Loading...
Renew (CE session 6)
Quiz by Elles van Asseldonk
Customize this quiz to suit your class
Instantly translate to 100+ languages
Tag the questions with any skills you have. Your dashboard will track each student's mastery of each skill.
Give this quiz to my class
Create 10 multiple choice questions from this tex : Un jour, ma grand-mère poisson, Nukumi, m'a appelé... GRAND-MÈRE : Kwis, petit poisson... Juwkalul ! Te voilà, Kwis. Je t'attendais. PETIT POISSON : Nikumi, vais-je grandir pour être aussi grand et fort que toi ? GRAND-MÈRE : Eh bien... Au commencement du temps, le Grand Esprit, Kisulkw, a créé toutes les choses de la nature également. Le Soleil crée la vie et nous donne nos ombres. Les ombres reflètent les esprits de nos ancêtres. M’sit Nokomaq. PETIT POISSON : Nukumi, qu'est-ce que cela signifie ? GRAND-MÈRE : Cela signifie que nous sommes tous liés. Les gens de cette terre ont réalisé que nous étions tous d'esprit, placés ici sur Mère Terre pour nous aider mutuellement. Kluscap nous a appelés, nous, les poissons, Neme’jik, à venir à terre et à donner nos vies. Il ne prenait que ce qui était nécessaire et rendait grâce pour notre existence. Nous appelons cela Netukulimk. PETIT POISSON : Ensuite, que s'est-il passé, Nukumi ? GRAND-MÈRE : Pendant des milliers d'années, nous avons continué à compter sur nos frères et sœurs des bois et des eaux. Les Mi’kmaq nous appelaient Peju, la morue. Ils utilisaient de petits bateaux appelés canots, faits d'écorce de bouleau, et de petits filets pour nous attraper. Ils nous utilisaient pour la nourriture et pour échanger avec d'autres choses qu'ils n'avaient pas. Ils nous séchaient au soleil et utilisaient le sel de la mer pour nous conserver. Les L’nu, le peuple, étaient reconnaissants pour l'aide et nous honoraient. Souviens-toi de Netukulimk ? Eux aussi ne prenaient que ce dont ils avaient besoin. Nous avons vécu en harmonie avec le peuple, la terre et toutes les choses. Nous remplissions la mer ! Et nous devenions grands et gras. Ton arrière-arrière-arrière-grand-père était de la taille d'un dauphin, ou d'un Mutch petch ! PETIT POISSON : Mais pourquoi n'ai-je jamais vu de morue si grande ? GRAND-MÈRE : Eh bien, il y a environ cinq cents ans, des gens de contrées lointaines sont arrivés. Ils sont venus pour nous, étonnés de ne pas pouvoir ramer à travers les eaux à cause de notre foule... Ils sont venus avec plus de bateaux et de filets plus grands. Et ils nous ont emmenés. Sans honneur. Sans remerciements... Ils en ont attrapé trop de nous... Ils nous ont pris avant que nous puissions devenir grands et gras... Ils nous ont pris avant que nous puissions avoir des bébés. Ils ont détruit nos foyers. Ils n'ont pas appris à vivre en harmonie. Ils n'ont pas compris Netukulimk. PETIT POISSON : Que va-t-il advenir de nous maintenant ? GRAND-MÈRE : Cette histoire est encore en train d'être racontée, Kwis ! Pour que tu vives fort, pour que toi et tes enfants grandissiez aussi grands que ton arrière-arrière-arrière-grand-père - niscamish - pour que nous remplissions de nouveau la mer... PETIT POISSON : ... pour cela, nous devons trouver à nouveau un moyen de vivre en harmonie avec nos frères et sœurs. M’sit Nokomaq. Tous mes parents. GRAND-MÈRE : Et voilà la fin de l'histoire.Riassunto lezione precedente Caratteristiche generali degli epiteli: ● avascolarizzati ● innervati ● capacità rigenerativa Funzioni: ● Barriera ● Secrezione Specializzazioni del dominio apicale: ● Microvilli, orletto a spazzola ● Stereociglia ● Ciglia Specializzazioni del dominio laterale ● Giunzioni cellulari [Qui inizia la lezione di oggi] Classificazione morfo-funzionale degli epiteliali di rivestimento ⮚ Epiteli pavimentosi: se le cellule sono pavimentose ⮚ Epiteli cubici: se le cellule sono cubiche, quindi altezza e larghezza si equivalgono ⮚ Epiteli cilindrici: se le cellule hanno altezza maggiore della larghezza. Possono essere sia monostratificati quindi epiteli semplici, oppure pluristratificati Nell’ epitelio pluristratificato il nome dell’epitelio lo capiamo dall’ultimo strato, per esempio se l’ultimo strato ha cellule appiattite l’epitelio sarà pavimentoso, se l’ultimo strato ha cellule cubiche sarà cubico stratificato. Non importa la forma delle