Sin embargo, recientes observaciones sugieren que la importancia relativa de los HLA ha disminuido en décadas recientes. Posibles explicaciones para este fenómeno incluyen la reciente utilización de terapias inmunosupresoras más potentes, una mayor importancia relativa de antígenos no HLA y factores no inmunológicos.

The introduction of compatibility tests for human leukocyte antigens (HLA) in the selection of donors for renal transplant has improved the survival and the prognosis of the transplant itself at both short and long-term periods of time. However, recent observations suggest less importance of HLA typing. Possible explanations for this phenomenon include the recent utilization of more potent immunosuppressive therapies, a greater importance of non HLA antigens, and non immunologic factors.

The role of KIR2DL3/HLA-C*0802 in Brazilian patients with rheumatoid vasculitis

OBJECTIVES: Rheumatoid arthritis is a polygenically controlled systemic autoimmune disease. Rheumatoid vasculitis is an important extra-articular phenotype of rheumatoid arthritis that can result in deep cutaneous ulcers. The objective of this study was to establish a correlation between the frequency of major histocompatibility complex class I/II alleles and killer immunoglobulin-like receptor genotypes in patients with cutaneous rheumatoid vasculitis. METHODS: Using the Scott & Bacon 1984 criteria to diagnose rheumatoid vasculitis and after excluding any other causes such as diabetes, atherosclerosis, adverse drug reactions, infection, and smoking, patients who met the criteria were selected. All of the selected rheumatoid vasculitis patients presented deep cutaneous ulcers. Identification of the major histocompatibility complex class I/II and killer immunoglobulin-like receptor genotypes was performed by polymerase chain reaction assays of samples collected from the 23 rheumatoid vasculitis patients as well as from 80 controls (40 non-rheumatoid vasculitis RA control patients and 40 healthy volunteers). RESULTS: An association between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and cutaneous lesions in rheumatoid vasculitis patients and a correlation between the inhibitor KIR2DL3 and the HLA-C*0802 ligand in rheumatoid vasculitis patients were found. CONCLUSION: An association was found between the presence of the HLA-DRB1*1402 and HLA-DRB1*0101 alleles and the development of cutaneous lesions in rheumatoid vasculitis patients. Additionally, the HLA-C*0802 ligand protects these individuals from developing cutaneous lesions. .

MHC structure and function – antigen presentation. Part 1 / Estrutura do MHC e função – apresentação de antígenos. Parte 1

The setting for the occurrence of an immune response is that of the need to cope with a vast array of different antigens from both pathogenic and non-pathogenic sources. When the first barriers against infection and innate defense fail, adaptive immune response enters the stage for recognition of the antigens by means of extremely variable molecules, namely immunoglobulins and T-cell receptors. The latter recognize the antigen exposed on cell surfaces, in the form of peptides presented by the HLA molecule. The first part of this review details the central role played by these molecules, establishing the close connection existing between their structure and their antigen presenting function.

O cenário no qual ocorre a resposta imune é o da necessidade de fazer frente a uma vasta gama de antígenos diferentes, de fontes patogênicas e não patogênicas. Quando as primeiras barreiras contra infecção e a defesa inata falham, a resposta imune adaptativa entra em campo, para efetuar o reconhecimento dos antígenos, utilizando, para esse fim, moléculas extremamente variáveis, que são as imunoglobulinas e os receptores de células-T. Estes últimos reconhecem o antígeno, exposto na superfície das células como peptídeo apresentado pelas moléculas HLA. A primeira parte desta revisão detalha o papel central dessas moléculas, estabelecendo a conexão que existe entre a estrutura e a função de apresentação de antígenos.

MHC structure and function − antigen presentation. Part 2 / Estrutura do MHC e função − apresentação de antígenos. Parte 2

The second part of this review deals with the molecules and processes involved in the processing and presentation of the antigenic fragments to the T-cell receptor. Though the nature of the antigens presented varies, the most significant class of antigens is proteins, processed within the cell to be then recognized in the form of peptides, a mechanism that confers an extraordinary degree of precision to this mode of immune response. The efficiency and accuracy of this system is also the result of the myriad of mechanisms involved in the processing of proteins and production of peptides, in addition to the capture and recycling of alternative sources aiming to generate further diversity in the presentation to T-cells.

