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1
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.
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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.
2
Cassis, Linda 1977. "Role of progranulin in humoral immunity." Doctoral thesis, Universitat Pompeu Fabra, 2015. http://hdl.handle.net/10803/398398.
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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.<br>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.
3
Rydyznski, Carolyn E. "Natural Killer Cell Regulation of Humoral Immunity." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1535377157934852.
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Berkeley, Robert Anthony. "Immune cell carriers and humoral immunity in oncolytic virotherapy." Thesis, University of Leeds, 2018. http://etheses.whiterose.ac.uk/20532/.
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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.
5
Willems, Kristen N. "Regulation of Humoral Immunity by Pim Kinases: A Dissertation." eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/567.
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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.
6
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.
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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.<br>Ph. D.
7
Sallam, Jamal A. "Intestinal humoral immunity in man : IgA and anti-salmonella antibodies." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20766.
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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 <I>Salmonella</I> 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 <I>Salmonella</I> infection were tested against a panel of 11 <I>Salmonella</I> 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.
8
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.
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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.
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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/.
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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/.
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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.
12
Чорненька, Жанетта Анатоліївна. "CHARACTERISTIC OF INDICATORS OF CELLULAR AND HUMORAL IMMUNITY IN PATIENTS WITH DEMODECOSIS." Thesis, Материалы 72-й научно-практической конференции студентов-медиков и молодых ученых с международным участием «Актуальные проблемы современной медицины». Самарканд 11-12 мая 2018 г. С.382, 2018. http://dspace.bsmu.edu.ua:8080/xmlui/handle/123456789/14251.
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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.
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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.
14
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.
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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.<br>Master of Science
15
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.
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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.
16
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.
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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.
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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.
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Previous issue date: 2014-08-27<br>FACEPE<br>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.<br>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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Clyne, Erin Michele. "DIFFERENTIAL GENE EXPRESSION IN PERIPLANETA americana IN RESPONSE TO IMMUNIZATION WITH BEE PHOSPHOLIPASE A2." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin997793741.
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Clyne, Erin M. "DIFFERENTIAL GENE EXPRESSION IN PERIPLANETA AMERICANA IN RESPONSE TO IMMUNIZATION WITH BEE PHOSPHOLIPASE A2." University of Cincinnati / OhioLINK, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin998324478.
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Vickery, Karen. "The humoral and cellular responses to duck hepatitis B virus." Thesis, The University of Sydney, 1994. https://hdl.handle.net/2123/26913.
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Acute and chronic HBV infection and the resulting liver damage including hepatocellular carcinoma (HCC) are major health problems placing large demands on health resources. In high prevalence areas transmission occurs principally perinatally or in early childhood resulting in a high incidence of chronic life-long carriers. Progress in the study of HBV infection, replication and pathogenesis has depended to a large extent on the development of animal models such as the duck/DHBV model. Although less related to HBV than the mammalian models DHBV was used to demonstrate the unique replication strategy of hepadnaviruses and is now providing an insight into the immunological mechanisms of viral clearance or persistence. In this thesis the duck model was manipulated to provide models of both chronic carriage and acute hepatitis with viral clearance by varying the time and titre of DHBV inoculated. In addition a percutaneous needle liver biopsy which permitted multiple biopsies over a short time-span was developed.
The lack of systematic studies of the avian immune response to DHBV has limited our understanding of the epidemiology, natural history and pathogenesis of DHBV infection. There is insufficient cross reaction between avian and mammalian viral antigens to permit the use of human reagents. The development of virus-specific assays has been restricted by the lack of duck-specific reagents. A radioimmunoassay to detect anti-DHBs activity in serum was established and the humoral immune response in ducks which were either experimentally inoculated or naturally exposed to DHBV infection was studied. Anti-DHBs activity was detected in a significant number of ducks from DHBV infected flocks. The anti-DHBs activity was found to pass passively from dam to offspring and neutralised DHBV infectivity in vivo. Acquired immunity may explain the variable infectivity of DHBV when injected into day-old ducklings from different flocks from similar genetic stock.
Despite the importance of CMI in the pathogenesis of HBV infection the role of viral antigens in determining the outcome of infection is not clear. In order to determine the nature and timing of the specific immune response involved in clearance of infection the CMI of the duck/DHBV model was studied. Initially, the conditions were defined for optimum splenocyte responses to commonly used non-specific mitogens PHA, ConA and LPS and found to differ from those reported for peripheral blood mononuclear cells. The optimal conditions for antigen-specific mononuclear transformation were determined. The duck model was then used to study the CMI of uninfected. transiently or chronically infected and vaccinated ducks to antigenic stimulation and related these findings to humoral response and outcome of infection.
The rate of clearance of viral particles from the circulation is related to the dosage given rather than the age of the duck. The infection rate of adult ducks also depends on the virus dose. In individual adult ducks with slow removal of viral inoculum or uptake of virus by blood mononuclear cells is unrelated to the development of infection.
In baby ducks appearance of progeny virus occurs by 24 hours after inoculation. The lack of replication within this time frame in adult ducks or in tissue culture supernatant may reflect a higher percentage of cells refractory to infection. Adult ducks demonstrated a viraemia of limited duration and low titre while the viraemia in baby ducks was of high titre and constant. The IDso endpoint of 26-day—old ducks was found to be 1000 times the 11?0 dose of day-old ducks. A Chi-square analysis comparing livers with or without inflammation showed that DHBV positive livers had significantly (P<0.01) more inflammation than DHBV negative livers.
The repeated inoculation of adult ducks with small doses of DHBV resulted in the production of neutralising antibody and anti-DI-[Bs activity. The presence of anti-DHBs activity was determined in 168 day-old duckling, 77 two month old, 20 six month old and 99 twelve month old ducks from 3 commercial farms. Significant anti-DHBs activity was detected in 1/53 ducklings from non exposed flocks compared with 28/117 ducklings hatched from DHBV infected flocks (p<0.01). Significant anti-DHBs activity was detected in only 1/40 non-exposed ducks compared with 42/ 1 56 ducks from infected flocks (p<0.01). However, naturally occurring anti-DI-[Bs levels are lower than levels obtained in the vaccinated ducks and showed a positive correlation to DHBV exposure but a negative correlation to infection. The anti-DHBS activity in day-old ducks fiom DHBV endemic flocks suggests that immunity is transferred from dam to offspring via the egg. This passively acquired anti-DHBs activity was able to neutralise DHBV infectivity in vivo in 75% of cases (p<0.02)..
