Tesi sul tema "Tuberculosis immunity"
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Elias, Daniel. "Helminths and immunity against tuberculosis /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7357-035-4/.
Testo completoRonan, Edward. "Understanding vaccine induced protective immunity to Mycobacterium tuberculosis". Thesis, University of Oxford, 2011. http://ora.ox.ac.uk/objects/uuid:c0d7b20f-e144-42f8-aa52-301d0938b0b3.
Testo completoHicks, Alice Sophie. "Defining biomarkers of protective immunity and disease for tuberculosis". Thesis, St George's, University of London, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.589943.
Testo completoRedford, Paul Stuart. "Regulatory mechanisms inhibiting anti-mycobacterial immunity following Mycobacterium tuberculosis infection". Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445023/.
Testo completoSutiwisesak, Rujapak. "Natural Polymorphism of Mycobacterium tuberculosis and CD8 T Cell Immunity". eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1076.
Testo completoTemmerman, Stéphane. "Etude de la réponse à médiation cellulaire indute par l'héparin-binding hemagglutinin chez le sujet infecté par Mycobacterium tuberculosis". Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211117.
Testo completoLa « heparin-binding hemagglutinin (HBHA) » est une protéine de 28-kDa, sécrétée et exprimée à la surface de M. tuberculosis et de M. bovis BCG. Montrant une affinité importante pour les gycoconjugués sulfatés, elle favorise la dissémination hématogène du bacille de Koch.
Nos résultats démontrent que la HBHA stimule l’immunité à médiation cellulaire humaine avec, toutefois, des différences selon que le sujet infecté souffre ou non de tuberculose active. En effet, les cellules mononuclées circulantes, de la majorité des individus infectés mais non-malades, secrètent de l’IFN-? en réponse à la HBHA, alors qu’une minorité de sujets malades produit de faibles quantités d’IFN-? après stimulation in vitro avec l’antigène. Lors de l’infection naturelle par le bacille de Koch, la HBHA devient dès lors une cible pour le système immunitaire, et plus particulièrement au sein des sujets, généralement considérés, comme protégés.
L’analyse de la réponse cellulaire, spécifique à l’adhésine, démontre que les lymphocytes T CD4+, mais également T CD8+, des sujets infectés mais non-malades, produisent de l’IFN-? L’antigène est effectivement présenté aux lymphocytes T grâce aux glycoprotéines du complexe majeur d’histocompatibilité de classe I et de classe II. Le phénotypage des cellules productrices d’IFN-? témoigne également la participation des cellules « natural killer (NK) » dans la réponse immunitaire contre la HBHA. En l’absence des lymphocytes T restreints à l’antigène, les cellules NK se montrent toutefois incapables de secréter de l’IFN-? au contact de la HBHA. Les interactions entre les lymphocytes T, spécifiques à l’antigène, déterminent également la production de cytokines. Alors que la déplétion des cellules T CD8+ diminue légèrement la production d’IFN-? l’absence des lymphocytes T CD4+ abolit toute sécrétion résiduelle d’IFN-? lors de la stimulation avec la HBHA. Par contre, les lymphocytes T CD8+, pré-stimulés avec l’antigène en présence de cellules T CD4+, répondent secondairement à la présentation de la HBHA par des macrophages. Ce résultat suggère une coopération entre ces deux sous-populations cellulaires, afin de produire de l’IFN-? à l’encontre de la HBHA. Grâce à un contact cellulaire, les lymphocytes T CD4+ spécifiques à la HBHA soutiennent effectivement l’activation des cellules T CD8+.
Outre la production de cytokines, la participation des lymphocytes T CD8+ à la lutte contre M. tuberculosis, se traduit également par leurs fonctions cytotoxique et bactéricide. La caractérisation des cellules T CD8+, spécifiques à la HBHA, s’est dès lors poursuivie par l’évaluation de leur potentiel cytolytique. Après expansion clonale, les lymphocytes T CD8+ induisent la mort des macrophages présentant la HBHA. Le mécanisme cytotoxique engage la libération du contenu des granules cytoplasmiques, comme le montre l’augmentation de la synthèse de perforine et de granzyme A, lorsque les cellules T CD8+ sont stimulées avec la HBHA. Privés de ces médiateurs solubles, les lymphocytes T CD8+, spécifiques à la HBHA sont alors incapables de lyser les cellules cibles. En définitive, l’activité microbicide constitue actuellement le meilleur corrélat de protection. La culture de macrophages infectés par M. bovis BCG, en présence de cellules T CD8+ spécifiques à la HBHA, limite partiellement la croissance de la bactérie phagocytée, soulignant le pouvoir anti-mycobactérien de l’immunité cellulaire induite par la HBHA, chez le sujet infecté mais non-malade.
D’autre part, l’analyse biochimique, menée à l’Institut Pasteur de Lille, démontre que la HBHA subit une modification post-traductionnelle, lors de sa synthèse. Il s’agit d’une méthylation des multiples résidus lysine, qui composent son extrémité C-terminale. La comparaison des formes native méthylée et recombinante non-méthylée de la HBHA démontre que la méthylation détermine l’immunogénicité et le pouvoir protecteur de la HBHA. En effet, contrairement à la HBHA native, la forme recombinante stimule faiblement la production d’IFN-? chez les individus infectés mais non-malades, et ne protège pas la souris contre l’infection par le bacille de Koch. La sécrétion d’IFN-? est, par ailleurs, partiellement restaurée lorsque la HBHA est artificiellement méthylée in vitro. Les splénocytes murins se comportent également différemment, selon qu’ils ont été immunisés avec la forme méthylée ou non. Alors que la HBHA recombinante est immunogène chez la souris et chez l’homme, l’immunité cellulaire murine induite demeure impassible face à l’infection des phagocytes par les mycobactéries, ce qui se traduit par l’absence de protection.
En conclusion, la HBHA se compose d’épitopes protecteurs, qui dépendent de la présence des groupements méthyls, associés à son domaine C-terminal. Il s’agit, à notre connaissance, de la première mise en évidence de l’implication de la méthylation dans la réponse d’immunité cellulaire à l’encontre d’une protéine. De plus, l’immunité adaptative spécifique à la HBHA, chez le sujet infecté mais non-malade, se caractérise par les trois principaux corrélats de protection, actuellement décrits chez l’homme. Le potentiel vaccinal de cette adhésine mycobactérienne est donc bien réel.
Doctorat en sciences biomédicales
info:eu-repo/semantics/nonPublished
Sigola, Lynnette Brenda. "The role of innate immunity in the host response to Mycobacterium bovis". Thesis, London School of Hygiene and Tropical Medicine (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265950.
Testo completoLorgat, Faizel. "Proliferative and cytotoxic cellular immune responses in human tuberculosis". Thesis, University of Cape Town, 1992. http://hdl.handle.net/11427/26373.
Testo completoBeamer, Gillian L. "IMMUNOLOGIC MECHANISMS AND PREDICTORS OF SUSCEPTIBILITY TO MYCOBACTERIUM TUBERCULOSIS". The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243993142.
Testo completoSfondrini, Lucia. "Enhancement of anti-tumour immunity by transduction with a Mycobacterium tuberculosis gene". Thesis, Open University, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.342892.
Testo completoLam, Yin. "Association of polymorphisms in NRAMP1 gene and host susceptibility to tuberculosis /". Hong Kong : University of Hong Kong, 2002. http://sunzi.lib.hku.hk/hkuto/record.jsp?B25205687.
Testo completoDintwe, One Bridget. "Characterisation of Mycobacterium tuberculosis specific T cell immunity with HLA class II tetramers". Doctoral thesis, University of Cape Town, 2014. http://hdl.handle.net/11427/8713.
Testo completoTuberculosis (TB) remains a global health burden, with an estimated 1.3 million people dying from the disease in 2012. Protective immunity against TB is thought to depend on specific T cells. However, exactly which T cell characteristics are required for immunological protection is unknown. To gain a better understanding of M. tuberculosis (M.tb)-specific memory T cell immunity, we studied longevity and function of M.tb-specific memory T cells. We reasoned that such knowledge would facilitate rational vaccine design of a TB vaccine. We designed and developed a set of new HLA class II tetramers to perform in-depth studies of M.tb-specific CD4 T cell responses. We studied persons vaccinated with a novel TB vaccine, MVA85A, as well as persons naturally infected with M.tb. Antigen-specific CD4 T cells were detected with HLA class II tetramers and functional and phenotypic attributes of these T lymphocytes characterised by standard flow cytometric techniques. Comprehensive transcriptional analyses of M.tb-specific CD4 T cells, which were also sorted by FACS, were performed by microfluidic quantitative real-time PCR. Early after intradermal vaccination with MVA85A a large proportion of Ag85Aspecific CD4 T cells were highly activated, expressed skin homing markers and displayed an effector T cell phenotype. This effector response waned rapidly and gave way to antigen-specific central memory CD4 T cells with high proliferative potential, which we proposed may be desirable for protection. However, recent results from the first efficacy trial of MVA85A in infants suggested that these cells are not sufficient to enhance protection beyond that induced by BCG vaccination at birth. Further, we characterised surface marker expression and transcriptional signatures of a newly detected and described population of M.tb-specific CD4 T cells, that displayed a CD45RA+CCR7+CD27+ naïve-like T cell phenotype. We hypothesised that these unique M.tb-specific naïve-like CD4 T cells had a transcriptional profile distinct from truly naïve, central memory and effector bulk CD4 T cells, as well as other M.tb-specific memory CD4 T cell subsets. Gene expression of CFP10-specific naïve-like CD4 T cells reflected an mRNA profile that was very distinct from truly naïve bulk CD4 T cells. Rather, naïvelike CD4 T cells clustered with bulk effector CD4 T cells in unsupervised analysis methods such as hierarchical clustering and principle component analyses. Further analyses revealed that naïve-like CFP10-specific CD4 cells expressed mRNAs coding for effector cytokines, cytotoxic molecules and chemokine receptors consistent with effector memory T cells. However, the overall transcriptional profile was more similar to CFP10-specific central memory CD4 T cells than that of the effector CD4 T cells. We concluded that M.tb-specific naïve-like CD4 T cells may possess an ability to traffic to sites of infection or inflammation, where they may contribute to effector function. These hypotheses need confirmation on a protein level. The HLA class II tetramers developed in this thesis are valuabe tools for assessing direct ex vivo M.tb-specific CD4 T cell responses without activation and cell perturbation. Our findings contribute to a more comprehensive understanding of T cell immunity induced by vaccines and/or natural M.tb infection.