A segunda parte desta revisão trata das moléculas e processos envolvidos no processamento e apresentação dos fragmentos antigênicos ao receptor de célula-T. Apesar de variar a natureza do antígeno apresentado, a classe mais significativa é a das proteínas, as quais são processadas dentro da célula para enfim serem reconhecidas na forma de peptídeos, o que confere um grau extraordinário de precisão a essa forma de resposta imune. A eficiência e a precisão desse sistema se devem também à miríade de mecanismos envolvidos no processamento de proteínas e produção de peptídeos, além da captura e reciclagem de fontes alternativas de antígenos com o objetivo de gerar ainda maior diversidade na apresentação à célula-T.

Microquimerismos en la enfermedadde Alzheimer y la demencia frontotemporal / Microchimerism in Alzheimer’s disease and frontotemporal dementia

Resumen: las enfermedades neurodegenerativas constituyen un problema global de salud pública que tiende a incrementarse. En la búsqueda de alternativas terapéuticas frente a estas afecciones aparecen los microquimerismos fetomaternales (células fetales en estados inmaduros de diferenciaciónadquiridas durante el embarazo) que, al tratarse de células madre, suponen una opción terapéutica similar a la terapia celular. Estudios recientes han demostrado el papel protector de los microquimerismos en la enfermedad de Alzheimer y la esclerosis múltiple; sin embargo, al tratarse de células provenientes de otro organismo surge la posibilidad de que induzcan una respuesta inmune que lleve a la aparición o potenciación de los procesos inflamatorios propios de las enfermedadesneurodegenerativas. De acuerdo con lo anterior, diversos estudios han sugerido un papel de los microquimerismos en el desarrollo de enfermedades autoinmunes. El esclarecimiento de las características, funciones, vías de ingreso, localización e interacciones de los microquimerismos con el sistema inmune del organismo hospedero es relevante en la medida en que pueden guiar el desarrollode tratamientos frente a este tipo de enfermedades. En esta revisión se describen algunos de estos aspectos relevantes.

Abstract: neurodegenerative diseases represent a major and increasing public health problem around the world. In the search for therapeutic alternatives against these conditions, feto-maternal microchimerisms (immature fetal cells acquired during pregnancy) appear as a possible therapeutic option similar to stem cell therapy. In fact, several studies have found that the microchimerisms play a protective role against Alzheimer´s disease and multiple sclerosis. Nonetheless, given the fact that the microchimerisms are ®foreign cells¼, they could induce an immune response, leading to the apparition or exacerbation of the inflammatory responses characteristic of neurodegenerative diseases.According to this, several studies have suggested a role for microchimerisms in the development of autoimmune diseases. The elucidation of characteristics, functions, ways of acquisition, paths of entry, localization, and interactions between microchimerisms and the immune system of the host can serve as a guide towards the development of a treatement against these disease. In this review, some of these important aspects are described.

Entre o campo e o laboratório: a dinâmica de produção de conhecimento no Ambulatório de Menopausa do Caism/Unicamp / Between the country and the laboratory: the dynamics of the production of knowledge at the Menopause Outpatients Clinic at Caism, Unicamp

Este estudo investiga as práticas de produção de conhecimento sobre a menopausa no Caism/Unicamp, centro de referência para políticas públicas em saúde da mulher. Foram realizadas observações de consultas ginecológicas, entrevistas com mulheres e médicos e observação de reuniões de apoio psicológico, buscando identificar os discursos que circulam no lugar e o processo de alistamento de diferentes atores para que os conhecimentos ali produzidos alcancem credibilidade e “viajem” além dos limites do hospital-escola, tornando-se “universais”. A análise baseia-se nos “estudos localistas”, alinhados aos estudos sociais de ciência e tecnologia.

This study investigates the practices involved in the production of knowledge about menopause at Caism, Unicamp, a reference center for public policies for women’s health. Gynecological appointments and psychological support meetings were observed, and women and doctors were interviewed in order to identify what discourse circulates there and how different actors are brought in to ensure that the knowledge produced attains credibility and “travels” beyond the boundaries of the teaching hospital to become “universal”. The analysis is based on localized studies aligned with social studies of science and technology.

