IMMUNOLOGY

Author: BRAZIS CAUBET PILAR.
Year: 2001.
University: AUTÓNOMA DE BARCELONA.
Place of defense: FACULTAD DE VETERINARIA.
Place of preparation: ESCUELA DE DOCTORADO Y DE FORMACIÓN CONTINUADA.

Summary: The canine atopic dermatitis is a chronic inflammatory disease of the skin that course with an increase in serum IgE alérgeno-específica. One of the more cell populations involved in the initiation and development of this disease are skin mast cells. The mast cells are activated in the body after the interaction of IgE with the allergens attached to its membrane and the resulting intersecting of the high affinity receptor for IgE (Ec * IR). Thus, triggering desgranulación of mastocios and the synthesis and release of cellular mediators to encourage the development of inflammation. In name and in mice there are studies that show that IgE has a regulatory role for the expression of the Fc receptor * RI membrane mast. Thus, a high concentration of IgE induces overexpression of the receptor FceRI, and causes the release by the mastociotos of higher concentrations of mediators inflamtorios contributing to the development of allergic diseases. So far, the dog no data on the subject, and yet it is a species that suffers allergic diseases with a high incidence. Thus, the present study aims to assess how the changes affect the level of IgE in the microenvironment of mastocito canine on its ability to release and synthesis of inflammatory mediators, in particular of histamine and necrosis factor tumoal (TNF-alpha ).

Author: VICENTE ARROYO ANA BELÒâ°N.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE CIENCIAS BIOLÒâGICAS.
Place of preparation: FACULTAD DE CIENCIAS BIOLÒâGICAS.

Summary: The quimioquina RANTES/CCL5 is a potent quimioatrayente for diverse populations leucocitarias. Fibroblasts actÃÂ seventh an, regardless of funciÃÂ charges within structural tissues such as modulating the immune response through expresiÃÂ ³ n mediators of the inflamaciÃÂ ³ n. A regulaciÃÂ ³ n inappropriate in the producciÃÂ ³ n of these mediators may lead to inflamaciÃÂ ³ n crÃÂ ³ nica and fibrosis. This paper has studied cÃÂ ³ mo regulates expresiÃÂ charges of RANTES/CCL5 in fibroblasts dÃÂ © rmicos growing stimulated with TNF-alpha and IFN-gamma as an in vitro model that mimics the funciÃÂ charges of fibroblasts during the inflammatory process. AsÃÂ same estudiÃÂ ³ the effect of pro - and anti-inflammatory factors (IL-17, IL-4, IL-10, IL-13 and ÃÂ ¡cido retinoic) on the expresiÃÂ charges of RANTES/CCL5 induced by TNF-alpha and IFN - gamma. The results show that TNF-alpha and IFN-gamma increase so sinÃÂ © rgica the producciÃÂ charges of proteÃÂna and mRNA and RANTES/CCL5 in fibroblasts. This regulaciÃÂ ³ n is exercised transcriptional level in the case of TNF-alpha, and post-level in the case of IFN-gamma. The regions involved in the regulaciÃÂ charges of activaciÃÂ ³ n promoter RANTES/CCL5 are regions R (AB), which joins the proteÃÂan p65/p65. The estimulaciÃÂ charges with TNF-alpha, regiÃÂ ³ n R (D), which unites IRF-2 / 3 of a constituent and regiÃÂ ³ n R (G) joining the proteÃÂnas c-Jun, Jun D Jun D/CREM-1. The mutaciÃÂ ³ n each one of these regions carried the pÃÂ © partial or complete loss of promoter activity in fibroblasts. The inducciÃÂ charges of RANTES/CCL5 is inhibited mainly by IL-17, which actÃÂ eighth to transcriptional level to travÃÂ © s of regiÃÂ ³ n R (AB). The IL-4, IL-10, IL-13 and ÃÂ ¡cido retinoic inhibit the increase in producciÃÂ charges of proteÃÂna in response to TNF-alpha. The inhibiciÃÂ ³ n produced by the ÃÂ ¡cido retinoic is exercised transcriptional level, although none of the regions studied in this work estÃÂ ¡involved in such regulaciÃÂ ³ n.

Author: VICENTE ARROYO ANA BELÉN.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE CIENCIAS BIOLÓGICAS.
Place of preparation: FACULTAD DE CIENCIAS BIOLÓGICAS.

Author: GONZALO IBAÑEZ PILAR.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FAC. CC. BIOLOGICAS.
Place of preparation: FAC. CC. BIOLOGICAS.

