Дисертації з теми "Humoral and cellular immunity"
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Tran, Mai Hue. "Investigations of humoral and cellular immune responses directed against MUCI epithelial mucin in ovarian and breast carcinoma /." St. Lucia, Qld, 2002. http://www.library.uq.edu.au/pdfserve.php?image=thesisabs/absthe17997.pdf.
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SILVA, Fabiana Leticia da. "Efeitos da amamentação em camundongos esquistossomóticos na imunidade anti-ovalbumina de descendentes adultos deficientes na produção das citocinas IL-12/IL-23." Universidade Federal de Pernambuco, 2014. https://repositorio.ufpe.br/handle/123456789/17158.
Анотація:
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O contato prévio com o leite de mães esquistossomóticas induziu, em camundongos adultos, potencialização da produção de anticorpos e aumento da capacidade de apresentação de antígeno pelos linfócitos B, em resposta ao antígeno heterólogo ovalbumina (OVA). Considerando a imunização com OVA um modelo vacinal, as reações inflamatórias e a produção de anticorpos em resposta a esse antígeno são importantes para o desenvolvimento de uma imunidade satisfatória do hospedeiro. Nesse sentido, as células Th1 e Th17 são importantes fatores para o desenvolvimento dessas respostas. Dessa forma, os camundongos deficientes na produção de IL-12/IL-23 (12p40 knockout-KO) são predispostos a desenvolverem uma resposta Th2 polarizada, tornando-se menos responsivos às vacinações. Diante disso, o presente trabalho investigou o efeito da amamentação em mães infectadas pelo Schistosoma mansoni sobre as imunidades humoral e celular de camundongos adultos C57BL/6 12p40 KO, em resposta ao modelo vacinal acima citado. Foram avaliados: a cinética das reações de hipersensibilidade in vivo; os níveis plasmáticos das imunoglobulinas IgG1 e IgG2a; a produção das citocinas IFN-γ, IL-17, IL-5, IL-6, IL-10 e TGF- pelas células esplênicas e a reação inflamatória provocada no coxim plantar. Para isso, camundongos machos, deficientes na produção de IL-12 e IL-23 (IL-12p40 KO) e camundongos selvagens (wild-type/WT) foram divididos nos seguintes grupos: camundongos IL-12p40 KO amamentados em mães infectadas (AI IL-12p40 KO); camundongos IL-12p40 KO amamentados em mães sem infecção (NANI IL-12p40 KO); camundongos selvagens amamentados em mães infectadas (AI WT) e camundongos selvagens amamentados em mães sem infecção (NANI WT). Cinquenta por cento dos animais de cada grupo foram imunizados com OVA em adjuvante. Os outros 50% porcento restantes permaneceram sem imunização. No grupo AI WT houve aumentado de produção de IgG2a, IL-5, TGF-β e IL-6, com baixos níveis de IL-17, em comparação ao NANI WT. Nos animais AI IL-12p40 KO, a produção de IgG2a, IL-5 e TGF-β foi mais alta do que o grupo NANI IL-12p40 KO e similar ao grupo AI WT, mas a produção de IL-6 foi mais baixa. O grupo AI WT mostrou intenso infiltrado inflamatório de eosinófilos na reação de hipersensibilidade tardia (RHT), com acentuado edema em comparação com o edema menos intenso e infiltrado inflamatório de neutrófilos do grupo NANI WT. Os animais NANI IL-12p40 KO e AI IL-12p40 KO não apresentam RHT, porém a reação inflamatória no AI IL-12p40 KO foi menos intensa que nos NANI IL-12p40 KO. Em conclusão, o contato com antígenos do parasito, através da amamentação, induziu, no descendente adulto, uma melhor resposta de anticorpo neutralizante, mesmo diante da deficiência na produção de IL-12e IL-23. Nesta condição, embora tenha havido uma notável produção de IL-5, a lactação em mães infectadas atenuou a reação inflamatória, provavelmente através da regulação cruzada entre TGF-β e IL-6, modulando, desta forma, o status de hiperativação desses animais.
The previous contact with mothers milk schistosomiasis induced in adult mice enhancement of antibody production and increased antigen presentation capacity by B lymphocytes in response to the heterologous antigen ovalbumin (OA). Considering immunization with OA one vaccine model, inflammatory reactions and antibody production in response to antigen are important for the development of a suitable host immunity. In this sense, the Th1 and Th17 cells are important factors for the development of these responses. Thus, mice deficient in IL-12/IL-23 (12p40 knockout-KO) are likely to develop a polarized Th2 response, making it less responsive to vaccination. Therefore, the present study investigated the effect of breastfeeding in mothers infected with Schistosoma mansoni on the humoral and cellular adult C57BL/6 12p40 KO in response to vaccination model mentioned above. Were evaluated: the kinetics of in vivo hypersensitivity reactions; plasma levels of IgG1 and IgG2a immunoglobulins; the production of the cytokines IFN-γ, IL-17, IL-5, IL-6, IL-10 and TGF-β by spleen cells and the inflammatory reaction induced in the footpad. To this end, male mice deficient in IL-12 and IL-23 (IL-12p40 KO) and wild-type mice (Wild-type/WT) were divided into the following groups: IL-12p40 KO mice suckled by infected mothers (IL-12p40 KO- SIM); IL-12p40 KO mice suckled by uninfected mothers (IL-12p40 KO); Wild-type mice suckled by infected mothers (SIM) and wild-type mice suckled by uninfected mothers (CONTROL). Fifty percent of animals in each group were immunized with OA in adjuvant. The other 50% remaining percent remained without immunization. In the SIM group was increased production of IgG2a, IL-5, TGF-β and IL-6, IL-17 with low levels compared to CONTROL. In animals IL-12p40 KO-SIM the production of IgG2a, IL-5 and TGF-β was higher than the IL-12p40 KO similar to group SIM, but IL-6 production was lower. The SIM group showed intense inflammatory infiltrate of eosinophils in the delayed hypersensitivity reaction (DTH), with severe edema compared with the less intense edema and inflammatory infiltration of neutrophils CONTROL group. The animals IL-12p40 KO and IL-12p40KO-SIM not have DTH, but the inflammatory reaction in the IL-12p40KO-SIM was less intense than in IL-12p40 KO. In conclusion, contact with parasite antigens, through breastfeeding, induced in adult offspring, better neutralizing antibody response, despite the deficiency in the production of IL-12 and IL-23. In this condition, though there has been a remarkable IL-5 production in lactating mothers infected with attenuated inflammatory response, probably via cross regulation between TGF-β and IL-6 modulate thereby the status of hyperactivation of these animals.
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Santos, Liliane Almeida Carneiro. "Estudo prospectivo sobre a dinâmica da evolução clínica e imunológica da infecção canina por Leishmania (Leishmania) infantum chagasi em área endêmica de leishmaniose visceral no estado do Pará." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-27102016-142051/.
Анотація:
Leishmaniose visceral canina (LVC) é um dos problemas de saúde pública mais importantes da América Latina, pois geralmente precede a doença humana, a leishmaniose visceral americana (LVA), causada pela Leishmania (L.) infantum chagasi. No presente estudo prospectivo analisou-se durante período de dois anos a prevalência, incidência e dinâmica da evolução clínico-imunológica da infecção canina pela L. (L.) i. chagasi em uma coorte de 316 cães mestiços que vivem em área endêmica de LVA no município de Barcarena, Pará, Amazônia Brasil, pelo uso combinado do teste de imunofluorescência indireta (RIFI-IgG) e de hipersensibilidade tardia (RIM), bem como a pesquisa do parasita pela aspiração do linfonodo poplíteo para o diagnóstico da infecção. A reatividade para RIFI e RIM reconheceu três diferentes perfis de resposta imunológica: (I) RIFI (+) / RIM (-) (81 cães), (II) RIFI (-) / RIM (+) (17 cães), e (III) RIFI (+) / RIM (+) (13 cães), proporcionando uma prevalência global da infecção de 35,1% (111/316). Desta forma, a prevalência específica do perfil I (25,6%) foi superior as dos perfis II e III, 5,4% e 4,1%, respectivamente. Além disso, a frequência destes perfis entre 111 cães infectados mostrou que a taxa de 73% do perfil I também foi maior do que os dos perfis II (15,3%) e III (11,7%). A prevalência da infecção de acordo com as faixas etárias revelou que a taxa de 27,5% do grupo ≥1ano <7 anos foi maior do que as de <1 ano (5,3%) e ≥7anos (2,2%), respectivamente. Por outro lado, a incidência global da infecção foi de 5,7% cães / mês (5,4% perfil I, 0,3% perfil II e 0,0% perfil III). No entanto, observou-se uma progressiva diminuição nas taxas de incidência nos seguintes pontos de tempo: seis (3,6% cães / mês), doze (1,7% cães / mês) e vinte e quatro (0,4% cães / mês) meses do estudo. Além disso, a incidência da infecção de acordo com os grupos etários demonstraram que a taxa de 6,6% cães / mês no grupo <1 ano foi maior em comparação com as de 5,3% e 3,3% cães / mês nos grupos ≥1ano e <7 anos, e <1 ano, respectivamente. O diagnóstico parasitológico da infecção foi confirmado em 19% (21/111) no estudo da prevalência, sendo a maioria dos cães (85,7%) do perfil I, onde 61,1% eram sintomáticos e 38,9% assintomáticos. Entre o restante (14,3%), o diagnóstico foi associado ao perfil III, sendo 66,6% assintomáticos e 33,3% sintomáticos. No levantamento da incidência, o diagnóstico foi confirmado em 11% dos cães, todos pertencentes ao perfil I, sendo 60% assintomáticos e 40% sintomáticos. Com relação ao estado clínico de todos os 179 cães diagnosticados infectados durante o período de dois anos, observou-se que entre 145 (81%) cães do perfil I, 82% eram assintomáticos e 18% sintomáticos; entre os 21 (11,7%) cães do perfil II, todos (100%) eram assintomáticos; e entre 13 (7,3%) cães do perfil III, 84,6% eram assintomáticos e 15,4% sintomáticos. Além disso, observou-se que a conversão do estado clínico assintomático ao sintomática foi registado principalmente em cães do perfil I (40,2%) do que aqueles dos perfis II (5,8%) e III (9%). Por outro lado, apenas 3,2% dos cães do perfil I [RIFI (+) / RIM (-)] converteu resposta RIM (+), enquanto 80% de cães do perfil II [RIFI (-) / RIM (+)] converteu resposta RIFI (+). Por fim, demonstrou-se que 100% dos óbitos por LVC ocorreu entre os cães do perfil I, sendo 85,7% na prevalência e 14,3% na incidência. Considerando todos esses resultados, parece razoável que a interação entre parasita e resposta imune canina é suportada principalmente pelo perfil imunológico claramente vulnerável, o perfil I [RIFI (+) / RIM (-)], o qual não oferece qualquer resistência ao parasita, tornando o cão altamente susceptível à infecçãoCanine visceral leishmaniasis (CVL) is one of the most important public health problems in Latin America because it usually precedes human disease, American visceral leishmaniais (AVL), being caused by Leishmania (L.) infantum chagasi. In the present prospective study it was analyzed during two years period the prevalence, incidence and dynamics of the clinical-immunological evolution of canine L. (L.) i. chagasi-infection in a cohort of 316 mongrel dogs living in endemic area of AVL in Barcarena municipality, Pará State, Amazonian Brazil, by the combined use of the indirect fluorescence antibody test (IFAT-IgG) and delayed-type hypersensitivity (DTH), as well as the