Hallazgo de patrones para péptidos-vacuna con capacidad de acople universal en moléculas de HLA-II / Identification of patterns for peptide-vaccines in universal capacity coupling HLA-II molecules / Identificagáo de padroes para peptídeos-vacina com capacidade de acoplamento universal em moléculas HLA-II

Partiendo del alineamiento múltiple de secuencias proteicas humanas obtenidas de las bases de datos del National Center of Biotechnology Information (NCBI) y su posterior análisis espacial tridimensional, se estableció la existencia de un patrón de acople universal para péptidos presentados por las moléculas de histocompatibilidad HLA-II (DR, DP y DQ), siendo una base para el diseño de vacunas proteicas. Estos patrones espaciales fueron claramente exhibidos por los residuos altamente conservados de los tres tipos de moléculas de HLA-II. La aplicación de este nuevo hallazgo permitió diseñar péptidos con mejores valores de acople péptido-HLA-II, que los generados por el péptido de acople universal conocido como CLIP (class Il-associated invariant chain peptide).

Starting from the multiple alignment of human protein sequences obtained from the NCBI database (National Center of Biotechnology Information) and subsequent three-dimensional spatial analysis, the existence of a pattern of universal coupling to peptides presented by MHC molecules HLA-II (DR, DP and DQ) was established, being a basis for the design of protein vaccines. These spatial patterns were clearly exhibited by highly conserved residues of the three kinds of HLA-II molecules. The application of this new finding made it possible to design peptides with better Peptide -HLA-II coupling values than those generated by the universal coupling peptide called CLIP (class II-associated invariant chain peptide).

FA partir do alinhamento múltiplo de sequéncias de proteínas humanas obtidas a partir das bases de dados do NCBI (National Center of Biotechnology Information) e análise espacial tridimensional subsequente, estabeleceu-se a existéncia de um padráo de acoplamento universal para peptídeos apresentados pelas moléculas de histocompatibilidade HLA-II (DR, DP e DQ), sendo uma base para o desenho de vacinas proteicas. Estes padroes espaciais foram claramente exibidos pelos residuos altamente conservados dos trés tipos de moléculas de HLA-II. A aplicagáo deste novo achado permitiu desenhar peptídeos com melhores valores de acoplamento peptídeo-HLA-II, do que aqueles gerados pelo peptídeo de acoplamento universal conhecido como CLIP (classe II-peptídeo associado a cadeia invariante).

A human astrocytoma cell line is highly susceptible to infection with Trypanosoma cruzi

Astrocytes play a vital role in neuronal protection, homeostasis, vascular interchange and the local immune response. Some viruses and parasites can cross the blood-brain barrier and infect glia. Trypanosoma cruzi, the aetiological agent of Chagas disease, can seriously compromise the central nervous system, mainly in immune-suppressed individuals, but also during the acute phase of the infection. In this report, the infective capacity of T. cruzi in a human astrocyte tumour-derived cell line was studied. Astrocytes exposed to trypomastigotes (1:10 ratio) produced intracellular amastigotes and new trypomastigotes emerged by day 4 post-infection (p.i.). At day 6 p.i., 93% of the cells were infected. Using flow cytometry, changes were observed in both the expression of major histocompatibility complex class I and II molecules and the chemokine secretion pattern of astrocytes exposed to the parasite. Blocking the low-density lipoprotein receptor on astrocytes did not reduce parasite intracellular infection. Thus, T. cruzi can infect astrocytes and modulate the immune response during central nervous system infection.