Summary: In this thesis has described the first cases of lymphoid cell differentiation type B NK-T/NK in the first third of gestation of a mouse. The linfopoieis B originates from day 10 of gestation in localized regions intra-embrionarias as Esplanchnopleura-Paraaortica (Ep-P/AGM), the Fetal Liver (HF), and to a lesser extent in the Saco Vitelino (SV). We describe here the first parent unipotencial B, as a population CD117 + AA4.1 + CD19 + CD45R-, PAX-5 dependent. These parents are capable of establishing cell lines in culture B on the line stromal ST2 in the presence of IL-7. Crops survive in these conditions in vitro for a long time, without being processed. These data show that the onset of the linfopoiesis B is earlier (days 10-11) as described so far (14th), and its appearance is close to that of the first HSC detected in the embryo (day 8). Using these same crops, with total SV parents, we see the emergence of cell lines and aspect polarized phenotype CD117 + CD90 + CD19-CD1b-. Studies of its broader phenotype have allowed us to characterize them with NK-T/NK: NK1.1 + CD49b + CD122 +. Have also been detected populations CD3 + alpha GalCerCD1d +, together with the expression of Valfa14 by RT-PCR, these lines NK-T/NK, are generated primarily from parents located in SV (9th), and later in other niches as Ep-P/AGM and HF days 10-11. This paper has described a differentiation NK-TNK prior to the hitherto accepted (day 13 of gestation), which essentially is the origin SV. This study characterizes progenitor populations at times early in ontogeny, and the compartmentalization of the specific linfopoiesis B in Ep-P/AGM, (day 10 of gestation) and NK T / NK, SV (day 9 of gestation) .

Author: CORREA ROCHA RAFAEL.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD CIENCIAS BIOLOGÍCAS.
Place of preparation: HOSPITAL GENERAL UNIV.GREGORIO MARAÑON.

Summary: The main consecuencisa of HIV infection is a marked depletion of T lymphocytes CD4 leading to the immunodeficiency associated with enfermedad.Los treatments antirretroviales are able to markedly reduce the replication road and lead to an increase in T-lymphocyte CD4, but they fail to recuaperarlas answers VIH-específicas or get eradicate virus.Por this seha focused interest in the patient's immune system as a possible alternative to eradicate the virus or at least prevent the progression of enfermedad.El thymus, as the body responsible the repopulation of T lymphocytes could juagar a key role in this recovery and reconstitution system inmunológico.Por it was studied in niós, which retain the functionality of the thymus, the immune reconstruction and its potential benefit in the contro l HIV infection. The results demonstrate the inhibitory effect of HIV on the role tímica and the key role that the thymus plays in the maintenance of gracious people CD4 in niñós infectados.La decrease in viral load after therapy antirretrovial leads to a restocking of T lymphocytes CD4 having mayotitariamente tímico origin and IL-7 appears to be implicated in the homeostasis mechanism that would trigger the production tímica of these cells CD4.Esta restocking tímica allow rebuilding the portfolio of specific features of this population and is associated with the preservation of various parameters inmunológicos.La restocking tímica T lymphocytes CD4 observed in children, asoción with a preservation lymphocyte memory VIH-específicos that could confer immunity protectivaa versus VIH.Estos results allow a better understanding of HIV infection in niñós and support the use of strategies encamiandas to improve the function tímica as a tool for achieving the reconstruction inmuni and effective control of infection

Author: AGULLÓ ORTUÑO M. TERESA.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: CIENCIAS BIOLÓGICAS.
Place of preparation: FACULTAD DE BIOLOGÍA DE LA UCM.