cellule degli strati inferiori. Possono inoltre essere pluristratificati o epiteli di transizione. Classificazione in base alle specializzazioni ⮚ Epiteli ciliati ⮚ Epiteli non ciliati La morfologia dell’epitelio riflette un po’ la sua funzione, per esempio l’epitelio semplice si trova dove non serve una grande protezione da stress meccanico. Per esempio: epitelio squamoso semplice: nel polmone, dove devono essere facilitati gli scambi gassosi di ossigeno e anidride carbonica. Epitelio cubico semplice: nei dotti delle ghiandole esocrine; nei tubuli renali dove abbiamo sempre assorbimento o secrezione Epitelio colonnare semplice: riveste l’intestino, anche qui con funzione di assorbimento. Pseudostratificato: già visto nella lezione precedente, lo troviamo ad esempio nella trachea, ed è un epitelio ciliato, dove le ciglia non servono a spostarsi. Gli epiteli semplici li troveremo in zone non sottoposte a grandi stress meccanici, ma dove c’è bisogno di facilitare la funzione di assorbimento e scambio. Mentre gli epiteli stratificati li troviamo per esempio dell’epidermide, cavità orale dell’esofago, vagina, ovvero sedi anatomiche solitamente esposte a stress meccnici. Epitelio di transizione: tipico della vescica, la cui caratteristica fondamentale è l’estensione. Esempio di epitelio pavimentoso semplice: Endotelio ovvero l’epitelio dei vasi sanguigni I vasi possono essere molto diversi fra loro ⮚ Capillare: epitelio associato alla lamina basale ⮚ Arterie: endotelio e lamina basale, e lamina elastica (formata da elastina, favorisce la dilatazione del vaso) che formano la tonaca intima; strato intermedio, tonaca media dove troviamo cellule muscolari lisce; tonaca avventizia di tessuto connettivo ⮚ Vene: stessa struttura, ma è più abbondante lo strato di tonaca avventizia (tessuto connettivale) rispetto alle arterie, dove la più abbondante è la tonaca media. Nell’immagine si vede come la dimensione di vene e arterie può cambiarne la morfologia. CAPILLARI La funzione dell’epitelio è di favorire gli scambi tra il torrente circolatorio e i tessuti. I capillari sono costituiti da una “barriera” formata dalle cellule dell’endotelio e la lamina sottostante. dall’immagine possiamo vedere all’interno del capillare un globulo rosso, quindi il diametro di un capillare è molto ridotto, può essere anche più piccolo di un globulo rosso, che per passare si deve deformare. Si vede il globulo rosso, la piastrina e la cellula endoteliale a formare la parete del capillare, dove c’è l’asterisco è una zona più elettrondensa che rappresenta la giunzione occludente. Le strutture più sottili sono capillari Le arteriole le riconosciamo dalle cellule muscolari lisce. Possiamo vedere le cellule endoteliali che costituiscono la parete di questi vasi. Classificazione dei capillari A seconda della zona anatomica dove ci troviamo cambia la morfologia dei capillari. ⮚ Capillari continui: cellule endoteliali giustapposte fra loro, giunzioni occludenti, lamina basale contigua, passaggio di sostanze è ampiamente regolato dalla cellula stessa. Possiamo trovare associati al capillare i periciti, che sono cellule staminali e vescicole che fanno pinocitosi (endocitosi di particelle liquide) ⮚ Capillari fenestrati: dove devono essere favoriti gli scambi. Si formano fenestrazioni tra le cellule della parete del capillare. Recenti studi pensano che queste fenestrazioni siano il risultato di un’abbondante pinocitosi. ⮚ Capillari discontinui/sinusoidi: le fenestrazioni sono ancora più grandi e la lamina basale è discontinua, quindi passaggio favorito. Esempio in microscopia elettronica del capillare continuo e fenestrato nella prima immagine il capillare è continuo, non ci sono interruzioni della lamina basale, non ci sono fenestrazioni, sono evidenti le giunzioni cellulari, si vedono le vescicole di pinocitosi. Nella seconda immagine ci sono interruzioni delle cellule endoteliali. In questa immagine invece vediamo un e sinusoide in cui le fenestrazioni sono più grandi, la lamina basale è discontinua, quindi passa anche il plasma. Associato alla cellula endoteliale possiamo trovare il Pericita, cellula staminale mesenchimale (cellula mesenchimale da origine a tessuto osseo, muscolare). Queste cellule hanno capacita di migrare