Importância das disparidades genéticas nos genes HLA e KIR na resposta de pacientes submetidos ao transplante alogênico de células progenitoras hematopoiéticas para o tratamento de doenças onco-hematologicas / Importance of genetic differences in HLA and KIR genes in the response of patients undergoing allogeneic hematopoietic stem cell transplantation for treatment of onco-hematological diseases

No organismo humano, as moléculas HLA (Human Leukocyte Antigens) são proteínas expressas na superfície da maioria das células nucleadas e são codificadas por genes localizados no braço curto do cromossomo 6 na região do Complexo Principal de Histocompatibilidade (CPH). Essas proteínas são caracterizadas pelo alto grau de polimorfismo, e também faz a ligação com receptores KIR (Immunoglobulin-like Receptors), expressos nas células Natural Killer. Os receptores KIR, que reconhecem moléculas do complexo HLA de classe I, estão entre os principais receptores inibidores dos linfócitos NK. Células infectadas por vírus e células tumorais perdem ou têm diminuída a expressão de moléculas HLA de classe I e, por isso, são eliminadas pela ausência de ligação entre moléculas HLA e receptores KIR inibitórios. Atualmente, muitos estudos têm destacado a importância dos genes KIR e HLA no Transplante de Células Progenitoras Hematopoiéticas (TCPH). O TCPH é o tratamento de escolha para muitas doenças hematológicas e dependem de vários fatores incluindo o estágio da doença, o regime de condicionamento, a fonte de células, o grau de identidade HLA entre doador e receptor e o desenvolvimento da doença do enxerto contra o hospedeiro (DECH). Estudos recentes indicam que a presença de células NK alorreativas no enxerto representa um fator favorável à recuperação de pacientes, uma vez que essas células têm a capacidade de eliminar células tumorais residuais pela ausência ou diminuição da expressão de moléculas HLA e sem a indução da DECH. Também outros fatores podem estar envolvidos na resposta pós-transplante, como a presença e ausência de determinados alelos HLA e genes KIR, os quais podem estar ligados à melhor ou pior resposta pós-transplante.

In the human organism, the HLA (human leukocyte antigens) are proteins expressed on the surface of most nucleated cells and are encoded by genes located on the short arm of chromosome 6 in the region of the Major Histocompatibility Complex (MHC). These proteins are characterized by a high degree of polymorphism, and also make the connection with KIR (Immunoglobulin-like Receptors), expressed in Natural Killer cells. KIR receptors that recognize HLA molecules of class I are among the major inhibitory receptors of NK-cells. Virus infected cells and tumor cells have lost or diminished expression of HLA class I molecules and therefore are eliminated by the absence of binding between HLA molecules and inhibitory KIR receptors. Currently, many studies have highlighted the importance of KIR and HLA genes in Hematopoietic Stem Cell Transplantation (HSCT). HPCT is the treatment of choice for many hematological malignancies and depends on various factors including stage of disease, the conditioning regimen, the source of cells, the degree of identity between donor and recipient HLA and development of chronic graft-versus-host (GVHD). Recent studies indicate that the presence of alloreactive NK cells in the graft is a factor aiding the recovery of patients, since these cells have the ability to eliminate residual tumor cells by the absence or diminution of expression of HLA molecules and without inducing GVHD.

Estudo da influência dos alelos do HLA classe I e II e do polimorfismo dos genes de citocinas na infecção pelo HTLV-1 / Study of the influence of hla class i and ii alleles and the polymorphism of cytokines genes in htlv-1 infection

O vírus linfotrópico para células T humanas (HTLV-1) é o principal agente causador da Paraparesia Espástica Tropical / Mielopatia associada ao HTLV-1 (PET/MAH) e da Leucemia da célula T do Adulto (LTA). [...]Fatores da interação HTLV-1/ hospedeiro estão envolvidos no risco de desenvolver doença. A lesão neurológica na PET/MAH parece ser consequência de uma reação inflamatória, desencadeada pelo reconhecimento de células infectadas por linfócitos T citotóxicos, com consequente liberação de citocinas e lesão medular. OBJETIVO: Identificar marcadores genéticos, que possam ajudar no prognóstico e tratamento dos pacientes portadores do HTLV-1. MÉTODOS: Nas amostras de 117 portadores do HTLV-1 assintomáticos e 171 pacientes com acometimento neurológico em acompanhamento na cidade do Rio de Janeiro, foram realizadas as tipificações dos genes do HLA Classe I e II, dos polimorfismos dos genes das citocinas -308TNF-α,-174IL-6, +874IFN-γ, códon 10 e 25TGF-β1 e -1082 - 819-592IL-10, e a quantificação da carga proviral. Os dados foram organizados em um banco de dados no programa SPSS. As frequências alélicas e genotípicas foram obtidas por contagem direta. O equilíbrio de Hardy-Weinberg foi avaliado para os polimorfismos das citocinas no sitio http://bioinfo.iconcologia.net/ubbweb/SNPStats_web, em relação ao HLA foram utilizadas as ferramentas disponíveis no sítio “Los Alamos HIV database tools”. As comparações entre os grupos foram realizadas através de tabelas de contingência 2x2 (quiquadrado, exato de Fisher e odds ratios), valores de p≤0,05 foram considerados significantes...