Summary: This paper presents the chemical biodirigido of endemism canary Senecio bollei Kunk & Sound. (Asteraceae). The crude extract was subjected to a chemical fractionation guided by bioassay for different insects, producing a chemical fractionation guided by bioassay for different insects, for a * 5 sterol, beta-sitosterol (1), a triterpeno pentacíclico, lupeol (2 ), eight sesquiterpenos, comprising three isolated from the aerial part of the plant are the type eremofilanolida, 6beta-hidroxi-8alfa-etoxi-eremofil-1 (10), 7 (11) -dien-8beta, 12-odia (3), a compound with a methylene exocíclico on his ring C (4) and 6beta-isobutanoiloxi-8alfa-hidroxi-eremofil-1 (10), 7 (11) -dien-8beta, 12-odia (5). All five of the roots are sesquiterpenos with processed skeleton furanoeremofilano: 6beta-isobutanoiloxi-9-oxo-10betaH-furanoeremofilano (9), 6beta- (2-metilbutanoiloxi) -9-oxo-1 (10) -en-furanoeremofilano (11) and 6beta-isobutanoiloxi-9-oxo-1 (10) -en-furanoeremofilano (12). Besides three phenolic compounds: ferulato of hexacosanilo (7), 4-hidroxibenzaldehido (10) and 3,6-dimetoxi-4-hidroxibenzaldehido (13) and an alkaloid pirrolizidínico, senecivernina (6). It was also isolated five mixtures of compounds whose main components were acid esters ftálico along with alcanos different length of string. These products are characterized on the basis of their physical and spectroscopic properties. The fractions containing acid esters ftálico were fagorrepelentes of L.decemlineata, as a result of the presence in mixtures of compounds PM 330 and 386 of unknown structure. The sesquiterpenos 5 (aerial part) and 9 (roots transformed) showed activity antialimentaria in L.decemlineata. The only sesquiterpeno which showed activity antialimentaria in larvae S.littoralis was composed 9 of the roots processed. In sesquiterpenos of the air we proved that the substituents at position C-6 and C-8 of the molecule are the ones who determine the activity antialimentaria. Possession of a group alfa-metileno exocíclico in the C ring of the molecule, by contrast, has not been correlated with the replacement C-6 and the absence of unsaturated C-1, C-10. The allelopathic activity of this plant is attributable to the presence of phenolic compounds in the root, being composed 10 which introduced greater inhibition of germination, but the AP isolated from the air, senecivernina (6), also showed an activity allelopathic moderate. Compounds of the aerial part of S.bollei showed reduced activity cytotoxic compounds that the roots processed in tumor lines mammalian ensaydas, sienod SW480 line tumor most affected by these compounds. Compared with other access points connected structurally, the alkaloid senecivernina (6) showed the citotoxidad highest in lines tumor ensaydas. After made these bieonesayos, we can conclude that the defensive role in S.bollei is taken primarily by the root, but with little selectivity of action. By contrast, in the aerial part of this role is modulated by herbivores that colonize. Moreover, the cytotoxic activity shown in tumor lines tested, these compounds makes good candidates as "seed" for further pharmacological studies.

Author: CORREA ROCHA RAFAEL.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE BIOLÓGICAS.
Place of preparation: HOSPITAL GENERAL UNIV. GREGORIO MARAÑÓN.

Summary: The main consequence of HIV infection is a marked depletion of T lymphocytes CD4 leading to the immunodeficiency associated with the disease. Antiretroviral therapy is able to reduce markedly and viral replication and lead to an increase in T-lymphocyte CD4, but they fail to retrieve the answers VIH-específicas or get eradicate the virus. Thus has focused interest in the patient's immune system as a possible alternative to eradicate the virus or at least prevent the progression of the disease. The thymus, as the body responsible for the restocking of T lymphocytes, pordía play a key role in this recovery and reconstitution of the immune system. Thus was studied in children, which retain the functionality of thymus, immune reconstitution and its potential benefit in controlling HIV infection. The results demonstrate the inhibitory effect of HIV on the role tímica and the key role that the thymus plays in the maintenance of the population CD4 in infected children. The decrease in viral load after antiretroviral therapy leads to a restocking linfoctios T CD4 which are mostly home tímico and IL-7 appears to be implicated in the homeostasis mechanism that would trigger the production tímica of these cell sCD4. This restocking tímica would reconsturir the repertoire specified in this population and is associated with the preservation of various immunological parameters. Restocking tímica T lymphocytes CD4 observed in niñós, was associated with preservation of lymphocytes memory VIH-específicos, which might confer protective immunity against HIV. These results allow a better understanding of HIV infection in children and supports the use of strategies aimed at enhancing the role tímica as a tool to achieve immune reconstitution and effective control of the infection.

Author: FLORES JIMÉNEZ NATALIA.
Year: 2003.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE BIOLÓGICAS.
Place of preparation: CENTRO NACIONAL DE MICROBIOLOGÍA (INSTITUTO DE SALUD CARLOS III).