parasite research by the popliteal lymph node aspiration for the diagnosis of infection. The IFAT and DTH reactivity recognized three different immune response profiles: (I) IFAT(+)/DTH(-) (81 dogs), (II) IFAT(-)/DTH(+) (17 dogs), and (III) IFAT(+)/DTH(+) (13 dogs), providing an overall infection prevalence of 35,1% (111/316). In this way, the specific prevalence of profile I 25,6% was higher than those of profiles II 5,4% and III 4,1%. Moreover, the frequency of these profiles among 111 infected dogs showed that the rate 73% of profile I was also higher than those of profiles II 15,3% and III 11,7%. The infection prevalence according to the age groups revealed that the rate 27,5% of ≥1year <7years was higher than those of <1year 5,3% and ≥7years 2,2%, respectively. On the other hand, the overall incidence of infection was 5,7% dogs/month (5,4% profile I, 0,3% profile II and 0,0% profile III). However, it was noted a progressive decreasing in the incidence rates at the following time-points: six (3,6% dogs/month), twelve (1,7% dogs/month) and twenty four (0,4% dogs/month) months of the study. In addition, the infection incidence according to the age groups demonstrated that the rate 6,6% dogs/month of <1year was higher compared to those of 5,3% and 3,3% dogs/month of ≥1year and <7years, and <1year, respectively. The parasitological diagnosis of infection was confirmed in 19% (21/111) at the prevalence survey, being most dogs (85,7%) of the profile I, 61,1% symptomatic and 38,9% asymptomatic ones. Among the remainder 14,3%, the diagnosis was associated to the profile III, 66,6% in asymptomatic and 33,3% in symptomatic dogs. At the incidence survey, the diagnosis was confirmed in 11% of dogs, all from the profile I, 60% asymptomatic and 40% symptomatic ones. With regards to clinical status of all 179 infected dogs diagnosed during two years period, it was observed that among 145 (81%) dogs from the profile I, 82% were asymptomatic and 18% symptomatic ones; among 21 (11,7%) from the profile II, all (100%) were asymptomatic; and among 13 (7,3%) from the profile III, 84,6% were asymptomatic and 15,4 % symptomatic ones. Besides this, it was noted that the clinical conversion from asymptomatic to symptomatic status was principally recorded in dogs from the profile I (40,2%) than those from the profiles II (5,8%) and III (9%). By the other side, only 3,2% dogs from the profile I [IFAT(+)/DTH(-)] converted DTH(+) response, while 80% dogs from the profile II [IFAT(-)/DTH(+)] converted IFAT(+) response. At last, it was demonstrated that 100% of death by CVL occurred amongst dogs from the profile I, being 85,7% from the prevalence and 14,3% from the incidence. Taking together all these results, it seems reasonable that interaction between parasite and canine immune response is principally supported by immunologic profile clearly vulnerable, the profile I [IFAT(+)/DTH(-)], which does not offer any resistance to parasite, became the dog highly susceptible to infection
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Rahman, Bhuiyan Taufiqur. "Humoral and cellular immune responses to Helicobacter pylori in Bangladeshi children and adults that may be related to protection /." Götborg : Department of Microbiology and Immunology, Institute of Biomedicine at Sahlgrenska Academy, University of Gotheburg, 2010. http://hdl.handle.net/2077/21536.
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Moreira, Iramirton Figueirêdo. "Imunidade humoral e celular de crianças com desnutrição crônica semi-internas no centro de recuperação e educação nutricional, CRE Maceió/AL - 2008." Universidade Federal de Alagoas, 2009. http://repositorio.ufal.br/handle/riufal/643.
Анотація:
The World Health Organization defines protein-energy malnutrition as a range of pathological conditions that appear by a deficient supply, transport or use of nutrients by the body s cells causing an essential amino acid deficiency in DNA and RNA synthesis, which can lead to a substantial immune system impairment. The focus of this research was to evaluate humoral and cellular immunity in children suffering from moderate to severe chronic malnutrition. The cross-sectional study was conducted with children 24-59 months old and 29 days, semi-interned at the Nutritional and Education Recovery Center (CREN), Maceió/AL, suffering from chronic malnutrition. At the same time creating a control group using normal similar aged children, randomly selected enrolled elementary school students from the same community. For data collection a standardized questionnaire was administered to children s parents and guardians addressing the history of infectious diseases. Cellular immunity assessment was performed by counting leukocytes and lymphocytes, B lymphocytes and T and delayed hypersensitivity test. Humoral immunity assessment was determined by immunoglobulins IgA, IgG and IgM in serum and IgG antibody by tetanus toxoid. Nutritional status was determined by the height-for-age (H/A) index. Data analysis used parametric and nonparametric statistics with a significance level (p<0.05). Research participants consisted of 68 children, 34 chronically malnourished and 34 well nourished. Among the malnourished 56% were male versus 47% normal weight, and the (H/A) index ranged from -4.61 to -2.02 in malnourished children versus -0.99 to 1.17 in eutrophic children. The history of airway infections, acute diarrhea, mumps and whooping cough was higher among the malnourished, but there was no statistical difference. The number of leukocytes and lymphocytes was significantly higher in malnourished children (p = 0.00). The number of B and T lymphocytes and delayed hypersensitivity test was not statistically different between the two groups. Serum immunoglobulins IgG and IgA were significantly (p = 0.00) higher among malnourished. Among the malnourished children an apparent decrease of 70.5% of IgG antibodies specific for tetanus toxoid versus 41.2% for normal weight (p = 0.01). Conclusion: There was no humoral and cellular immunity impairment in malnourished children but the number of T lymphocytes was lower and the production of IgG antibodies to tetanus toxoid was significantly lower in severely malnourished children.A Organização Mundial da Saúde define Desnutrição Energético-Protéica como uma gama de condições patológicas que aparece por deficiência de aporte, transporte ou utilização de nutrientes pelas células do organismo provocando uma deficiência de aminoácidos essenciais na síntese de DNA e RNA, que pode levar a um considerável comprometimento do sistema imune. O objetivo do presente estudo foi avaliar a imunidade humoral e celular de crianças com desnutrição crônica moderada e grave. Estudo do tipo transversal realizado com crianças de 24 a 59 meses e 29 dias, semi-internas no Centro de Recuperação e Educação Nutricional, Maceió/AL, portadoras de desnutrição crônica. No mesmo período constituiu-se um grupo controle composto de crianças eutróficas da mesma faixa etária, selecionado aleatoriamente entre os alunos matriculados na escola de ensino fundamental da mesma comunidade. Para coleta de dados foi utilizado um questionário padronizado, aplicado aos pais ou responsáveis, abordando o histórico das crianças sobre doenças infecciosas. A avaliação da imunidade celular foi realizada através da contagem dos leucócitos e linfócitos totais, linfócitos B e T, e do teste de hipersensibilidade tardia. Para avaliar a imunidade humoral foi feita a determinação das imunoglobulinas IgA, IgG e IgM séricas, e anticorpo do tipo IgG para toxóide tetânico. O estado nutricional foi determinado pelo índice altura para idade (A/I). Na análise dos dados utilizou-se estatística paramétrica e não-paramétrica com nível de significância (p<0,05). Participaram do estudo 68 crianças, sendo 34 desnutridas crônicas e 34 eutróficas. Entre os desnutridos 56% eram do sexo masculino versus 47% dos eutróficos; o índice A/I variou de -4,61 a -2,02 nas crianças desnutridas versus -0,99 a 1,17 nas eutróficas. O histórico de infecções das vias aéreas, diarréia aguda, caxumba e coqueluche foi maior entre os desnutridos, porém não foi observada diferença estatística. O número de leucócitos e linfócitos totais foi significativamente maior nas crianças desnutridas (p = 0,00). O número de linfócitos B e T, e o teste de hipersensibilidade tardia não diferiu estatisticamente entre os dois grupos. As imunoglobulinas séricas IgA e IgG foram significativamente (p = 0,00) mais elevadas entre os desnutridos. Entre as crianças desnutridas 70,5% apresentaram diminuição de anticorpos específicos do tipo IgG para toxóide tetânico versus 41,2% das eutróficas (p = 0,01). Concluiu-se que não houve comprometimento da imunidade celular e humoral nas crianças desnutridas, porém é preciso ressaltar que o número de linfócitos T foi menor e a produção de anticorpos do tipo IgG para toxóide tetânico foi significativamente menor nas crianças desnutridas crônicas.
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SILVA, Bárbara Brooklyn Timóteo Nascimento. "Aspectos imunológicos do caramujo Pomacea lineata (Spix, 1827) sob condições de estivação induzida." Universidade Federal Rural de Pernambuco, 2014. http://www.tede2.ufrpe.br:8080/tede2/handle/tede2/5039.
Анотація:
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Pomacea lineata (Spix, 1827) is a pulmonate gastropod that has a large dependence on humidity, Ampullaridae belongs to the family whose geographic distribution includes almost all the Neotropical Region , which inhabits waters of course slow and stagnate. Pulmonate gastropods have a conspicuous ecological feature, aestivation, which is a form of resistance and adaptation probably best defined as a survival strategy to cope with the arid conditions, but is also typically associated with lack of food availability, and often with high ambient temperatures. During these periods of aestivation some physiological aspects can be changed, as in molluscs, most of these is temperature dependent and can be altered by its variation, including the activity of the immune system. The innate immune system of invertebrates involves humoral and cellular response similar to that found in vertebrates. The cellular defenses occurs in combination with humoral defenses. Humoral responses include the production of reactive oxygen species (ROS) and nitric oxide (NO) and phenol oxidase enzyme activity, and cellular immune reactions are performed by hemocytes, performing, among other functions, encapsulation and phagocytosis of the pathogen. Thus, this research aimed to obtain information on some immunological parameters snail P. lineata in conditions of induced aestivation. The snails were induced to aestivation through the gradual withdrawal of water in the aquarium and abstention from food, getting in these conditions for 60 days. After this period, hemolymph of 40 individuals were collected for analysis of the total haemocyte count, measurement of nitric oxide, phenol oxidase activity and total protein. The results revealed that animals under aestivation showed a significant increase in the total number of hemocytes and measurement of nitric oxide, which may confer greater chance of survival.