Sow, Fatoumata B. "Expression and regulation of the iron regulatory hormone and antimicrobial peptide hepcidin in mycobacteria-infected mice and macrophages". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180299600.
Testo completoBowers, Desiree Ann. "Immune responses of patients with tuberculosis and healthy controls of different ages". Thesis, Stellenbosch : Stellenbosch University, 2003. http://hdl.handle.net/10019.1/53457.
Testo completoENGLISH ABSTRACT: The immune system matures progressively from infancy to adulthood, thus children may differ from adults in their immune function. The immature immune system demonstrates a higher naive to memory T cell ratio, defective macrophage function and antigen presentation which, cumulatively, results in diminished production of cytokines such as IFN-y. This cytokine has been shown to play a pivotal role in protection against Mycobacterium tuberculosis (M. tuberculosis) disease. Other cytokines, such as IL-12 and TNF-a, are also involved in the defence against M. tuberculosis. Epidemiological evidence suggests an agerelated incidence of tuberculosis (TB) irrespective of prevalence in a given region. Reports in the literature also demonstrate depressed immune responses in TB patients, at diagnosis, (before TB therapy) with subsequent improvement after TB therapy. The aims of this study were to optimise a whole blood assay in order to characterise immune responses, as measured by proliferation and cytokine production, in TB patients (after TB therapy) and healthy controls of different ages. Immune responses of TB patients would also be compared, before, and after TB therapy. A total of 68 subjects were included in this study. These comprised 27 TB patients and 41 healthy Mantoux positive controls. All subjects were stratified into two age groups: <12 years and >12 years. Diluted whole blood was cultured and stimulated with the mitogen, phytohaemagglutinin (PHA) and the specific mycobacterial antigen, purified protein derivative (PPD) to measure proliferation and IFN-y, IL-2, TNF-a and IL-10 production in the supernatant of cultures. Age was a significant variable for the following PHA-stimulated cytokines: IFN-y, TNF-a and IL-10. Proliferation and IL-2 production after PHA stimulation did not demonstrate any relationship with age. None of the PPD-stimulated proliferative or cytokine responses demonstrated any correlation with age. Concentrations of PHA- and PPD-induced IFN-y for all subjects (patients and controls) were increased “after therapy”, compared to “before therapy”. This phenomenon could possibly be due to maturation in the capacity of the immune system to produce this cytokine. Patients >12yrs demonstrated improvement in all proliferative and cytokine responses (except for PPD-induced IL-2 and TNF-a) “after therapy”, compared to “before therapy”. This is probably a valid finding and is thus in accordance with the literature. The whole blood assay is a simple, non-laborious assay that, according to the literature, produces results that seem to correlate well with that of conventionally used PBMCs. Age appears to be an important variable in the quantitative assessment of cellular immune responses (when the mitogen, PHA is used as a stimulant) and immune responses of older TB patients appear to improve after TB therapy, compared to before TB therapy.
AFRIKAANSE OPSOMMING: Die immuunsisteem matureer stelselmatig van kind na volwassene. Dus sal kinders se immuniteit verskil van volwassenes s’n. Die immature immuunsisteem het ‘n hoer nai'witeit vir geheue T-sel verhouding, defektiewe makrofaag funksie en antigeen presentering wat gesamentlik lei tot verminderde produksie van sitokiene soos byvoorbeeld IFN-y. Daar is bewys dat hierdie sitokien ‘n deurslaggewende rol speel in die beskerming teen Mycobacterium tuberculosis (M. tuberculosis). Ander sitokiene, soos IL-12 en TNF-a speel ook ‘n rol in die beskerming teen M. tuberculosis. Epidemiologiese data dui aan dat daar ‘n ouderdomverwante insidensie van tuberkulose (TB) is sonder dat dit beinvloed word deur die voorkoms van TB in ‘n sekere area. Verslae in die literatuur wys ook op onderdrukte immuniteitrespons in TB-pasiente by diagnose (voor TB-behandeling) met uiteindelike verbetering na TB-behandeling. Die doel van hierdie studie was om ’n volbloed metode te optimaliseer in ’n poging om die immuunrespons te karakteriseer soos gemeet met behulp van proliferasie en sitokien produksie by TB-pasiente (na TB-behandeling) en gesonde kontrole persone van verskillende ouderdomme. Die immuunrespons van TB-pasiente word ook vergelyk voor en na TBbehandeling. ‘n Totaal van 68 gevalle is vir die studie gebruik. Dit sluit in 27 TB-pasiente en 41 gesonde Mantoux positiewe kontroles. A1 die gevalle is in twee ouderdomsgroepe verdeel: <12 jaar en >12 jaar. Kulture is gemaak van verdunde volbloed en gestimuleer met phytohaemaglutinin (PHA) en gesuiwerde proteien derivaat (purified protein derivative-PPD) om proliferasie en IFN-y, IL- 2, TNF-a en IL-10- produksie in die supernatant van die kulture te meet. Ouderdom was ‘n beduidende veranderlike vir die volgende PHA-gestimuleerde sitokiene: IFN-y, TNF- a en IL-10. Daar was geen korrelasie tussen proliferasie en IL-2-produksie na PHA-stimulasie aan die een kant en ouderdom aan die ander kant nie. Geen van die PPDgestimuleerde proliferasie response of sitokien response het enige korrelasie met ouderdom getoon nie. Konsentrasies van PHA- en PPD-geinduseerde IFN-y vir alle gevalle (pasiente en kontrole) was verhoog “na behandeling”, vergeleke met “voor behandeling”. Hierdie fenomeen kan moontlik toegeskryf word aan maturasie in die vermoe van die immuunsisteem om sitokiene te vervaardig. Pasiente >12 jaar het bewyse getoon van verbetering in alle proliferasie en sitokien response (behalwe vir PPD-gei'nduseerde IL-2 en TNF-a) “na behandeling”, vergeleke met “voor behandeling”. Dit is waarskynlik ‘n geldige bevinding en is dus in ooreenstemming met verslae in die literatuur. Die volbloed metode is ‘n eenvoudige metode wat nie baie arbeidsintensief is nie, wat volgens die literatuur, resultate lewer wat goed korreleer met die konvensionele gebruik van perifere bloed mononukliere selle (PBMC’s). Dit wil voorkom asof ouderdom ‘n belangrike veranderlike is in die kwantitatiewe beoordeling van sellulere immuunrespons (wanneer PHA gebruik word as ‘n stimulant), en of die immuunrespons van ouer TB-pasiente verbeter na TB-behandeling in vergeleke met die respons voor TB-behandeling.
Murray, Lyle W. "The impact of HIV-1 disease and its treatment on mycobacterium tuberculosis-specific immunity". Thesis, University of Oxford, 2014. http://ora.ox.ac.uk/objects/uuid:c4a292ca-d49d-4aac-9de8-910836a96983.
Testo completoCorral, Dan. "Régulation métabolique de la plasticité des ILC2 au cours de l'infection par Mycobacterium tuberculosis". Thesis, Toulouse 3, 2020. http://www.theses.fr/2020TOU30177.
Testo completoMucosal tissues harbor resident immune cells that play a dual role in maintaining both tissue integrity and protection against infection by pathogens. Among these, innate lymphoid cells (ILCs) are key players in tissue homeostasis and immune response. The last few years have revealed the existence of different types of ILCs, classified according to their similarity to T cells based on expression of dedicated transcription factors and the execution of specific effector functions. These include ILC1, ILC2 and ILC3, which form the innate counterparts of CD4+ T cells of the Th1, Th2 and Th17 types respectively, as well as NK for CD8+ cytotoxic lymphocytes. Similar to the associated Th subtypes, the different types of ILC have been implicated in various diseases. Within lung tissue, ILC2 is the quantitatively dominant subtype of ILC and its role has been characterized in particular in type 2 pathologies (asthma, allergies, parasitic infections). The lung is the site of entry for many infectious agents: yet the role of ILC2 in bacterial lung infections remains poorly explored. During my thesis, I was interested in the role of ILC, particularly ILC2, in the mouse model of Mycobacterium tuberculosis (Mtb) infection, the etiological agent of tuberculosis. Infection with Mtb typically induces a type 1 immune response: IFNƴ production allows the activation of the microbicidal functions of infected macrophages. Nevertheless, this dominant mechanism of TB immunity barely predicts the outcome of infection, and the current view is that other cellular actors are likely to contribute significantly to protection. Based on their presence in the lung at the entry of the pathogen and the diversity of their antimicrobial and tissue-protective effector potential, I hypothesized that ILC could be activated and participate in the antituberculous immune response. In the mouse model of tuberculosis, I could show that ILC are differentially regulated during infection: while ILC1 and ILC3 expand and become activated, ILC2 contract and become functionally inhibited. Interestingly, inhibition of ILC2 is associated with a plasticity mechanism characterized by the loss of ILC2 markers, such as GATA3, ST2, Arg1 and IL-5, together with the acquisition of ILC1 characteristic markers, such as T-bet, IL-18Ra, CD49a and IFNƴ. Different stages of ILC2 plasticity were identified based on the expression of CD49a and IL-18Ra, leading to the formation of ILC1-like cells, which display a protective potential during infection. In this infectious model, as well as through the development of an easier model of plasticity based on the administration of cytokines, we showed that IFNƴ, originating from ILC1 and NK cells, as well as the expression of the transcription factor STAT1, were essential components for the generation of ILC1-like cells. With the aim to identify the molecular mechanisms governing this plasticity, we hypothesized that the ILC2-to-ILC1-like cell plasticity was associated with a marked metabolic change. [...]