Summary: The experimental allergic encephalomyelitis (EAE) is an inflammatory disease of the central nervous system (CNS) and serves as an animal model for human multiple sclerosis (MS). It is considered that has an autoimmune origin and is mediated cell subtype 1 T lymphocytes cooperators (Th1), characterized by secretion of cytokines such as interleukin 2 (IL2) and interferon gamma (IFNgamma) among others. We have studied processes related to cell activation via the T cell receptor (TCR) lines and clones Th1-Th2 reagents to myelin basic protein (MBP); proliferation, production of interleukins, activation of the transcription factor NFkB and union of factors NFAT and Stat6 element P1 promoter interleukin 4. Furthermore, we have studied the effect of IFNbeta in vivo on the symptoms of EAE, the number of perivascular infiltrates in the CNS and the induction of nuclear factor in lymph node cells (LNC). It also has analyzed the effect of IFNbeta in vitro induction of NFkB in the online human Jurkat. Finally, we performed a study of the binding capacity of NFkB and AP1 in PBMC from healthy subjects and patients with multiple sclerosis. Of all the work that is presented is concluded that IFNbeta significantly reduces symptoms of EAE, this effect is accompanied by a decrease of perivascular infiltrates in the central nervous system, a decrease of the activity of NFkB and an increase in phosphorylation of Stat6.

Author: BERTRAN RODRÍGUEZ ESTHER.
Year: 2003.
University: BARCELONA.
Place of defense: FACULTAD DE BIOLOGÍA, UNIVERSIDAD DE BARCELONA.
Place of preparation: INSTITUTO DE INVESTIGACIÓN ONCOLÓGICA.

Summary: The platelet activation in response to a vascular injury or an inflammatory process causes the secretion of soluble mediators able to modulate the functions of the cells involved in inflammation. The F4P (Factor 4 Plaquetar) is a protein specific to platelets and member of the superfamília proteins called chemokines. It has been extensively studied the ability of F4P by its effect antiangiogénico and enhancer of clotting, but they knew little about their involvement in the regulation of inflammation. This study demonstrates the ability of F4P stimulate cells "Natural Killer (NK) to synthesize proinflammatory cytokines such as IL-8, IL-1beta, IL-6, INFgamma, TNFalfa and GM-CSF, as well as stimulate antibody dependent cytotoxic activity (ADCC). It shows that these effects are maintained even if the F4P is coupled with heparin, as a result important physiological conditions in the F4P is linked to glycosaminoglycans in vascular endothelial cells. Stimulation of NK cells via receptor Fcgamma RIIIA increases in a synergistic effect F4P. In contrast, F4P has no effect on those functions stimulated by IL-2 in these cells. He started the study of the mechanism of signal transduction that triggers these effects, several evidences suggest that F4P does not induce this effect through the activation of protein G, Gi and G0, nor is associated with a transient increase of CA2 + intracitoplasmático. But it has been associated with the activation of the fosfatidilinositol 3-quinasa. This study demonstrates, therefore, the ability of F4P to enhance the inflammatory response by NK cells. One of the lesser known features of these cells.

Author: SÁNCHEZ MUÑOZ BEGOÑA LAURA.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: HOSPITAL RAMÓN Y CAJAL.

Summary: From the knowledge of the close interrelationship between SI and the digestive system, there has been great progress in understanding the inmunopatogenia of gastrointestinal diseases. Thanks to Flow Cytometry is a better understanding of the intestinal lymphoid subpopulations and the alterations that characterize various pathological conditions, thus contributing to both the diagnosis and profundiar in inmunopatogenia of them. This paper focuses, first, on the analysis of the characteristics of populations intestinal lymphoid both phenotypic and functional, and in identifying the differences between the various sections of normal intestinal mucosa. Taking into account these results have been analyzed characteristics of mucosal lymphocytes of various enteropatías, focusing on: 1 - The Celiac Disease, validating the identification of alterations of the LIE as complementary diagnostic test that allows differential diagnosis of other enteropatías. 2-Intestinal Inflammatory Disease, describing the phenotypic and functional characteristics of the inflammatory infiltrate of the inflamed mucosa. 3 - The Intestinal Transplantation, determining the evolution of populations of mucosal lymphoid in a case of intestinal transplantation asylee, as evidence for the diagnosis and monitoring of graft rejection.