Pomacea lineata (Spix, 1827) é um gastrópode pulmonado que apresenta uma grande dependência da umidade, pertencente à família Ampullaridae cuja distribuição geográfica inclui quase toda a Região Neotropical, na qual habita águas de curso lento e estagnadas. Gastrópodes pulmonados apresentam uma característica ecológica conspícua, a estivação, que é uma forma de resistência e adaptação provavelmente melhor definida como uma estratégia de sobrevivência para lidar com as condições áridas, mas também é tipicamente associada com a falta de disponibilidade de alimentos e, frequentemente, com as altas temperaturas ambientais. Durante estes períodos de estivação alguns aspectos fisiológicos podem ser alterados, pois nos moluscos, a maioria desses, é dependente da temperatura e podem ser alterados pela sua variação, incluindo a atividade do sistema imunitário. O sistema imunológico inato dos invertebrados envolve a resposta celular e humoral similarmente ao encontrado nos vertebrados. As defesas celulares ocorrem em combinação com as defesas humorais. As respostas humorais, incluem a produção de espécies reativas de oxigênio (ROS) e óxido nítrico (NO) e a atividade da enzima fenoloxidase, e as reações imunes celulares são realizadas pelos hemócitos, que executam, dentre outras funções, o encapsulamento e fagocitose do patógeno. Assim, esta pesquisa teve por objetivo obter informações sobre alguns parâmetros imunológicos do caramujo P. lineata em condições de estivação induzida. Os caramujos foram induzidos à estivação através da retirada gradual de água no aquário e abstenção de alimento, ficando nestas condições por 60 dias. Após este período, hemolinfa de 40 indivíduos foram coletadas para as análises de contagem total de hemócitos, dosagem de óxido nítrico, atividade da fenoloxidase e proteínas totais. Os resultados revelaram que os animais estivantes apresentavam um aumento significativo no número total de hemócitos e na dosagem de óxido nítrico, o que pode conferir maior chance de sobrevivência.
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Hein, Héber Eduardo. "Influência da imunidade de matrizes suínas na resposta à vacinação de leitões contra Mycoplasma hyopneumoniae." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2015. http://hdl.handle.net/10183/127074.
Анотація:
A suinocultura está amplamente difundida no Brasil, o quarto maior produtor mundial de carne suína. Seu efetivo está concentrado em maior parte na região Sul, com 48,8% dos suínos. Porém, a intensificação e o confinamento das criações expõem os animais a agentes patogênicos, como o Mycoplasma hyopneumoniae (Mhyo), causador da Pneumonia Enzoótica Suína (PES). A doença é caracterizada pela ocorrência de tosse seca não produtiva e lesões pulmonares de consolidação, denominadas hepatização. A vacinação de leitões é uma importante ferramenta empregada no controle da PES. Contudo, é relatado que a imunidade passiva adquirida pelos leitões através do colostro das matrizes suínas pode interferir na sua resposta à vacinação contra o Mhyo. Desta forma, este trabalho teve como objetivo avaliar a influência da imunidade materna na resposta à imunização de leitões contra Mhyo ao desmame. Dez matrizes foram divididas em dois grupos baseado na Razão S/P de um teste ELISA comercial , um com baixo nível de anticorpos (Ac) anti-Mhyo (BAc, Razão S/P <0,75) e outro com alto nível (AAc, Razão S/P ≥0,75). De cada fêmea, dois leitões eram controles (contr) e nove vacinados (vac) contra Mhyo. Estes grupos e tratamentos foram comparados entre si quanto a parâmetros de imunidade humoral, celular e comprometimento pulmonar ao abate. Após a ingestão de colostro, os leitões das fêmeas AAc mantiveram os maiores níveis de Ac, até os 56 dias de idade. Quando avaliados através do teste ELISA, dos 13 aos 99 dias depois de vacinados os leitões BAc-vac apresentaram níveis de Ac mais estáveis, com um aumento significativo aos 113 dias pós-vacinação. Os parâmetros celulares não diferiram entre grupos e tratamentos, com exceção dos linfócitos T CD4+CD8+, com menores percentuais entre os vacinados. Independente do grupo, os vacinados tiveram menor comprometimento pulmonar, porém os BAc-vac tiveram menos lesões que os AAc-vac. Os resultados demonstraram que a vacinação dos leitões contra Mhyo ao desmame os protege contra o agente, levando ao menor comprometimento pulmonar, principalmente quando a imunização ocorre na presença de baixos níveis de Ac passivos.Swine production is widespread in Brazil, being the fourth largest producer of pork meat. Swinesare concentrated in the Southern region, comprising 48.8%of pig population. However, due to confinement system, pigs are exposed to pathogens such as the bacteria Mycoplasma hyopneumoniae (Mhyo), responsible for swine enzootic pneumonia (SEP). The disease is characterized by a dry, nonproductive cough, and macroscopic areas of consolidation in the lung. The piglet vaccination is an important practice to SEP control. However, it is reported that passive immunity acquired by the piglets through the colostrum of sows may affect their response to vaccination against Mhyo. The objective of this study was to evaluate the influence of maternal immunity in the pig vaccination against Mhyo after weaning. Ten sows were divide in two groups according with the ELISA’s S/P Ratio, with low (LAb, S/P Ratio <0.75) or high (HAb, S/P Ratio ≥0.75) level of antibodies (Ab). From each sow, two piglets were controls (contr) and nine vaccinated (vac) against Mhyo. Piglets' humoral and cellular immunity and pulmonary lesions were compared between the treatments and groups of sows.The Ab level after colostrum intake was higher in piglets from HAb group of sows until 56 days of age. When evaluated by ELISA, LAb-vac piglets showed a more stable Ab levels from 13 to 99 days post-vaccination, with a significant increase at 113 days post-vaccination. No differences were detected between groups and treatments according with cellular parameters, except T CD4+CD8+ lymphocytes percentages, that were lower in vaccinated piglets. Regardless of the group, vaccinated pigs had lower pulmonary lesions, but the LAb-vac piglets had less damage than the HAb-vac. These results demonstrated that piglet vaccination against Mhyo at weaning protects them against the pathogen and provides lower pulmonary lesions, especially when the immunization occurs in the presence of low levels of maternal Ab.
8
Beattie, Lynette. "The role of the spleen in Malaria : Cellular changes that affect the development of immunity." Queensland University of Technology, 2006. http://eprints.qut.edu.au/16195/.
Анотація:
Malaria, caused by the apicomplexan parasite Plasmodium, is a major cause of morbidity and mortality throughout the world. This study has focused on the role of the spleen in the control of the blood stage of infection. Three aspects have been examined specifically: the effect of infection on the architecture of the spleen, the role of the spleen in parasite clearance and the formation of B cell memory. Firstly, the effect of infection on the splenic microarchitecture was examined. An essential component of the splenic architecture is the marginal zone (MZ), an area of the spleen that separates the reticuloendothelial red pulp of the spleen from the lymphoid white pulp compartment. Two unique populations of macrophages are found in the marginal zone: marginal zone macrophages (MZM) and marginal metallophilic macrophages (MMM). In the current study, parasitised red blood cells (pRBC) as well as normal RBC located to the MZ thirty minutes after intravenous injection and formed close associations with both MMM and MZM. Eight days after infection, at the time of peak parasitemia, a complete loss of both MMM and MZM was observed. Assays to detect cell death revealed that the loss of both MMM and MZM appeared to occur as a result of apoptosis. The apoptosis was not induced by up regulation of the inflammatory cytokines tumour necrosis factor or interferon-γ and could not be blocked by over expression of the apoptosis inhibitor Bcl2. Significantly, MMM were retained in the absence of CD8+ T cells implicating CD8+ T cells in the loss of MMM. Finally, infection of CD95-/- mice demonstrated that CD95/CD95-ligand (Fas/Fas-ligand) interactions were responsible for some of the CD8+ T cell-mediated loss of MMM. These data provide evidence for a novel interaction between MMM and CD8+ T cellsfollowing infection with Plasmodium. Secondly, the role of the spleen in the control of parasitemia and disease was monitored with an emphasis on determining the role of splenic macrophage populations (MMM, MZM and red pulp macrophages [RPM]) in parasite clearance. A clodronate liposome-mediated macrophage depletion technique was used, and caused a complete loss of all three macrophage sub-populations, as well as 50% of splenic dendritic cells, within 24 hours of administration. Each of the macrophage populations, as well as splenic DC, demonstrated different repopulation kinetics following their depletion from the spleen and these kinetics were utilised to examine each cell population in isolation. RPM depleted mice had significantly higher peak parasitemias than the controls. This peak returned to the level observed in undepleted control animals only after the repopulation of RPM was complete, suggesting that RPM play a role in the control of peak parasitemia following infection. Neither MMM nor MZM played a role in the control of parasitemia. The role of non-splenic macrophages and splenic dendritic cells also was investigated and shown to be insignificant in the absence of splenic macrophages. Finally, the role of RPM in mice immune to infection was investigated and their role shown to be dispensable, with immune mice clearing parasitemia efficiently in the absence of RPM. RPM therefore are important for the innate control of infection with P. chabaudi but are dispensible once adaptive immunity is established. Finally, the role of the spleen in the development of parasite-specific B cell memory was examined. Initial studies demonstrated that germinal centre (GC) development was compromised following infection with P. chabaudi, with an involution of B cell follicles noted early in infection. Adoptive transfer of memory B cells from immunised to naïve mice demonstrated that some protection was conferred on recipient mice by parasite-specific memory B cells. But, the memory B cells could not protect the host from developing parasitemia and did not produce significant amounts of parasite-specific immunoglobulin within seven days of challenge infection. Memory B cells could not be detected ten weeks after infection, indicating that the development, or survival, of parasite-specific memory B cells was compromised. The development of bystander memory B cells was not affected by infection. Finally, long-lived plasma cells were shown to develop in response to infection, although re-exposure of the cells to parasites in the form of recrudescent parasitemia resulted in their loss. This study therefore has identified a defect in the development of long-term, B cell-mediated, protection against infection with P. chabaudi. Each of these factors has significant implications for the understanding of how the spleen contributes to the control of infection with Plasmodium and potential applications for the further development of malaria vaccines and treatment regimens.
