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Analysis of immune modulators in rainbow trout (Oncorhynchus mykiss)Mourich, Dan V. 20 March 1996 (has links)
The immune systems of various teleost fish have been studied in some detail for
the past several decades. One aspect of fish immunity, that of endogenously produced
modulating factors, has recently received a great deal of attention. Understanding the
functions and roles of endogenous factors that regulate fish immunity is paramount to
expanding the fields of fish immunology and vaccinology. It is know that several
lymphoid cell derived factors are detectable in in vitro cell culture systems and exhibit
immune modulating effects similar to well studied proteins in mammals. However in
comparison, few genes or gene products involved in the modulation of the trout immune
responses have been isolated, cloned and characterized.
The studies described herein were designed to isolate specific genes from rainbow
trout (0ncorhynchus mykiss) and characterize their involvement in the modulation and
regulation of the trout immune system. Two distinct genes were isolated cloned and
sequenced. The first, non-specific cytotoxic cell enhancement factor (NCEF) gene is
closely related to a human gene termed "natural killer enhancement factor" (NKEF) which
is important in the modulation of human natural killer cell activity. The second gene is
closely related to a group of recently characterized mammalian genes involved in the signal
transduction of cytokines termed "STATs". The role of these genes and their respective
protein products will be examined and discussed.
The antigenic structures of the fish proteins (NCEF and STAT5) were examined
by western blot and immunohistochemistry. Monoclonal antibodies derived against the
respective human proteins were found to cross react with the corresponding trout proteins,
demonstrating antigenic relatedness. The monoclonal regents were also used to analyze
the expression of these proteins in fish cells of lymphoid and non lymphoid origin.
In vitro cell culture analysis was used to determine the effects and roles of NCEF
and STAT5 gene products in the trout immune system. The cytolytic and apoptotic killing
activities of spleen, head kidney and peripheral blood leukocytes were found to be
enhanced by NCEF. Mitogenic stimulation of peripheral blood lymphoid cells resulted in
the trout STAT5 protein binding to a know sequences contained with in the promoters of
genes transcriptionally activated in response to cytokine exposure. / Graduation date: 1996
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Immune response of the small intestinal mucosa in children with celiac disease : impact of two environmental factors, resident microbiota and oatsSjöberg, Veronika January 2013 (has links)
Celiac disease (CD) is an immune-mediated enteropathy caused by permanent intolerance to dietary gliadin in wheat gluten and related prolamines in barley and rye. The pathogenesis of CD is still unknown and several different environmental factors have been associated with CD, such as dysbiosis of the microflora. In this translational study we investigated the immune status and the interplay of T-cells and Tregs in the mucosa of children with CD and controls, as well as the immune status in treated CD patients, provoked by either dietary oats, CD associated bacteria or gluten. The major findings in the studies were: First, indicators of extrathymic T-cells maturation (ETCM), i.e., the RAG1 enzyme required for recombination of the T cell receptor (TCR) genes and the preTα-surrogate chain in the immature TCR, were both expressed at lower levels in CD patients compared to controls. In addition, IELs expressing RAG1 were less abundant in CD patients compared to controls. The levels of these two indicators stayed low in treated CD patients as well, suggesting that impaired capacity of ETCM is an inherent feature of CD patients. Second, IL-17A, a cytokine involved in both inflammation and anti-bacterial responses was increased in active CD. The major cellular source was CD8+IELs. Furthermore, ex vivo challenge of biopsies from treated CD patients with gluten and with CD-associated bacteria induced an IL-17A response. The CD-associated bacteria also influenced the magnitude of the IL-17A response to gluten. Third, we investigated the effect of dietary oats on local immune status in the intestinal mucosa by comparing CD patients receiving GFD with and without oats. 22 different mRNAs for immunity effector molecules and tight junction proteins were analyzed. We found that expression of two down-regulatory cytokines, two activating NK-receptors and the tight-junction protein claudin-4 normalized in patients on a standard GFD while they did not normalize in patients on a GFD with oats. Fourth, we analyzed the expression level of mRNAs for chemokines, cytotoxic effector molecules, NK-receptors and their ligands in IELs and epithelial cells. Expression levels of several of these genes follow disease activity, suggesting massive recruitment of immune cells by both cell types accompanied by increased IEL-mediated cytotoxicity in the epithelium of inflamed mucosa. In this thesis we have identified three potential risk factors for development of CD: 1) an inherent lower level of ETCM in the small intestinal mucosa than in controls. This could lead to decreased generation of regulatory T cells and less capacity to tolerate gluten and adapt to the local milieu in the mucosa. 2) Dysbiosis of the resident microbiota with increased IL-17A production that could promote local inflammation and immune cell infiltration as well as antibacterial reactions. 3) Dietary oats may provoke a local immune response in a sub-population of CD patients. These patients should probably avoid oats in their GFD but larger studies are needed.