Optimisation of mitogen concentration for stimulation of duck splenic mononuclear cell cultures was 5x105cells/well. Once the cell concentration increased to le0 cells/well the unstimulated cultures exhibited blastogenesis and uptake of 3H thymidine, so that the high counts obtained for the mitogen stimulated cultures were not significantly different from those obtained for unstimulated controls. Cell numbers below 5x105cells/well resulted in decreased 3I-I thymidine uptake and lower SI. The response to each mitogen was different and there was also substantial duck to duck variation in response to mitogen stimulation. PHA at concentrations between 5 and 20pg/ml, produced good transformation (SI>3 00) from day l to 4 of culture. Peak transformation was achieved with Con A concentrations of between 10 to 20ug/ml for all four ducks tested. The transformation of SMC in response to LPS was poor when compared with that obtained with PHA or Con A in the three ducks tested. The concentration of LPS required to give maximal transformation responses varied between 10 and 40ug/ml and resulted in SI of up to 20.The optimum cell concentration for peripheral blood mononuclear cells (PBMC) varied between ducks and in order to maximise antigen or mitogen, cell concentrations needed to be optimised on an individual basis.
Maximum antigen-specific transformation varied from duck to duck but occurred between days 4 and 7. The optimum antigen concentration varied between ducks from 1 to lOOOng/ml for DHBsAg and between 10 and lOOng/ml for DHBcAg. As expected the level of transformation (SI) was not as great as that obtained with stimulation with PHA which would be expected to stimulate a greater number of cells non-specifically. However, the antigen specific transformation response was similar to that obtained by stimulation with LPS.
In acute DHBV infection PBMC from 2/8 and 3/8 responded to stimulation core or surface antigen respectively with one duck responding to both antigens. Both ducks that responded to core antigen cleared DHBV from the serum and the liver, while the ducks that responded to surface antigen cleared DHBV DNA from the serum , albeit only temporary in R89.In ducks that developed chronic DHBV infection 3/5 and 2/5 ducks responded to core and surface antigen respectively. The two ducks with the greatest liver pathology responding to DHBsAg. Vaccination with the 17kDa S protein produced a poor immunological response in the majority of ducks with only 2/4 responding with significant DHBsAg specific proliferation and one with concurrent anti-DHBs production. In the majority of immune ducks whether vaccinated or convalescent from infection the PBMC responded to stimulation by both antigens following a challenge with DHBV. However, this CMI response was temporary falling to non-significant levels quickly. The two sample Wilcoxon's rank sum test was applied to test for any significant difference between the above groups. The PBMC transformation response to both surface and core antigen in the immune ducks following challenge was significantly different from the transformation responses obtained from non-exposed ducks and ducks acutely infected with DHBV (P<0.05).
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Moran, Michael. "Moving in for the Kill: Natural Killer Cell Localization in Regulation of Humoral Immunity." University of Cincinnati / OhioLINK, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446618.
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Bin, Sofia <1990>. "Erythropoietin reduces pathogenic humoral immunity by inhibiting T Follicular Helper cell differentiation and function." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2021. http://amsdottorato.unibo.it/9694/1/TesiPhD_SofiaBin_Final.pdf.
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A large fraction of organ transplant recipients develop anti-donor antibodies (DSA), with accelerated graft loss and increased mortality. We tested the hypothesis that erythropoietin (EPO) reduces DSA formation by inhibiting T follicular helper (TFH) cells.
We measured DSA levels, splenic TFH, TFR cells, germinal center (GC), and class switched B cells, in murine models of allogeneic sensitization, allogeneic transplantation and in parent-to-F1 models of graft versus host disease (GVHD).
We quantified the same cell subsets and specific antibodies, upon EPO or vehicle treatment, in wild type mice and animals lacking EPO receptor selectively on T or B cells, immunized with T-independent or T-dependent stimuli.
In vitro, we tested the EPO effect on TFH induction. We isolated TFH and TFR cells to perform in vitro assay and clarify their role.
EPO reduced DSA levels, GC, class switched B cells, and increased the TFR/TFH ratio in the heart transplanted mice and in two GVHD models.
EPO did also reduce TFH and GC B cells in SRBC-immunized mice, while had no effect in TNP-AECM-FICOLL-immunized animals, indicating that EPO inhibits GC B cells by targeting TFH cells. EPO effects were absent in T cells EPOR conditional KO mice, confirming that EPO affects TFH in vivo through EPOR.
In vitro, EPO affected TFH induction through an EPO-EPOR-STAT5-dependent pathway.
Suppression assay demonstrated that the reduction of IgG antibodies was dependent on TFH cells, sustaining the central role of the subset in this EPO-mediated mechanism.
In conclusion, EPO prevents DSA formation in mice through a direct suppression of TFH. Development of DSA is associated with high risk of graft rejection, giving our data a strong rationale for studies testing the hypothesis that EPO administration prevents their formation in organ transplant recipients. Our findings provide a foundation for testing EPO as a treatment of antibody mediated disease processes.
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Cox, Rebecca Jane. "The humoral immune response in the peripheral blood and upper respiratory tract after influenza vaccination." Thesis, Queen Mary, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.369509.
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Flanagan, Brian. "The immunogenicity of a recombinant adenovirus expressing the SIV gag gene in mice." Thesis, University of Warwick, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265616.
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Barrault, Denise Viviane. "The putative role of humoral antibacterial peptides on Onchocerca spp. transmission by simuliids (Diptera: Simuliidae)." Thesis, Keele University, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.311729.
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Cooley, Lauren Folgosa. "The role of ADAM10, ADAM17, and Spag6 in humoral immunity and secondary lymphoid tissue architecture." VCU Scholars Compass, 2015. http://scholarscompass.vcu.edu/etd/3808.
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ADAM10, ADAM17, and SPAG6 contribute significantly to humoral immunity and secondary lymphoid tissue architecture. ADAM10 and ADAM17 are two closely related zinc-metalloproteinases. Through cleavage of their ligands CD23 and TNF, respectively, they greatly influence IgE production and secondary lymphoid tissue architecture maintenance. Th1 prone WT strains initially exhibit increased ADAM17 and TNF yet reduced ADAM10 relative to Th2 prone WT strains. In the absence of B cell ADAM10, a compensatory increase in ADAM17 and TNF cleavage is noted only in Th1 prone C57Bl/6, not Th2 prone Balb/c. B cell TNF homeostasis is important for maintaining secondary lymphoid tissue architecture. We show for the first time that excessive B cell TNF production in C57-ADAM10B-/- lymph nodes contributes to loss of B/T segregation, increased HEV number and size, fibrosis, loss of FDC networks, and impaired germinal center formation. Furthermore, B cell ADAM10, which enhances IgE production through CD23 cleavage, is shown to be a marker of Th2 susceptibility. B cell ADAM10 is elevated in Th2 prone mouse strains and allergic patients compared to Th1 prone controls and as B cell ADAM10 level increases, so does IgE production. Lastly, the B cell profile of allergic patients is determined to be B cell ADAM10highADAM17lowTNFlow.
Furthermore, the mechanism underlying reduced class-switched antibody production in C57-ADAM10B-/- mice is explored. C57-ADAM10B-/- B cells exhibit a B10, or IL-10 producing, phenotype, which is linked to reduced antibody production. Furthermore, increased Tregs noted in C57-ADAM10B-/- mice contributed to reduced class switched IgE production and disease parameters following a house dust mite airway inflammation challenge.