9
Silva, Milton Thiago Guerino da. "Avaliação de potencial agente vacinal contra o S.pyogenes em camundongos transgênicos, portadores de genes HLA de classe II humanos." Universidade de São Paulo, 2011. http://www.teses.usp.br/teses/disponiveis/5/5146/tde-20122011-155537/.
Анотація:
A faringite estreptocócica desencadeada pelo Streptococcus pyogenes pode resultar em uma série de doenças humanas e complicações como a febre reumática (FR) em indivíduos predispostos não tratados. A FR é uma doença autoimune que afeta mais de 20 milhões de crianças em países em desenvolvimento. A proteína M presente na membrana do S. pyogenes representa o maior fator de virulência da bactéria, e é objetivo de estudos para o desenvolvimento de uma vacina contra essa patologia. Atualmente mais de 200 tipos de proteínas M foram descritos na literatura e a sua porção Cterminal é conservada entre os diferentes tipos. Desenvolvemos um protótipo de vacina que compreende 55 resíduos de aminoácido da porção C-terminal, denominado StreptInCor. Neste trabalho analisamos a resposta humoral e celular específica contra o peptídeo sintético StreptInCor, usando camundongos transgênicos portadores de HLA de classe II humanos DR2, DR4, DQ6 e DQ8. O protocolo de imunização consistiu em administrar 50 g do StreptInCor adsorvido em 300 g de hidróxido de alumínio nos dias 0 e 14. Os grupos controles foram injetados com salina nas mesmas condições. O soro obtido no 28º dia foi testado por ensaio imunoenzimático (ELISA) para verificarmos a presença de anticorpos contra o StreptInCor e os esplenócitos destes animais, obtidos nessa data, foram utilizados para ensaios de proliferação celular na presença do StreptInCor. Testes de segurança foram efetuados e não observamos reação cruzada contra a miosina cardíaca e após 12 meses de acompanhamento, amostras de tecidos desses animais foram submetidas à análise histológica. Em conclusão não verificamos indícios de reações autoimunes nos animais imunizados com o StreptInCor e os resultados obtidos mostram a capacidade do StreptInCor em desencadear uma resposta imune, duradoura e segura em camundongos portadores de moléculas HLA de classe IIStreptococcal pharyngitis triggered by Streptococcus pyogenes throat infection can result in rheumatic fever (RF) and rheumatic heart disease (RHD) in untreated susceptible individuals. RF is an autoimmune disease that affects more than 20 million children in developing countries. M protein is the major factor of virulence of the bacteria, and it has been studied to develop a vaccine. Currently more than 200 M protein types have been described and its Cterminal domain is conserved in many different serotypes. We developed a vaccine epitope (StreptInCor) composed by 55 amino acid residues of the Cterminal portion of the M protein. In the present work we analyze the ability of the StreptInCor of induce immune response in HLA class II transgenic mice. The transgenic mice harboring the HLA Class II DR2, DR4, DQ6 and DQ8 were immunized subcutaneously with 50 g StreptInCor adsorbed onto 300 g of aluminum hydroxide gel on days 0 and 14. Control groups were immunized with vehicle (Saline) in same conditions. The sera were obtained on day 28 and tested by ELISA to verify the presence of antibodies. The specific cellular immune response was evaluated by proliferation assay using splenocytes. No cross reaction with cardiac myosin were observed. Tissue samples from immunized mice followed by 12 months were analyzed in order to verify if StreptInCor induces some histological damage. No autoimmune or deleterious reactions were observed. In conclusion our results indicate that StreptInCor Induces a good and prolonged and safe immune response in HLA class II transgenic mice
10
Shidani, Babak. "Effet de la cyclosporine a sur le systeme immunitaire de la souris." Paris 7, 1987. http://www.theses.fr/1987PA077159.
11
Reidel, Ivana. "Análisis de nuevos vehículos y adyuvantes para inmunización con antígenos de Staphylococcus aureus utilizando diferentes modelos experimentales." Thesis, Poitiers, 2020. http://www.theses.fr/2020POIT1803.
Анотація:
Les infections à Staphylococcus aureus représentent un enjeu majeur en santé humaine et en médecine vétérinaire. L’usage excessif d’antibiotiques pour traiter ces infections a conduit à l’émergence de souches multirésistantes et incite à développer d’autres méthodes préventives comme la vaccination. A ce jour aucun vaccin n’est approuvé en médecine humaine et seulement 2 vaccins, peu satisfaisants, sont utilisés dans le contrôle de la mastite bovine. Il est donc nécessaire de développer de nouvelles formulations vaccinales plus efficaces.L’objectif de ce travail de thèse est de tester de nouvelles formulations liposomales incluant des antigènes de S. aureus et différents agents immunostimulants tels que des oligodésoxynucléotides (ODN)- CpG, l’hydroxyde d’Aluminium (Al(OH)3), des protéolipides de type gemini (AG2-C16) ou des oligosaccharides modifiés dérivés de mannane (OPM). Les capacités adjuvantes de ces molécules ont été testées dans plusieurs modèles animaux. Dans le modèle bovin, l’immunisation de veaux, de génisses et de vaches enceintes montrent l’efficacité de formulations liposomales incluant l’antigène de S. aureus associé aux ODN-CpG, induisant une réponse immune humorale forte par la production d’anticorps spécifiques de type IgG1 et IgG2, capables d’inhiber les toxines de S.aureus. Dans le modèle murin, l’injection intradermique de formulations vaccinales a révélé l’efficacité des adjuvants ODN-CpG, AG2-C16 et OPM à la fois dans l’induction d’une réponse humorale forte (production d’anticorps spécifiques) mais aussi le développement d’une réponse cellulaire impliquant notamment des lymphocytes T CD8+ sécréteurs d’IFN-γ, qui jouent un rôle important dans les mécanismes de défense contre les bactéries intracellulaires. Enfin dans le but d’étudier le potentiel des vaccins liposomaux à traverser la peau, considérée comme un site d’immunisation d’intérêt, des études in vitro ont été menées sur des épidermes reconstruits de souris montrant que l’adjuvant protéolipidique AG2-C16 associé aux liposomes favorise leur passage transcutané, permettant d’envisager une utilisation en topique de ces vaccins. D’autres expériences réalisées sur des cultures de kératinocytes et de fibroblastes murins ont également montré la capacité de l’adjuvant oligosaccharidique OPM à stimuler les fibroblastes pour la production de chimiokines et de cytokines proinflammatoires, conduisant au développement d’une réponse immunitaire au vaccin plus forte.L’ensemble des résultats présentés dans cette thèse démontre que les liposomes cationiques constituent un système polyvalent de vectorisation permettant une sélection de substances immunostimulantes appropriées en fonction des caractéristiques de la réponse immunitaire souhaitéesStaphylococcus aureus infections represent a major concern for human health and veterinary medicine. The excessive use of antibiotics to treat these infections has led to emergent multi-resistant strains of bacteria and encourages us to develop alternative methods for prevention such as vaccination. To date, there are no vaccines approved for use in humans and only two vaccines are used in the control of bovine mastitis, with a low efficacy. Therefore, new tools are needed to prevent infections caused by S. aureus.The objective of this thesis work is test new vaccine liposomal formulations composed of antigen from S.aureus and different immunostimulating agents including oligodesoxynucleotides (ODN)-CpG, aluminum hydroxide (Al(OH)3), gemini-type proteolipids (AG2-C16) or modified oligosaccharides (Mannan-derived molecules, OPM). The adjuvant capacities of these molecules have been tested in different animal models. In the bovine model, immunizations of calves, heifers and pregnant cows show the efficacy of liposomal formulations composed of S. aureus antigens associated with ODN-CpG, eliciting a strong humoral immune response by the production of specific IgG1 and IgG2 antibodies, able to inhibit S. aureus toxins. In the murine model, intradermal injection of vaccine formulations revealed the efficacy of the adjuvants ODN-CpG, AG2-C16 and OPM in the induction of a robust humoral response (production of specific antibodies) and the development of a cellular response involving IFN-γ-secreting T CD8+ lymphocytes which play a crucial role in the defense against intracellular bacteria. Finally, in order to study the potential of liposomal vaccines to penetrate the skin, considered as an immunization site of interest, in vitro experiments realized on reconstituted mouse epidermis have shown that the proteolipid adjuvant AG2-C16 associated with liposomes promotes their transcutaneous migration, allowing their use for topical administration. Other experiments were carried out on mouse keratinocyte and fibroblast cultures demonstrating the capacity of the oligosaccharide adjuvant OPM to stimulate fibroblast to produce proinflammatory chemokines and cytokines, leading to the development of a stronger immune response toward the vaccine.Together, the results presented in this thesis demonstrate that cationic liposomes constitute a versatile vectorization system, which allows the selection of the proper immunostimulants, depending on the needed immune response characteristics
12
Quiniou, Debrie Marie-Christine. "Immunité anti-ilots chez des diabétiques insulino-dépendants de type 1." Paris 6, 1986. http://www.theses.fr/1986PA066085.
Анотація:
La destruction sélective des cellules bêta des ilots de Langerhans pourrait être due à une réaction immunitaire dirigée contre elles. Etude de la phase effectrice de la réponse auto-immune c'est-à-dire l'immunité cellulaire, l'immunité humorale complément dépendante, la cytotoxicité cellulaire dépendante d'anticorps chez les diabétiques de type 1. L'évolution de ces paramètres a été étudiée en fonction de la durée clinique de la maladie et de la présence ou de l'absence de manifestations auto-immunes extra-pancréatiques.
13
Meissonnier, Guylaine. "Effets toxiques de l'aflatoxine b1 et de la toxine t-2 sur les systèmes de défenses métaboliques et immunitaires chez le porc, évaluation des effets protecteurs de glucomannanes." Toulouse 3, 2007. http://www.theses.fr/2007TOU30153.