Pollock, Katrina Mary. "Dissection of the immunomodulatory effects of human immunodeficiency virus and Mycobacterium tuberculosis on cellular immunity". Thesis, Imperial College London, 2012. http://hdl.handle.net/10044/1/39459.
Testo completoPoyntz, Hazel Claire. "Evaluation of the immunological mechanisms induced by mycobacteria and the potential effect this may have on immunity induced by tuberculosis vaccines". Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:e7f1890e-577e-4346-b7fa-7ae810aa1be4.
Testo completoKiritsy, Michael C. "Functional Genomics of Mammalian Innate Immunity". eScholarship@UMMS, 2020. https://escholarship.umassmed.edu/gsbs_diss/1102.
Testo completoKleynhans, Leanie. "The impact of the steroid hormones medroxyprogesterone acetate, cortisol and progesterone on protective immunity to tuberculosis". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20371.
Testo completoBibliography
ENGLISH ABSTRACT: Most individuals latently infected with Mycobacterium tuberculosis (Mtb) contain the infection by a balance of effector and regulatory immune responses. However, this balance can be influenced by steroid hormones such as glucocorticoids (GCs), which are known to increase the risk of reactivation of TB. The contraceptive medroxyprogesterone acetate (MPA), which also possesses selective glucocorticoid activity, is widely used in developing countries with approximately 60% of women on contraceptives using MPA in our study cohort. Therefore, our aim was to investigate the effect of this hormone on protective immune responses to BCG in HIV negative household contacts of active TB patients. When PBMCs of TB household contacts were stimulated with BCG in the presence of 10 μM MPA; this hormone displayed both glucocorticoid as well as progestogenic properties. Similarly to cortisol, MPA suppressed antigen specific expression of a range of cytokines including IL-1α, IL-1ra, IL- 17, TNFα, IL-5 and IFNγ. Dose response curves showed that MPA can also alter expression of some cytokines at lower contraceptive doses (in the nano molar range). To assess whether this effect of MPA in vitro also occurs in women using this hormone as contraceptive the PBMCs of MPA users and controls were stimulated with BCG and the levels of up to 29 different cytokines measured by luminex analysis. PBMCs of MPA users produced significantly lower levels of cytokines involved in immune responses against Mtb such as IL-12p40, IL-1α, IL-10, IL-13 and G-CSF, which corresponds with lower numbers of circulating monocytes observed in these women. These findings warrant further investigation and clinical trials should investigate the risk of progression from latent to active TB disease in women using this contraceptive. These trials, however, require a large number of participants and are prohibitively expensive; therefore it was decided to setup an Mtb/MPA mouse model to determine the effect of MPA on the disease outcome. BALB/c and C57BL/6 mice were injected with a weekly dose of one mg MPA or PBS and infected with 30 colony forming units of Mtb H37Rv one week after commencing the hormonal treatment. Both strains were included to establish which strain best represents the human model. Three and eight weeks post infection the MPA treated C57BL/6 mice had a significantly higher bacterial load in their lungs compared to untreated mice, whereas no difference was found in the bacterial loads of the BALB/c mice. MPA treated C57BL/6 mice had significantly lower serum levels of IL-10 and G-CSF and MPA treated BALB/c mice lower serum levels of IFNγ, when compared to untreated mice. Furthermore, cells isolated from the MLNs of MPA treated C57BL/6 mice, produced significantly less TNFα, significantly more IP-10 and less IL-10 in response to PPD, while MLN cells of MPA treated BALB/c mice produced significantly less IFNγ, IL-2, IL-17, GM-CSF and MCP-1. Data of the C57BL/6 mouse strain correlated with our human data and can it therefore be said that the C57BL/6 mouse strain, together with the serum concentration of MPA used in these experiments, is a good model to determine the effect of MPA in the context of a low dose Mtb infection. To conclude MPA use could therefore alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult of adolescent women in the future.
AFRIKAANSE OPSOMMING: Die meeste mense wat latent met Mycobacterium tuberculosis (Mtb) geïnfekteer is, hou die infeksie onder beheer deur ʼn balans te handhaaf tussen effektor en regulatoriese immuunresponse. Hierdie balans kan egter beïnvloed word deur steroïedhormone soos glukokortikoïede (GCs), wat bewys is om die risiko van die heraktivering van TB te verhoog. Die voorbehoedmiddel medroksiprogesteroon-asetaat (MPA), wat ook selektiewe glukokortikoïed-aktiwiteit toon, word wyd gebruik in ontwikkelende lande en omtrent 60% van die vrouens in ons studie-bevolking wat voorbehoedmiddels gebruik, gebruik MPA. Om dié rede wou ons die effek van hierdie hormoon op die beskermende immuun-response teenoor M.bovis Bacilli Calmette-Guérin (BCG) in HIV negatiewe huishoudelike kontakte (HHKe) van pasiënte met aktiewe TB ondersoek. Ons het gevind dat wanneer perifere bloed mononukleêre selle (PBMSe) met BCG gestimuleer word in die teenwoordigheid van 10 μM MPA, hierdie hormoon beide glukokortikoïede en progesterogeniese eienskappe toon. Soos kortisol het MPA die antigeenspesifieke-uitdrukking van ʼn reeks sitokiene, insluitend IL-1α, IL-1ra, IL-17, TNFα, IL-5 en IFNγ, onderdruk. Respons kurwes wat verskillende konsentrasies van hormoon insluit, het getoon dat MPA ook by laer (nano-molare) dosisse die uitdrukking van sommige sitokiene kon verander. Om te bepaal of hierdie in vitro effek van MPA ook in vrouens wat MPA as voorbehoedmiddel gebruik voorkom, het ons PBMSe van MPA-gebruikers and kontroles met BCG gestimuleer en die vlakke van tot 29 verskillende sitokiene met behulp van Luminexanalise gemeet. PBMSe van MPA-gebruikers produseer beduidende laer vlakke van IL-12p40, IL-1α, IL- 10, IL-13 en G-CSF, wat elk in imuunafweerreaksies teen Mtb betrokke is. Die afname in dié sitokiene het gepaard gegaan met laer hoeveelhede sirkulerende monosiete. Ons resultate regverdig verdere ondersoeke en kliniese proewe behoort die risiko van progressie vanaf latente tot aktiewe TB in vrouens wat hierdie voorbehoedmiddel gebruik te bepaal. Sulke proewe vereis egter groot getalle deelnemers en is skrikwekkend duur, om die rede het ons besluit om ʼn Mtb/MPA muis-model op te stel om sodoende die algehele effek van MPA op die uitkoms van die siekte te bepaal. BALB/c en C57BL/6 muise is met ʼn weeklikse dosis van een mg MPA of sout oplossing ingespuit en een week na die aanvang van die hormoon behandeling met 30 kolonie-vormende eenhede Mtb H37Rv geïnfekteer. Beide muis tipes was ingesluit om sodoende te bepaal watter tipe die mens data die beste verteenwoordig. Drie en agt weke na die infeksie het die MPA-behandelde C57BL/6 muise ‘n beduidende hoër bakteriële lading in hul longe gehad as die onbehandelde muise, maar was daar geen verskil in die bakteriële ladings in die longe van die BALB/c muise nie. MPA-behandelde C57BL/6 muise het beduidende laer serumvlakke van IL-10 en G-CSF gehad, terwyl MPA-behandelde BALB/c muise laer serumvlakke van IFNγ gehad het. Verder het ons gevind dat die geisoleerde limfosiete van MPA-behandelde C57BL/6 muise beduidend minder TNFα, beduidend meer IP-10 en minder IL-10 geproduseer het na stimulasie met PPD, terwyl die limfosiete van MPA-behandelde BALB/c muise beduidend minder IFNγ, IL-2, IL-17, GM-CSF en MCP-1 geproduseer het. Data van die C57BL/6 muise stem ooreen met die van ons mens studie en ons kan dus vermeld dat die C57BL/6 muise, tesame met die spesifieke serumkonsentrasie van MPA wat gebruik is, ʼn goeie model is om die effek van MPA in die konteks van ʼn lae-dosis Mtb-infeksie te bestudeer. MPA gebruik kan dus die vatbaarheid vir TB, asook die erns van die siekte verander en kan ook die effektiwiteit van nuwe BCG-gebaseerde entstowwe, veral prima-hupstoot enstowwe, wat moontlik in die nabye toekoms vir volwasse en adolessente vroue toegedien kan word, verander.