The human T cell lymphotropic vírus (HTLV-1) is the main causingagent of Tropical Spastic Paraparesis/HTLV-1 Associated Myelopathy (HAM/TSP) aswell as of Adult T Cell Leukemia (ATL). [...] Factorsrelated to the HTLV-1/host interaction may be involved in the risk of developing thediseases. The neurological lesion in HAM/TSP may be the consequence of aninflammatory reaction, triggered by the recognition of infected cells by cytotoxic Tlymphocytes, followed by the release of cytokines and central nervous system lesion.OBJECTIVE: This work aims to identify genetic markers, which may help in theprognosis and treatment of HTLV-1 patients. Methods: The polymorphism of the HLAClass I and II genes, as well as the TNF-α, IL6, IFN-γ, TGF-β and IL-10 cytokinegenes, and the proviral load were analysed in 117 asymptomatic HTLV-1 carriersand 171 HTLV-1 symptomatic carriers from Rio de Janeiro city. Data were organizedinto a database using SPSS. The Hardy-Weinberg equilibrium was evaluated forcytokine polimorphisms using the site http://bioinfo.iconcologia.net/ubbweb/SNPStats_web. The tools available in the site “Los Alamos HIV database tools” were used toanalyze the HLA polimorphisms. Comparisons between groups were made using 2x2contingency tables (Fisher Exact test/ χ2 and odds ratios), p values p≤0,05 wereconsidered significant...

Importance of immune response genes in hemophilia A

Hemophilia A is a disease caused by a deficiency of coagulation factor VIII resulting from genetic inheritance linked to chromosome X. One treatment option is the administration of plasma or recombinant FVIII. However, some patients develop inhibitors or antibodies against this factor. Inhibitors are alloantibodies that bind to the epitope of factor VIII causing it to be recognized by the immune system as a foreign peptide. This is the most serious complication in hemophilia patients in respect to replacement therapy. Some studies have suggested that genetic factors influence the development of factor VIII inhibitors such as ethnicity, family history, mutations in the factor VIII gene and in genes of the immune system. The aim of this study was to conduct a literature review to assess the influence of genetic factors of immune response genes, especially genes of the major histocompatibility complex and cytokines, which may be related to the development of factor VIII inhibitors in hemophilia A patients. Understanding these risk factors will help to determine future differential treatment in the control and prevention of the development of inhibitors.

Herpes simples: atualização clínica, epidemiológica e terapêutica / Herpes simplex: clinical update, epidemiology and therapeutics

Herpes é uma infecção causada por dois vírus da família Herpesviridae (herpes simples tipos 1 e 2; HSV-1 e HSV-1), que apresenta curso clínico variável e para o qual atualmente não existe cura. As manifestações da infecção por HSV-1 incluem herpes simples orofacial primário e recorrente, enquanto as do HSV-2 em geral ocorrem na forma de herpes simples genital, embora casos de lesões genitais pelo HSV-1 e orais pelo HSV-2 possam ocorrer. As infecções pelo vírus herpes simples (HSV-1 e HSV-2) representam as doenças sexualmente transmissíveis mais comuns a nível global, alcançando uma soroprevalência de 80% em adultos. Nesta revisão da literatura, abordaremos os aspectos clínicos da infecção pelo HSV, incluindo a epidemiologia, etiologia, manifestações clínicas, métodos diagnósticos e tratamento, bem como uma breve descrição da imunogenética da infecção pelo HSV