e differenziarsi. Se per esempio rimuoviamo i periciti e induciamo una lesione per esempio a livello della spina dorsale dell'animale c’è impossibilità di rigenerazione del tessuto. CONDIZIONI PATOLOGICHE È importante mantenere la continuità di questo epitelio, infatti la lesione dell’endotelio è patologica, si chiama Arterosclerosi una delle maggiori cause di morte. la lesione parte dalla tonaca intima (endotelio, lamina basale), per esempio causata da alti livelli di colesterolo. Infiltrazione, i monociti si depositano tra lamina elastica ed endotelio, i monociti migrano in questa zona, assorbono lipidi intorno a queste cellule schiumose e si può formare questa lesione che può far sforzare di più il cuore, o provocare un embolo. Istologia di un vaso normale e un vaso con arterosclerosi. La colorazione è la Tricromica di Masson, che colora in viola i nuclei, in rosso il citoplasma e tessuto muscolare, in blu il collagene. Essendo il collagene il principale componente del tessuto connettivo nella seconda immagine notiamo deposizioni di tessuto connettivo in seguito alla lesione. [il professore nomina Histology guide, un sito consultabile online dove troviamo la maggior parte delle sezioni e immagini istologiche che lui spiega a lezione] MESOTELIO Altro esempio di epitelio pavimentoso semplice è il mesotelio, che riveste o le parti interne del corpo: mesotelio parietale; o gli organi: mesotelio viscerale. Per esempio la pleura viscerale riveste direttamente il polmone e la pleura parietale la parete del torace. Mesotelio che riveste il rene: singolo strato di cellule pavimentose. Mesotelio cardiaco: abbiamo una parete esterna: pericardio parietale; poi il liquido pericaridico che riduce l’attrito; e pericardio viscerale: diretto contatto col cuore. Nell’istologia del mesotelio vediamo uno strato di cellule e sotto la lamina basale le grosse cellule bianche sono di tessuto adiposo. Questo tipo di epitelio lo troviamo per esempio nell’intestino. Peritoneo parietale: parte esterna Dopo la parete muscolare c’è la sierosa, mesotelio Viscerale, composto da cellule pavimentose semplici, lamina basale. ALVEOLO POLMONARE Nell’alveolo Polmonare l’epitelio pavimentoso semplice svolge un ruolo fondamentale, perché deve facilitare gli scambi gassosi. Strato sottile: pneumocita dell’epitelio alveolare Capillare con globulo rosso Giunzioni occludenti tra pneumociti PATOLOGIA Rottura degli alveoli polmonari, per esempio inalando particolato, o col fumo di sigaretta, c’è il collasso dell’alveolo polmonare, quindi infiltrazione di particolato: Enfisema; oppure con un’infezione per esempio polmonite vediamo la presenza di essudato ricco di leucociti, quindi le cellule infiammatorie. EPITELIO CUBICO SEMPLICE Il nucleo della cellula è rotondo, non pù schiacciato come nelle cellule pavimentose. La cellula ha larghezza e altezza simili. Questo tipo di tessuto si trova nei dotti di alcune ghiandole, o le cellule secernenti dei follicoli tiroidei. Quindi con funzione di trasporto o secrezione. EPITELIO CILINDRICO SEMPLICE Nucleo solitamente posizionato nella parte più vicina alla lamina basale, la cellula è alta e stretta. Tra le cellule epiteliali troviamo le cellule mucipare caliciformi. Cripte intestinali Spesso troviamo una presenza abbondante di microvilli che formano l’orletto. Nelle immagini vediamo lo stesso tessuto trattato con due colorazioni diverse, nella Tricromica di Masson la struttura colorata di azzurro è la lamina basale. Nelle cripte intestinali abbiamo sia assorbimento e secrezione. ● Enterociti: dedicati all’assorbimento ● Enteroendocrine: disperse nell’epitelio, considerate i maggiori organi esocrini del nostro organismo, rilasciano Somatotossina e istamina ● Cellule di Paneth: secernono sostanze antimicrobiche, funzione di protezione ● Cellule staminali: soprattutto nella parte più basale della cripta ● Cellule caliciformi Quelle indicate dalla freccia sono giunzioni occludenti PATOLOGIA La morfologia egli epiteli è importante, alterazioni di questi tessuti sono associate a patologie. Per esempio perdita di continuità dell’epitelio dell’intestino che è rivelatore di una trasformazione neoplastica. Le cellule epiteliali assumono funzione mesenchimale e possono invadere la sottomucosa. È