Анотація:
L'aflatoxine B1 (AFB1) et la toxine T-2 sont des mycotoxines, métabolites secondaires de micromycètes qui peuvent contaminer les denrées alimentaires notamment les céréales. Les objectifs de nos travaux ont été de déterminer chez le porc, une espèce cible et sensible aux mycotoxines, les effets toxiques de l'AFB1 et de la toxine T-2 sur deux systèmes de défense, les enzymes de biotransformation et l'immunité. De plus, nous avons évalué in vivo l'effet protecteur d'un potentiel liant de toxine. Chez le porc, l'exposition à l'AFB1 aux doses testées n'a pas provoqué de manifestations cliniques majeures d'intoxication. Toutefois, nous avons observé des lésions du tissu hépatique, une altération spécifique de certaines activités de biotransformation (mono-oxygénases cytochrome P450 dépendantes), et lors du protocole d'immunisation nous avons montré un défaut d'activation de la réponse à médiation cellulaire spécifique de l'antigène vaccinal. L'exposition à la toxine T-2 n'a provoqué aucune manifestation d'intoxication ni lésion tissulaire chez le porc. Nous avons montré une altération spécifique de certaines activités de biotransformation, et lors du protocole d'immunisation cette toxine a diminué la production d'anticorps spécifiques de l'antigène vaccinal. L'ajout de glucomannanes dans la ration alimentaire a réduit les effets toxiques des deux mycotoxines étudiées. Dans le cas de l'AFB1, bien que nous n'ayons observé aucune réduction de l'absorption de la toxine, les glucomannanes ont amélioré les activités hépatiques de biotransformation et restauré la réponse immunitaire à médiation cellulaire. .Aflatoxin B1 (AFB1) and T-2 toxin are mycotoxins, secondary metabolites from fungi that sporadically contaminate food and feed, particularly cereals. The mains objectives of our work were to determine in pigs, a target species and highly sensitive to mycotoxin, the toxic effects of AFB1 and T-2 toxin on two defence systems, liver drug-metabolizing enzymes activities et the immune system. We also evaluate in vivo the protective effect of a potent mycotoxin binder. In pigs, AFB1 exposure for the doses investigated did not induce major clinical sign of intoxication. But, we observed lesions in liver tissue, a specific impairment of liver drug-metabolizing enzymes activities (monooxygenase cytochrome P450 dependant) and during immunization we showed a reduced cellular-mediated immune response specific for the vaccine antigen. T-2 toxin exposure did not induce any clinical sign of intoxication, or any tissue lesion in pigs. We observed a specific impairment of liver drug-metabolizing enzymes activities in liver, and during immunization T-2 toxin reduced the production of antibodies specific for the antigen. The addition of glucomannans in feed reduced the toxic effects of both mycotoxins. .
14
Pelletier, Lucette. "Mecanismes cellulaires impliques dans l4 autoimmunite induite par hgcl : :(2) chez le rat." Paris 6, 1987. http://www.theses.fr/1987PA066573.
15
Florentin, Irène. "Caracterisation fonctionnelle comparative de substances immunomodulatrices." Paris 6, 1987. http://www.theses.fr/1987PA066374.
16
Gougerot-Pocidalo, Marie-Anne. "Processus oxydants et reponses immunitaires : mecanismes biochimiques et cellulaires." Paris 7, 1988. http://www.theses.fr/1988PA077063.
17
Schmitt, Christian. "Etude de clones de lymphocytes t humains specifiques de l'anatoxine tetanique." Paris 7, 1987. http://www.theses.fr/1987PA077003.
18
Nohr, Carl William. "Humoral immunity in surgical patients." Thesis, McGill University, 1988. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75969.
Анотація:
Humoral immune function was studied in surgical patients. The antibody response to vaccination with a protein antigen, tetanus toxoid (TT), was reduced among all patients, especially those with reduced delayed type hypersensitivity (DTH) and increased degree of physiological derangement. The antibody response to a polysaccharide antigen, pneumococcal polysaccharide (PPS), was normal. In trauma patients, the antibody response to TT was normal. The in vitro production of specific and total immunoglobulin (Ig) by blood mononuclear cells was studied. Patients that failed to produce a serum antibody response to TT also failed to produce anti-TT in vitro. Anti-PPS production was normal. More total Ig was produced by patients, especially those with reduced DTH responses. Some patients showed a reduction, rather than the normal increase, in Ig synthesis with mitogen stimulation. These data show evidence of humoral immune deficiency to protein antigens, and in vivo activation of the B cell system.
19
Cassis, Linda 1977. "Role of progranulin in humoral immunity." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/398398.
Анотація:
Human spleen is continually exposed to blood-borne antigens derived from autologous apoptotic cells and commensal bacteria. This chronic stimulation of the marginal zone (MZ) results in the generation of a steady-state antibody response that occurs under non-inflammatory conditions. Immunoregulatory signals, still poorly understood, are required to avoid continuous inflammation.
Our group identified a population of splenic neutrophils called B cell-helper neutrophils (NBH cells) that contribute to the induction of steady-state antibody responses in the MZ1. NBH cells express B cell-activating and immunoregulatory factors, including progranulin (PGRN).
PGRN is an anti-inflammatory protein highly expressed at sites constantly exposed to antigens. It was shown to regulate several processes, including embryogenesis, neuronal survival, and wound repair. However, the role of PGRN in the immune response is still largely unknown. Here we show that PGRN actively participates in the pre-immune and post-immune responses against splenic microbial antigens, regulating the frequency and/or function of innate and adaptive immune cells such as neutrophils, dendritic cells, T and B cells. These findings suggest that PGRN functions as an endogenous adjuvant that may facilitate the development of novel strategies for modulating protective immune responses against invading pathogens.El bazo humano está continuamente expuesto a antígenos provenientes de la sangre derivados de células apoptóticas autólogas y bacterias comensales. Esta estimulación crónica de la zona marginal (ZM) resulta en la generación de una respuesta de anticuerpos que se produce de forma fisiológica bajo condiciones no inflamatorias. Para evitar la inflamación continua, se requieren señales inmunorreguladoras, todavía poco conocidas. Nuestro grupo identificó una población de neutrófilos esplénicos llamada neutrófilos ayudantes de células B (células NBH)1 que contribuyen a la inducción de anticuerpos en la ZM en condiciones fisiológicas. Las células NBH expresan factores activadores de las células B y factores inmunorreguladores, incluyendo progranulina (PGRN). PGRN es una proteína antiinflamatoria altamente expresada en lugares constantemente expuestos a antígenos. Regula varios procesos, incluyendo la embriogénesis, la supervivencia neuronal, y la reparación de heridas. Sin embargo, el papel de PGRN en la respuesta inmune sigue siendo en gran medida desconocido. En este estudio demostramos que PGRN participa activamente en las respuestas pre- y post-inmunes contra antígenos microbianos en el bazo, regulando la frecuencia y / o la función de células inmunitarias innatas y adaptativas como neutrófilos, células dendríticas, células T y B. Estos hallazgos sugieren que PGRN actúa como un adyuvante endógeno que puede facilitar el desarrollo de nuevas estrategias para modular la respuesta inmunitaria protectora contra patógenos invasores.
20
Rydyznski, Carolyn E. "Natural Killer Cell Regulation of Humoral Immunity." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852.
21
Fayette, Jérôme. "Effet des cellules dendritiques humaines générées in vitro sur la réponse immunitaire humorale." Lyon 1, 1998. http://www.theses.fr/1998LYO1T259.
22
Berkeley, Robert Anthony. "Immune cell carriers and humoral immunity in oncolytic virotherapy." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/20532/.
Анотація:
Oncolytic viruses (OV) represent an emerging modality in cancer therapy. Antiviral immunity is currently viewed as a barrier to systemic OV efficacy. Approaches have been taken to promote OV activity by attenuating virus-neutralising antibodies (NAb). However, the presence of NAb does not prevent intravenously administered OV, such as reovirus, reaching tumours in patients. Recent evidence suggests that NAb may in fact support virotherapy in mice by facilitating reovirus carriage upon circulating immune cells, principally monocytes. In this thesis, the applicability of these observations to the human setting is examined, modelling the loading of monocytes with reovirus in virus-immune patients. A novel in vitro cell carriage assay was employed, involving clinical trial patient-derived sera, isolated primary human monocytes, and human tumour cell lines. It was discovered that monocytes treated with fully neutralised reovirus reliably delivered the virus to kill melanoma targets. This was transferable across target cell histologies, and applicable to another OV, CVA21. Neutralised reovirus successfully accessed syngeneic melanoma flank tumours in mice. Prior murine studies suggested a role for surface Fc receptors in facilitating the antibody-dependent enhancement (ADE) of monocyte infection. A major role for Fc receptors in antibody-mediated entry of neutralised reovirus to human monocytes was confirmed. Yet no overall enhancement of virus loading or hand-off was conferred by the presence of NAb, in contrast to existing observations from mouse monocytes. Transcriptomic and secretory profiling identified discrete variations in the effects of free and neutralised reovirus upon monocyte phenotype. NAb significantly attenuated the monocyte IFN response to reovirus in vitro. However, in the presence of monocytes, reo-NAb successfully induced NK cell degranulation and killing of melanoma targets. Therefore this study identifies a mechanism by which, following neutralisation, reovirus may rely on circulating monocytes to gain tumour access, and to initiate oncolytic and/or immune-mediated tumour cell death.
23
Willems, Kristen N. "Regulation of Humoral Immunity by Pim Kinases: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/567.
Анотація:
Pim (Provirus Integration site for Moloney murine leukemia virus) kinases are a family of three serine/threonine kinases involved in cell cycle, survival and metabolism. These kinases were first identified in malignant cells and are most often associated with their role in cancer. Their role in immunity and lymphocytes is less well known. To date, it has been shown that Pim 1 and/or Pim 2 are important for T lymphocyte survival and activation when the Akt signaling pathway is inhibited by rapamycin. In addition, our laboratory has shown that Pim 2 is critical for BLyS-mediated naive B lymphocyte survival in the presence of rapamycin.
This thesis extends the role(s) for Pim 1 and/or 2 to include functions during B cell activation and the generation of immune responses. We found that during in vitro activation of purified resting splenic B cells from wild type mice with a variety of activators that use multiple signaling pathways, including the BCR, TLR and CD40 receptors, both Pim 1 and 2 kinases were induced by 48 hours post-activation, suggesting that they could play a role in B cell activation and differentiation to antibody secreting or memory B cells. Immunization of Pim 1-/-2-/- knockout mice with T cell dependent antigens showed impairment in antibody and antibody secreting cell generation as well as lack of germinal center formation clearly demonstrating an involvement of Pim 1 and/or 2 in the immune response. FACS examination of B cell populations from naive Pim 1-/-2-/- knockout mice revealed normal levels of splenic marginal zone and follicular B cells and T cells, however, decreased numbers of all peritoneal B cell populations and decreased B cells in Peyer's Patches was seen. An examination of serum antibody found in naive Pim 1-/-2-/- knockout mice showed decreased levels of natural antibody, which is likely due to loss of the peritoneal B1 cells but does not explain the significantly decreased TD immune response. To determine whether the defect was B cell intrinsic or a more complex interaction between B and T cells, we determined whether Pim 1-/-2-/- mice would respond to T cell independent, TI-1 and TI-2, antigens. Antibody production and antibody secreting cell formation were also significantly decreased in these mice supporting our notion of a B cell intrinsic defect. To further examine the B cell response problem, we attempted to establish chimeric mice using either bone marrow derived cells or fetal liver cells from WT or Pim 1-/-2-/- donors so that the B cells were derived from Pim 1-/-2-/- mice and the T cells would be WT. Unfortunately, we were not able to consistently engraft and develop mature Pim 1-/-2-/- B cells, which indicate that there is a stem cell defect in these knockout mice that requires further investigation. Because one of the major failures in activated Pim 1-/-2-/- B cells is the generation of antibody secreting cells, an analysis of the expression of transcription factors IRF-4 and BLIMP-1, known to play a role in this process was carried out. Although IRF-4 induction was not affected by the loss of Pim 1 and 2, the number of cells able to increase BLIMP-1 expression was significantly decreased, revealing a partial block in the generation of ASCs. Taken together the data presented in this thesis reveals a new and critical role for Pim 1 and 2 kinases in the humoral immune response.
