RESUMO
In general, a long-lasting immune response to viruses is achieved when they are infectious and replication competent. In the mouse, the neutralizing antibody response to Friend murine leukemia virus is contributed by an allelic form of the enzyme Apobec3 (abbreviated A3). This is counterintuitive because A3 directly controls viremia before the onset of adaptive antiviral immune responses. It suggests that A3 also affects the antibody response directly. Here, we studied the relative size of cell populations of the adaptive immune system as a function of A3 activity. We created a transgenic mouse that expresses all seven human A3 enzymes and compared it to WT and mouse A3-deficient mice. A3 enzymes decreased the number of marginal zone B cells, but not the number of follicular B or T cells. When mouse A3 was knocked out, the retroelement hitchhiker-1 and sialyl transferases encoded by genes close to it were overexpressed three and two orders of magnitude, respectively. We suggest that A3 shifts the balance, from the fast antibody response mediated by marginal zone B cells with little affinity maturation, to a more sustained germinal center B-cell response, which drives affinity maturation and, thereby, a better neutralizing response.
Assuntos
Formação de Anticorpos , Linfócitos B/imunologia , Citidina Desaminase/imunologia , Citosina Desaminase/imunologia , Centro Germinativo/imunologia , Desaminases APOBEC , Animais , Citidina Desaminase/genética , Citosina Desaminase/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Viroses/genética , Viroses/imunologia , Viroses/patologiaRESUMO
Immunoglobulin E (IgE) production is tightly regulated at the cellular and genetic levels and is believed to be central to allergy development. At least two cellular pathways exist that lead to systemic anaphylaxis reactions in vivo: IgE-sensitized mast cells and IgG1-sensitized basophils. Passive anaphylaxis, by application of allergen and allergen-specific antibodies in mice, indicates a differential contribution of immunoglobulin isotypes to anaphylaxis. However, analysis of a dynamic immunization-mediated antibody response in anaphylaxis is difficult. Here, we generated IgE knock-in mice (IgE(ki) ), which express the IgE heavy chain instead of IgG1, in order to analyze the contribution of IgG1 and IgE to active anaphylaxis in vivo. IgE(ki) mice display increased IgE production both in vitro and in vivo. The sensitization of IgE(ki) mice by immunization followed by antigen challenge leads to increased anaphylaxis. Homozygous IgE(ki) mice, which lack IgG1 due to the knock-in strategy, are most susceptible to active systemic anaphylaxis. The depletion of basophils demonstrates their importance in IgE-mediated anaphylaxis. Therefore, we propose that an enhanced, antigen-specific, polyclonal IgE response, as is the case in allergic patients, is probably the most efficient way to sensitize basophils to contribute to systemic anaphylaxis in vivo.
Assuntos
Anafilaxia/imunologia , Anafilaxia/patologia , Basófilos/imunologia , Basófilos/patologia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Alérgenos/administração & dosagem , Alérgenos/imunologia , Anafilaxia/genética , Animais , Anticorpos Monoclonais/biossíntese , Anticorpos Monoclonais/imunologia , Técnicas de Introdução de Genes , Homozigoto , Humanos , Imunização , Imunoglobulina E/genética , Imunoglobulina G/genética , Mastócitos/imunologia , Mastócitos/patologia , Camundongos , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Índice de Gravidade de DoençaRESUMO
Introduction: Digitalization and gamification offer numerous motivation-enhancing opportunities to design biology lessons. For example, digital, gamified learning settings can enhance lessons by offering intense experiences. Such lessons might offer the opportunity to witness flow during the learning activity. For learners, flow can be positively influenced by perceived autonomy, competence, and relatedness. However, previous research on biology lessons has not focused on the impacts of the basic need satisfaction on the flow experience in digital learning settings. Methods: To address this research gap, using the topic of the locomotion systems of animals, we investigated students' perceived autonomy, competence, and relatedness as possible predictors of their flow experience while processing a digital, gamified learning environment. The teaching unit was thematically focused on the locomotion system of animals. Our sample consisted of 161 students (46.6% female) from sixth to eighth grade. Students' perceived satisfaction of their basic needs and their flow experience were evaluated. Results and Discussion: Results confirmed perceived autonomy and perceived competence as predictors of students' flow experience. However, perceived relatedness had no impact on the flow experience. Our findings are in line with the current state of research and prove to be mostly consistent with previous results.