importante individuare la lesione prima che invada la sottomucosa perché mentre l’epitelio è avascolarizzato nella sottomucosa ci sono i vasi sanguigni, e il tumore può fare metastasi. EPITELIO CILINDRICO SEMPLICE CILIATO nelle tube uterine abbiamo sia cellule ciliate che non ciliate, che provengono dalla stessa cellula iniziale che poi differenzia. [legge la slide accanto] EPITELIO PSEUDOSTRATIFICATO Come si può riconoscere? A prima vista sembra pluristratificato perché i nuclei sono posti su nuclei differenti, ma non è così, perché tutte le cellule poggiano sulla lamina basale. Ma non tutte le cellule arrivano nello strato apicale. Quindi il nucleo è delocalizzato nella parte più grande della cellula. Possono essere ciliati o non ciliati. L’epididimo per esempio ha specializzazioni ma sono Stereociglia, quindi è epitelio pluristratificato non ciliato. Mentre un esempio di epitelio pseudostratificato ciliato è la trachea. Le ciglia sono un po’ più corte. (si riconosce la trachea perché sotto l’epitelio ci sono dischi di cartillagine) All’interno dell’epitelio della trachea possiamo trovare cellule mucipare caliciformi, che secernono muco, e non sono ciliate. Evidente nell’immagine con microscopio elettronico a scansione. TESSUTO EPITELIALE Epiteli pluristratificati Abbiamo visto gli epiteli semplici, quindi un unico strato di cellule e zero stratificazioni. Adesso vedremo alcune delle caratteristiche degli epiteli pluristratificati, che ovviamente presentano più strati di cellule; spesso la forma delle cellule cambia all’interno dei vari strati, e il nome viene dato dallo strato più superficiale. In questo caso abbiamo epitelio pluristratificato pavimentoso, anche se in effetti la cellula dello strato basale è cubica. Qual è il ruolo di questi epiteli? È quello di garantire maggiore protezione. Una delle caratteristiche di questi epiteli è che la rigenerazione, il turn-over che si fa, cioè il cambio del tessuto, è garantito dallo strato basale, perché nello strato profondo abbiamo le cellule staminali. Può essere non cheratinizzato, e lo troviamo nella bocca, nella faringe, nell’esofago, nella vagina e nel retto, oppure cheratinizzato, che è l’epitelio caratteristico dell’epidermide. Ad esempio in questo caso (foto sopra) che tipo di epitelio è? Pluristratificato pavimentoso, perché le cellule circondate di azzurro nell’ultimo strato, danno un epitelio pavimentoso. Nell’esofago abbiamo un epitelio pluristratificato non cheratinizzato. Come si può notare subito sotto l’ultimo strato abbiamo il tessuto connettivo, con la presenza di vasi sanguigni e con la mucosa muscolare. Qual è una delle caratteristiche istologiche che già si può apprezzare, come prima osservazione di questo epitelio? Cosa cambia tra questo strato (1) e questo altro strato (2) ? La densità dei nuclei. L’aspetto dello strato basale, normalmente, è appunto caratterizzato dalla maggior presenza dei nuclei, perché come accennato, sono presenti le cellule staminali, quindi le cellule sono ancora capaci di replicarsi, per rimpiazzare le cellule che sono presenti negli strati più superficiali, che sono sfaldate dallo stress meccanico. In alcuni animali anche l’esofago ha un epitelio cheratinizzato. Una delle tecniche che possiamo utilizzare per rivelare la presenza di cellule staminali, di cellule che stanno proliferando nello strato basale, è l’immunoistochimica, con la quale usiamo un anticorpo, in questo caso un anticorpo rivolto verso una proteina chiamata CD156, che è un marcatore, una proteina, presente solo nelle cellule staminali; quindi se noi coloriamo il tessuto, facciamo un’ibridazione con un anticorpo rivolto verso questa proteina, questo anticorpo è legato ad un enzima, che fa precipitare il substrato (in foto di colore marrone), e al microscopio ottico possiamo vedere dove sono presenti le cellule staminali. L’alternativa è invece coniugare l’anticorpo con il fluoroforo, e andare ad osservare con un microscopio a fluorescenza. La pelle: l’epidermide Spesso troviamo in questo tipo di epiteli, questi ripiegamenti degli strati basali, ma anche negli strati più superficiali, cosa che è evidente anche nell’epidermide. La cute è composta sia da un epitelio chiamato epidermide, sia dal derma sottostante