24
Smith, Karen. "Cellular and humoral mechanisms of allergic disease." Thesis, University of Brighton, 2012. https://research.brighton.ac.uk/en/studentTheses/57df8daa-8006-4dff-8d44-ba39572913aa.
Анотація:
CD 154 is a T cell activation marker, transiently expressed following ligation of the T cell receptor, therefore providing direct access to an antigen-specific T cell population. Using peripheral blood samples taken from allergic individuals and healthy non-atopic controls, this project identified and phenotyped CD 154 + T helper cells following ex vivo stimulation with native allergen extracts (birch pollen, cat dander, grass pollen). Peripheral blood mononuclear cells were stimulated with allergen extract for 16 hours in the presence of Brefeldin A. Responding CD 154 + T cells were identified and phenotyped using multiparametric flow cytometry. Activated CD154+ TH1, TH2 and TRl-Iike cells, that co-expressed IFNy, IL4 and ILIO respectively, were identified in allergic and non-allergic participants. A close correlation was observed between TH1, TH2 and TR1-like cell frequency in non- allergic participants, such that the three parameters increased together to maintain a low TH2:TH1 ratio. The relationship between TH1, TH2 and TR1-like responses was dysregulated in allergic individuals, with abrogation of the IL10 response and a higher TH2:THI ratio. A close correlation was observed between Th2 cell frequency and the absolute concentration of birch-specific IgE. This work confirms previous reports of a more differentiated T cell phenotype in allergic subjects with regard to seasonal allergens. The detection of CD154+ T cells after short-term antigen stimulation may be a useful method for the detection of T cell responses to allergens when cost, speed and convenience are priorities. The CD 154 assay was also used to investigate allergen-specific T cells in two situations: [1] during allergoid immunotherapy and [2] at peak pollen season compared to out of season. This preliminary data suggests an increased frequency of TH2 cells in allergic individuals during the birch pollen season compared to healthy non-allergic controls, and a decrease in the TH2:THI ratio following successful immunotherapy. A proliferation assay utilising the cell surface PKH dye was also optimised to investigate proliferative responses to native allergen extracts in allergic and non- allergic subjects. Colonisation with superantigen-producing staphylococci is common in atopic diseases and may contribute to the initiation and maintenance of allergic sensitisation. However, little is known regarding T cell responses to superantigens in atopic individuals. This project sought to investigate T helper cell responses to the superantigen Staphylococcal Enterotoxin B (SEB) from Staphylococcus aureus in non-atopic individuals and highly atopic polysensitised individuals. Peripheral blood mononuclear cells were stimulated with SEB for 16 hours in the presence of Brefeldin A. Responding TH1, TH2, TH17, TR1-like and naturally occurring regulatory T cells were identified using multiparametric flow cytometry. This preliminary study identified a downregulated T H 17 response to the superantigen SEB in highly atopic individuals that does not relate to T Reg cell frequency or TCRVP3 expression. The Pollen-Food Syndrome (PFS) is caused by sensitisation to homologous panallergens within aeroallergens and food proteins. Information regarding the sensitisation profiles of individuals with PFS in the UK is limited and investigations into causative panallergens are not routinely performed. In a small study, patients with symptoms suggestive of PFS were recruited. from the Allergy Clinic at Brighton and Sussex University Hospital NHS trust. A standardised food allergy questionnaire was completed and serum analysed by component-resolved diagnosis using ImmunoCAP ISAC technology. This study cohort conformed to the Northern European pattern of birch-pollen associated PFS with cross-reactivity between the major birch pollen allergen Bet v 1 and homologues in food proteins. Sensitisation to LTPs and profilins was also noted, but the clinical relevance of these remains to be elucidated. Profilin sensitisation was associated with reactions to a significantly larger number of foods compared to PR-10 mono sensitised individuals.
25
Rembert, Audrey. "Les vaccins antivarioliques : pathogénicité-innocuité, immunogénicité humorale et cellulaire, protection." Aix-Marseille 2, 2006. http://www.theses.fr/2006AIX20707.
Анотація:
La variole, éradiquée en 1980, a représenté l’un des plus grands fléaux. Le risque de réémergence du virus de la variole rend nécessaire l’évaluation de nouveaux vaccins. Le but de notre étude était d’étudier les facteurs immunitaires essentiels à la résistance naturelle contre les orthopoxvirus et d’évaluer de nouveaux vaccins antivarioliques. La caractérisation du modèle d’infection souris/cowpox virus nous a permis de constater que la protection de la souris était due à l’ensemble des réponses immunitaires spécifiques. Un vaccin de 2ème génération (2G) et trois souches de vaccines non réplicatives (3G) ont été évaluées dans notre modèle d’infection. Le vaccin de 2G a montré la même efficacité vaccinale que le vaccin traditionnel de référence. Parmi les trois vaccins de 3G, seule la souche MVA a induit chez la souris une protection similaire au vaccin traditionnel à long terme après un rappel. Cependant, son immunogénicité induite à long terme reste inférieure au vaccin traditionnelSmallpox, eradicated in 1980, was one of the most dreaded infectious diseases. The threat of re-emerging variola virus induced the evaluation of new smallpox vaccines. The aim of our study was to determine immune factors induced in natural protection against orthopoxviruses and to assess new smallpox vaccines. The characterisation of the mice/cowpoxvirus rodent-like model had put in evidence the important role of all the component of the specific immune system in natural protection of mice. A second generation vaccine (2G) and tree non replicative vaccinia virus strains (3G) was evaluated in our model. The 2G smallpox vaccine showed similar vaccine efficacy than the traditional vaccine. Among the different 3G vaccines assessed, the MVA strain was the only vaccine candidate inducing a similar long-term protection than the traditional vaccine but only after a vaccine boost. However, the long-term induced MVA immunogenicity was inferior to this induced by the traditional smallpox vaccine
26
Shimokata, Kaoru. "Cytokines and Local Cellular Immunity." 名古屋大学医学部, 1997. http://hdl.handle.net/2237/6185.
27
Wendling, Daniel. "Aspects immunologiques et systemiques des spondylarthropathies." Besançon, 1991. http://www.theses.fr/1991BESA3703.
28
Bruns, Nicholas Joseph. "Humoral and cell-mediated immunity in vitamin A-deficient lambs." Diss., Virginia Polytechnic Institute and State University, 1988. http://hdl.handle.net/10919/53919.
Анотація:
Antigen-specific and polyclonal serum immunoglobulin G (IgG) concentrations were measured in control (Con), vitamin A-deficient (A-def), and vitamin A-repleted (A-rep) lambs. In Trial, I ewe lambs were injected with primary and secondary antigenic challenges of ovalbumin (1mg) and lysozyme (.1mg). The A-def lambs were then repleted with vitamin A and all lambs were injected with primary and secondary antigenic challenges of human gamma globulin (HGG) (.1mg). In Trial II Con and A-def wether lambs were given primary and secondary antigenic challenges of ovalbumin (20μg). Half of the A-def lambs were then repleted with vitamin A. All lambs were subsequently given a primary and secondary challenge of HGG (20 μg). Spleen wt were similar for all treatments in Trial I while A-def V lambs in Trial II had greater spleen wt (P<.01) than Con or A-rep lambs. Polyclonal serum IgG concentrations were unaffected by treatment in Trial I while in Trial II concentrations were greater (P<.05) in the A-def lambs during the HGG challenge period. Antigen-specific IgG concentrations in both trials tended to be greater in the Con lambs towards the end of both the ovalbumin (Trial I and II) and lysozyme (Trial I) challenge periods. Control and A-rep lambs in Trial I responded similarly to the HGG challenges. In Trial II both the A-def and A-rep lambs had lower (P<.10) HGG specific serum IgG concentrations on the last 3 wk of the HGG challenge period as compared to A-def lambs. Humoral immune function appears to be impaired in A-def lambs and a 2-wk repletion period was not sufficient in this study to restore humoral immune function to normal levels.Ph. D.
29
Sallam, Jamal A. "Intestinal humoral immunity in man : IgA and anti-salmonella antibodies." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20766.
Анотація:
Studies of gut immunity must be carried out on intestinal fluid and jejunal biopsies. Recent work from Edinburgh has shown that the use of Whole Gut Lavage (WGL) technique is a non-invasive, direct and reliable method of obtaining intestinal fluids. My thesis describes the use of WGL technique in a variety of studies on gastro-intestinal mucosal immunity. The effect of the newly licensed oral live typhoid vaccine Ty21a on gut immunity was investigated in a group of 22 healthy British volunteers. Later on, the intestinal immune responses to naturally acquired Salmonella infection were investigated in a group of patients who had had the infection within the preceding 12 months. Results obtained in these studies were compared with results obtained from healthy individuals, patients with inflammatory bowel disease (IBD) and African children from Sierra Leone. I investigated further the effect of heavy smoking and non-smoking in healthy volunteers on gut immunity and the effect of administration of the live oral vaccine Ty21a on the intestinal mucosal immune responses of smokers and non-smokers. I also studied agglutinating antibodies in WGL fluids and sera. Patients with a variety of GI diseases and patients who had had Salmonella infection were tested against a panel of 11 Salmonella antigens using a modified Widal test in microtitration plates. In the course of the above studies, I found that there were patients who had very low or absent intestinal IgA but had normal levels of IgA in the serum. Therefore, I investigated further this phenomenon by counting plasma cells in the lamina propria of intestinal biopsies from patients with "intestinal IgA deficiency" and normal controls using image analysis.
30
Casas, Rosaura. "Transfer of humoral immunity from the mother to her off-spring /." Linköping : Univ, 2001. http://www.bibl.liu.se/liupubl/disp/disp2001/med692s.pdf.
31
Wuttge, Dirk Marcus. "Cellular immunity and inflammation in atherosclerosis /." Stockholm : Karolinska Univ. Press, 2001. http://diss.kib.ki.se/2001/91-7349-051-2/.
32
Lucin, Kurt M. "Mechanisms of impaired humoral immunity after high thoracic spinal cord injury." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1186411177.