SPAG6, a component of the central apparatus of the “9+2” axoneme, plays a central role in flagellar stability and motility. Immune cells lack cilia, but the immunological synapse is a surrogate cilium as it utilizes the same machinery as ciliogenesis including the nucleation of microtubules at the centrosome. We demonstrate that Spag6 localizes in the centrosome and is critical for centrosome polarization at and actin clearance away from the synapse between CTL and target cells. Furthermore, improper synapse formation and function likely explains reduced CTL function and class-switched antibody production in Spag6KO mice.
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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/.
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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 infecção<br>Canine 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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Effertz, Bernard Stephen. "The humoral immune response to streptococcal cell wall-induced arthritis in the rat." Diss., The University of Arizona, 1989. http://hdl.handle.net/10150/184877.
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I investigated the humoral immune response to streptococcal cell walls (SCW) in arthritis susceptible Lewis and resistant Fisher rats. All rats were given a single intraperitoneal injection of either SCW or saline (controls). Rats were sacrificed, three rats per time point, over an eleven week period and serum was collected for ELISA. SCW injected Lewis rats produced anti-SCW antibody, whereas control rats did not. Anti-SCW antibody was significantly elevated over controls between days 14-28 (post injection). Both saline and SCW injected Fisher rats produced anti-SCW antibody, but with different kinetics. Anti-SCW antibody increased by day 7 and remained elevated over controls till day 21, after which there was no difference. ELISA were designed to determine the SCW epitope(s) recognized by anti-SCW antibody. Formamide extracts of SCW, peptidoglycan and polysaccharide, were investigated along with the terminal epitope of polysaccharide, N-acetyl-D-glucosamine, and the peptidoglycan precursor peptide. The data revealed that anti-SCW antibody was directed against a combined SCW epitope, given the lack of significant binding to any of the SCW epitopes tested. Isotype analysis of anti-SCW antibody revealed that the Lewis response was composed primarily of IgG2a whereas the Fisher response was composed primarily of IgM. Binding of rat IgG isotypes to whole streptococcus, SCW, peptidoglycan, and polysaccharide was investigated, given the possibility of background binding by the streptococcal Fc-receptor. Streptococcal binding of rat IgG was specific for IgG2c and the polysaccharide portion of SCW was necessary for binding. Passive immunization of naive Lewis rats with antibody from rats with active arthritis was ineffective at transferring the disease. However, subcutaneous injection of affinity purified anti-SCW antibody or IgG into Lewis rats, followed twenty-four hours later by a single intraperitoneal injection of SCW, suppressed the acute phase and inhibited the chronic disease. IgM rheumatoid factor (RF) was present in the serum of both saline and SCW injected Lewis and Fisher rats. However, SCW injection only induced a significant increase in IgM RF (between days 3-7) in Lewis rats. Passive immunization of Fisher rats with affinity purified IgM RF (from Lewis serum), three days post SCW injection, was ineffective at inducing arthritis.
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Tsukuda, Lilia Rios. "Imunidade humoral na toxoplasmose ocular." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-29012008-155252/.
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T. gondii é um protozoário amplamente disseminado pelo mundo que pode causar doença em animais e humanos. A evolução e a gravidade da doença dependem de características genéticas do parasita e do hospedeiro. A prevalência varia geograficamente, em Erechim, RS, 88% da população é soropositiva e 18% destes apresentam toxoplasmose ocular (TO). A resposta imune humoral contra T. gondii é persistente em todas as fases da infecção. O objetivo deste retrospectivo estudo foi correlacionar a imunidade humoral e a resposta contra peptídeos cepa-específicos com a gravidade da TO em pacientes de Erechim. 327 amostras de soro foram testadas (ELISA) para a pesquisa dos isótipos específicos e contra peptídeos cepa-específicos de regiões polimórficas (GRA6 e GRA7) do parasita. Nossos resultados sugerem que IgG2 e IgG3 estão associados à infecção adquirida recente, porém não há associação entre os isótipos e a evolução clínica da TO. Entretanto, embora seis diferentes sorotipos infectem estes pacientes, a gravidade da TO está associada a um novo padrão sorotípico (Atípico D).<br>T. gondii is a widespread protozoan parasite that is associated with a large spectrum of diseases in both humans and animals. The progression and severity of disease is quite variable and presumably due to some combination of host and parasite genetics. Prevalence varies with geography. In Erechim, Brazil, it is 88% prevalent and is related with a high incidence (18%) of ocular toxoplasmosis (OT). Humoral immune response against the parasite is effective. The aim of this retrospective study was to correlate the humoral immunity and response against the strain-specific peptides with the severity of the TO in Erechim`s patients. 327 sera were evaluated by ELISA to isotypes, IgG avidity and serotyped using strain-specific polymorphic peptides (GRA6 and GRA7). Our results suggest that IgG2 and IgG3 were associated with recent acquired infection. However, there is no association between isotypes and clinical evolution of OT, and also 6 different serotype-strains were detected in this population, but only one of these (Atypical D) was strongly associated with severe OT.
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Skott, Pia. "HIV induced humoral immune response with specific relevance to IgA /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-240-x/.
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Suppiah, Aravind. "Humoral immunity in colorectal cancer : evaluation of the anti-p53 and anti-hTERT auto-antibody responses." Thesis, University of Hull, 2010. http://hydra.hull.ac.uk/resources/hull:5741.
