RESUMEN
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1Mmar, Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4+ T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination. Finally, recent studies suggest beneficial non-specific effects of BCG on immunity, which should be taken into account when considering these vaccines for BCG replacement.
Asunto(s)
Vacuna BCG/inmunología , Linfocitos T CD4-Positivos/inmunología , Mycobacterium bovis/inmunología , Mycobacterium tuberculosis/inmunología , Tuberculosis/inmunología , Animales , Apoptosis , Autofagia , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Ingeniería Genética , Humanos , Memoria Inmunológica , Mycobacterium bovis/genética , Tuberculosis/prevención & control , Vacunación , Vacunas SintéticasRESUMEN
BACKGROUND: The rising life expectancy in the developed world leads to an increase in the number of older patients and the complexity of their complaints in general practice. Although interventions and support for general practitioners are available, implementation lags. Knowledge on what determines a complex older patient, the problems of which general practitioners encounter and the situations they actually need support for, is necessary for better implementation. METHODS: To provide support to general practitioners in their struggle with complex older patients, the aim of this research was to disentangle the concept of the complex older patient in general practice. A qualitative approach was used consisting of 15 semi-structured interviews with general practitioners. The general practitioner was asked to prepare a case of a complex older patient out of their own practice that could be discussed during the interview. Transcripts of the interview were analysed using inductive thematic analysis. RESULTS: Analysis of the interviews resulted in twelve themes that could be categorised into five factors that contribute to the complexity of cases of older patients. The five factors are: not being in charge, different views on necessary care, encountering the boundaries of medicine, limits to providing social care, ill-equipped. CONCLUSION: The factors that were found imply that a better organisational structure for elderly care and consulting elderly care physicians could support general practitioners in providing care for older complex patients. Furthermore, understanding the current concept of patient autonomy seems unjustified in cases of complex older patients.
Asunto(s)
Comorbilidad , Medicina General , Geriatría , Adulto , Anciano de 80 o más Años , Competencia Clínica , Atención a la Salud , Femenino , Humanos , Comunicación Interdisciplinaria , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente/organización & administración , Investigación Cualitativa , Derivación y Consulta , Autoeficacia , Apoyo Social , Negativa del Paciente al TratamientoRESUMEN
BACKGROUND: Exposure to antigens of the fish parasite Anisakis is associated with the development of protein contact dermatitis in seafood-processing workers. Understanding the basic mechanisms controlling allergic sensitization through the skin is critical for designing therapies that will prevent the progression of allergic disease. OBJECTIVE: To investigate the roles of interleukin (IL)-4, IL-13 and the IL-4Ralpha in both local skin pathology and systemic sensitization following epicutaneous exposure to Anisakis proteins. METHODS: BALB/c wild-type (WT) mice and mice deficient in IL-4, IL-13 or IL-4 and IL-13, as well as mice with cell-specific impairment of IL-4Ralpha expression, were sensitized to Anisakis antigen by repeated epicutaneous application of Anisakis extract. Following this sensitization, skin pathology was recorded and systemic responses were investigated. Intravenous challenge with Anisakis extract was performed to test for the development of biologically relevant systemic sensitization. RESULTS: In WT mice, epicutaneous sensitization with Anisakis larval antigens induced localized inflammation, epidermal hyperplasia, production of T(H)2 cytokines, antigen-specific IgE and IgG1. Intravenous challenge of sensitized mice resulted in anaphylactic shock. Interestingly, IL-13 deficient mice failed to develop epidermal hyperplasia and inflammation, whilst anaphylaxis was reduced only in strains deficient either in IL-4 only, or deficient in IL-4 and IL-13 concurrently, as well as in mice deficient in IL-4Ralpha or with impaired IL-4Ralpha expression on CD4(+) T cells. CONCLUSIONS: Interleukin-13 plays a central role in protein contact dermatitis associated with repeated epicutaneous exposure to Anisakis extract, whereas IL-4 drives systemic sensitization and resultant anaphylactic shock.
Asunto(s)
Anisakis/inmunología , Antígenos Helmínticos/inmunología , Dermatitis por Contacto/parasitología , Interleucina-13/inmunología , Subunidad alfa del Receptor de Interleucina-4/inmunología , Interleucina-4/inmunología , Alérgenos/inmunología , Anafilaxia/inmunología , Anafilaxia/metabolismo , Animales , Anticuerpos Antiprotozoarios/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Dermatitis por Contacto/inmunología , Dermatitis por Contacto/patología , Inmunoglobulina E/sangre , Inmunoglobulina G/sangre , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Subunidad alfa del Receptor de Interleucina-4/genética , Subunidad alfa del Receptor de Interleucina-4/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones Noqueados , Ovalbúmina/inmunología , Piel/inmunología , Piel/patologíaRESUMEN
BACKGROUND: Actinidin has previously been reported as the major allergen in kiwifruit. Objectives To investigate the relevance of actinidin in a well-characterized population of UK patients with kiwifruit allergy. METHODS: To identify the allergens in kiwifruit, using Western blots, we examined the IgE-binding patterns of 76 patients with a history of kiwifruit allergy, 23 of who had had a positive double-blind, placebo-controlled food challenge. In addition, IgE binding to purified native actinidin was studied in 30 patients, and to acidic and basic isoforms of recombinant actinidin in five patients. Inhibition of IgE binding to kiwifruit protein extract by purified native actinidin was investigated by both inhibition immunoblots and inhibition ELISAs using pooled sera. RESULTS: Twelve protein bands in kiwifruit protein extract were bound by IgE. A protein band with a molecular weight of 38 kDa was the major allergen recognized by 59% of the population. IgE did not bind to actinidin in the kiwifruit protein extract, or to purified native or recombinant forms of actinidin during Western blotting. Pooled sera bound to kiwifruit protein extract but not purified actinidin on ELISA, and pre-incubating sera with actinidin did not inhibit IgE binding to kiwifruit protein extract on immunoblot or ELISA. CONCLUSION: A novel 38 kDa protein, not actinidin, is the major allergen in this large study population. Identification of major allergens in one patient group is therefore not necessarily reproducible in another; therefore, major allergens should not be defined until there is a sufficient body of data from diverse geographical and cultural populations.