Author: MARTÍN FERNÁNDEZ JOSÉ M..
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The understanding of the biology of T lymphocyte depends on the degree of knowledge of the receiver for antigen or complex TCR/CD3. The study of natural human mutants provides a window to understanding how to operate each of the components of this receiver. The absence of the chains CD4 complex, causing a group of well immunodeficiencies characterized by complete absence of lymphocytes To well llinfopenia compounded by a lack of expression of complex membrane and infections that can be lethal. Moreover, the gene therapy of mature T lymphocytes has been proposed as a treatment option for cancer and AIDS, but tamibén for congenital disorders of the cells T. This work is an experimental approach to the treatment of immunodeficiencies of CD3, but also provides new data on the structure and function of complex TCR/CD3. In addition to characterize the second human patient alive of this deficiency and analyze the biology of this receptor on models developed in vitro (T lymphocytes immortalized with herpesvirus saimiri and HTLV - I). The work confirms that the gene therapy of the weakness in the chain CD3gamma by retroviral transduction possible, but warns about the complications that arise when cells are home postímico, suggesting the use of parents as potential targets. He also warned about the need for more research in vitro processes supplementation gene mature T lymphocytes. This work raises new questions in cuentao to construcicón or assembly of the complex TCRT/CD3 before concepts established in previous work on T lines of tumor origin. It provides evidence to suggest a greater role assigned to so far to the area transmembranal or intracellular CD3gamma in the expression of complex membrane role that historically rested in part extramembranal of this chain.

Author: BERMEJO MARTÍN JESÚS FRANCISCO.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Nanotechnology is an emerging discipline that studies the application of devices on the scale nanoscópica different fields, including Biomedicine. The dendrímeros are polymers nanoscópicos of chemical synthesis that have received considerable attention in recent years because of its potential use in applications as diverse as catalysis nanoscale, chemical sensors, micelles unimoleculares, mimicking the function of enzymes, encapsulation of molecules, molecular recognition, diagnostic agents and also as a vehicle to transport genes and drugs. Moreover, the use d eoligonucleótidos being evaluated in various areas. The antisense oligonucleotide sequences are short (15-30 bases long), or similar synthetic DNA that are complementary (or antisense) to a target sequence (DNA or RNA), are designed to interfere with a biological fact, as the transcript , translation or splicing. The oligonucleotide sequences with CpG not metiladas immunomodulatory properties presented to interaciconar with the receiver TLR-9 and are being evaluated for the treatment of allergic diseases, infectious or tumor. One of the main problems of therapy oligonucleotides is to achieve adequate levels to achieve therapeutic effect. There is a need to manage large quantities of oligonucleotides to get biological effect, because they show high affinity to join plasma proteins, such as albumin. In this work we present new dendrímeros structure carbosilano water soluble cationic groups with peripherals that have been evaluated in terms of biocompatibility, binding to DNA, transport capacity of oligonucleotides and protection of the same face whey proteins. These dendrímeros would aim at increasing the average life of these oligonucleotides, their bioavailability and decrease your dose. It provides further evidence for the potential of these dendrdímeros to interfere with the life cycle of HIV. For all these works have been used peripheral blood mononuclear cells (CMSP) because it is good physiological model. It lays the foundation for the further development of future biomedical applications with these dendrímeros.

Author: LÓPEZ VÁZQUEZ DE LA TORRE MÁRIA DE LA O.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The type of cellular immune response plays an important role at the center of viral infections. This type of response is essential to control viral replication during primary infection by VIH.Sin however, the role of this response during chronic infection is a item controvertido.Se have proposed several mechanisms that could be involved in the inability of this reply satisfactorily to control HIV replication and halt the progression of inmunodeficiencia.Para study the various mechanisms that could contribute to the failure of CTL response in this thesis discusses various quantitative and qualitative aspects of lymphocytes TCD8 + specific epítopos against two proteins from GAG, POL, respectivamente.Ademas was esamina factors virological (plasma viremia mutations and exhaust) and immunological (level and lymphoproliferative response of CD4 + T cells) on the CTL response in 61 patients with infeción chronic HIV and untreated antirretroviral.Por Finally, he examines the effect of anti-HIV therapy on various aspects of the CTL response front both epítopos in 26 of these patients. This work shows that a high proportion of patients with chronic HIV infection and untreated no detectable response of CD8 + T cells compared with epítopos two proteins other than the presence of mutations virus.La exhaust is associated with an absence of such a response. Furthermore, it was shown that cells CD8 + show alterations in the process of differentiation, in the production of cytokines and in the ability of expansión.Por Finally, the levels of plasma viremia in a manner inversely associated with the ability to produce IFN-Y by cells CD8 +. A finding of interest has been the demonstration of the emergence of novoo cell CD8 + specific anti-HIV after a partial control of viral replication enough therapy in the short term, although these cells appear to be dysfunctional.