Herpes is an infection caused by two viruses in the Herpesviridae family (herpes simplex types 1 and 2; HSV-1 and HSV-2), which presents a variable clinical course and for which there is currently no cure. The manifestations of HSV-1 infection include primary and recurrent orofacial herpes simplex, while HSV-2 infection usually manifests in the form of genital herpes simplex, although cases of genital lesions from HSV-1 infection and oral lesions form HSV-2 infection can occur. Infections by the herpes simplex virus (HSV-1 and HSV-2) represent one of the most common sexually transmitted diseases globally, reaching a serum prevalence of 80% in adults. In this review of the literature, we discuss the clinical aspects of HSV infection, including epidemiology, etiology, clinical manifestations, diagnosis and treatment, as well as a brief description of the immunogenetics of HSV infection.

Vaccines for finfish aquaculture: what do we need to know to make them work?

Aquaculture still faces serious economic impacts due to the loss of animals to disease. A conservative estimate of 5 percent losses due to disease means that the finfish aquaculture industry loses over $1 billion annually on a global scale. One proven way to prevent costly disease outbreaks is to vaccinate fish against common or known pathogens. Current vaccination schemes still result in losses, however, and this may be due in part to vaccine design. Vaccines are currently designed using state of the art knowledge of immune responses, which is based primarily on mammalian studies. Just how applicable is this information to fish immunity and vaccine design, however? This review discusses what is currently known for teleost fish about two key processes that drive immune response: antigen presentation and cytokine regulation. In both cases many of the genes known to be involved have been identified; in the case of cytokines recent genome projects have added to the total rapidly in recent years. Most functional studies to date in these areas have focused on gene expression and mRNA levels, due to a lack of available antibodies that are required for studies at the protein level. These studies are confounded by the fact that in many cases the teleost equivalents of single copy mammalian genes are duplicated and are regulated in very different ways. This suggests that vaccines designed around mammalian immunological principles will not be as efficient as they could be. Future research goals for fish immunologists should be to develop the antibodies required for protein level functional studies in order to provide the true understanding of fish immunity that is required for the design of finfish aquaculture vaccines that are truly effective.

Bajo polimorfismo en el sistema de antígenos de leucocitos humanos en población mestiza colombiana / Low HLA polymorphism in Colombian mestizos

Objetivo. Este trabajo tiene como objetivo describir la frecuencia de alelos y de haplotipos de antígenos HLA de clases I y II en población mestiza colombiana. Metodología. Se estudiaron 197 individuos colombianos no emparentados y 157 individuos emparentados que conformaban 53 familias, provenientes de diferentes regiones del país, remitidos para estudios de HLA de clases I y II por el método PCR-SSP a los laboratorios de inmunología del Hospital Militar Central de Bogotá y al Instituto de Referencia Andino. Resultados. El haplotipo HLA-A*24 B*35 DR*04 fue el más frecuente en la población estudiada, lo cual concuerda con otros estudios de mestizos colombianos. Conclusiones. El desequilibrio de Hardy-Weinberg hallado en la población analizada en el presente estudio, debe alertar sobre una eventual reducción en el repertorio de respuesta inmunitaria en los colombianos, lo cual podría ser el origen de una consecuente fragilidad de la población frente a nuevas infecciones que podrían convertirse en epidemias.

Objective: This paper aims to describe the allele frequency and haplotype of HLA class I and II molecules in a Colombian mestizo population. Methodology: HLA class I and II molecules on 197 unrelated Colombian individuals and 157 unrelated individuals making up 53 families from different regions of the country were studied at the Immunology Laboratory at the Military Hospital Central of Bogotá and at the Instituto de Referencia Andino by the PCR-SSP method. Results: The haplotype HLA-A * 24 B*35 DR*04 was the most common, which is consistent with other studies carried out in Colombian mestizos. Conclusions: The Hardy-Weinberg disequilibrium found in the population analyzed in this study should alert on a possible reduction of the immune response repertoire in Colombia, which could be the origin of a consequent fragility of the population in face of new infections that could eventually become epidemic.