33
Yassine, Daadaa. "Network Decontamination with Temporal Immunity." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/20633.
Анотація:
Network decontamination is a well known mobile agent problem with many applications. We assume that all nodes of a network are contaminated (e.g., by a virus) and a set of agents is deployed to decontaminate them. An agent passing by a node decontaminates it, however a decontaminated node can be recontaminated if any of its neighbours is contaminated. In the vast literature a variety of models are considered and different assumptions are made on the power of the agents.
In this thesis we study variation of the decontamination problem in mesh and tori topologies, under the assumption that when a node is decontaminated, it is immune to recontamination for a predefined amount of time t (called immunity time). After the immunity time is elapsed, recontamination can occur.
We focus on three different models: mobile agents (MA), cellular automata (CA), and mobile cellular automata (MCA). The first two models are commonly studied and employed in several other contexts, the third model is introduced in this thesis for the first time. In each model we study the temporal decontamination problem (adapted to the particular setting) under a variety of assumptions on the capabilities of the decontaminating elements (agents for MA and MCA, decontaminating cells for CA). Some of the parameters we consider in this study are: visibility of the active elements, their ability to make copies of themselves, their ability to communicate, and the possibility to remember their past actions (memory). We describe several solutions in the various scenarios and we analyze their complexity. Efficiency is evaluated slightly differently in each model, but essentially the effort is in the minimization of the number of simultaneous decontaminating elements active in the system while performing the decontamination with a given immunity time.
34
Makedonas, George. "Cellular immunity among HIV exposed, uninfected individuals." Thesis, McGill University, 2005. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111828.
Анотація:
Two models of HIV infection have been studied extensively with the goal of identifying immune correlate(s) of protection against HIV: (1) the simian immunodeficiency virus (SIV) infection of rhesus macaque monkeys and (2) individuals with repeated exposure to HIV who remain uninfected by the virus (EUs). Both paradigms suggest that T cell-mediated immunity plays an important role in controlling HIV replication. Evidence from the SIV/macaque system, however, predicts that HIV vaccines aimed at eliciting T cell responses will fail to induce sterilizing immunity against HIV. The aim of the work presented in this thesis was to correlate HIV-specific T cell immunity in EUs with protection from HIV infection. The study cohort was comprised of (a) men who have unprotected sexual intercourse with HIV-infected men (MSM), (b) intravenous drug users (IVDU) who share syringes with HIV-infected peers, and (c) heterosexual partners of HIV-infected subjects. EUs were shown to exhibit HIV-specific IFN-gamma secretion, IL-2 production, and T cell proliferation, whereas low-risk negative controls did not. Furthermore, HIV-specific IFN-gamma secretion and T cell proliferation were not observed among a population of EUs who seroconverted soon after the tested time point. HIV-specific IL-2 secretion and T cell proliferation were shown to be correlated in our cohort of EUs. These effector functions are considered hallmark properties of central memory T cells (TCM), the subset of memory T cells that has been shown to mediate sterilizing immunity in mouse models of viral infection. The presence of TCM in EUs implies the development of immunity against HIV that is either fully protective or partially so, by increasing the threshold for HIV infection. Since these HIV-specific effector functions were absent in EUs who eventually seroconverted, it can be inferred that EUs in our cohort develop HIV-specific T cell immunity that mediates protection from HIV infection. Thus, our contribution to the EU paradigm is that sterilizing immunity is an attainable goal of prospective HIV vaccines.
35
Patel, Mihil. "Regulation of cellular immunity by human cytomegalovirus." Thesis, Cardiff University, 2018. http://orca.cf.ac.uk/114496/.
Анотація:
The success of HCMV as a lifelong pathogen is attributed at least in part to the broad range of encoded immune evasion molecules that inhibit the host cellular immune response. Indeed, HCMV has become a paradigm for immune evasion, the study of which has revealed a number of basic immunological processes. To screen for novel immune evasion genes, HCMV-specific CD8+ T-cell lines were grown from seropositive donors and used against a series of block deletion viruses, each missing a region of genes non-essential for replication in vitro. UL13-UL20 was flagged as important for inhibition of CD8+ T-cells. Further screening with individual gene knockout HCMVs showed that the published NK-cell inhibitor UL16 could inhibit CD8+ T-cells, but also revealed UL19 as a previously unrecognised strong immune evasin, inhibiting 3 separate CD8+ T-cell lines. UL19 had no effect on HLA-I downregulation indicating that it may affect other pathways involved with T-cell activation. Proteomic data showed that surface TNFR2 was increased by HCMV infection. This is important as this would influence the response to TNF, a major inflammatory cytokine and soluble effector molecule released by T and NK cells. Screening using different HCMV strains and knockout viruses identified UL148 and UL148D as responsible for the increase in surface TNFR2 but prevented the release of soluble TNFR2, indicating that UL148 and UL148D were influencing the ability of TNFR2 to be retained at the cell surface. Infection with HCMV Merlin profoundly downregulated surface ADAM17, the metalloproteinase responsible for cleaving TNFR2 from the cell surface. Deleting UL148 and UL148D recovered ADAM17 expression, blocking the function of which returned surface and soluble TNFR2 levels to those observed with Merlin. This was also true of TNFR1. HCMV infected cell lysates showed that UL148 and UL148D interfered with the maturation of ADAM17. Thus, UL148 and UL148D allow upregulation of TNFR2 and maintain TNFR1 expression during and HCMV infection by impairing surface ADAM17 expression through impairment of ADAM17 maturation. Given that ADAM17 is involved with the cleaving of multiple cytokines, cytokine receptors, adhesion molecules and immune cell receptors, this work identifies a novel mechanism through which HCMV can alter the surface and soluble proteome by preventing the shedding of inflammatory/immune receptors and mediators. More detailed studies will be required to define the global impact of this on the immune system.
36
Tye, Gee Jun. "Combined adjuvant for stimulation of cellular immunity." Thesis, King's College London (University of London), 2012. https://kclpure.kcl.ac.uk/portal/en/theses/combined-adjuvant-for-stimulation-of-cellular-immunity(b1be07ae-b8d4-40a8-9258-bc3e3413df9d).html.
Анотація:
Vaccination has important clinical potential in the immunotherapy of both infectious disease and cancer. The central aim of the studies reported in this thesis has been the development of vaccination strategies that will be effective for therapeutic applications in cancer. Using ovalbumin antigen in a mouse model, we have examined a combination of recently developed adjuvants referred to as CASAC (combined adjuvants for synergistic stimulation of cellular immunity) to optimise the efficacy of vaccination induced T cell mediated immunity. These studies have examined the effect of repeated rounds of vaccination with one, or alternating cycles of two different helper peptides. The hypothesis was that repeated stimulation of the same clonal population of CD4+ T helper cells with a single MHC class II peptide could induce anergy, exhaustion, clonal deletion and/or stimulation of regulatory T-cells, resulting in reduced and shorter lived immunity. These studies have also examined the effect of inclusion of other immune regulatory components, and in particular a cocktail of cytokines generated by phytohemagglutinin stimulation of human peripheral blood mononuclear cells (referred to as IRX-2). Another important issue for vaccination mediated immune therapy that was addressed is the age-associated loss of immunological competence (immunesenescence). A comparative analysis is reported of the magnitude and duration of responses to vaccination with a single MHC class-I presented peptide in combination with the same or alternating MHC class-II presented peptides. In addition, we have quantified the number of antigen specific CDS T cells, their effector and memory subsets and in vivo antigen specific cytolytic activity to examine the effect of CASAC vaccination alone or in combination with IRX-2. The induction of immunological responses in young and aged immune backgrounds was also examined. Vaccinations with ovalbumin peptides in the CASAC adjuvant have shown higher percentages and numbers of antigen specific CDS T cells with improved cytolytic activity when helper functions are stimulated by two different class-II peptides used in alternating cycles of vaccination, rather than repeated stimulation by the same class-II peptide. This conclusion can be confirmed with a repeated experiment. Analysis of T cells with a regulatory (Treg) phenotype (CD4+CD25+Foxp3+) showed that their expansion was reduced with the alternating T-helper peptide vaccination regimen. The addition of IRX-2 to the CASAC vaccination regimen was found to enhance the in vivo antigen specific cytolytic activity. This was particularly significant in the aged mice which were found to have increased levels of Tregs.
37
Titanji, Kehmia. "Mechanisms underlying impaired humoral immunity in primary and chronic HIV-1 infection /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-728-6/.
38
Ng, D. H. L. "Loss and recovery of humoral immunity to influenza virus following malaria infection." Thesis, University College London (University of London), 2012. http://discovery.ucl.ac.uk/1349451/.
Анотація:
The mechanisms of maintenance of humoral immunity to infectious pathogens, particularly the contributions of memory B cells and long-lived plasma cells in maintaining specific serum antibody titres, are not well understood. Furthermore, it is not clear whether sequential heterologous humoral immune responses and disease pathology can result in the dysregulation and loss of previously acquired antibody-mediated immune responses to unrelated antigens. Here, depletion of memory B cells using anti-hCD20 monoclonal antibodies in hCD20 transgenic mice was used to dissect the role of memory B cells and long-lived plasma cells in maintaining long-term serum antibodies after intranasal Influenza A infection. Next, an experimental model of sequential infections with Influenza A/PR/8/34 and Plasmodium chabaudi chabaudi (AS) was set up, with a 15-20 week interval between the infections, in order to investigate whether sequential infection with P. chabaudi would affect pre-established humoral immunity to Influenza A. This study demonstrates that memory B cells are essential for the maintenance of long-lived serum Ab titres to Influenza A, as depletion of memory B cells results in the eventual loss of long-lived plasma cells and serum antibodies. Sequential infection with P. chabaudi results in the loss of pre-established serum antibodies to Influenza A by inducing the loss of long-lived plasma cells in an FcγRI,II,III-dependent manner, and this renders mice susceptible to secondary infection with Influenza A. However, this loss of pre-established humoral immunity is temporary, as serum antibodies do eventually return to normal levels. These findings demonstrate a mechanism shared by memory B cells and long-lived plasma cells which ensures that serum antibodies are maintained for long periods of time in the face of continuous generation and incorporation of new specificities throughout the lifetime of the host. A more complete understanding of the parameters that affect the longevity of immunological memory and how heterologous infections influence this will be vital in our understanding of the effect of continuous exposure to infectious pathogens on the efficacy and longevity of previously established immune memory.
39
Lownik, Joseph C. "The Role of ADAM10 and ADAM17 in Humoral and Type 2 Immunity." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5680.