che è un tessuto di natura connettivale. A seconda della sede anatomica che si sta analizzando, possiamo avere una cute sottile o una cute più spessa, quello che cambia è proprio lo spessore dell’epidermide, in particolare dell’ultimo strato. Questo è un esempio di cute sottile (sx), mentre questa è una cute spessa (dx). Si può apprezzare come, ad esempio, siano presenti dei ripiegamenti degli strati basali, ma in parte anche degli strati più superficiali. Dove sono più evidenti queste pieghe, ad esempio? Dove si formano le impronte digitali, viene accentuato il ripiegamento dello strato superficiale. Qui (sempre immagine sopra a dx) possiamo notare che nello strato superficiale, rispetto allo strato basale, non sono presenti i nuclei. A differenza dell’esofago in cui i nuclei sono presenti anche negli strati più superficiali, nell’epidermide le cellule proprie degli strati superficiali (i cheratinociti) perdono i nuclei. Infatti così facendo viene creato lo strato chiamato cheratina. Ovvero nello strato corneo, quello più superficiale, non abbiamo la presenza di nuclei. Quello che cambia all’interno dei vari strati è la presenza o meno di determinati tipi di giunzioni. Nello strato basale sicuramente troviamo una giunzione, che non è presente negli altri strati, ovvero gli emidesmosomi. Questo perché l’emidesmosoma è una giunzione che si trova tra la cellula epiteliale e la lamina basale, che ovviamente è a contatto solo con l’ultimo strato. Quindi l’emidesmosoma qui colorato di verde (immagine sopra), è presente solo nello strato basale. Mentre cominciamo a vedere la presenza di desmosomi tra una cellula e l’altra, che si mantengono nello strato basale ma anche nello strato spinoso. Lo strato granuloso è caratterizzato ad esempio dalla presenza di giunzioni occludenti e aderenti, che quindi rendono impermeabile l’epidermide e impediscono il passaggio di sostanze attraverso questo strato. Questi ultimi tipi di giunzioni le troviamo anche nello strato lucido, mentre i desmosomi corneificati o corneodesmosomi, li troviamo nello strato corneo. Anche il numero di cellule dei vari strati è pressoché costante. Strato basale Tramite questa sezione dell’epidermide andiamo ad ingrandire lo strato basale, a contatto con il tessuto connettivo sottostante, e possiamo vedere, come è rappresentato questo stato, ovvero la presenza massiva di nuclei, dovuti alla proliferazione delle cellule, che infatti sono positive a quest’altro marcatore, che è un importante regolatore del ciclo cellulare Ki67. Se facciamo l'immunoistochimica per questo fattore, le cellule degli strati basali lo respingono, perché sono in attiva proliferazione. Quindi se per esempio abbiamo una lesione dell’epidermide, sicuramente questo marcatore non reagirà. Quindi le cellule perdono la capacità di proliferare, nello strato spinoso e nello strato granuloso la perdono totalmente, e addirittura nello strato corneo perdono proprio il nucleo, quindi è impossibile che la cellula si replichi. E questa è l’importanza dello strato basale, che regola il turnover di questo tessuto che è di circa 30-40 giorni, cioè una cellula passa dallo strato basale a quello corneo in 30-40 giorni, e così facendo si rinnova totalmente l’epidermide. Se guardiamo lo strato basale o germinativo, abbiamo una cellula piuttosto piccola, tondeggiante, prolifera e sono presenti sia desmosomi, sia emidesmosomi. Strato spinoso Nello strato spinoso, è presente uno spazio intercellulare tra una cellula e l’altra. Si possono osservare delle spine, questi sono dei processi citoplasmatici, che servono poi a connettere un cheratinocita e l’altro. Ovvero in queste spine sono presenti i desmosomi. In questo strato inizia il differenziamento cellulare, il cheratinocita inizia ad esprimere le cheratine, quindi perde la capacità di proliferare. Strato granuloso Lo strato granuloso è chiamato così, proprio per il suo aspetto istologico, per la presenza di granuli all’interno del citoplasma in ambiente cellulare. Normalmente dovrebbe riportare 3 file di cellule in questo strato, visualizzando la presenza dei granuli in ogni cellula. Questi granuli contengono proteine come cheratoialina, filegrina e loricrina, sostanze che serviranno, poi, a rendere l’epidermide