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Investigation of functionalized carbon nanotubes as a delivery system for enhanced gene expression with implications in developing DNA vaccines for hepatitis C virusChen, Wenting 13 January 2009
Hepatitis C virus (HCV) causes a significant health problem worldwide due to the lack of effective vaccines. It has been recognized that a rapid, vigorous, and broadly targeted cell-mediated immune response (Th1-like) is often associated with the clearance of HCV infections. DNA vaccines represent a promising means for HCV vaccination because they tend to induce a Th1-biased cell-mediated response in the host cell. Currently, the delivery of DNA vaccine for HCV in large animals as well as in humans is not as effective as in small animals. Nano delivery systems would be a promising approach to overcome this problem. Carbon nanotubes (CNTs) have been extensively studied for delivering drugs, proteins, peptides, and nucleic acids including plasmid DNA to cells and organs with varying degrees of success, but few of them have been applied to DNA vaccine for HCV.<p>
This thesis presents a study of using functionalized CNTs (f-CNTs) to improve the efficacy of plasmid DNA vaccine delivery for HCV. First, CNTs were functionalized via 1,3-dipolar cycloaddition reaction with the appropriate amino acids and aldehydes. NMR and TEM results suggested that the CNTs were successfully functionalized and became soluble in water. Then plasmid DNAs which encode green fluorescence protein reporter gene, luciferase reporter gene, and HCV core protein, respectively, were delivered into human hepatoma cells via calcium phosphate precipitation method, f-CNT delivery system, and a combination of f-CNT and calcium phosphate method, respectively. The result showed that f-CNTs, in combination with the calcium phosphate method, significantly enhanced the gene expression in human hepatoma cells.<p>
Consequently, this study concludes that the f-CNT can significantly enhance gene expression in liver cells conferred by a plasmid DNA when combined with calcium phosphate precipitation method. Even though the mechanisms of this enhancement await further investigation, the results of this thesis may have important implications in developing DNA vaccines for infectious diseases in general and for hepatitis C in particular.
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Investigation of functionalized carbon nanotubes as a delivery system for enhanced gene expression with implications in developing DNA vaccines for hepatitis C virusChen, Wenting 13 January 2009 (has links)
Hepatitis C virus (HCV) causes a significant health problem worldwide due to the lack of effective vaccines. It has been recognized that a rapid, vigorous, and broadly targeted cell-mediated immune response (Th1-like) is often associated with the clearance of HCV infections. DNA vaccines represent a promising means for HCV vaccination because they tend to induce a Th1-biased cell-mediated response in the host cell. Currently, the delivery of DNA vaccine for HCV in large animals as well as in humans is not as effective as in small animals. Nano delivery systems would be a promising approach to overcome this problem. Carbon nanotubes (CNTs) have been extensively studied for delivering drugs, proteins, peptides, and nucleic acids including plasmid DNA to cells and organs with varying degrees of success, but few of them have been applied to DNA vaccine for HCV.<p>
This thesis presents a study of using functionalized CNTs (f-CNTs) to improve the efficacy of plasmid DNA vaccine delivery for HCV. First, CNTs were functionalized via 1,3-dipolar cycloaddition reaction with the appropriate amino acids and aldehydes. NMR and TEM results suggested that the CNTs were successfully functionalized and became soluble in water. Then plasmid DNAs which encode green fluorescence protein reporter gene, luciferase reporter gene, and HCV core protein, respectively, were delivered into human hepatoma cells via calcium phosphate precipitation method, f-CNT delivery system, and a combination of f-CNT and calcium phosphate method, respectively. The result showed that f-CNTs, in combination with the calcium phosphate method, significantly enhanced the gene expression in human hepatoma cells.<p>
Consequently, this study concludes that the f-CNT can significantly enhance gene expression in liver cells conferred by a plasmid DNA when combined with calcium phosphate precipitation method. Even though the mechanisms of this enhancement await further investigation, the results of this thesis may have important implications in developing DNA vaccines for infectious diseases in general and for hepatitis C in particular.