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Carcinogenesis is a multi-factorial and multi-aetiological process involving suppressions, alterations and re-activation of key biomolecular markers. Some of these changes are recognised by the humoral system and are known as Tumour Associated Antigens (TAA) against which the humoral system is able to mount an auto-antibody response. Cancer cells are subject to two key mortality barriers (M1 & M2) as described in the "2-hit" hypothesis which are overcome by p53 dysfunction (M1) and hTERT re-expression (M2). These two molecular events generate TAA which are recognised by the humoral immune system with a corresponding auto-antibody response. The aim of this thesis was to investigate the significance of the humoral anti-p53 auto-antibody and anti-hTERT auto-antibody responses in colorectal cancer (CRC). This was performed by evaluating all published literature (1979-2009) on anti-p53 auto-antibody response and its association with p53 mutation to provide the largest cumulative sample size to date spanning 30 years. A critical review was performed of all anti-p53 auto-antibody studies in CRC, followed by an investigation into the long-term prognostic significance (minimum 5 years follow-up) of anti-p53 auto-antibody in CRC. The second aim of this thesis was to optimise a method of detecting anti-hTERT in CRC patients and correlate this with anti-p53 auto-antibody in order to investigate the significance of a joint humoral response against the two key TAA responsible for CRC immortality. The overall prevalence of anti-p53 auto-antibody was 18.4% (3292/17,859) in all cancers and 2.2% (88/3,946) in normal/benign disease controls. The anti-p53 autoantibody presence in all published cancers reports was plotted against the reported p53 mutational rates in individual cancers and showed partial correlation (R2=0.5, correlation=0.7) between anti-p53 auto-antibody presence and p53 mutation. Anti-p53 was present in 21.5% (786/3,653) in all CRC only studies, and 19.9% (479/2,409) in CRC studies using ELISA. Anti-p53 was not associated with clinico-pathological factors or prognosis in majority of the studies. Only 4 studies associate anti-53 autoantibody with adverse clinico-pathological parameters, mostly in selective groups. The weaknesses of these studies are discussed. This association leads to anti-p53 association with adverse prognosis but only in selective analysis. The prognostic significance is observed in univariate analysis but lost in multivariate analysis when stronger traditional prognostic factors are incorporated. This thesis initially compared serum with plasma anti-p53 auto-antibody titres and excluded plasma titres from further analysis due to the potential contamination by non-specific binding leading to falsely elevated levels (17-73% variation) of anti-p53 auto-antibody. Serum anti-p53 auto-antibody was present in 21.7% (20/92) CRC patients and 0% (0/20) controls. There was no association with age (p=0.750), sex (p-0.468), Dukes' / TNM stage (p=1.000), T- (p=0.900), N- (p=0.912), M-stage (p=0.632), location (p=0.175), differentiation (p=0.117) or mucinous component (p=0.699). The median follow-up was 97 months with median DPS and OS of 73 months and 62 months respectively. Dukes' / TNM stage, T-, N-, M-stage were prognostic indicators in univariate DFS and OS analysis. Only Dukes'/TNM stage remained an independent prognostic indicators in multivariate analysis (p=0.001). Anti-p53 auto-antibody did not display prognostic significance in univariate or multivariate analysis of OS or DFS. Anti-hTERT auto-antibody has only been reported once in the literature, using molecular recombination to develop hTERT antigen. This thesis optimisation processes aimed develop a method of detecting anti-hTERT using less restrictive technology, and further development of a WB or ELISA to allow mass detection of serum anti-hTERT. The first step aimed to isolate hTERT using a streptavidin immune-affinity column with biotinylated anti-hTERT to capture hTERT from cancer cell lysates. This was unsuccessful and further attempts were made at identifying hTERT using Western blot (WB). Five different anti-hTERT antibodies and a multitude of WB conditions were trialled in duplicate (>100 WB), each with multiple ECL exposures. hTERT was not identified. The reason for this was narrowed down in the final experiments to the lack of specificity of the primary antibodies available. The raising of a sufficiently specific anti-hTERT antibody is required to isolate hTERT antigen. Early CRC detection is vital in improving outcomes. The humoral response to TAA incarcinogenesis could enable earlier identification of CRC and impact prognosis.
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Thyagarajan, Radha. "Anomalies in humoral immunity in the NOD mouse : contribution to the progression of type 1 diabetes." Doctoral thesis, Umeå universitet, Immunologi/immunkemi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125001.
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The non-obese diabetic (NOD) mouse is widely used model Type 1 diabetes (T1D), a chronic inflammatory disease characterized by destruction of the insulin producing β cells in the islets of Langerhans by immune cells. The classical symptoms include increased glucose levels in urine and blood, frequent urination and enhanced thirst. The disease has a strong genetic component and is also influenced by the environment. NOD mice develop T1D spontaneously. The disease occurs in two phases; insulitis - the infiltration of immune cells in the islets of Langerhans and overt diabetes caused by the destruction of insulin producing β cells. Several disease associated gene regions or loci [termed insulin dependent diabetes (Idd) loci] have been associated with T1D development. Although, T1D is recognized as a T cell mediated disease in both mouse and man, many studies have shown the importance of B cells in the pathogenesis of the disease. Autoantibodies appear prior to islet infiltration and several molecular and cellular events precede this beta-cell autoimmunity. Although the pathogenesis of T1D is well characterized, less is known about the environmental and immunological factors that trigger the disease. In this thesis, we studied the contribution of B cell anomalies to the skewed immune response observed in the NOD mouse. In our studies covered in the thesis we observed that NOD mice display enhanced IgE in the serum already at one week of age. In addition, upon treatment of pre-diabetic NOD mice with anti-IgE antibodies, diabetes incidence was delayed. We hypothesize that the presence of IgE in the system may be explained due to enhanced class switching. Antibody feedback however, is an essential component of the immune response and can lead to either enhanced or dampened responses. Thus, increased IgE may provide positive feedback that might sustain an immune response. We also aimed to analyze the biological consequence of this feature. In vitro stimulation of B cells by the TACI ligand APRIL resulted in enhanced plasma cell differentiation accompanied with increased class switching and IgG production. In addition, TACI+ cells were observed in NOD germinal centers facilitating increased BAFF uptake and subsequent escape of low affinity antibody producing clones. NOD mice elicited an enhanced and prolonged immune response towards T-dependent antigens such as hen-egg lysozyme (HEL). Serum HEL-specific IgG level was significantly increased and was predominantly of the IgG1 isotype. Immunofluorescence analysis of NOD spleen revealed the presence of spontaneous germinal centers which others have perceived to provide a ready niche for the entry of naïve B cells that encountered novel antigen. Adoptive transfer experiments of purified B and T cells from NOD into NOD.Rag2-/- (NOD-RAG) mice illustrated the importance of B cell intrinsic defects in the reproduction of the original phenotype as observed in NOD.
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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.
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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.<br>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.
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Previous issue date: 2014-02-21<br>Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES<br>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.<br>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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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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Zorzeto, Tatiane Queiroz. "Resposta humoral e celular de lactentes vacinados com pertussis celular total ou modificada pela extração de lipopolissacarideo." [s.n.], 2008. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311081.