Mayer, Oren Michael. "Trigger Factor, Mycobacterium tuberculosis' Double-Edged Sword| Immunity to a Mycobacteriophage at the Cost of Virulence". Thesis, Yeshiva University, 2017. http://pqdtopen.proquest.com/#viewpdf?dispub=10306458.
Testo completoThe struggle for survival between phages and their bacterial hosts is best exemplified by the diverse mechanisms bacteria utilize to block phage infection, and the methods phages use to surmount them. Mycobacteriophage DS6A is unique amongst the more than 8000 identified mycobacteriophages in that its host range is restricted to mycobacteria that are members of the Mycobacterium tuberculosis Complex (MTBC). However, the molecular mechanism for this specificity remains unknown. To study the relationship DS6A has to both MTBC and non-tuberculous mycobacteria (NTMs), we generated two novel recombinant DS6A shuttle phasmids containing fluorescent reporter mVenus. These phages were utilized to clearly demonstrate that 50 years of previous scientific dogma was incorrect, and DS6A can in fact infect NTM mycobacteria to a wide range of degrees. Work teasing out the mechanisms of resistance is underway. Additionally, we identified the chaperone trigger factor (Tig; Rv2462c) to be required for a productive DS6A infection in Mtb. Interestingly, no host range mutants have been generated that can overcome this resistance to plaguing. Deleting tig did not affect the lysis profile of any of the other >30 mycobacteriophages able to infect Mtb. Susceptibility of Mtb Δ tig to DS6A infection was rescued by complementation of tig on an integrating plasmid. DS6A fluorophage infection of Mtb Δ tig induced high levels of detectable fluorescence, suggesting Tig is not required for the adsorption of phage or introduction of DS6A DNA. Additionally assays determined that Tig was not involved in transcriptional or translational activation. However, deleting tig did yield an additional phenotype in Mtb; significant attenuation in both immunocompetent and immunocompromised mice. Lipidome and secretome assays showed stark differences between the lipid makeup and secreted protein profiles of the tig mutant versus the WT that could explain the cause of attenuation. For Mtb, the loss of tig is a double edged sword; total resistance to DS6A is afforded in the clonal population, but at the cost of virulence in eukaryotic hosts.
Roy, Eleanor. "Response of dendritic cells to Mycobacterium tuberculosis infection and the induction of protective immunity using dendritic cells infected with an auxotrophic mutant of M. tuberculosis". Thesis, University College London (University of London), 2005. http://discovery.ucl.ac.uk/1446801/.
Testo completoDeschamps, Matthieu. "Étude de la variabilité de réponse immunitaire innée chez l'Homme : une approche évolutive et moléculaire". Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066648/document.
Testo completoInfectious diseases remain one of the leading causes of death worldwide. The immune response to pathogens, one of the most complex phenotypes that exist, presents substantial variability among individuals and populations. This thesis aims to identify genetic factors and molecular mechanisms underlying differences in susceptibility to infectious diseases using a combination of in silico and ex vivo approaches. First, we performed population and evolutionary genetics analyses to assess the impact of natural selection on innate immunity genes. Our analyses reveal the widespread and heterogeneous nature of the selective pressures acting on those genes. In addition, we suggest that the introgression of Neanderthal alleles in some of these sequences contributed to the adaptation of European and East Asian populations to local pathogens. Second, we profiled the miRNA response to Mycobacterium tuberculosis infection in human dendritic cells. Our results highlight the impact of infection on miRNA-mediated gene regulatory networks and show that the expression of 3% of miRNAs is associated with proximate genetic variants. More specifically, we identify two infection-specific associations. The work presented here provides the largest evolutionary genetics analysis of innate immunity genes to date and the first attempt to characterize the genetic architecture of the miRNA response to infection. Our work offers new insights into the genetic basis of inter-individual variability in immune responses and provides a set of candidate genetic variants for future functional validation to elucidate novel molecular mechanisms underlying differences in susceptibility to infectious diseases
Bekker, Linda-Gail. "TNF-[alpha] in host immunity to tuberculosis : in vivo and in vitro studies of protection and pathogenesis". Doctoral thesis, University of Cape Town, 2000. http://hdl.handle.net/11427/3361.
Testo completoTuberculosis has been widespread from earliest history as demonstrated by skeletal deformities suggestive of spinal tuberculosis (Potts Disease) seen in Neolithic man (5000 BC) [Sager P, Schalimtzek M and Moller-Christensen V, 1972]. The earliest written reports similar of tuberculosis probably come from Chinese writings of about 2700 BC, which mention "lung fever" and "lung cough".
Lam, Yin, e 林燕. "Association of polymorphisms in NRAMP1 gene and host susceptibility totuberculosis". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B3122619X.
Testo completoBrooks, Michelle Nichole. "Nucleotide-binding Oligomerization Domain Containing 2 Characterization and Function during Mycobacterium tuberculosis Infection of Human Macrophages". The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1312480140.
Testo completoMarshall, Benjamin Giles. "Genetically modified mycobacteria as potential anti-tuberculous vaccines : an investigation of the links between inflammation, immunity and fibrosis in mycobacterial disease". Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324918.
Testo completoRitz, Nicole. "The influence of BCG vaccine strain on the immune response and protection against tuberculosis". Connect to thesis, 2009. http://repository.unimelb.edu.au/10187/8392.
Testo completoThe principal aim of this thesis was to investigate the influence of BCG vaccine strain on the mycobacterial-specific cellular immune response in infants. Related to this, three additional studies addressed questions that provided critical information for the design and interpretation of the main study. These studies investigated: (i) the BCG vaccine strains used in each country worldwide, (ii) the susceptibility of different BCG vaccine strains to antimycobacterial drugs; and (iii) the difference in the immune response induced by BCG immunisation in children and adults.
For the main study in this thesis, newborns were randomly allocated to be immunised soon after birth with one of the three BCG vaccine strains currently most commonly used worldwide (BCG-Denmark, BCG-Japan or BCG-Russia). Ten weeks after BCG immunisation, the mycobacterial-specific cellular immune response was investigated using a comprehensive panel of immunological assays. This comprised flow cytometric analysis of intracellular cytokines and cytotoxicity in T cells, as well as the measurement of cytokines and chemokines in supernatants, from in vitro whole blood stimulation assays.
Data from 167 BCG-immunised infants was included in the final analysis. Infants immunised with BCG-Denmark or BCG-Japan had significantly higher proportions of multifunctional CD4 T cells than infants immunised with BCG-Russia. Similarly, infants immunised with BCG-Japan had significantly higher levels of Th1 cytokines in supernatants than infants immunised with BCG-Denmark or BCG-Russia.
These findings are particularly important in the light of recent evidence from animal studies that the frequency of multifunctional CD4 T cells induced by immunisation correlates with protection against intracellular pathogens such as Mycobacterium tuberculosis. This suggests that immunisation with BCG-Denmark or BCG-Japan is associated with better protection against TB than immunisation with BCG-Russia. Until correlates of protection against TB are determined in humans, cautious interpretation of these findings is warranted. Nonetheless, the findings from this thesis have important implications. The use of a BCG vaccine strain with even a moderately higher protective efficacy would have a large effect on TB morbidity and mortality in infants on a global scale. This thesis may therefore inform future BCG immunisation policy worldwide.
Carlson, Tracy Karin. "The Effects of Pulmonary Surfactant Protein-D on Innate Immune Cells and Tuberculosis Pathogenesis". The Ohio State University, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=osu1299708141.
Testo completoBull, Naomi. "The role of lung tissue-resident memory T cells in protection against tuberculosis". Thesis, University of Oxford, 2017. https://ora.ox.ac.uk/objects/uuid:45ee10ce-0ca3-4459-9da8-5cf9078f2cbb.
Testo completoRaffetseder, Johanna. "Interplay of human macrophages and Mycobacterium tuberculosis phenotypes". Doctoral thesis, Linköpings universitet, Avdelningen för mikrobiologi och molekylär medicin, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-132321.
Testo completoAlaniz, Robert Christopher. "Development of T cell immunity to Listeria monocytogenes and Mycobacterium tuberculosis : dendritic cells as an "Achilles' heel" and immune deficiency in dopamine beta-hydroxylase knock-out mice /". Thesis, Connect to this title online; UW restricted, 2002. http://hdl.handle.net/1773/8357.
Testo completoHougardy, Jean-Michel. "Role of regulatory T cells in the pathogenesis of human tuberculosis". Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210370.
Testo completoConsidérant ces données, il est désormais crucial d'améliorer nos outils de dépistage de l'infection latente, de diagnostic de la maladie active, de prévention (vaccins) et de traitement. Pour atteindre ces objectifs, une des pistes est la caractérisation détaillée des réponses immunitaires. En comparant les réponses immunitaires des sujets infectés de manière latente à celles liées à la maladie active, nous pourrons peut-être comprendre certains mécanismes de protection. L'étude des réponses immunitaires induites par la « Heparin-Binding-Hemagglutinin » (HBHA) s'est faite dans cet objectif. La HBHA est une adhésine exprimée par le complexe M. tuberculosis. Elle est impliquée dans la dissémination extrapulmonaire du bacille et constitue donc un facteur de virulence. Par ailleurs, une vaccination de souris par seulement 3 doses de 5 µg de HBHA suffit à protéger de l'infection avec une efficacité comparable à celle du vaccin BCG. Chez l'homme, les sujets sains mais infectés développent d'importantes sécrétions d'interféron-gamma (IFN-γ) en réponse à cet antigène, alors que la majorité des patients tuberculeux ne le font pas. Cette différence est importante pour comprendre une des raisons d'échappement de M. tuberculosis au contrôle immunitaire. La HBHA est une protéine méthylée et la méthylation s’avère essentielle pour ses propriétés immunoprotectrices.