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Genomic Approaches to Study Innate Immune Response to Salmonella Enteritidis Infection in ChickensChiang, Hsin-I 14 January 2010 (has links)
Salmonella enterica serovar Enteritidis (SE) is one of the most common food-borne
pathogens that cause human salmonellosis. Contamination of consumed poultry products
continues to be a global threat to public health. Genetic resistance using genomic
approach provides a promising solution to controlling SE infection in poultry. The
mechanism of SE resistance in chickens remains elusive. Three different approaches,
microarray techology, gene silencing, and computational gene analysis, have been
utilized to study SE-induced transcriptional changes of host immune response in the
chicken.
A whole genome chicken 44K microarray was used to analyze the transcriptome of
heterophils from SE-resistant (line A) and SE-susceptible chickens (line B) with/without
in vitro SE stimulation. Many differentially expressed immune-related genes were found
in the SE-infected to non-infected comparison, where more immune-related genes were
down-regulated in line B than line A. These results suggested a similar Toll-like receptor
(TLR) regulatory network might exist in heterophils of both lines, and provided strong
candidates for further investigating SE resistance and susceptibility in chickens. In the gene silencing study, small interfering RNAs (siRNA) were used to specifically inhibit the expression of NFkB1 in the chicken HD11 macrophage cell line with SE challenge.
Genes related to the NF-kB signaling pathway were selected to examine the effect of
NFkB1 inhibition on TLR pathway. With 36% inhibition of NFkB1 expression, the
results showed an increased expression of TLR4 and interleukin (IL)-6 following SE
challenge and suggested a likely inhibitory regulation of NFkB1 on TLR signal pathway.
Finally, two novel chicken C-type lectin-like receptors were identified and annotated to
chicken CD69 and CD94/NKG2-like with multiple evidences generated by computational (in-silico) sequence analysis. Both genes located in a region on chicken
chromosome 1 that is syntenic to mammalian Nature Killer Receptor Complex (NKC)
region, which may have existed before the divergence between mammals and aves.
While siRNA lays the foundation of using loss-of-function approach on testifying
gene-gene interactions, in-silico analysis aids in gathering information of unknown
genes of great interest. Both approaches provide great potential to use for down-stream
analysis following microarray study.
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Circadian regulation of innate immunity and microRNAs in Drosophila melanogasterLee, Jung-Eun, January 2008 (has links)
Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Biochemistry." Includes bibliographical references (p. 110-125).
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The comparison of co-stimulatory surface molecule expression on human monocyte-derived dendritic cells infected with two strains of influenza virusSimmon, Jessie M., January 2009 (has links)
Thesis (M.S.)--Northern Michigan University, 2009. / Includes bibliographical references (leaves 54-65).
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Mechanisms of immune protection against simian immunodeficiency virus唐娴, Tang, Xian January 2012 (has links)
The lack of an effective HIV vaccine calls for efforts to investigate the
mechanism of protective immunity against AIDS viruses. It has been previously
demonstrated that the live replication-competent modified vaccinia virus Tiantan
(MVTT) is superior to non-replication vaccinia MVA in inducing high levels of
neutralizing antibodies against SARS-CoV infection via mucosal vaccination.
Therefore, the hypothesis was that MVTT could be a better HIV vaccine vector
given its highly attenuated phenotypes such as no neurovirulence and safe in severe
combined immunodeficiency disease (SCID) mice. Here, a recombinant MVTT
expressing SIVmac239 Gag-Pol and Env (rMVTTSIVgpe) was constructed and its
immunogenicity was assesed when administered via different routes using
homologous prime-boost strategies or in heterologous regimens boosted with a
recombinant adenovirus-based vaccine inserted matched SIVmac239 genes
(rAd5SIVgpe). Results show that the heterologous prime-boost immunization with
rMVTTSIVgpe and rAd5SIVgpe induces significantly greater humoral and T cell
responses specific to SIV Gag, Pol and Env than homologous inoculations in mice
with remarkable improvements in quality and quantity.
