1,721,338 research outputs found
Immunomodulatory properties of cholera toxin B subunit
Full text linkL'immunità innata antigene-non-specifica e l'immunità adattativa antigene-specifica collaborano per debellare i patogeni che invadono l'organismo tramite l'intervento delle cellule del sistema immunitario e delle loro molecole effettrici, che includono le proteine del complemento, gli anticorpi, le citochine e i fattori deputati alla lisi cellulare. Le risposte immunitarie adattative vengono indotte, coordinate e regolate dalle cellule dendritiche (DC). Le DC avviano le risposte immunitarie attivando i linfociti B e T naïve – che sono le cellule effettrici dell'immunità adattativa – e stimolando le cellule natural killer, che sono le principali cellule effettrici dell'immunità innata. Accanto al loro ruolo di collegamento tra immunità innata e adattativa, le DC hanno il delicato compito di limitare le risposte infiammatorie eccessive, che potrebbero causare danni tissutali, con lo scopo di prevenire l'insorgenza di reazioni indesiderate contro antigeni autologhi o innocui. A questo scopo, le DC inducono nei linfociti uno stato di “non-responsività” contro gli antigeni sia negli organi linfoidi primari che in quelli secondari, attraverso meccanismi che includono la delezione e l'induzione di cellule T regolatorie (Tregs). Dal momento che presentano questo ruolo centrale sia nell'immunità che nella tolleranza, le DC dimostrano di essere un candidato ideale come bersaglio di farmaci immunomodulanti.
Nel presente studio abbiamo esaminato la possibilità che la CTB ricombinante (rCTB) possa influenzare le funzioni delle DC in risposta alla stimolazione tramite toll-like receptors (TLR), rendendo le DC capaci di indurre il differenziamento di Tregs.
La CTB – la subunità B della tossina colerica – è un'efficace proteina trasportatrice a livello mucosale, in quanto facilita l'internalizzazione degli antigeni ad essa legati tramite l'interazione con il proprio recettore di membrana GM1, e favorisce l'attivazione delle risposte immunitarie dirette contro tali antigeni.
Inoltre è stato dimostrato che la CTB agisce come un immunosoppressore, dal momento che è in grado di inibire l'attivazione delle linee cellulari monocito-macrofagiche e di sopprimere le risposte di tipo Th1.
Le nostre ricerche dimostrano che la rCTB previene parzialmente la maturazione di DC derivanti da monociti (MDDC) indotta da lipopolisaccaride (LPS) e ne diminuisce la produzione di IL-12p70 senza influenzarne la produzione di IL-10. Le DC pretrattate con CTB e stimolate con LPS sono così in grado di promuovere l'induzione di cellule T scarsamente proliferanti che mostrano un'aumentata produzione di IL-10 associata ad una ridotta produzione di interferon-γ (IFN-γ) e ad analoghi elevati livelli di trasforming growth factor-b (TGF-β), quando paragonati a quelli delle cellule di controllo.
Le cellule T così indotte sono capaci di sopprimere la proliferazione di cellule T autologhe attivate, tramite la produzione di fattori solubili, come dimostrano gli esperimenti effettuati mediante Transwell o con anticorpi bloccanti il recettore dell'IL-10 (IL-10R) ed il TGF-β. Tutte queste caratteristiche rendono le cellule T indotte da DC condizionate con rCTB simili alle Tregs di tipo 1 (Tr1) producenti IL-10.Antigen-non-specific innate immunity and antigen-specific adaptive immunity synergize to eradicate invading pathogens through the actions of immune cells and their effector proteins, including complement, antibodies, cytokines and cytolytic factors. Adaptive immune responses are induced, coordinated and regulated by dendritic cells (DC). DC initiate immunity by the activation of naïve B and T cells - the effector cells of the adaptive immune system - and by the stimulation of natural killer cells - the crucial cellular instigators of innate resistance. Besides linking innate and adaptive immunity, DC limit excessive, tissue-damaging immune responses in order to prevent autoimmunity and non-essential reactions to innocuous agents through their ability to induce antigen-specific unresponsiveness of lymphocytes in primary and secondary lymphoid tissues by mechanisms that include deletion and induction of regulatory T cells (Tregs). Given the central role of these antigen presenting cells in immunity and tolerance, they are ideal therapeutic targets for pharmacological modulation of immune responses.