Nos travaux présentés ici se sont axés sur deux éléments de la réponse immunitaire à la HBHA chez l'homme :d'une part, l'exploitation de la réponse périphérique d'IFN-γ à la HBHA comme outil de dépistage de l'infection latente et, d'autre part, l'étude des raisons de la faible sécrétion d'IFN-γ spécifique de la HBHA lors de la maladie active.
L'évaluation de la sécrétion périphérique d'IFN-γ en réponse à la HBHA a permis de démontrer rétrospectivement que celle-ci permet de détecter plus de 90 % des sujets réagissant positivement à l'injection intradermique de tuberculine. De manière intéressante, l'utilisation d'un test commercial, le QuantiFERON TB Gold IT (QFT-IT) n'a permis de détecter que la moitié des sujets infectés sains. De notre point de vue, le QFT-IT ne peut être recommandé seul pour le dépistage systématique de l'infection latente par M. tuberculosis. De manière parallèle, un test de stimulation basé uniquement sur la sécrétion d’IFN-γ suite à une stimulation à l'ESAT-6, composant du QFT-IT, n'a pas permis d'augmenter la sensibilité, ni d'ajouter une plus-value au test basé sur la HBHA. A l'instar de l'intradermoréaction à la tuberculine, le dépistage de la maladie active reste décevant que ce soit par l'utilisation de la HBHA ou de l'ESAT-6.
La TB active est caractérisée par une basse sécrétion périphérique d'IFN-γ en réponse à la stimulation par la HBHA. Cette faible sécrétion est cependant réversible, puisque un traitement efficace permet d'atteindre des taux d'IFN-γ significativement plus élevés. Ceci nous démontre qu'il s'agit d'une suppression associée à la phase active de l'infection. Nous avons d'abord évalué l'importance de la modulation de la sécrétion d'IFN-γ en réponse à la HBHA par 2 cytokines immunomodulatrices, l'interleukine-10 (IL-10) et le Transforming-Growth-Factor-Beta (TGF-ß). De manière intéressante, alors que ces 2 cytokines sont associées à l'infection par M. tuberculosis, la HBHA n'est inductrice ni d'IL-10, ni de TGF-ß. Les lymphocytes T régulateurs (Treg) expriment 2 marqueurs d'intérêt :le CD25, composant du récepteur à l'IL-2, et Foxp3, un gène régulateur majeur des cellules Treg. Ces cellules sont décrites comme suppressives de réponses immunitaires déclenchées par des antigènes du Soi et du non-Soi. Nous avons montré que la proportion de lymphocytes Treg périphériques est augmentée en cas de TB active. Par ailleurs, nous avons également démontré que ces cellules suppriment la sécrétion d'IFN-γ et la prolifération induite par la HBHA après stimulation des cellules mononucléées sanguines périphériques de patients tuberculeux in vitro. Cependant, la réponse anti-HBHA des patients tuberculeux, qui est démasquée par la déplétion des lymphocytes Treg, n'est pas dirigée contre des épitopes protecteurs. En effet, la méthylation n'influence pas leur sécrétion d'IFN-γ. De ce point de vue, les lymphocytes Treg sont impliqués dans la maladie tuberculeuse et influencent négativement les réponses dirigées contre un antigène protecteur. Cependant, il semble que la TB active soit également associée à une ignorance d'épitopes protecteurs.
Enfin, nous avons également démontré qu'il était possible d'induire des lymphocytes Treg au départ de cellules sanguines périphériques de sujets infectés sains. En effet, la stimulation in vitro des cellules sanguines périphériques en présence de BCG et de TGF-ß est un moyen rapide pour induire l'apparition de lymphocytes Treg fonctionnels in vitro. Ceci nous interroge quant aux rôles des lymphocytes Treg dans la pathogenèse de la maladie. En effet, un excès de TGF-ß circulant est observé dans certaines conditions cliniques à haut-risque de TB post-primaire. De ce point de vue, les lymphocytes Treg pourraient être des acteurs déterminant dans la perte du contrôle à long terme de l'infection et, par là, pourraient être des cibles thérapeutiques d'intérêts lors de l'infection par M. tuberculosis. /Mycobacterium tuberculosis is the causative agent of tuberculosis (TB). It is estimated approximately one third of the World’s population is infected with M. tuberculosis. Fortunately, only 5 to 10 % of the infected individuals will develop the disease throughout their life. However, the other healthy infected individuals remain infected for life: this is the latent TB infection (LTBI). Every year, 8 to 10 million new cases of TB are recorded globally, and about 2 to 3 million of people die from the disease. During the last several decades the co-infection of M. tuberculosis and the human immunodeficiency virus have worsened the picture. This dreadful association currently affects mostly the poorest people of the World. Unfortunately, bad news never stands alone. We now witness increasing emergence of multi-drug-resistant and even of extensively-multi-drug-resistant M. tuberculosis strains. Against these strains current therapeutics are virtually useless.
The development of new tools for prevention (vaccines), diagnostics and treatment is crucial. In order to fulfill these objectives, detailed studies on the immune responses is one of the main tracks to explore. Indeed, the comparison of immune responses in LTBI subjects with those in TB patients may provide some clues to understand immune mechanisms of protection. Studies of the immune responses that are specific to Heparin-Binding-Hemagglutinin (HBHA) may be one of these clues. HBHA is an adhesin, which is expressed by the micro-organisms of the M. tuberculosis complex. It largely contributes to the extrapulmonary dissemination of the tubercle bacilli. Hence, HBHA may be qualified as an important virulence factor. Furthermore, vaccination of mice with three doses of only 5 µg HBHA each affords the same level of protection as vaccination with BCG. In humans, peripheral blood mononuclear cells (PBMC) from LTBI subjects secrete significant levels of IFN-γ in response to HBHA, whereas PBMC from TB patients do not. This discrepancy may be a cornerstone in the understanding of some of the mechanisms underlying the immune escape mediated by M. tuberculosis. HBHA is a methylated protein, and the methylation is crucial for its immuno-protective properties.
This work focused on 2 major issues of the HBHA-specific immune response in humans: the use of the peripheral IFN-γ secretion in response to HBHA as a diagnostic tool for LTBI and the analysis of the underlying mechanisms to the low IFN-γ secretion during active TB.
In our study, the measurement of HBHA-specific IFN-γ secretion resulted in the detection of more than 90 % of the tuberculin-skin-test (TST) positive LTBI. Strikingly, the QuantiFERON TB Gold IT (QFT-IT), a commercial test, failed to identify those LTBI subjects in more than 50 % of the cases. Therefore, we cannot recommend the use of QFT-IT alone instead of the TST for the detection of LTBI. Similarly, a test relying on the detection of IFN-γ secretion upon ESAT-6 stimulation, one of the antigens used in the QFT-IT, was not sufficiently sensitive for the LTBI detection, nor did it improve the sensitivity or the specificity of the HBHA-based test. In contrast to the diagnosis of LTBI, the tests based on HBHA- or ESAT-6-induced IFN-γ secretions displayed poor sensitivity for the diagnosis of active TB.
During active TB, the HBHA-specific IFN-γ secretion in the periphery is low. However, this weak secretion is reversible upon effective treatment, as the IFN-γ response to HBHA is increased after completion of chemotherapy. This is strongly suggestive of an immune suppression during active disease. Therefore, we have first evaluated the role of two immunomodulatory cytokines, interleukin-10 (IL-10) and Transforming-Growth-Factor-Beta (TGF-ß), in the suppression of the HBHA-specific IFN-γ secretion. We found that neutralization of neither IL-10 nor TGF-ß with specific antibodies induced HBHA-specific IFN-γ secretion by PBMC of TB patients in vitro. In contrast, depletion of regulatory T cells (Treg) that express 2 major markers, CD25, a constituent of the IL-2 receptor, and Foxp3, a master regulatory gene, resulted in increased HBHA-specific IFN-γ secretion by the PBMC of TB patients. These cells are known to be involved in the suppression of immune responses to both Self and non-Self antigens. We further show that the size of the peripheral Treg cell population increases during active disease. In addition to suppressing the HBHA-specific IFN-γ secretion these cells suppress T cell proliferation in response to HBHA in vitro. However, even after depletion of the Treg cells, the uncovered HBHA-specific immune responses are not directed to the methylated epitopes during TB disease.
Finally, we show that Treg cells can be induced (or expanded) from the PBMC of LTBI subjects. Stimulation of those PBMC with BCG in the presence of TGF-ß resulted in a quick appearance of functional Treg cells in vitro. This observation strongly suggests a role of Treg cells in the pathogenesis of TB, in particular in the progression of latency to reactivation. Interestingly, excessive concentration of TGF-ß, associated with various clinical conditions, is high risk factor for post-primary TB. Thus, Treg cells may result in the loss of immune control against latent M. tuberculosis infection. Therefore, Treg cells may represent potential therapeutic targets during M. tuberculosis infection.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
Schölvinck, Elisabeth Henriëtte. "The influence of age on the cellular immune response in patients with tuberculosis and healthy controls". Thesis, Stellenbosch : Stellenbosch University, 2002. http://hdl.handle.net/10019.1/53126.