Author: ROSA MANRIQUE DE LARA GONZALO DE LA.
Year: 2004.
University: COMPLUTENSE DE MADRID.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: HOSPITAL GREGORIO MARAÑON.

Summary: The dendritic cells belong to the group of antigen presenting cells (CPA), which are so important for the establishment of an appropriate immune response, and certainly the type with greater ability to stimulate lymphocytes all leukocytes. This is mainly due to a combination of high mobility with a great ability to capture antigen and presentación.Así, one of the objectives of this work has been studying the response of migratory dendritic cells that are found in peripheral blood front chemiotactic to different stimuli and the ability to change their pattern of migration when they encounter a stimulus activator that lead to lymphoid tissues; of the two subtypes analyzed myeloid and lymphoid, there are marked differences in the ability of basal migration, the response towards proinflammatory chemokines, and the stimuli they change their pattern of migration in response to chemokines produced in lymph nodes secundarios.La another part of this work has focused on the study of one of the recipients that some dendritic cells: DC lead SIGN he has described as host of different types of antigens, such as bacteria, viruses and protozoa parasitarios.Hemos seen as the ability to fagocitios particles of yeast (zimosán) lectina of this is dependent on some mechanism outside the molecule; furthermore, we noticed how it regulates its location in membrane when it comes into contact with these particles.

Author: BLANCO MOLINA MARIA MAGDALENA.
Year: 2004.
University: CÓRDOBA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: It is understood by all that herbal plant containing one or more active ingredients, which are chemicals that exert a pharmacological action on the body, able to prevent, alleviate or cure diseases. The natural products with potential pharmaceutical are gaining a renewed interest because of the availability of new technologies that create new techniques to assess reproducible biological activities of the same. These technologies and techniques arising from them are particularly important in implementing programs for searching ge drugs against diseases such complejascomo cancer, AIDS and some inflammatory diseases. One of the major needs for exploring the medicinal flora is the introduction of bioassays quick and cost to evaluate the potential biological effects of natural products derived from plants chosen for use in Traditional Medicine. Thus, at present, the pharmaceutical industry has adopted as a strategy the rediscovery of natural sources, looking prototypes chemical (seeded) that show biological activity to be used, with or without chemical modifications later, as potential therapeutic agents. Of particular interest those natural products presenting activídad anti-inflamatoria and / or anti effects on which is ampliamenteinvolucradoel transcription factor NF-kB. The transcription factor NF-kB (Nuclear Factor Kappa B) is a family of factors transcripcíón diméricos composed of members belonging to the family Rel, which is characterized by its recognition of a consensus sequence in the promoters of a large number of activation genes.La the transcription factor NF-kB is also related to many aspects of oncogénesis, including control of apoptosis, cell cycle, differentiation and cell migration. As NF-kB is deregulated in many types of cancer and inflammatory diseases, the inhibition would be a logical therapy for treating them.

Author: SANCHO ZAPATERO ROCIO.
Year: 2004.
University: CÓRDOBA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The system canabinoide consists of lipid mediators (endocanabinoides and endovanilloides), enzymes that regulate metabolism, and their receptors that mediate biological actions. These lipid mediators exert their multiple biological actions by both dependent and independent mechanisms for binding to receptors known. The identification of the components of this system and its ability to pharmacological manipulation has represented a major breakthrough in the field of neuroinmunología. The occupation of TCR in T cells by antigen leads to a cascade of activation of intracellular signals transmitted culminating with the regulation of inducible transcription factors responsible for the reprogramming gene. Within these transcription factors is the nuclear factor kappa B (NF-? B). This transcription factor belongs to the family NF-kB/Rel, which includes a family of transcription factors that play a very important role in the regulation of genes associated with cell growth and development, immune and inflammatory response and in the replication of HIV-1. In this paper we have demonstrated that: 1) the endocannabinoideanandamida inhibits the canonical path activation NF-? B induced TNFa. This inhibition occurs at the IKK complex and more specifically acting on the subunit IKKB, being the independent effect of receptor CB and TRPV1; 2) The endovanilloides N-araquidonoil-dopaminay N-oleil-dopamina inhibit the proliferation of T lymphocytes induced antigen through a mechanism independent of the recipient and that implies a common element in the path of NF-kB activation, NFAT and AP-1; And 3) N-araquidonoil-dopaminainhibe replication of HIV-1 at transcriptional through a mecanismoque involves activaciónde NF-? B Yque is independientede the receptoresCB1y CB2. This represents a major step forward in practical knowledge of this novel system canabinoides endogenous, which can be modulated by WADA in diseases of the central nervous system that circulate with activaciónde NF-kB.

