RESUMEN
High-energy ionizing radiation in the form of solar energetic particles and galactic cosmic rays is pervasive on the surface of planetary bodies with thin atmospheres or in space facilities for humans, and it may seriously affect the chemistry and the structure of organic and biological material. We used fluorescent microarray immunoassays to assess how different doses of electron and gamma radiations affect the stability of target compounds such as biological polymers and small molecules (haptens) conjugated to large proteins. The radiation effect was monitored by measuring the loss in the immunoidentification of the target due to an impaired ability of the antibodies for binding their corresponding irradiated and damaged epitopes (the part of the target molecule to which antibodies bind). Exposure to electron radiation alone was more damaging at low doses (1 kGy) than exposure to gamma radiation alone, but this effect was reversed at the highest radiation dose (500 kGy). Differences in the dose-effect immunoidentification patterns suggested that the amount (dose) and not the type of radiation was the main factor for the cumulative damage on the majority of the assayed molecules. Molecules irradiated with both types of radiation showed a response similar to that of the individual treatments at increasing radiation doses, although the pattern obtained with electrons only was the most similar. The calculated radiolysis constant did not show a unique pattern; it rather suggested a different behavior perhaps associated with the unique structure of each molecule. Although not strictly comparable with extraterrestrial conditions because the irradiations were performed under air and at room temperature, our results may contribute to understanding the effects of ionizing radiation on complex molecules and the search for biomarkers through bioaffinity-based systems in planetary exploration.
Asunto(s)
Radiación Cósmica/efectos adversos , Electrones/efectos adversos , Exobiología/métodos , Medio Ambiente Extraterrestre/química , Rayos gamma/efectos adversos , Biomarcadores/análisis , Biopolímeros/análisis , Biopolímeros/química , Biopolímeros/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Haptenos/análisis , Haptenos/química , Haptenos/efectos de la radiación , Inmunoensayo/métodos , Análisis por Micromatrices/métodos , Estructura MolecularRESUMEN
PURPOSE OF REVIEW: The review summarizes the recent investigations focused on T regulatory cells in hapten diseases. RECENT FINDINGS: Multiple mechanisms ensure tolerance to small chemicals penetrating the skin. Among these, specific T regulatory cells play a major role in controlling harmful immune responses to environmental antigens. Most of the T regulatory cells involved in this process belongs to the CD4 subset and suppress hapten-specific immune response through the release of IL-10 and through direct interaction with effector T cells, blocking their function. SUMMARY: Methods for in-vitro and in-vivo expansion of specific T regulatory cells may represent an innovative approach for the cure of contact hypersensitivity.
Asunto(s)
Dermatitis por Contacto/inmunología , Modelos Animales de Enfermedad , Haptenos/inmunología , Autotolerancia/inmunología , Linfocitos T Reguladores/citología , Animales , Dermatitis por Contacto/terapia , Exposición a Riesgos Ambientales/efectos adversos , Haptenos/efectos adversos , Haptenos/efectos de los fármacos , Haptenos/efectos de la radiación , Humanos , Inmunoterapia Adoptiva/tendencias , Interleucina-10/metabolismo , Células de Langerhans/citología , Células de Langerhans/inmunología , Ratones , Autotolerancia/efectos de los fármacos , Autotolerancia/efectos de la radiación , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismoRESUMEN
UVB irradiation of the shaved dorsal skin of mice can cause both local and systemic suppression of contact hypersensitivity responses; the former demonstrated by administration of the sensitizing Ag/hapten to the irradiated site and the latter by its administration at least 72 h later to distal unirradiated sites. The immunological basis of systemic immunomodulation is not clear. When haptens (trinitrochlorobenzene, FITC) were administered to the shaved ventral skin 4 days after irradiation (8 kJ/m(2)) to the shaved dorsum of BALB/c mice, CD11c(+)/FITC(+) cells in the skin-draining lymph nodes from control and irradiated mice produced on a per cell basis similar levels of IL-12 and PGE(2) were phenotypically mature and efficient at presenting FITC to lymphocytes from FITC-sensitized mice. Ag presentation by FACS-sorted CD11c(+) lymph node cells isolated 4 days after UVB irradiation was as efficient as were cells from unirradiated mice at presentation in vitro of an OVA peptide (OVA(323-339)) to CD4(+) cells from OVA-TCR-transgenic DO11.10 mice. Further, IFN-gamma levels were increased in the cultures containing CD11c(+) cells from UVB-irradiated mice, suggesting that inflammation may precede downstream immunosuppression. These results suggest that the primary cause of reduced contact hypersensitivity responses in mice in which UV irradiation and the sensitizing Ag are applied to different sites several days apart must originate from cells other than CD11c(+) APCs that directly or by production of soluble mediators (IL-12, PGE(2)) affect cellular responses in the nodes of UVB-irradiated mice.
Asunto(s)
Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/efectos de la radiación , Diferenciación Celular/inmunología , Diferenciación Celular/efectos de la radiación , Factores Inmunológicos/biosíntesis , Factores Inmunológicos/efectos de la radiación , Ganglios Linfáticos/inmunología , Rayos Ultravioleta , Administración Tópica , Secuencia de Aminoácidos , Animales , Presentación de Antígeno/efectos de la radiación , Células Presentadoras de Antígenos/patología , Antígeno CD11c/biosíntesis , Movimiento Celular/inmunología , Movimiento Celular/efectos de la radiación , Técnicas de Cocultivo , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Células Dendríticas/efectos de la radiación , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/patología , Dinoprostona/biosíntesis , Dinoprostona/fisiología , Dinoprostona/efectos de la radiación , Femenino , Fluoresceína-5-Isotiocianato/administración & dosificación , Fluoresceína-5-Isotiocianato/metabolismo , Fluoresceína-5-Isotiocianato/efectos de la radiación , Haptenos/administración & dosificación , Haptenos/biosíntesis , Haptenos/efectos de la radiación , Factores Inmunológicos/fisiología , Interleucina-12/biosíntesis , Interleucina-12/fisiología , Interleucina-12/efectos de la radiación , Ganglios Linfáticos/citología , Ganglios Linfáticos/patología , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Datos de Secuencia Molecular , Cloruro de Picrilo/administración & dosificación , Cloruro de Picrilo/inmunología , Piel/inmunología , Piel/patología , Piel/efectos de la radiaciónRESUMEN
We investigated the induction and transfer of contact photosensitivity (CPS) to the photohapten 3,3',4',5-tetrachlorosalicylanilide (TCSA) using photo-TCSA-coupled syngeneic cells in mice. PhotoTCSA-modified spleen cells (photoTCSA-SC) with efficient immunogenicity were prepared with ultraviolet A (UVA) irradiation of spleen cells suspended in TCSA solution. Subcutaneous inoculation of photoTCSA-SC into syngeneic mice induced a highly specific CPS response detected by ear swelling upon epicutaneous challenge with TCSA painting plus UVA irradiation. The sensitivity was determined to be a cell-mediated, delayed-type hypersensitivity reaction from the time course of the reactivity, the characteristic histology, and the successful transfer of the sensitivity into syngeneic naive recipients by immune lymph node T cells with the phenotype of L3T4+, Lyt-2-. In contrast to the conventional TCSA painting plus UVA irradiation method, this immunization procedure did not evoke an ordinary contact sensitivity reaction to TCSA. The present procedure represented a new way to induce CPS.