Testo completoENGLISH ABSTRACT: Children and adults may differ in their immune function. An adequate function of the individual's immune system is crucial to the risk for development of tuberculosis (TB) after infection with Mycobacterium tuberculosis (Mtb). Epidemiological evidence suggests an age-related incidence of TB. Furthermore, the prevailing clinical expression t ' of TB varies between age groups. -The aims of this study were to characterise the cellular immune response at different ages in TB patients and healthy individuals living in a region highly endemic for TB and to relate the findings to the clinical expression of TB in different age groups. A total of 150 persons of different ages were included in this study: 50 TB patients, (identified on the basis of clinical, radiological and microbiological characteristics), 49 healthy Mantoux positive (~15mm) and 51 healthy Mantoux negative (<15mm) subjects. All patients <12yrs were identified as having primary TB and postprimary TB was only diagnosed in patients ~12yrs. Haematologic indices were obtained from all the included subjects and found to be agerelated. With the exception of the absolute lymphocyte counts, all indices were significantly different in TB patients when compared to healthy controls. Whole blood was cultured and stimulated with PHA, PPD and ESAT -6 to measure lymphocyte proliferation and IFN-y, TNF-a, IL-2 and IL-10 production in the supernatants of the cultures. After stimulation with PHA, the production of IFN-y, TNF-a and IL-10 as well as lymphocyte proliferation were all age-related. After stimulation with PPD, age correlated positively with IFN-y production in healthy Mantoux positive subjects< 12yrs. In the age groups <20 yrs, patients produced similar amounts of IFN-y when compared to healthy age-related Mantoux positive controls. TNF-a and IL-2 production were not different between patients and controls. In this whole blood system, measuring any of these cytokines on their own did not differentiate patients from controls at all ages. The ratio of PPD stimulated IFN-y to TNF-a production was significantly less in patients with primary TB and postprimary TB when compared to Mantoux positive controls, irrespective of age. These findings indicate that calculated ratios between several cytokines may be useful markers of disease at all ages. ESA T -6 stimulated IFN -y production did not result in any significant correlation with age, but was significantly less in healthy Mantoux positive subjects ~12 yrs when compared to healthy Mantoux positive subjects <12 yrs and TB patients of all ages. This finding suggests that a positive immune response to ESAT -6 is indicative of recent immunological contact with Mtb. Total IgE was measured in serum. In children <12 yrs these values correlated with age and were highest in healthy Mantoux positive controls, thereby not confirming any inverse correlation between IgE and TB. Age should be recognised as a significant variable in quantitative measurements of cellular immune responses.
AFRIKAANSE OPSOMMING: Die immuunsisteem van kinders en volwassenes kan verskillend wees. Die mate van immuniteit van 'n individu is deurslaggewend vir die risiko om tuberkulose (TB) na infeksie met die Mycobacterium tuberculosis (M tb) te ontwikkel. Epidemiologiese bevindings suggereer dat die insidensie van TB ouderdomgebonde mag wees. V erder verskil die voorkomende kliniese beeld van TB ook tussen ouderdomsgroepe. Die doelstellings van hierdie studie was om die sellulere immuunrespons op verskillende ouderdomme by TB-pasiente en gesonde individue wat in 'n streek met hoogs endemiese TB-insidensie woon te vergelyk. Die doel was ook om vas te stel hoe hierdie bevindings by die kliniese beeld van TB by verskillende ouderdomsgroepe inpas. Daar is l50 persone van verskillende ouderdomme in hierdie studie ingesluit: 50 TBpasiente (geidentifiseer op grond van kliniese, radiologiese en mikrobiologiese karakteristieke), 49 gesonde Mantoux -positiewe (:2':l5mm) en 5l gesonde Mantouxnegatiewe (
Thiel, Bonnie Arlene. "Bioinformatics approaches to studying immune processes associated with immunity to Mycobacterium tuberculosis infection in the lung and blood". Case Western Reserve University School of Graduate Studies / OhioLINK, 2021. http://rave.ohiolink.edu/etdc/view?acc_num=case1627247387242562.
Testo completoLeite, Gabriela Guimarães Sousa. "Perfil transcriptômico comparativo de macrófagos em cultura, infectados com isolados clínicos de Mycobacterium tuberculosis com diferentes perfis de resistência a quimioterápicos". Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/9/9136/tde-25092014-151103/.
Testo completoSince 1993 the tuberculosis is considered as a disease of worldwide impact and a problem of public health. A major concern is the continuing prevalence of multidrug resistant Mycobacterium tuberculosis strains, especially the hypervirulent W - Beijing genotype. It is believed that this genotype has a selective advantage over other genotypes of M. tuberculosis and has being associated with treatment failure, extrapulmonary tuberculosis, resistance to BCG vaccination and marked ability to spread. These strains have varying ability to survive within macrophages and granuloma, modulating specific metabolic pathways that culminate in the escape of the immune system response. To understand this selective advantage and ability to persist in infection, this study aimed to analyze and compare the transcriptomic profile of macrophages infected with strains of M. tuberculosis W - Beijing 1471 and H37Rv. The mRNAs of infected macrophages were sequenced in HiScan Illumina Genome Analyzer platform. Were generated approximately 30 million sequences per sample, in single-reads readings. More than 70 % of sequences had values of Q score superior or equal to 30. Were mapped and analyzed 35,581 transcripts. On average, 63% of the genes showed no differences in the expressions, 19% were downregulated and 18% were upregulated, for all samples sequenced macrophages. After tertiary analysis and validation by real-time PCR, samples infected with the strain W -Beijing in 1471 showed an increase in expression of IFN class I (p <0.001) and exacerbated increase of TNF- alpha (p < 0.001) when compared to the control samples and those infected with standard strain H37Rv. Additively was observed an increase in expressions of the two kinases RIPK1 and RIPK3 and molecules involved in the induction and control of reactive oxygen species (ROS). In infections by intracellular bacteria, activation of RIPK1, RIPK3, ROS and TNF-α, are correlated with death of macrophages by necroptosis. The hypervirulent M. tuberculosis W - Beijing 1471 strain showed reduced persistence inside macrophage and induced early death of macrophages in the fifth day of infection. The death observed in macrophages was associated with activation of IFNs class I/TNF-α/RIPK1/RIPK3 and ROS, indicating necroptosis. Also was observed an increase in the expression of TLR3 receptor in infected samples with W-Beijing 1471 strain compared to controls and those infected with H37Rv strain. Probably the initial activation of IFNs class I occurred by TLR3 through the recognition of M. tuberculosis dsRNAs.
Pyle, Charlie Jacob. "Impact of macrophage zinc metabolism on host defense against Mycobacterium tuberculosis". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1469135576.
Testo completoGoulart, Juliana Silva Pancini. "Helmintíase intestinal afeta negativamente a resposta celular específica contra o Mycobacterium tuberculosis em pacientes co-infectados". Universidade Federal do Espírito Santo, 2009. http://repositorio.ufes.br/handle/10/5911.
Testo completoMycobacterium tuberculosis (MTB) é um exemplo clássico de patógeno para o qual a resposta protetora depende da imunidade celular do tipo Th1, que é caracterizada pela presença de linfócitos T CD4+ produtores de IFN-g. Essa citocina ativa mecanismos microbicidas no macrófago infectado, levando à eliminação do bacilo. Evidências sugerem que a progressão para a tuberculose esteja relacionada à presença de mecanismos imunossupressores mediados por citocinas e por células T reguladoras. Acredita-se que a presença de helmintíase intestinal possa prejudicar o desenvolvimento de uma resposta adaptativa capaz de conter ou eliminar o MTB, tornando assim o indivíduo susceptível ao adoecimento. Para aquilatar a influência da infecção por helmintos intestinais na resposta celular durante a tuberculose pulmonar, neste trabalho, foram avaliados os perfis quantitativo e fenotípico de populações celulares de sangue periférico e o padrão de citocinas em culturas de sangue total estimuladas com antígenos de MTB, em pacientes portadores de tuberculose pulmonar apresentando ou não helmintíase intestinal no momento do diagnóstico e durante a terapia antituberculose. Para isso, foram arrolados 53 pacientes com diagnóstico recente de tuberculose pulmonar. Desses, 26% eram portadores de pelo menos uma espécie de helminto intestinal. Pacientes com tuberculose pulmonar apresentaram uma redução significativa nos números de linfócitos T CD8+, células NK e NKT. Os indivíduos com helmintíase intestinal associada à tuberculose apresentaram uma maior freqüência de células T reguladoras, com ambos os fenótipos CD4+CD25HIGH e CD4+CD25HIGHFoxp3+. Além disso, os resultados sugerem que a presença de infecção por helmintos intestinais tenha induzido um estado de hipoergia em pacientes portadores de tuberculose pulmonar, uma vez que esses pacientes apresentaram concentrações menores das citocinas IL-2, TNF-a, IL-4, IL-5 e IL-10 nos sobrenadantes de culturas em relação às concentrações encontradas no grupo TB e no grupo controle. Portanto, os resultados desse trabalho sugerem que a presença de infecção por helmintos intestinais tenha um impacto negativo na resposta imunitária à tuberculose em pacientes portadores de tuberculose pulmonar.