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Orientador: Maria Marluce dos Santos Vilela<br>Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas<br>Made available in DSpace on 2018-08-11T01:20:12Z (GMT). No. of bitstreams: 1
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Previous issue date: 2008<br>Resumo: A associação temporal de eventos adversos de variada gravidade à imunização com pertussis celular total (DTP) tem estimulado o desenvolvimento de vacinas antipertussis menos reatogênicas. Este ensaio clínico fase I visou à avaliação da imunogenicidade da vacina pertussis celular modificada pela extração do lipopolissacarídeo (DTPm) em comparação com a vacina convencional (DTP). Um total de 234 lactentes foi imunizado aos dois, quatro e seis meses de idade com DTPm ou DTP. Os títulos de anticorpos para os componentes pertussis, tétano, difteria e hepatite B foram determinados um mês após a terceira dose de vacina. A proliferação de células T CD3+ foi avaliada por citometria de fluxo após seis dias de cultivo de células mononucleares de sangue periférico estimuladas com células inativadas de B. pertussis ou com fitohemaglutinina (PHA). Células CD4+, CD8+ e TCR ?d+ foram identificadas no gate de blastos. Os níveis de IFN-?, TNF-a, IL-4 e IL-10 no sobrenadante de cultura foram quantificados por ensaio imunoenzimático (ELISA). A vacina modificada DTPm mostrou-se inferior à DTP quanto ao título de anticorpos antipertussis, mas não houve diferença de resposta aos outros componentes vacinais avaliados. A porcentagem líquida de blastos sob estímulo da B. pertussis foi menor no grupo que recebeu três doses de DTPm (mediana de 3,9% para DTPm e 6,2% para DTP, p=0,029), mas as freqüências de células CD4+, CD8+ e ?d+ em proliferação e as concentrações de citocinas não diferiram entre os grupos. A vacina DTPm não apresentou, portanto, imunogenicidade similar à da vacina DTP convencional nos ensaios laboratoriais<br>Abstract: Concerns about systemic reactions after immunization with whole-cell pertussis (wP) have stimulated efforts to produce less reactogenic vaccines. This phase I comparative trial aimed the efficacy evaluation of a cellular pertussis vaccine with low lipopolysaccharide (LPS) content (wPlow) in comparison to conventional wP vaccine. A total of 234 infants was vaccinated at 2, 4, and 6 months with conventional wP or wPlow. Serum antibody titers to pertussis, diphtheria, tetanus and hepatitis B were measured 1 month after the third dose of vaccine. Proliferation of CD3+ T cells was evaluated by flow cytometry after 6 days of peripheral blood mononuclear cells culture, with heat-killed B. pertussis or phytohemagglutinin (PHA) stimulation. CD4+, CD8+ and TCR ?d+ cells were identified in the gate of blast lymphocytes. IFN-?, TNF-a, IL-4 and IL-10 levels in supernatants were determined by ELISA. wPlow was inferior to wP in terms of anti-pertussis titers, but there was no diference in other serum antibody evaluations. Net percent blasts in cultures with B. pertussis was lower in the group vaccinated with wPlow (medians of 3.9% and for wPlow and 6.2% for wP; p=0.029), but the frequency of proliferating CD4+, CD8+ and ?d+ cells and the cytokine concentrations in supernatants were similar between vaccination groups. Therefore, wPlow wasn't as imunogenic as conventional wP in experimental evaluations<br>Mestrado<br>Saude da Criança e do Adolescente<br>Mestre em Saude da Criança e do Adolescente
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Feola, David James. "EFFECT OF COMBINATION EXPOSURE TO ZIDOVUDINE AND SULFAMETHOXAZOLE-TRIMETHOPRIM ON IMMUNE RESPONSE IN MICE AND HUMANS." UKnowledge, 2005. http://uknowledge.uky.edu/gradschool_diss/411.
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The drug-drug interaction involving zidovudine and sulfamethoxazole-trimethoprim was investigated using an in vitro culture system, an in vivo mouse model, and a clinical trial in HIV-infected patients. We hypothesized that combination exposure causes immune cell populations in the bone marrow to undergo apoptotic cell death, and that the toxicity would affect the host response to an infectious stimulus. Mice were dosed with zidovudine, sulfamethoxazole-trimethoprim, the combination of both drugs, or vehicle only control via oral gavage. Focusing on B-lineage cells in the bone marrow, we determined that cells of the rapidly cycling, early pre-B cell subset are targeted, as well as pro-B cells earlier in development. This toxicity was found to be cell cycle dependent, with an increase in percentage of cells in the S/G2/M phases of the cycle. In vitro experiments using the drugs in a bone marrow culture system demonstrated that the effect of cytotoxicity with combination exposure is synergistic and concentration-dependent. The mechanism of apoptosis that is induced appears to be caspase-independent. To measure host response in mice, animals treated with zidovudine plus sulfamethoxazole-trimethoprim were infected with Pneumocystis murina pneumonia, and the group that received the combination of agents had a blunted antigen-specific IgG response, possibly due to a decreased number of B cells and activated B cells in the draining lymph nodes of the lungs. A clinical trial was conducted in HIV-infected patients, dividing subjects into groups receiving zidovudine, sulfamethoxazole-trimethoprim, the combination of both, or neither agent. Upon vaccination with the influenza vaccine, the combination treatment group had a blunted humoral response, with reduced antigen-specific serum IgG titers as compared to the control group. We conclude that the drug-drug interaction involving zidovudine and sulfamethoxazole-trimethoprim is clinically-significant, and clinicians must consider this toxicity when treating patients with these agents concurrently.
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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.
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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.<br>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.
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Горбась, Вікторія Анатоліївна, Виктория Анатольевна Горбась, Viktoriia Anatoliivna Horbas, Олександр Іванович Сміян, Александр Иванович Смиян та Oleksandr Ivanovych Smiian. "Стан гуморального імунітету у дітей шкільного віку з негоспітальними пневмоніями". Thesis, Вид-во СумДУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/5647.
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Метою роботи явилось вивчення особливостей гуморального імунітету у дітей з негоспітальними пневмоніями (НП) в залежності від періоду захворювання, тяжкості перебігу запального процесу
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/5647
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Купина, Максим Вікторович, Максим Викторович Купина, Maksym Viktorovych Kupyna, Микола Микитович Каплін, Николай Никитович Каплин, Mykola Mykytovych Kaplin та В. В. Купина. "Стан гуморального імунітету в залежності від стадії захворювання у хворих різних вікових груп з деформуючим спондилоартрозом поперекового відділу хребта". Thesis, Вид-во СумДУ, 2007. http://essuir.sumdu.edu.ua/handle/123456789/5124.
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Купина, О. В., Максим Вікторович Купина, Максим Викторович Купина та Maksym Viktorovych Kupyna. "Ефективність лікування пневмоній залежно від стану гуморального імунітету". Thesis, Видавництво СумДУ, 2009. http://essuir.sumdu.edu.ua/handle/123456789/4550.
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Kummu, O. (Outi). "Humoral immune response to carbamyl-epitopes in atherosclerosis." Doctoral thesis, Oulun yliopisto, 2014. http://urn.fi/urn:isbn:9789526205670.
