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Estudio del papel inmunomodulador de antígenos peptídicos provenientes de Mycobacterium Tuberculosis como herramienta en la búsqueda de una vacuna contra la Tuberculosis

dc.contributor.advisorSánchez Barinas, Christian David
dc.contributor.advisorHernández Rojas, Edith
dc.contributor.authorGamboa Hernández, Claudia Marcela
dc.date.accessioned2021-09-09T19:57:02Z
dc.date.available2021-09-09T19:57:02Z
dc.date.issued2021-05-20
dc.identifier.urihttps://repositorio.unicolmayor.edu.co/handle/unicolmayor/2832
dc.description.abstractMycobacterium tuberculosis (Mtb) es el agente causal de la tuberculosis (TB), una enfermedad infecciosa que afecta las vías respiratorias1 . Se reporta que es la principal causa de muerte por un agente infeccioso 1, 2 . Actualmente, la vacuna BCG, única avalada por la OMS (Organización Mundial de la Salud) es utilizada para la prevención de las formas graves de TB en niños, pero su efectividad en adultos es variable1, 3. Por este motivo, en la Fundación Instituto de Inmunología de Colombia (FIDIC) se ha propuesto un modelo vacunal contra tuberculosis, basándose en la metodología lógica y racional empleada para la vacuna multiepitope sintética contra la malaria4, 5 . Se realizaron ensayos in silico para identificar el porcentaje de unión de 57 péptidos monoméricos (nativos y modificados) de Mtb a alelos DRβ1 del complejo mayor de histocompatibilidad tipo II (CMH II) de cada uno de los 18 donantes previamente genotipificados y clasificados por la prueba de diagnóstico PPD (purificate protein derivate). Luego, se desarrollaron ensayos in vitro de linfoproliferación; donde células mononucleares de sangre periférica (PBMCs), previamente marcadas con CFSE (Éster de succinimidil carboxifluoresceína) se estimularon con los péptidos de unión alelo/específica. Además, se evaluó el linaje de linfocitos T CD4 generados después de la estimulación con la identificación de factores de trascripción y citoquinas por métodos moleculares. Finalmente, se realizó la determinación del tipo de memoria inmunológica: centrales de memoria (CM), células madre de memoria (SCM) o efectoras de memoria (EM) mediante la identificación de moléculas de superficie (CD45RA, CD62L y CD45RO) características de estos tipos de células.spa
dc.description.tableofcontentsIntroducción 15 1. Planteamiento del problema 16 2. Justificación 17 3. Antecedentes 19 4. Objetivos 25 4.1 Objetivo general 25 4.2 Objetivos Específicos 25 3. Marco referencial 26 3.1 Generalidades de la tuberculosis 26 3.1.2 Epidemiología tuberculosis 26 3.1.2 Complejo Mycobacterium tuberculosis (MTB) 28 3.1.3 Diagnóstico de la tuberculosis 31 3.1.3.1 Criterio clínico: 31 3.1.3.2 Criterio microbiológico 31 3.1.3.3 Criterio radiológico 33 3.1.3.4 Criterio inmunológico 33 3.1.3.5 Pruebas moleculares 34 3.2 Presentación antigénica a través del CMH-II 35 3.3 Respuesta inmune contra Mtb 36 3.3 Linajes linfocitarios 39 3.4 Ensayo para la detección de la proliferación de linfocitos: Éster succinimidil de carboxifluoresceína (CFDASE) 42 3.5 Memoria Inmunológica 44 3.6 Modelos vacunales existentes 45 4. Diseño metodológico 47 4.1. Universo, población, muestra 47 4.2. Hipótesis, variables, indicadores. 47 4.3. Técnicas y procedimientos. 48 4.3.1 Selección de péptidos sintéticos 48 4.3.2 Análisis bioinformático de unión al CMH-II 49 4.3.3 Selección y clasificación de donantes 50 4.3.4 Síntesis de péptidos 51 4.3.5 Identificación de anticuerpos en plasma de los donantes 52 4.3.6 Ensayo de linfoproliferación 52 4.3.7 Identificación de linajes de linfocitos ayudadores 53 4.3.8 Evaluación de memoria inmunológica 56 5. Resultados 57 5.1 Análisis bioinformático de unión al CMH-II 57 5.2 Evaluación del reconocimiento de péptidos sintéticos provenientes de Mtb. 62 5.3 Determinación de la expansión clonal de linfocitos 64 5.4 Identificación de linajes de linfocitos T ayudadores 75 5.5 Evaluación de memoria inmunológica 78 6. Discusión 81 7. Conclusiones 84 Recomendaciones 85 Referencias bibliográficas 86 Anexos 91spa
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dc.format.mimetypeapplication/pdfspa
dc.language.isospaspa
dc.publisherUniversidad Colegio Mayor de Cundinamarcaspa
dc.rightsDerechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021spa
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0/spa
dc.titleEstudio del papel inmunomodulador de antígenos peptídicos provenientes de Mycobacterium Tuberculosis como herramienta en la búsqueda de una vacuna contra la Tuberculosisspa
dc.typeTrabajo de grado - Pregradospa
dc.description.degreelevelPregradospa
dc.description.degreenameBacteriólogo(a) y Laboratorista Clínicospa
dc.publisher.facultyFacultad de Ciencias de la Saludspa
dc.publisher.placeBogotá D.Cspa
dc.publisher.programBacteriología y Laboratorio Clínicospa
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dc.rights.accessrightsinfo:eu-repo/semantics/closedAccessspa
dc.rights.creativecommonsAtribución-NoComercial-CompartirIgual 4.0 Internacional (CC BY-NC-SA 4.0)spa
dc.subject.lembInmunomodulador
dc.subject.lembEnfermedad infecciosa
dc.subject.lembAgente infeccioso
dc.subject.proposalMycobacterium tuberculosisspa
dc.subject.proposalLinfocitos Tspa
dc.subject.proposalPéptidosspa
dc.subject.proposalVacunaspa
dc.subject.proposalLinajes linfocitariosspa
dc.subject.proposalTuberculosisspa
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dc.type.coarversionhttp://purl.org/coar/version/c_970fb48d4fbd8a85spa
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Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021
Excepto si se señala otra cosa, la licencia del ítem se describe como Derechos Reservados - Universidad Colegio Mayor de Cundinamarca, 2021