Анотація:
The proper regulation of inducible costimulator (ICOS) and its ligand (ICOSL) have been shown to be essential for maintaining immune homeostasis. Loss of either protein results in defective humoral immunity, and overexpression of ICOS results in aberrant antibody production resembling lupus. How ICOSL is regulated in response to ICOS interaction is still unclear. We demonstrate that ADAM10 is the primary physiological sheddase of ICOSL in both mouse and human. Using an in vivo system in which ADAM10 is deleted only on B cells (ADAM10B-/-), elevated levels of ICOSL were seen. This increase is also seen when ADAM10 is deleted from human B cell lines. Identification of the primary sheddase has allowed the characterization of a novel mechanism of ICOS regulation. In wildtype (WT) mice, interaction of ICOSL/ICOS results in ADAM10 induced shedding of ICOSL on B cells and moderate ICOS internalization on T cells. When this shedding is blocked, excessive ICOS internalization occurs. This results in severe defects in T follicular helper (TFH) development and Th2 polarization, seen in a house dust mite exposure model. In addition, enhanced Th1 and Th1 immune responses are seen in experimental allergic encephalomyelitis. Blockade of ICOSL rescues T cell ICOS surface expression and at least partially rescues both TFH numbers and the abnormal antibody production previously reported in these mice. Overall, we propose a novel regulation of the ICOS:ICOSL axis, with ADAM10 playing a direct role in regulating ICOSL as well as indirectly regulating ICOS, thus controlling ICOS:ICOSL-dependent responses.
Additionally, we report a specific role for the metalloprotease ADAM10 on B cells in regulating both ICOSL and ICOS in a mouse model of increased humoral immunity using mir146a-/- mice and a model of lymphoproliferative disease using the well characterized lpr model. B6lpr mice lacking ADAM10 on B cells (A10Blpr) have decreased nodal proliferation and T cell accumulation compared to control B6lpr mice. Additionally, A10Blpr mice have a drastic reduction in autoimmune anti-dsDNA antibody production. In line with this, we found a significant reduction in follicular helper T cells (TFH) and germinal center (GC) B cells in these mice. We also show that lymphoproliferation in this model is closely tied to elevated ICOS levels and decreased ICOSL levels. Overall, our data not only shows a role of B cell ADAM10 in controlling autoimmunity, but also increases our understanding of the regulation of ICOS and ICOSL in the context of autoimmunity.
Additionally, we found that ADAM17 is important for marginal zone (MZ) B cell development as well as responses to T-independent type 2 (TI2) immunizations. Mice which lack ADAM17 on B cells (A17B) have decreased MZ B cell numbers but have increased levels of antigen specific antibodies in response to TI2 Immunizations. ADAM17 also regulates the level of several surface molecules on plasma cells and MZ B cells necessary for their function and survival.
We also show a role for ADAM17 in ILC2 responsiveness to IL-33. In vivo, mice that lack ADAM17 specifically on ILC2s (ADAM17ILC2-/-) exhibit decreased ILC2 expansion in response to intranasal IL-33 as well as Nippostrongylus brasiliensis (Nb) infection. However, ADAM17ILC2-/- mice have normal ILC2 numbers in a naïve state, suggesting this defect in ILC2 function is limited to cell activation. In vitro, ADAM17 inhibited ILC2s have an increased level of apoptosis and less IL-13 production in response to IL-33 compared to vehicle treated ILC2s. The defect in cytokine production following ADAM17 inhibition is not observed in response to IL-25 stimulation, suggesting this defect is limited to IL-33 stimulation Mechanistically, ADAM17 inhibition in ILC2s specifically causes a defect in IL-33 mediated ERK activation, potentially explaining the defective survival and IL-13 production following ADAM17 inhibition in these cells. Additionally, ADAM17 regulates the level of surface IL1R2 which may affect IL-33 signaling in ILC2s.
40
Brock, Robert W. "The initiation of remote hepatic injury, humoral and cellular mediators." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/NQ58201.pdf.
41
Atta, Mustafa S. "Investigation of the humoral and cellular features of autoimmune diseases." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.281586.
42
Wong, Garret Drew. "Human humoral immunity to respiratory syncytial virus, correlates of disease severity and protection." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0004/MQ32975.pdf.
43
Majid, Amir Abdul Fattah Abdul. "Humoral immunity to melanoma antigens in patients with benign & malignant pigmented dermatoses." Thesis, University of London, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.362838.
44
White, Sarah Elise, and Sarah Elise White. "Can current methods of immune rejuvenation improve humoral immunity against a viral infection?" Thesis, The University of Arizona, 2017. http://hdl.handle.net/10150/626801.
Анотація:
The process of aging impacts immune defense against infection. This is attributed to
immunosenescence, which is defined as a gradual decline in the function of the immune system.
This decline is widespread, affecting both cell-mediated and humoral immunity, which both play
an integral role in pathogen recognition and elimination. Lymphoid organs are known to undergo
structural and functional changes with age and understanding these changes and how they can be
prevented or reversed is critical if we are to improve immunity in older adults. We studied two
immune rejuvenation methods: the administration of a gonadotropin-releasing hormone
antagonist, degarelix, and injection of interleukin-7:antibody complexes, and have specifically
addressed their impact on humoral immunity against West Nile virus (WNV). We found that
while each intervention improved certain aspects of immune cell generation and/or maintenance,
neither of the two was able to improve humoral immune responses or immune defense against
WNV. Results are discussed in light of current strategies for immune rejuvenation.
45
Blevins, Sarah. "Characterizing Compensatory Effects of Silymarin on Gossypol Toxicosis in Lines of Chickens Divergently Selected for Humoral Immune Response." Thesis, Virginia Tech, 2009. http://hdl.handle.net/10919/34609.
Анотація:
Feed costs are approximately 70% of total production cost for poultry producers.
Poultry diets in the United States generally consist of 2 grains: corn and soybean meal.
In recent years, the cost of these grains has dramatically increased. Due to these price
increases, producers seek alternative feeds that provide adequate nutrition, and are also
more affordable than â traditionalâ grains. Cottonseed meal is one alternative that is both
affordable and an excellent source of crude protein. However, cottonseed meal contains
gossypol, a pigment toxic to chickens.
This study had two main objectives. The first objective was to determine if
silymarin, an extract from milk thistle, could offset or prevent gossypol toxicosis. The
second objective was to determine if divergent selection for humoral immune response
would have an impact on the ability of the chicken to cope with gossypol toxicosis. Two
preliminary studies were conducted. One determined basal activities of liver
detoxification enzymes at various ages. The other determined concentrations of gossypol
and silymarin that should be added to the diet to elicit a response. The information
gathered from the second preliminary study was used to conduct the final experiment.
In the final experiment, chickens from each of 2 lines selected for humoral
immunity were exposed to diets containing gossypol, silymarin, gossypol and silymarin,
and a control. Humoral immunity had no impact on the ability of the chicken to cope
with gossypol toxicosis. Silymarin did not alleviate gossypol toxicosis. Future studies
will focus on using a lower gossypol concentration in the diet.Master of Science
46
Weber, Wilhelm Evert Jacob. "Cellular auto-immunity in central nervous system disease." Maastricht : Maastricht : Rijksuniversiteit Limburg ; University Library, Maastricht University [Host], 1988. http://arno.unimaas.nl/show.cgi?fid=5594.
47
Nickless, Jane Christina. "Cellular immunity to acetylcholine receptor in myasthenia gravis." Thesis, University of Bath, 1985. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.767550.
Анотація:
Nicotinic acetylcholine receptor (AChR) has been purified from Torpedo electric organ, foetal calf muscle, adult human leg muscle, and foetal human skeletal muscle, by extraction in non-ionic detergent followed by affinity purification on immobilised a-toxin. The purified AChR preparations were used to study cellular responses in vitro from patients with myasthenia gravis. In addition, several characterisation studies were carried out on the foetal calf AChR preparation. Purified foetal calf AChR was shown in isoelectric focussing experiments to focus as a single sharp peak at pH 5.2 +/- 0.1, and the receptor sedimented in sucrose density gradients as a single species with a sedimentation coefficient S20w= 9.35 +/- 0.10 S, when indirectly labelled with [125 I]-a-bungarotoxin. SDS-polyacrylamide gel electrophoresis of purified foetal calf AChR consistently showed five major protein bands with (Mr) 40, 44, 47, 52 and 57 K. The 57K protein sub-unit was always the most prominent band. A procedure by which to measure antigen-specific lymphocyte proliferation in vitro was developed and optimised in a system using tetanus toxoid and peripheral blood mononuclear leucocytes (PBL) from a normal donor recently immunised against tetanus. Conditions for the production of human T-cell growth factor (TCGF), or Interleukin 2 (IL-2) were optimised, and used in the tetanus toxoid system to develop a procedure by which antigen-specific reactive T-lymphocytes could be isolated, expanded into long-term lines, and ultimately cloned. Antigen and TCGF were required for the expansion and maintenance of the T-cell lines and clones. The AChR purification procedure was modified several times in order to obtain a workable, non-inhibitory AChR preparation for studies of myasthenia gravis in vitro. Lymphocytes, collected from myasthenic blood samples, were shown to proliferate weakly in response to purified AChR added in vitro, with a mean stimulation index (+/- SEM) of 1.72 +/- 0.12. The proliferative response did not appear to be related to the species of AChR employed, age, sex, or clinical classification of the patient, but higher stimulation indices were obtained from patients in a state of disease exacerbation at the time the sample was taken. T-cell fractionation, or reactive T-cell pre-selection steps, did not enhance the proliferative response of myasthenic lymphocytes to purified AChR in vitro, and attempts to isolate and expand AChR-autoreactive T-lymphocytes using antigen and IL-2 were unsuccessful.
48
Watkins, Marcia Linda Vivienne. "Cellular immunity of naïve and BCG vaccinated neonates." Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/10984.
Анотація:
Includes abstract.Includes bibliographical references (leaves 153-187).
Despite more than 95% vaccination coverage with Mycobacterium bovis Bacille Calmette-Guérin (BCG), tuberculosis (TB) remains epidemic in South Africa. The dichotomy that successful pregnancy is usually associated with a type 2 (Th2) cytokine profile in the newborn child, whereas immunity to Mycobacterium tuberculosis (Mtb) is associated with the development of a type 1 helper (Th1) cytokine response, could impact on the subsequent adaptive immune response to BCG vaccination. Previous studies have suggested that immune responses in early life may be defective and related to the immaturity of antigen-presenting cells and/or T cells.
49
Haque, Khawaja Mostaq Gausul. "The quantitation of cellular allo-immunity in preparation for monitoring of cellular tolerance." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.389232.
50
Zettervall, Carl-Johan. "Signaling pathways in the activation and proliferation of Drosophila melanogaster blood cells." Doctoral thesis, Umeå : Umeå centrum för molekylär patogenes (UCMP), 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-513.