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Abstract Carbamylation of proteins in vivo occurs by cyanate, non-enzymatically when urea is dissociated, and by myeloperoxidase-catalyzed oxidation from thiocyanate. Carbamylation of low-density lipoprotein is suggested to enhance atherogenesis in patients with with chronic kidney disease and uremia. This thesis study assessed the questions of whether healthy humans or uremic patients under enhanced carbamylation have antibodies recognizing carbamyl-epitopes in plasma, and what is their role in vivo. Also, humoral immune response to carbamyl-LDL immunization and its impact on atherogenesis in LDLR-/- mice was investigated. In this thesis study, plasma antibodies to carbamylated proteins were detected in humans, and IgG antibodies to carbamylated proteins were associated with uremia and smoking, conditions with enhanced carbamylation. The human IgG and IgM antibodies binding to carbamyl-epitopes were associated with oxidation-specific epitopes in plasma. Monoclonal Fab antibodies with characteristics of a natural antibody and ability to bind both carbamyl- and malondialdehyde-derived epitopes were cloned from healthy humans. An investigated Fab antibody was able to bind epitopes found in atherosclerotic lesions and inhibit the uptake of modified LDL by macrophages. Human plasma antibodies and the monoclonal Fab bound to epitopes found on apoptotic cells. Human B-cells secreted antibodies with similar cross-reactive binding properties between carbamyl- and malondialdehyde adducts and apoptotic cells in vitro. Immunization with mouse carbamyl-LDL without adjuvant resulted in specific IgG immune response in LDLR-/- mice, but also a cross-reaction with malondialdehyde-adducts was observed. Carbamyl-LDL immunized mice had enhanced plasma antibody binding to apoptotic cells. Carbamyl-LDL immunization did not affect atherogenesis in mice. This thesis demonstrates that IgG antibodies to carbamyl-epitope might serve as a novel indicator of carbamylation in vivo in uremic patients or smokers. The cross-reactivity between antibodies binding to carbamylated and oxidation-specific epitopes, and apoptotic cells may have a role in explaining the link between enhanced atherogenesis and kidney disease<br>Tiivistelmä Proteiinien karbamylaatiota tapahtuu syanaatin vaikutuksesta. Sitä muodostuu urean hajotessa tai myeloperoksidaasin katalysoimana tiosyanaatin hapettuessa. Low-density lipoproteiinin eli LDL:n karbamylaation on esitetty edistävän valtimonkovettumataudin eli ateroskleroosin kehittymistä munuaisten vajaatoimintaa sairastavilla ureemisilla potilailla. Väitöskirjatyössä tutkittiin, onko terveillä ihmisillä ja ureemisilla potilailla karbamyyli-epitooppeja tunnistavia vasta-aineita, ja mikä niiden merkitys on elimistössä. Humoraalista immuunivastetta karbamyyli-LDL-immunisaation jälkeen sekä sen vaikutusta ateroskleroosin kehittymiseen tutkittiin LDL-reseptoripuutteellisilla hiirillä. Tutkimuksessa osoitettiin, että ihmisillä on plasmassa karbamyloituja proteiineja tunnistavia vasta-aineita. IgG-luokan vasta-aineet ovat yhteydessä uremiaan ja tupakointiin, joissa karbamylaatio on lisääntynyt. Karbamyyli- ja hapettuneita epitooppeja tunnistavien plasman IgG- ja IgM-vasta-aineiden välillä havaittiin olevan yhteys. Työssä kloonattiin terveistä ihmisistä monoklonaalisia Fab-vasta-aineita, joilla on luonnollisten vasta-aineiden kaltaisia ominaisuuksia ja kyky sitoutua sekä karbamyyli- että malonidialdehydi-epitooppeihin. Yksi tutkittu Fab-vasta-aine sitoutui valtimonkovettumataudin ateroomissa oleviin epitooppeihin ja esti muuntuneen LDL:n sisäänoton makrofagi-soluihin. Ihmisen plasman vasta-aineet ja monoklonaalinen Fab-vasta-aine sitoutuivat apoptoottisten solujen pinnalla oleviin rakenteisiin. Soluviljelyolosuhteissa ihmisen B-solut tuottivat vasta-aineita, joilla oli samanlaisia ristireaktio-ominaisuuksia karbamyyli- ja malonidialdehydi-epitooppeja sekä apoptoottisia soluja kohtaan. Karbamyyli-LDL-immunisaatio sai aikaan IgG-immuunivasteen hiirillä karbamyyli-LDL:a kohtaan, mutta myös ristireaktio malonidialdehydi-rakenteita sekä apoptoottisia soluja kohtaan havaittiin. Karbamyyli-LDL-immunisaatio ei vaikuttanut ateroskleroosin kehittymiseen hiirillä. Tutkimus osoittaa, että IgG-vasta-aineet karbamyyli-epitooppeja kohtaan voivat olla uudenlainen karbamylaation merkkiaine elimistössä ureemisilla potilailla ja tupakoitsijoilla. Karbamyloituneiden ja hapettuneiden epitooppien sekä apoptoottisten solujen välillä havaituilla vasta-aineiden ristireaktioilla voi olla merkitystä valtimonkovettumataudin etenemiseen munuaisten vajaatoiminnassa
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Antonio, Aline Lavezo. "Carcinogênese induzida por DMBA em camundongo selecionados para a alta ou baixa produção de anticorpos." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-24092014-180622/.
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A tumorigênese cutânea é determinada pela combinação de diversos fatores genéticos e ambientais, que envolvem múltiplos eventos onde as células epiteliais podem progredir e se desenvolverem. Todo esse processo é associado com alterações da imunidade celular e humoral. Muitos fatores físicos e químicos podem predispor ao câncer de pele, como o carcinógeno DMBA, com ação iniciadora e promotora. Camundongos geneticamente selecionados para a alta (High) ou baixa (Low) produção de anticorpos constituem uma excelente ferramenta para o estudo da influência da imunidade humoral no desenvolvimento de tumores. Foram avaliados camundongos das linhagens High e Low submetidos ao tratamento com o DMBA na pele após 48 horas, 120 e 240 dias. Mostramos que a linhagem selecionada para a maior produção de anticorpos (High) é a mais sensível ao tratamento com formação de lesões que progrediram para o desenvolvimento de papilomas, apresentando maior incidência e multiplicidade tumoral que os animais Low. Os machos da linhagem High também desenvolveram tumores nos pulmões em decorrência do tratamento com o DMBA na pele. O perfil de citocinas avaliado mostrou que os animais Low tem maior expressão gênica de IFN-g e IL-6 do que os animais High, e estes maior expressão de IL-1b e Cxcl2 que os animais Low após 48 horas do tratamento. A secreção de IL-6 também foi maior nos animais Low com 48 horas, sendo que a produção de TGF-b foi maior nos animais High aos 120 dias. Estes resultados sugerem que na linhagem High o perfil de resposta celular seja do tipo Th2 com produção de IL-10 e TGF-b, o que favorece o surgimento de tumores, e na linhagem Low, a resposta celular seja do tipo Th1, pela presença de IFN-g e TNF-α, favorecendo o reparo tecidual. Como não foram encontradas diferenças na via de metabolização pelas enzimas do citocromo P450 e no polimorfismo do receptor Ahr, outros fatores podem estar relacionados aos fenótipos observados. Assim, estas linhagens geneticamente selecionadas que diferem quanto à capacidade de secreção de anticorpos, representam uma nova ferramenta para o estudo de fatores genéticos que influenciam o microambiente na predisposição ao câncer.<br>The skin tumorigenesis is determined by the combination of various genetic and environmental factors, involving multiple events, where epithelial cells can progress and develop. This entire process is associated with changes in cellular and humoral immunity. Many physical and chemical factors may predispose to skin cancer, such as DMBA carcinogen with initiating and promoting action. Mice genetically selected for high (High) or low (Low) antibody production are an excellent tool for studying the influence of humoral immunity in the development of tumors. High and Low mice were treated with DMBA on the skin and, after 48 hours, 120 and 240 days, they were evaluated. We showed that High mice are more sensitive to DMBA treatment, presenting lesions that progressed to the development of papillomas and showing higher incidence and tumor multiplicity than Low ones. Males of High strain have also developed lung tumors as a result of treatment with DMBA on the skin. The profile of cytokines evaluated of Low animals showed that gene expression of IFN-g and IL-6 is more elevated than the one observed in High mice; on the other hand, IL- 1b and CXCL2 are increased in High animals, 48 hours after treatment. The secretion of IL-6 was also greater in Low animals, and TGF-b was higher in High animals, after 120 days of treatment. These results suggest that the High mice response has a Th2 profile with secretion of IL- 10 and TGF-b, which favors the growth of tumors; on the other hand, Low mice have a Th1 response, due to the presence of IFNg and TNFα, favoring tissue repair. As no differences were found in the enzymes of cytochrome P450 and in the polymorphism of Ahr receptor, other factors may be related to the observed phenotypes. Thus, these genetically selected mice which differ in the ability to secrete antibodies represent a new tool for the study of genetic factors influencing the microenvironment in its predisposition to cancer.