The further study comparing different combinations of rMVTTSIVgpe and
rAd5SIVgpe demonstrates that the rMVTTSIVgpe prime-rAd5SIVgpe boost regimens
elicit systemic CD8+ T cell responses with augmented magnitude and
polyfunctionality, as compared with rAd5SIVgpe-rMVTTSIVgpe and
rAd5SIVgpe-rAd5SIVgpe regimens. Priming with rMVTTSIVgpe also increases
frequencies of gut-homing Gag-specific CD8+ T cells (CCR9+47+ and
CCR6+47+) and levels of CD8+ T cell ELISPOT responses against Gag, Pol and
Env in mesenteric lymph nodes (MLNs) post-boost. The mucosal route of
immunization is essential for rMVTTSIVgpe to induce rectal IgG with detectable
neutralizing activity against SIVmac1A11. Furthermore, the regimen involving
mucosal prime with rMVTTSIVgpe followed by systemic boost with rAd5SIVgpe
proves to be efficient in protecting monkeys from mucosal challenge of a high dose
of SIVmac239, a CCR5-tropic strain with high pathogenicity and
neutralization-resistance. SIV-specific T cell ELISPOT responses specific to Gag
and Pol but not Env and the frequency of Gag-specific IFN-+TNF-+CD8+
effector memory T cells (TEM) are likely associated with virological control after
challenge. Mucosal immunity induced by this vaccination strategy also has
important implications to the effectiveness of protection against disease
progression.
A hypothesis was generated that removal of non-protective but immune
dominant determinant of SIVmac239 Env may drive antibody responses to
protective domains. It was found that the neutralization-resistance of SIVmac239
could be partially explained by its high immunogenicity in eliciting CD4-induced
neutralizing antibodies, which are unable to protect the CCR5-binding site due to
the conformational masking and steric restriction. It was discovered that the
immunodominance of CD4-induced neutralizing antibodies on SIV envelope is
determined by a single highly conserved N-linked glycosylation site (N277) in the
C2 domain. Substitution of this N-linked site abolishes viral entry and the
immunogenicity of the CD4i domain while promotes V2-specific antibody
responses, which have recently been identified as an important immunological
correlate to HIV-1/SIV protection. Our findings demonstrate the concept that B cell
immunodominance is relative and eliminating the dominant antigenic region can
result in redirection of B cell recognition, which have critical implications for
immunogen design and the development of protective antibody-based HIV vaccine. / published_or_final_version / Microbiology / Doctoral / Doctor of Philosophy
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Studies of adaptive immune responses in zebrafish (Danio rerio), with a focus on the role of CD4+ cellsYoon, Sohye January 2014 (has links)
CD4+ lymphocytes (T helper cells) play a crucial role in orchestrating adaptive immune responses. This project aims to characterise the CD4+ cells in zebrafish (Danio rerio) for a better understanding of adaptive immunity in teleost fish. I cloned three CD4 homologues, termed zfCD4 and zfCD4 related (zfCD4rel1 and zfCD4rel2), with both reported previously in other bony fish species. The zfCD4 and zfCD4rels transcripts were detected in immune organs in zebrafish and were most highly expressed in the lymphocyte population. A moderate induction of the zfCD4 and zfCD4rels (and other immune related genes) was seen in kidney, spleen and intestine after poly (I:C) injection. Two antibodies against CD4 and IFN-γ, respectively, have been validated using various immunostaining approaches for further functional studies. The CD4 positive cells ranged from 20-30% of lymphocytes in zebrafish, similar to what is seen in other vertebrates. The expression level of IFN-γ and other Th cell related genes were analysed in immunised fish following re-stimulation with antigen, revealing that in zfCD4+ lymphocytes an increased expression of cytokines and master transcript factors was seen when the same antigen was used for boosting. This is the first demonstration of Th-type responses effected by CD4+ lymphocytes in a poikilotherm. Lastly, I studied an aspect of Treg function in zebrafish, focused on a master transcription factor of Tregs, the FoxP3 gene. Knocking down FoxP3 genes in zebrafish resulted in modulated gene expression of cytokines and transcription factors associated with Th and Treg cells, providing some evidence that the immune tolerance function of Treg cells may exist in teleost fish, with some sub-functionalisation of the two FoxP3 paralogues apparent. This thesis extends our knowledge into teleost adaptive immune responses mediated by CD4+ Th cells and putative FoxP3+ Treg cells and may aid future studies using zebrafish as a model of vertebrate immune function.
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Neuropilin-1 in immune regulation and formation of immunological memoryUtješanović, Nataša January 2012 (has links)
No description available.
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