The protection against Mycobacterium tuberculosis (MTB) depends on a cellmediated Th1 type-immune response. This response is characterized by IFN-g production by CD4+ T cells, which activates macrophages to enhance microbicidal mechanisms leading to the bacillus eradication. Factors related to tuberculosis resistance or susceptibility are not completely understood. There are evidences suggesting that the progress to active disease is related to immune downregulation caused by suppressors cytokines and regulatory T cells. It is believed that the association with helminth infection can disturb the protective immune response that should contain or eliminate MTB. Here, we investigated the role of intestinal helminth infection on M. tuberculosis specific immune response during active pulmonar tuberculosis in patients with associated tuberculosis and intestinal helminth infection at the time of diagnosis and during tuberculosis therapy. Quantitative and phenotypic analyses of peripheral blood cells populations were performed and the MTBstimulated whole blood culture cytokines production was evaluated. Fifty-three patients with newly diagnosed tuberculosis were enrolled for this study. Twenty-six percent of these patients were infected with at least one intestinal helminth (TB + HELM patients). Patients with pulmonary tuberculosis presented a significant reduction in the numbers of TCD8+, NK and NKT cells. Patients with both intestinal helminth infection and tuberculosis presented higher frequency of regulatory T cells, of both phenotype CD4+CD25HIGH and CD4+CD25HIGHFoxp3+, as compared to TB group, to HELM group, and to control group. In addition, the results suggest a hipoergy status in TB + HELM patients because the production of the cytokines IL-2, TNF-a, IL-4, IL-5 and IL-10 decreased in whole blood culture of these patients as compared to both TB patients and healthy controls. The data from this study indicated that the associated intestinal helminth infection has a negative impact on immunity to tuberculosis in patients with tuberculosis.
Campana, Maria Carolina Faiçal. "Avaliação dos diferentes parâmetros da resposta imune de indivíduos com teste tuberculínico positivo ou negativo perante isolados clínicos de M. tuberculosis sensíveis e multidroga resistentes". Universidade Federal do Espírito Santo, 2010. http://repositorio.ufes.br/handle/10/5923.
Testo completoImmunity against tuberculosis depends on the establishment of an effective Th1 response, with IFN- production, a pivotal cytokine to the activation of macrophages and bacilli destruction. It is known that several factors are related to the host s resistance to tuberculosis. In the present work, the influence of T regulatory cells (Tregs) in the immune response against Mtb was evaluated in whole blood and PBMC cultures from tuberculin skin test positive (TST+) and tuberculin skin test negative (TST-) individuals. Paralelly, we also evaluated if different levels of resistance to anti-mycobacterial drugs displayed by different Mtb clinical isolates could interfere with the cytokine profile, Tregs frequency, and with its proliferative capacity on both PBMC and whole blood cultures from TST+ and TST- subjects. Twenty-two healthy volunteers were invited to participate in our study, 11 TST+ and 11 TST-. Twelve Mtb clinical isolates were used, 6 drug-resistant and 6 drug-susceptible. Our data shows that differences in drug susceptibility did not affected any of the evaluated parameters. In the other hand, TST status correlated with differences in Treg frequencies, which was significantly elevated among TST+ when compared to TSTsubjects. The increase in Tregs was also associated with a decrease in the microbicidal effect observed in whole blood cultures from TST+, when compared to TST-. This association was confirmed through the depletion of Tregs, which restored the microbicidal activity and an increase in IFN-, IL-2, IL10, and TNF- when compared to undepleted cultures. Data presented here supports the hypothesis that pre-exposure to MTB, represented by a positive TST result, may increase the number of Treg cells, which in turn could affect negatively the establishment of a protective immunity against TB in TST+ individuals
A resposta imune contra a tuberculose é mediada por uma resposta do tipo Th1, com a produção de IFN-γ, citocina fundamental para a ativação dos macrófagos e, consequentemente para a eliminação do bacilo. Vários fatores podem estar relacionados com a resistência a tuberculose. Neste trabalho, foi avaliado o impacto das células T reguladoras na resposta imune contra o Mtb em infecções de amostras de sangue total e CMSP de indivíduos positivos para o teste com PPD (PPD+) e negativos ao teste com PPD (PPD-). Além disso, avaliamos também se o perfil de resistência dos isolados de Mtb tem relação com o perfil de citocinas secretadas, com a frequência de células T reguladoras e com sua capacidade proliferativa em culturas de sangue total e CMSP dos indivíduos estudados. Para isso, foram arrolados 22 voluntários saudáveis. Desses indivíduos, 11 eram PPD+ e 11 eram PPD-. Foram também utilizados 12 isolados de Mtb, sendo 6 sensíveis e 6 resistentes a drogas antituberculose. Não foram encontradas diferenças entre os perfis de resistência dos isolados de Mtb e os parâmetros avaliados. O número de células T reguladoras encontrado nos indivíduos PPD+ foi maior em relação aos PPD- e a presença dessas células afetou negativamente o efeito microbicida nas culturas de sangue total de indivíduos PPD+, nas quais os isolados de M. tuberculosis proliferaram mais. Quando foram feitas infecções com isolados de Mtb em culturas de CMSP nas quais as células T reguladoras foram depletadas uma diminuição na proliferação do Mtb foi encontrada tanto nas amostras de indivíduos PPD+ quanto PPD-. Essa alteração na proliferação do Mtb foi acompanhada de maiores níveis de INF-γ, IL-2, IL-10 e TNF-α em relação às culturas de CMSP na presença das células T reguladoras. Os resultados desse trabalho sugerem que a pré-exposiçã o ao Mtb, evidenciada pelo teste positivo com o PPD, pode aumentar o número de células T reguladoras que, por sua vez, podem prejudicar a resposta imune protetora contra a tuberculose nos indivíduos PPD+
Nouhin, Janin. "Roles of cellular innate immunity and inflammatory markers in the immune reconstitution syndrome observed during co-infection with tuberculosis in HIV infected patients in Cambodia". Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC330.
Testo completoSimultaneous anti-tuberculosis and antiretroviral (ARY) therapy in HIV and tuberculosis (TB) co-infected patients can be complicated due to the occurrence of TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). The diagnosis test of TB-IRIS is not yet available and mainly based on clinical data. A better understanding of TB-IRIS immunopathology is crucial to improve diagnostic test and patients’ clinical outcomes. Innate immunity seems increasingly play a role in TB-IRIS. In the present doctoral thesis, is studied the role of cellular innate immunity, including NKT and γδ t cells, and as well as the implication of IL-1Ra, sCD14 and sCD163 plasma soluble markers related to the activation of monocytes/macrophages in the development of iris in HIV and TB co-infected patients in Cambodia. The results have shown that 1/. TB-IRIS is associated with a strong activation of γδ t cells and γδ2+ subset before initiation of ARY, 2/. None of IL-1Ra, sCD14 and sCD163 markers was predictive of the onset of iris. Longitudinal analysis of IL-1Ra plasma level could be useful for the diagnosis of the iris occurrence and for the evaluation of response to TB-IRIS In conclusion, our results reveal the association between important activation of innate immunity and the emergence of TB-IRIS in the physiopathology. In addition, our data provides new element of TB-IRIS and markers for evaluation of TB treatment efficacy
Lu, Yu-Jung. "The Role of CD4 T Cell Help in Effective CD8 T Cell Responses during Mycobacterium Tuberculosis Infection". eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1139.
Testo completoChen, Xinchun. "Effective Combination of Syngeneic HCT with CRCL Vaccination to Treat BCR-ABL+ Leukemia and CD4+CD25+FoxP3+ Regulatory T Cells Suppress Mycobacterium Tuberculosis Immunity in Patients with Active Disease". Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/305143.
Testo completoBotella, Hélène. "Étude du zinc et des ATPases de type P dans l'interaction entre Mycobacterium tuberculosis et les cellules hôtes". Toulouse 3, 2011. http://thesesups.ups-tlse.fr/1386/.
Testo completoMycobacterium tuberculosis thrives within macrophages by residing in phagosomes and preventing them from maturing and fusing with lysosomes. A parallel transcriptional survey of intracellular mycobacteria and their host macrophages revealed signatures of heavy metal poisoning, in particular, mycobacterial genes encoding P-type ATPases CtpC, CtpG, and CtpV. These proteins are predicted to export heavy metals, such as Zn2+, Cd2+ or Cu+. In the host cell transcriptome, genes coding for metallothioneins and the zinc exporter ZnT1, were induced during infection. Consistent with this pattern of gene modulation, we observed a burst of free zinc inside macrophages, and Intraphagosomal zinc accumulation within a few hours postinfection. Zinc exposure led to rapid CtpC induction, and ctpC deficiency caused zinc retention within the mycobacterial cytoplasm, leading to impaired intracellular growth of the bacilli. Using a deficient strain of Escherichia coli in zntA, coding for its main zinc exporter, we obtained the same results of zinc accumulation and impairment of the growth in macrophages. Thus, the use of P1-type ATPases represents a M. Tuberculosis strategy to neutralize the toxic effects of zinc in macrophages. We propose that heavy metal toxicity and its counteraction might represent yet another chapter in the host-microbe arms race
Castanier, Romain. "Structure-fonction des lipoglycanes et remodelage de l'enveloppe de mycobacterium tuberculosis dans les macrophages". Toulouse 3, 2013. http://www.theses.fr/2013TOU30258.
