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5.
Inmunología (1987) ; 31(2): 49-57, abr.-jun. 2012. ilus
Article in English | IBECS | ID: ibc-108927

ABSTRACT

The immune system is probably one of the most complex cellular organizations in the body. Its complexity is not superfluous, but rather it is required to fulfill the complicated purpose of the immune system, namely: the recognition of the diverse repertoire of microorganisms and pathogens; the detection of neoplastic lesions originating from a range of tissues; and, while executing these tasks, the maintenance of peripheral tolerance by suppressing detrimental responses against healthy tissues. Since they were discovered by R. Steinman et al. nearly 40 years ago, dendritic cells (DCs) have emerged to be critical players in conducting the immune response to fulfill these roles. Here, we provide a general view on some aspects of DC immunology, highlighting the crucial role that R. Steinman’s research in the DC field has played during all those years. This review will also give an outline on DC research in the particular aspects that represent the focus of research groups in Spain(recently organized as the DC.esp working group within SEI). Firstly, some of the subtypes of DC will be described, particularly thymic DC and their role on tolerance; then the DC role intolerance will be examined, followed by their implications in viral infections. Finally, antigentargeting DCs will be reviewed taking into account the crucial contributions made by R. Steinman et al. This chapter will end by reviewing some DCs based therapies in viral infections (AU)


El sistema inmune es probablemente una de las estructuras más complejas del cuerpo. Esta complejidad no es superflua, sino que es necesaria para realizar todas las complicadas tareas a las que se enfrenta, tales como el reconocimiento de un amplísimo espectro demicroorganismos y patógenos, la detección de lesiones oncogénicas en un amplio rango de tejidos y, mientras ejecuta estas tareas, el mantenimiento de la tolerancia periférica mediante la supresión de respuestas perjudiciales dirigidas a tejidos sanos. Desde que fueron descubiertas por R. Steinman y colaboradores hace casi cuarenta años, las células dendríticas (CD) se han posicionado como elementos clave que dirigen el sistema inmune para acometer las tareas propias del mismo. En esta revisión, mostraremos una visión general sobre algunos aspectos de la inmunología de las CD así como subrayaremos el papel primordial que la investigación de R. Steinman ejerció en el campo de las CD durante todos estos años. Además, esta revisión da unas pinceladas sobre la investigación en CD que abordan la mayoría de los grupos de investigación en este campo en España (recientemente organizados en un grupo de trabajo llamado DC.esp, dentro de la SEI). En primer lugar, se describen la mayoría de subtipos de CD, y en concreto las CD tímicas y su papel en tolerancia, para después hablar de la tolerancia y las CD, seguido de los descubrimientos sobre las implicaciones de las CD en infecciones virales. Finalmente, se revisará el direccionamiento de antígenos a CD, teniendo en cuenta las importantes contribuciones de R. Steinman y colaboradores en el campo. Este capítulo finalizará con una revisión sobre las terapias basadas en CD en infecciones virales (AU)


Subject(s)
Humans , Dendritic Cells/immunology , Immunotherapy/methods , Immunotherapy/trends
6.
Int. microbiol ; 10(4): 261-269, dic. 2007. ilus
Article in En | IBECS | ID: ibc-62540

ABSTRACT

Recombinant adenoviruses, poxviruses, and plasmid DNA vaccines encoding different hepatitis B virus (HBV)/murine cytomegalovirus (MCMV) protein chimeras were used to immunize mice. Processing of the chimeras resulted in presentation of a protective Ld/CD8+ T-cell epitope of the immediate early 1 protein pp89 (IE1 pp89) of MCMV to the immune system. Different levels of immunogenicity were observed depending on: (i) the type of viral vector used, (ii) whether the antigens were included in the cellular secretion pathway, and (iii) the location of the protective epitope within the chimeric protein. An adenovirus expressing a secretory HBV core protein with the MCMV epitope in its C-terminus induced the highest immune response. When the most immunogenic adenovirus and vaccinia virus were used in a heterologous prime-boost immunization protocol, even higher levels of epitope-specific T cells were obtained. Furthermore, responses were protective against a challenge with MCMV, inducing up to a 96% reduction of viral load in immunized animals, as determined by a sensitive real-time PCR assay. Together, these results confirmed previous observations of the efficient use of adenoviral and poxviral vectors in prime-boost protocols for immunization against diseases whose resolution depends on cellular immunity, as well as the aptness of correctly designed chimeric carrier proteins to facilitate this goal (AU)


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Subject(s)
Animals , Mice , Cytomegalovirus/pathogenicity , Cytomegalovirus Infections/prevention & control , Immunization/methods , Muromegalovirus/pathogenicity , Vaccines, Synthetic/immunology , Adenoviridae , Poxviridae , Hepatitis B virus , Hepatitis B , Chimera/microbiology , Immunity, Cellular , Mice/immunology , Gene Expression/immunology
7.
J Gen Virol ; 85(Pt 11): 3229-3238, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15483236

ABSTRACT

Human respiratory syncytial virus (RSV) is a major cause of respiratory infection in children and in the elderly. The RSV fusion (F) glycoprotein has long been recognized as a vaccine candidate as it elicits cytotoxic T-lymphocyte (CTL) and antibody responses. Two murine H-2K(d)-restricted CTL epitopes (F85-93 and F92-106) are known in the F protein of the A2 strain of RSV. F-specific CTL lines using BCH4 fibroblasts that are persistently infected with the Long strain of human RSV as stimulators were generated, and it was found that in this strain only the F85-93 epitope is conserved. Motif based epitope prediction programs and an F2 chain deleted F protein encoded in a recombinant vaccinia virus enabled identification of a new epitope in the Long strain, F249-258, which is presented by K(d) as a 9-mer (TYMLTNSEL) or a 10-mer (TYMLTNSELL) peptide. The results suggest that the 10-mer might be a naturally processed endogenous K(d) ligand. The CD8(+) T-lymphocyte responses to epitopes F85-93 and F249-258 present in the F protein of RSV Long were found to be strongly skewed to F85-93 in in vitro multispecific CTL lines and in vivo during a secondary response to a recombinant vaccinia virus that expresses the entire F protein. However, no hierarchy in CD8(+) T-lymphocyte responses to F85-93 and F249-258 epitopes was observed in vivo during a primary response.


Subject(s)
Epitopes, T-Lymphocyte/immunology , Respiratory Syncytial Virus, Human/immunology , T-Lymphocyte Subsets/immunology , T-Lymphocytes, Cytotoxic/immunology , Viral Proteins/immunology , Amino Acid Motifs/immunology , Animals , CD8-Positive T-Lymphocytes/immunology , Cell Count , Cells, Cultured , Epitopes, T-Lymphocyte/genetics , Humans , Immunodominant Epitopes , Interferon-gamma/analysis , Ligands , Mice , Respiratory Syncytial Virus Vaccines/biosynthesis , Respiratory Syncytial Virus Vaccines/immunology , Species Specificity , Spleen/immunology , Vaccines, Synthetic/biosynthesis , Vaccines, Synthetic/immunology , Vaccinia virus/genetics
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