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Vila, Nova Ana Beatriz de Matos Machado. "Avaliação da resposta imunitária humoral induzida pela vacinação para esgana e parvovirose caninas." Master's thesis, Universidade de Lisboa, Faculdade de Medicina Veterinária, 2017. http://hdl.handle.net/10400.5/13950.
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Dissertação de Mestrado Integrado em Medicina Veterinária<br>O vírus da esgana (CDV) e o parvovírus (CPV) são dois vírus responsáveis por elevadas taxas de mortalidade nas populações caninas, que infetam cães não vacinados ou com protocolos vacinais incompletos.
As vacinas têm desempenhado um papel fundamental na prevenção destas doenças no entanto, a vacinação não é um procedimento inócuo e deve ser realizado apenas com a frequência necessária para manter os cães imunizados. Por outro lado, são vários os fatores que podem originar falhas na imunização, sendo a neutralização do antigénio vacinal por anticorpos maternos a causa mais comum.
Neste estudo foi avaliada a proteção humoral para o CDV e CPV a 13 cachorros durante a primovacinação (Grupo A e Grupo B) e, a 7 cães adultos, não vacinados há pelo menos 3 anos (Grupo C). O grupo A incluiu 5 cachorros com início do protocolo vacinal às 6 semanas e o grupo B contemplou 8 animais que iniciaram a primovacinação entre as 8 e as 12 semanas. De cada animal foram recolhidas três amostras de sangue, coincidentes com as consultas de vacinação, com 3 a 4 semanas de intervalo.
A resposta humoral foi avaliada recorrendo a testes rápidos, baseados na técnica de ELISA indireta para deteção de anticorpos, que permitem avaliar de forma rápida, simples e económica a proteção ou suscetibilidade de cada animal.
Verificámos que a resposta à vacinação para CDV foi mais precoce em comparação com a resposta para CPV. Relativamente ao CPV, 80% dos animais do grupo A, ainda se encontravam desprotegidos após a administração de duas doses da vacina. Já os animais do grupo B revelaram proteção humoral para CPV após duas administrações vacinais, sendo que quatro animais (50%) ficaram logo protegidos após a primeira dose.
Nos cães adultos foi realizada apenas uma colheita de sangue que funcionou como um rastreio serológico para aferir a necessidade de revacinação.
Os resultados obtidos sugerem que, durante a primovacinação, a resposta à vacinação é individual e depende sobretudo do título inicial de anticorpos maternos adquirido pelo neonato. A variabilidade encontrada reforça a necessidade da determinação dos níveis de imunidade humoral individuais. Deste modo, os kits de ELISA são uma ferramenta muito vantajosa, pois permitem avaliar a proteção a um custo relativamente reduzido. Estes testes deverão ser utilizados para validar a eficácia vacinal induzida pela primovacinação, auxiliando o médico veterinário a estabelecer protocolos vacinais individuais.<br>ABSTRACT - EVALUATION OF THE HUMORAL IMMUNE RESPONSE INDUCED BY VACCINATION FOR CANINE DISTEMPER AND PARVOVIRUS - Canine distemper virus (CDV) and parvovirus (CPV) are two viruses responsible for high mortality rates in the canine population that infect unvaccinated dogs and dogs with incomplete vaccination protocols.
Vaccines continue to play a key role on the prevention of these diseases however vaccination is not an innocuous procedure and must be done only with the required frequency to keep dogs immunized. On the other hand, there are several factors that can lead to immunization failures, being the neutralization of the vaccine antigen by the maternal antibodies the main cause.
In this study, the humoral protection for CDV and CPV was evaluated in 13 dogs during primary vaccination (Group A and Group B) and in 7 adult dogs that had not been vaccinated for at least 3 years (Group C). Group A included 5 dogs which started the vaccine protocol at 6 weeks and group B included 8 animals that started primary vaccination at 8 to 12 weeks. Three blood samples were collected from each animal, coincident with the vaccination visits, at 3 to 4 weeks apart.
The humoral response was evaluated using rapid tests based on the indirect ELISA technique for antibody detection, which allow a rapid, simple and economical evaluation of the protection or susceptibility of each animal.
We found that the response to CDV vaccination was precocious compared to the response to CPV. With regard to CPV, 80% of group A dogs were still unprotected after administration of two doses of the vaccine. In contrast, the dogs of group B showed humoral protection for CPV after two vaccination administrations, with four dogs (50%) being protected immediately after the first dose.
In adult dogs, only one blood sample was taken for serological screening to estimate the need for revaccination.
The results suggest that during primary vaccination the response to vaccination is individual and mostly depends on the initial titer of maternal antibodies acquired by the neonate. The variability found supports the need to measure individual humoral immunity levels. Thus the ELISA kits are a very helpful tool, because they allow the evaluation of the protection at a relatively reduced cost. These tests should be used to validate the vaccine efficacy induced by primary vaccination, helping the veterinarian to establish individual vaccination protocols.<br>N/A
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Blanc, Pascal. "Expression et fonction du récepteur antigénique B membranaire sur les plasmocytes médullaires producteurs d'IgM." Thesis, Lyon 1, 2015. http://www.theses.fr/2015LYO10026/document.