In the present study, we examined the possibility that recombinant CTB (rCTB) may affect human DC functions in response to toll-like receptor (TLR) stimulation and may induce the generation of DC with the capacity to generate Tregs. CTB - cholera toxin B subunit - is an efficient mucosal carrier molecule for the generation of immune responses to linked antigens, since it facilitates entry into the cell of the CTB-antigen complex by ligation of its surface receptor GM1. There is also good evidence that CTB acts as an immunosuppressant, as it is able to down-modulate human monocyte/macrophage cell line activation and to suppress Th1-type responses. Our findings show that rCTB partially prevents the lipopolysaccharide (LPS)-induced maturation process of monocyte-derived DC (MDDC) and decreases their interleukin-12p70 (IL-12p70) production with no relevant effect on IL-10 production. LPS-stimulated MDDC pre-treated with rCTB are able to promote the induction of low proliferating T cells, which show an enhanced IL-10 production associated with a reduced interferon-γ (IFN-γ) production and the same high levels of trasforming growth factor-β (TGF-β) as the control. These T cells suppress proliferation of activated autologous T cells. Transwell experiments and blockade of IL-10R and TGF-β showed that the immunomodulatory effect is mediated by soluble factors. Thus, T cells induced by rCTB-conditioned MDDC acquire a regulatory phenotype and activity similar to those described for IL-10 producing type 1 Tregs (Tr1)
Continuity and Variety: The Allocation of Symbolic Rewards in Elite Italian Winemaking
No full textThe authors investigate how innovative cultural products are rewarded by considering a producer's structural network position, conformity to innovation norms for production and assessment, and the extent to which gatekeepers recognize variety or continuity. They empirically test their arguments in the field of elite Italian winemaking, which is characterized by a semi-independent reward system. In this field, critics, who serve as gatekeepers, allocate symbolic rewards to socially recognize producers' work. An analysis of the awards received by 287 winemakers between 2001 and 2005 reveals both convergence towards innovation norms (i.e., continuity) and openness to innovative products that deviate from norms (i.e., variety) within the same reward system. The authors discuss the empirical evidence in light of both reward system theory and elite Italian winemaking as a cultural field
Got to be real: An investigation into the co-fabrication of authenticity by fashion companies and digital influencers
No full textThis article investigates how fashion companies build their relationships with digital influencers (DIs), a new group of cultural intermediaries who are increasingly central to brand communication strategies. Scholars have mostly studied DIs' role in influencing the market, but largely neglected the process through which they build their work. Through a qualitative inductive research directed at 21 Italian fashion companies, we describe the process through which companies fabricate the authenticity work, while collaborating with DIs. By taking the overlooked perspective of the company brand owner, we identify the underlying dynamics of achieving co-fabricated authenticity, unpacking the mechanisms through which companies select DIs, shape the connections and regulate the reciprocity with them. Our findings highlight how companies and DIs' practices become intertwined, with the commodity of authenticity being constructed at the crossroads between the former's commercial needs and the latter's grassroots narratives and practices. 'Co-fabricated authenticity' ultimately emerges as the result of the work of those actors who are engaged in managing the authenticity or processes of authentication of marketable goods: the intangible and ephemeral value of authenticity is made tangible and co-produced through the collaboration between brands and cultural intermediaries such as DIs
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Evaluating non-disclosure of errors and healthcare organization: a case of bioethics consultation
No full textSometimes medical errors should not be disclosed. We report a case of semen samples exchange, during a homologous artificial insemination procedure, where a bioethics consultation was required. The bioethics consultation addressed ethical and legal elements in play, supporting non-disclosure to some of the subjects involved. Through a proper methodology, gathering factual and juridical elements, a consultant can show when a moral dilemma between values and rights—privacy versus fatherhood, in our case—is unsubstantial, in a given context, because of the groundlessness of the value or the right itself. However, being the error elicited by organizational factors, a broader ethical pronouncement was needed. Under such circumstances, ethical evaluation should engage in a sort of ‘ethical-based root-cause analysis’, linking ethical principles to quality aims and showing the opportunity to integrate ethical methodology in healthcare management. From this perspective, errors may become an inc..
La residenza contesa. Rapporto 2022 sulle migrazioni interne in Italia
No full textIl volume mette al centro la questione della residenza anagrafica a partire dai flussi migratori interni e internazionali, tema che ha attirato recentemente polemiche e conflitti. I contributi ne ripercorrono le diverse sfaccettature con un approccio multidisciplinare: le implicazioni statistiche, le radici storiche, le battaglie politiche, le considerazioni di carattere sociologico, la ricostruzione delle dinamiche riscontrate dagli operatori nei quartieri delle grandi città. Ogni volta che spostiamo la nostra residenza entriamo nelle statistiche sulle migrazioni interne, fornendo un dato di flusso fondamentale per l’analisi sociale e le relative considerazioni politiche e amministrative. Ma cosa succede quando gli spostamenti effettivi non sono accompagnati da registrazioni ufficiali? Quali sono gli effetti della mancata iscrizione anagrafica? Gli orizzonti che si delineano sono complessi e includono anche esclusione sociale e disuguaglianze nell’accesso ai diritti, che nel Rapporto vengono ricostruite in profondità
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