Author: GONZALEZ ROJAS SANDRA JOVANNA.
Year: 2005.
University: CANTABRIA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: Study prior to our laboratory have shown that hiperexpresión a transgene of the molecule antiapoptótica hBcl-2 in B-cells causes the development of a syndrome lúpà ¬ co (LES) in mice (NZW x B6) F1-SV40-Eu-hBcl -2 (line 1). However, this effect was not observed with another line of transgenic mice (Tg) (NZW x B6) F1-Ig-hBcl-2 (line 2), which also hiperexpresa hBcl-2 in B cells In this Doctoral Thesis, we demonstrated that the inhibitory effect of LES observed in the mice Tg line 2, there is also a second model of disease utoinmune: arthritis induced after immunization of mice susceptible (DBA / 1 Xb6) F1- hBcl-2 Tg line 1 developed severe arthritis, there were no major injuries joints in animals (DBA / 1 x B6) F1-hBcl-2 Tg line 2. When we study the dferencias between two lines of Tg mice, line 2 showed expression of the transgene in a subpopulation of T cells CD4 + (7-15%) and CD8 + (20-35%) in addition to its experesión in B cells, while the Tg line 1 alone expressing hBcl-2 in B cell The absence of CIA in mice (DBA / 1 x C3H) F1 that overexpression hBcl-2 specific T lymphocytes (C3H-LcK-hBcl-2 line 3), indicates that the aberrant expression of the transgene of Bcl- 2 in T lymphocyte subpopulations the cause of protecting against the development of autoimmunity observed in the mice Tg line 2. In studies ulteriors demostrams that overexpression of hBcl-2 in CD4 + cells promotes the expansion of CD + CD25 + regulatory whom are directly involved in the inhibition of utounmunidad observed in the mice Tg lines 2 and 3. In conclusion, our study suggests that the inhibition of lymphocyte apoptosis, secondary to overexpression of Bc11-2, B lymphocytes were favorecela appearance of autoimmunity. By contrast, overexpression of Bcl-2 in B lymphocytes, it favors the onset of autoimmunity. By contrast, overexpression of Bcl-2 in CD4 + T cells, promotes the generation of CD4 + cell D25 + regulations that inhibit the development of autoimmune diseases.

Author: CRESPO MAULL MARTA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE MEDICINA.
Place of preparation: FACULTAD DE MEDICINA.

Summary: The chronic lymphocytic leukemia (CLL), the most frequent in the western world, is a disease caused by the proliferation and accumulation of B lymphocytes immuno-incompetentes. Approximately 50% of the cases have mutations in the gene of imunoglobulinas (IgVH) 5, which states that may have passed through the center germ. In addition, patients who do not have mutations in IgVH are more likely to have a worse prognosis. For these reasons, it is now working on getting markers that indicate the state mutacional of immunoglobulinas and make them easier to detect and fast. Recently there has described the presence of mRNA gene ZAP-70 cells LLC without mutations in IgVH. It has also been described that the protein ZAP-70, involved in the signal transduction through the receptor lymphocytes To TCR, it is essential for the proper development of lymphocytes pro / preB mice. This finding is the first description of the involvement of the protein ZAP-70 in a lymphocyte lineage B. The working hypothesis of this dissertation is that the expression of the protein ZAP-70 in the LLC might be related to the state mutacional of immunoglobulinas and, therefore, with the prognosis of the disease. Moreover, the protein ZAP-70 may be expressed in lymphocytes pro / pre-B normal humans, as well as acute linfoblásticas B leukemia (LAL-B) derived from these. Among all populations normal B analyzed by various analytical methods expression was detected only ZAP-70 in those lymphocyte phenotype with pro / pre-B, while ZAP-70 were not detected in any subpopulation of B lymphocytes mature in different anatomical origins. In neoplastic B lymphocytes, in contrast, we find expression of ZAP-70 in both neoplasms arising from lymphocytes pro / pre-B (LAL-B) and mature B lymphocytes (LLC and limfoma Burkitt) in varying proportions. In the case of LLc addition, the detection of the expression of the protein ZAP-70 through citometría flow is a fast and efficient method for determining the prognosis of patients with very useful clinical LLC.