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Le plasmocyte (PC), stade terminal de la différenciation du lymphocyte B induite par l'antigène, est la cellule effectrice de l'immunité humorale responsable de la production des anticorps. La population plasmocytaire se divise en deux grands sous-types différant par leur durée de vie et par leur localisation anatomique. On distingue ainsi les PC à durée de vie courte ou PC effecteurs (dans les tissus lymphoïdes secondaires) et les PC à longue durée de vi (LLPC ou PC à mémoire) localisés principalement dans la moelle osseuse. Ces derniers contribuent à la mémoire humorale en continuant à sécréter des anticorps protecteurs après résolution de l'infection. Nos résultats expérimentaux montrent que les Ags thymo-dépendants (TD) et les Ag thymo-indépendants (TI) induisent des PC médullaires exprimant des caractéristiques phénotypiques et fonctionnelles différentes. Ainsi, l'expression d'une forme membranaire fonctionnelle du récepteur antigénique (BCR) persiste sur les LLPC TI alors qu'elle est perdue sur les LLPC TD. Cette fonctionnalité nouvelle portée par les PC médullaires TI n'est pas dépendante de la sous population lymphocytaire B recrutée ni de la nature de l'Ag, mais de l'isotype IgM. Nos résultats montrent également que cette population de PC médullaires a les caractéristiques des LLPC : ces PC sont quiescents, ils demeurent dans la moelle osseuse jusqu'à 180 jours et sont phénotypiquement semblables aux LLPC. Nos travaux ont permis de montrer que les LLPC à IgM sont capables de reconnaître l'Ag et que l'engagement de leur BCR par l'Ag conduit à la production d'IL10<br>Plasma cells (PC) represent the terminal differentiation stage of B lymphocytes. Their canonical function is to secrete antibodies (Abs). PC differentiation is driven by remodeling of the B cell transcriptional program, highlighted by the induction of the transcriptional repressor Blimp-1 and repression of Pax5, considered as the guardian of B cell identity. The dogma holds that PC, as opposed to B cells, have lost the Ag recognition capacity because they have switched from expression of a membrane-bound Ag receptor (mBCR) to production of the secreted form of the BCR (Abs). Here, we have compared the phenotypical and functional attributes of memory PC generated by the T cell-dependent (TD) and T-cell independent (TI) forms of the hapten NP. Our data show that TI NP-specific bone marrow (BM) PC generated by NP-dextran retain an Ag-binding capacity comparable to that of B cells long after immunization while TD NP-specific BM PC do not. We found that this difference is not imputable to the structure of the immunogen but is a specific feature of IgM-expressing PC, which are prominent in response to TI Ag. Upon Ag recognition in vitro, the mBCR of IgM+ BM PC promotes: i) Ca++ mobilization, ii) phosphorylation of Syk and Blnk, iii) Ag internalization and phosphorylation of the late endosomal kinase Erk. Finally, we demonstrate that Ag recall in vivo induces significant changes in the gene expression profile of NP-specific IgM+ BM PC with evidence for activation of a cytokine production program characterized in particular by up-regulation of the CCL5 and IL10 transcripts. In conclusion, our data show that IgM-expressing BM PC can sense Ag and may be driven to express a regulatory function upon Ag recall
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Neville, Judith Anne. "The extent of genotype specific humoral immunity produced on infection with hepatitis C virus : relevance for serological screening and diagnosis." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/27115.
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Sequence variation in the antigenic determinants in core, NS3, NS4A/B and NS5A/B proteins, may produce genotype-specific antibodies which do not cross-react with the antigens used in current screening assays for detection of antibody to HCV. The extent of type-specific and type-common components of the humoral immune response were investigated by measuring the antibody levels in samples of each genotype with type-homologous and type-heterologous antigens. Reactivity directed against the individual genotype 1 antigens used in a commercially available anti-HCV screening assay (VK48; Murex Biotech) was compared with corresponding core, NS3 and NS4A/B antigens of genotype 3, and NS3, NS4A/B and NS5A/B antigens from genotype 4 using a panel of samples from individuals infected with different genotypes (genotype 1: n=41, 3: n=39 and 4: n=42). A combined ELISA was subsequently assembled using the core, NS3 and NS5A/B recombinant proteins and NS4A/B synthetic peptide of genotype 3a sequence, and serological reactivity in this ELISA compared quantitatively with reactivity in the (type 1-based) Murex VK48 assay, using a similar panel of samples from individuals infected with different HCV genotypes. The overall proportion of type-specific reactivity in the combined ELISAs was 46% (with the type-common component making up the other 54%). Type-specificity of reactivity to each region depended on the extent of amino acid divergence between genotypes, with the more conserved core region eliciting 26% type-specific reactivity, compared with 60% and 62-77% to the NS3 and NS5A/B regions. To investigate whether antigenic variability influenced the effectiveness of type-1 based serological assays for screening, blood donor samples collected in regions where non-genotype 1 HCV predominated, such as genotype 3 infection in Pakistan and genotype 4a infection in Egypt and the Middle East, were screened by ELISAs based on genotype 3a or 4a antigens. Additionally, samples from seroconversion panels, individuals identified with a serum positive PCR result, but a commercial assay negative result and individuals with cryptogenic hepatitis, were tested for reactivity to antigens of genotype 2, 3 or 4. Although several samples were identified with type-specific reactivity confined to non-type 1 antigens, none were PCR positive. These results therefore indicate that while some (past, resolved) HCV infections may not be detectable using commercially available type 1-based screening assays, the lack of detectable viraemia in the samples provides no evidence at present that these serological “misses” risk the safety of blood transfusion. However, the results do indicate that a proportion of past HCV infections may remain undetected by current diagnostic methods.
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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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Rogers, Kenneth Alton. "Immunoglobulins and Immunoglobulin Fc Receptors in Nonhuman Primates Commonly Used in Biomedical Research." Digital Archive @ GSU, 2006. http://digitalarchive.gsu.edu/biology_diss/6.
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Antibodies neutralize and eliminate pathogens, malignancies, and toxins by acting either alone or in association with Fc receptors which, once engaged, activate the elimination mechanisms of phagocytic cells. Based on structural differences, antibodies are divided into functionally distinct classes (IgM, IgD, IgG, IgE and IgA). Structure-function relationships within these classes are not well characterized. In addition, animal models for the assessment of potential therapeutic strategies for the modulation of the interaction between antibodies and Fc receptors are not established. Nonhuman primates are widely used to model human diseases and, represent excellent in vivo systems for this assessment. Therefore, we have studied nonhuman primate IgD as well as IgG and IgA specific Fc receptors in rhesus macaques, cynomolgus macaques, baboons and sooty mangabeys. IgD genes had not been identified in nonhuman primates nor the IgD receptors characterized in any species. We characterized IgD genes of the four monkey species, as well as chimpanzees and dogs. In contrast to other antibody classes, the IgD hinge regions are highly conserved between human and nonhuman primates, thus indicating a role in Fc receptor binding. In humans, Fc receptors CD16a (natural killer cells) and CD16b (neutrophils) bind IgG1 and IgG3, and CD89 (myeloid cells) binds IgA. To assess ligand binding and glycosylation properties of nonhuman primate CD16a, CD16b, and CD89, we sequenced, cloned, and generated recombinant molecules in a mammalian expression system. Our results verify the presence of CD16a, but not CD16b in nonhuman primates. CD16a is expressed on monocytes and a subpopulation of lymphocytes. In sooty mangabeys, CD16 is also expressed on neutrophils. Recombinant sooty mangabey/baboon CD16a binds to human IgG1 and IgG2, but not IgG3 and IgG4. Monkey CD89 has the same peripheral blood leukocyte expression profiles as humans, and binds human and recombinant macaque IgA. Blocking of N-glycans inhibited expression of CD89, but only marginally CD16a expression. Although extensive similarities of antibody/Fc receptor interactions exist between human and nonhuman primates, several differences must be considered when evaluating therapeutic strategies. However, these differences can be exploited to further characterize the structure-function relationships existing within antibody molecules and respective receptors.
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Siba, Valentine. "EFFECT OF BED NETS ON ACQUIRED HUMORAL IMMUNITY TO PLASMODIUM FALCIPARUM ANTIGENS IN CHILDREN FROM MUGIL, MADANG PROVINCE, PAPUA NEW GUINEA." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1485675594752553.
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