Testo completoStructure/function relationship of lipoglycans and remodeling of M. Tuberculosis cell envelope in macrophages Abstract: Tuberculosis is still responsible for 2 million deaths and 9 million new cases each year and remains a major health problem, particularly due to the increase in multi-drug resistant TB cases. It is therefore necessary to develop new antibiotics targeting M. Tuberculosis metabolic pathways active in the infected host. The literature data show that in the intracellular context, M. Tuberculosis adapts to the acid and hypoxic phagosomal environment. This adaptation leads, particularly, to changes in the ultrastructure of the envelope and in the structure of some glycolipids. In this context, we sought to determine what could be the impact of the intracellular environment on the structure of lipoglycans (LM, LAM), involved in the interaction of with the innate immune system, and arabinogalactan (AG), playing a major in the M. Tuberculosis envelope structure (Chapter IV). In this way, we developed a protocol to recover intramacrophage mycobacteria and remove the maximum of macrophages debris. The development of the 13C labeling of intracellular M. Tuberculosis and whole bacteria analysis by HR-MAS NMR allowed us to study the LAM and AG structures and to characterize altered signals constitutive of Ara4 and Ara6 patterns in mycobacteria in cellulo. This alteration may be due to changes in the structure or different dynamics of the molecules in the envelope. Structural analyzes of purified lipoglycans show an alteration of their structure. These structural changes could have an impact on the organization of the envelope of M. Tuberculosis and on its interaction with the innate immune system. Concurrently to this work, we were interested in the contribution of lipoglycans, in the physiological context of the infection, to the detection of mycobacteria by the innate immune system (Chapter II). Until now, lipoglycans/TLR2 studies were performed with purified compounds. The construction and use of mutants of the model organism Mycobacterium smegmatis with an altered lipoglycans production allowed us to show that, as lipoproteins, lipoglycans from the envelope are bona fide TLR2 ligands and participate in the detection of mycobacteria by the innate immune system. We also studied the structure/function relationship of lipoglycans in the detection by TLR2 and the lipid anchor role in this interaction. We analyzed the ability of Actinobacteria lipoglycans produced by Micrococcus luteus, Stomatococcus mucilaginosus and Corynbacterium glutamicum, whose lipid anchor is based on a glycosylated diacylglycerol rather than a mannosyl-phosphatidylinositol as in mycobacterial lipoglycans, to be recognized by TLR2 and to induce an immune response. We showed that these lipoglycans activate TLR2 and induce the production of cytokines and expression of surface markers by macrophages. This work extends the repertoire of TLR2 ligands to lipoglycans based on glycosylated diacylglycerol lipid anchor and confirm that bacterial compounds with a lipid anchor can induce TLR2-dependent immune response
Hartman, Michelle L. "M.tb Killing by Macrophage Innate Immune Mechanisms: A Dissertation". eScholarship@UMMS, 2011. https://escholarship.umassmed.edu/gsbs_diss/606.
Testo completoDanijela, Vukosav. "Karakteristike toka plućne tuberkuloze kod obolelih od šećerne bolesti". Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2019. https://www.cris.uns.ac.rs/record.jsf?recordId=110192&source=NDLTD&language=en.
Testo completoIntroduction: The association of diabetes mellitus and tuberculosis has long been observed and has been the subject of many studies. The diagnosis of diabetes before the discovery of insulin meant death within five years, a leading cause of death were infections, including tuberculosis. Last years the incidence of tuberculosis has declined, but there is still a significant number of TB patients in developing countries. On the other hand, the incidence of diabetes is on the rise, primarily due to the tendency of an increasing number of obese people. It is estimated that the prevalence of patients with diabetes will reach 438 million sufferers by 2030, and 80% of all cases will be people in developing countries where it is still a high prevalence of tuberculosis. As a result of the epidemiological situation, these two diseases will increasingly occur in parallel, modifying the current one another. Aim: The aim of this study was to investigate the influence of diabetes mellitus on the course of pulmonary tuberculosis, primarily in the bacteriological status, radiological presentation of disease, duration of the treatment regimen and the frequency of disease relapse. Materials and Methods: The study included two groups of fifty patients who were hospitalized at the Institute for pulmonary diseases. The first group consisted of patients with pulmonary tuberculosis and concomitant diabetes mellitus, a second group consisted of patients with pulmonary tuberculosis without associated diabetes. All patients were analyzed by the following characteristics: age, gender, clinical picture, bacteriological status, radiological presentation, the presence of side effects of antituberculosis drugs, the presence of M. tuberculosis resistant to the drugs, the duration of the therapeutic regimen, treatment outcome, recurrence and length of hospitalization. Diabetics were further analyzed with respect to: the type of disease, duration of disease, a metabolic disease and the regulation for the presence of a complication. All patients completed this study were subjected to a diagnostic algorithm comprising: history and physical examination, direct microscopy of sputum, cultivation of sputum, radiographs of the chest, chest CT scan in case positioned on clinical indications. Invasive diagnostic will be performed in patients in whom the diagnosis could not be set previously conducted noninvasive diagnostics. The treatment regimen will be started during the hospitalization in the Institute of pulmonary diseases and is set under the control of ambulatory pulmonary dispensaries. Results: The study showed that in the group of TB patients without concomitant diabetes mellitus was a similar number of patients male and female, a greater number of respondents was in the age groups up to the age of 50, while in the group of TB patients with diabetes mellitus was significantly more frequent male half and significantly more respondents were in the age groups over 50 years of age. Significantly higher number of relapses is recorded in a group of TB patients with diabetes mellitus (p = 0,001). Between the two study groups was not significant difference in the clinical presentation of the disease. In the group of TB patients with diabetes mellitus, is statistically significant higher number of smear positive findings (p = 0,046). There is a statisticaly significant difference in the average length of time required for the smear conversion (p = 0,000) and average length of time needed for the conversion of sputum cultures (p = 0,000). In both cases, the group of TB patients with associated diabetes mellitus had a longer average time needed for the conversion. In the group of patients with tuberculosis associated with diabetes mellitus was statistically significantly more patients with the presence of the cavern (p = 0,006), and the localization of the pulmonary changes in all three lobes (p = 0,000). Between the two study groups was not observed a statistically significant difference in duration of the treatment regimen, the expression of adverse drug effects, develop resistance to the drugs, and the outcome of the treatment. Group of patients with tuberculosis associated with diabetes had a statistically significantly greater number of hospital days (p = 0,000). Between the groups of patients with tuberculosis associated with satisfactory controlled diabetes and the group of TB patients with poorly controlled diabetes was statistically significantly longer duration of the therapeutic regimen in diabetic patients with poor regulation of the disease (p = 0,018). There was no significant difference in the appearance of relapses, the clinical presentation of disease, the bacteriological status, radiology, the expression of adverse drug effects, develop resistance to the drugs, outcome of the treatment, number of hospital days between the two study groups. Comparing the three groups (tuberculosis without associated diabetes mellitus, TB patients with associated satisfactorily controlled diabetes and TB patients with associated poorly controlled diabetes), it was observed that the group of patients suffering from tuberculosis with poorly controlled diabetes takes the longest time to smear conversion and conversion of sputum culture and to have the highest number of hospital days. In the group of patients with tuberculosis associated with poorly controlled diabetes was significantly greater number of patients who were treated for eight months compared to the other two groups (p = 0,011). Comparing the group of TB patients with type 1 diabetes and type 2 diabetes is not a statistically significant difference between the groups in all variables. In the group of diabetic patients with satisfactorily controlled diabetes, there are a large number of those with type 2 disease, in comparison to the group of patients with poorly controlled diabetes. Group of diabetics with poorly regulated disease has a significantly greater number of diabetes comlications. Conclusion: It has been shown that diabetes mellitus has a significant effect on the bacteriological status, radiological presentation, the length of the treatment regimen, the frequency of recurrence of tuberculosis and the number of hospital days of patients with tuberculosis, and that the adjustment of diabetes had a significant effect on the length of the treatment regimen.
Le, Moigne Vincent. "Étude de la réponse immunitaire anti-peptidique en fonction du contexte du peptide et du vecteur d'immunisation". Brest, 2004. http://www.theses.fr/2004BRES2006.
Testo completoVarions PAMPs (complete Freund's adjuvant, bacterial DNA and flagel in), bacterial patterns inducing innate immune response receptors, are used as vectors and as adjuvants for three antigens (a peptid from Clostridium tyrobutyricum flagellin, the P27 Mycobacterium tuberculosis and POMP91B Chlamydophyla abortus proteins). Cellular and humoral immune responses are analyzed in mice immunized with the différent formulations. Observed responses are specific of antigens used and of immunization modes practiced. Generally, responses present an adjuvant effect of recombinant flagellin fused with antigen on Thl cellular response. Cellular responses induced with this formulation are better than those obtained from genetic immunization. Otherwise, anti-P27 antibodies allowed to allocate a peripheral localization for this PPE M. Tuberculoses protein
Decout, Alexiane. "Bases moléculaires et conséquences fonctionnelles de l'interaction entre les mycobactéries et les lectines de type C Mincle, Dectine-1 et Dectine-2". Thesis, Toulouse 3, 2015. http://www.theses.fr/2015TOU30224.
Testo completoMycobacterium tuberculosis is the causative agent of human tuberculosis leading to more than 1 million deaths every year and infecting latently one third of the population worldwide. Once in the lungs, mycobacteria are detected by innate immune cells through several pattern recognition receptors such as C-type lectins. The aim of my thesis was to characterize the molecular bases and the functional consequences mycobacteria recognition by three C-type lectins: Mincle, Dectin-1 and Dectin-2. We have characterized the structure/function relationships of the glycolipid ligands recognition by Mincle and Dectin-2 and synthesized ligands of Mincle with a minimal structure that could be used as vaccine adjuvants inducing Th1 and Th17 responses. We also identified Dectin-1 as a possible silent entry gate for mycobacteria into phagocytic cells allowing binding to immune cells without triggering intracellular signaling
Miyara, Makoto. "Cellules T régulatrices et maladies inflammatoires systémiques". Paris 6, 2006. http://www.theses.fr/2006PA066067.
Testo completoKorf, Johanna Elizabeth. "The modulating properties of mycobacterial mycolic acids on murine macrophage function". Diss., 2003. http://hdl.handle.net/2263/28500.
Testo completoDissertation (MSc (Biochemistry))--University of Pretoria, 2005.
Biochemistry
unrestricted