Author: ESPEJO RUIZ CARMEN.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAT DE BIOLOGÍA.
Place of preparation: UNIVERSIDAD DE BARCELONA.

Summary: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating and central nervous system (CNS) is the leading cause of disability in young adults after injuries. Its prevalence in our geographic area is approximately 60-70 patients per 100,000 inhabitants. The cause of the disease is still unknown and has been involved both genetic and environmental factors. It is considered to be a disease mediated by the immune system, which activated T lymphocytes in the periphery are able to recognize the myelin antigens in the CNS and trigger the autoimmune process leading to the destruction of myelin, so that the nerve conduction can affected appear and the clinical signs and symptoms characteristic of the disease. There is evidence that oxidative stress has an important role in the development of the lesion in the CNS. In this regard, it has been observed that oxidative stress may cause damage and axonal damage axonal contributes to the neurological disability that occurs in MS. In the CNS in MS patients has been observed expression of markers of oxidative stress, correlacionándose with demyelinating and inflammatory process that occurs in the disease. Moreover, patients with MS have diminished with respect to healthy controls, serum levels of different antioxidants as natural enzymes, vitamins, ubicuinona, etc.. The metalotioneínas (MT) are proteins for which have been described antioxidant properties, anti-inflammatory and neuroprotective in situations where there is oxidative stress. In this context, we are studying the role of MT in the pathogenesis of multiple sclerosis and its potential therapeutic implications, for it used the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Note that the expression of MT is included in the CNS of mice with EAE and that correlates with the severity of the disease. The astrocytes and macrophages / microglía reagents are the main source of these proteins. The pattern of expression of MT deviates from the pattern of expression of markers related processes and neurodegeneration, however, coincides with the markers associated with tissue repair processes. Moreover, the deficiency in MT makes them more susceptible to mice to develop the SEA enhancing inflammation and neurodegeneration processes in the CNS, whereas tissue repair processes are significantly diminished. These findings are corroborated in human disease, MS lesions, which observed the same pattern of expression that had been previously observed in the animal model. These results suggest that the MT have an important role in the pathogenesis of EAE and may have therapeutic potential in the treatment of this disease, limiting processes of neurodegeneration and enhancing the mechanisms of endogenous tissue repair.

Author: BRUCET VINYALS MARINA.
Year: 2005.
University: BARCELONA.
Place of defense: FACULTAD DE BIOLOGÍA.
Place of preparation: UNIVERSIDAD DE BARCELONA (FACULTAD DE BIOLOGÍA) Y PARQUE CIENTÍFICO DE BARCELONA.

Summary: The overall aim of the thesis has been conducted to characterize the protein Trex 1, a exonucleasa that seems to develop an important role in immune system cells. Studies conducted for this purpose can be divided into three main sections: 1-Determination of the three-dimensional structure of Trex 1. It has been determined the three-dimensional structure of Trex1. Continued methods crystallization and X-ray diffraction to carry out this objective. The results showed that this protein has a structure homodimérica you position the active centers of each monomer on opposite ends of the front face of dímero, and that the organization's active center of Trex1 presents high similarity with the active centers of exonucleasas the family DEDDh whose structure has been determined. Moreover, the structure of Trex1 has been determined in the presence of a nucleotide deoxitimidina monophosphate in each of the active centers, in two different conditions: in the presence of lithium ions, and in the presence of magnesium ions. The lithium ions inhibit the activity of Trex1 probably by inhibiting the electronic transfer necessary for the reaction. In addition, causing a slight shift some of the active waste. The structure analysis has also identified a possible new residue catalytic unidentified so far in the exonucleasas the family DEDDh, histidine 124. Finally, we have identified a source poliprolina in Trex1 candidate to be involved in the interaction with other proteins through domains SH3. 2, - Interaction Trex1 with DNA. The objective was to determine the DNA sequences for which Trex1 presents greater affinity, selecting those that best helped with the protein. This technique was used for the selection of binding sites. It was noted that Trex1 presents different binding affinity to different Dna sequences, and identified what the DNA sequences to which Trex1 joins with higher affinity. 3-subcellular location. By confocal microscopy techniques identified the subcellular localization of trex1 in response to IFN-gamma. It was noted that Trex1 is located in the nucleus in macrophages treated with IFN-gamma and that the region responsible for their retention in the cytoplasm is the region rich in leucinas extreme C-terminal