resistente. Le giunzioni tra una cellula ed un’altra sono desmosomi e giunzioni occludenti, infatti, se noi facciamo l’immunofluorescenza per proteine come la claudina, che colora le giunzioni più immature, possiamo colorare anche cellule degli strati limitrofi; se invece utilizziamo l’immunofluorescenza per l’occludina, che è una giunzione più matura, si può vedere com’è proprio più localizzata e ristretta allo strato granuloso. Inoltre si può notare (foto sotto) anche la microscopia elettronica con le giunzioni occludenti. Qui (sotto) possiamo vedere una bellissima immunoistochimica proprio con la claudina, dove possiamo vedere la sezione dell’epidermide con l’immunoistochimica. E qui già possiamo vedere alcune cellule, che perdono il nucleo negli strati più superiori dello strato granuloso, e la cosa risulta poi evidente nello strato corneo, dove i nuclei sono assenti, che è la caratteristica fondamentale, con la quale si riconosce questo strato. Strato corneo La cellula quindi forma queste lamine, prive di nucleo, il citoplasma è farcito di cheratina aggregata, le giunzioni sono dei desmosomi modificati e sono rivestiti da un involucro cellulare corneificato, ovvero: involucrina, loricrina, filamenti di cheratina e molecole lipidiche, che rendono lo strato impermeabile. La cheratina va classificata tra i filamenti intermedi importanti nel citoscheletro. Infatti si ricordi la presenza dei filamenti sottili di actina, di tubulina e poi a seconda del tessuto possiamo avere dei determinati filamenti intermedi. In particolare, la cheratina forma il filamento intermedio nell'epitelio. I desmosomi, ovvero la giunzione tra un cheratinocita e l’altro, è regolata dal pH. Per questo è importante mantenere il pH della cellula, perché via via che aumentiamo l’acidità del pH, promuoviamo lo sfaldamento dei cheratinociti e quindi il ricambio dello strato più superficiale. In alcune sedi come, ad esempio, il palmo della mano e dei piedi, è presente un ulteriore strato, che è definito lucido, proprio per il suo aspetto istologico, ed è presente tra lo stato corneo e lo strato granuloso. Qui (sotto) abbiamo una microscopia elettronica a trasmissione di una sezione di tessuto di epidermide sottile, dove si possono vedere i cheratinociti nei vari strati. Questa la si può sempre colorare artificialmente e si può così riconoscere la struttura dei vari strati. Quindi sostanzialmente salendo dallo strato basale allo strato corneo, abbiamo il differenziamento dei cheratinociti dalle cellule staminali che sono in grado di replicarsi. Si ricordi infatti che per cellula staminale non si intende solo una cellula che è in grado di differenziarsi ma è anche in grado di autoregolarsi. Dunque da una parte formerà una nuova progenie di cellule staminali in grado di differenziarsi, dall’altra i cheratinociti iniziano il processo di differenziamento passando allo strato spinoso. Iniziano quindi ad esprimere le cheratine, cambiano la forma, cambiano il tipo di giunzione, fino a produrre l’involucro di cheratina nello strato corneo e questo ha un timing ben preciso a seconda della zona. Per capire l’importanza dell’aspetto molecolare di questo differenziamento (non verrà richiesto all’esame) si faccia presente che tutti i geni del differenziamento dell’epidermide sono presenti nei cluster presenti nel cromosoma umano. Ovvero sono presenti tutti i geni necessari per il progredire del differenziamento dei cheratinociti all’interno dell’epidermide. All’interno degli epiteli non abbiamo solo i cheratinociti, ma abbiamo quattro tipi cellulari: -i cheratinociti -i melanociti - le cellule di Langerhans - le cellule di Merkel I melanociti Sono i responsabili della produzione della melanina, che è un pigmento, che viene formato dalla ossidazione della tirosina, ad opera della tirosinasi, viene accumulata all’interno dei melanosomi, di queste vescicole, e poi vengono rilasciate dal melanocita e vanno a fondere con le cellule dei cheratinociti dello strato spinoso, e formano una sorta di barriera, al di sopra del nucleo delle cellule dello strato spinoso. La funzione importante della melanina è (oltre a “renderci più attraenti d’estate”) proteggere il nucleo delle cellule dell’epidermide dai raggi ultravioletti, per impedire l’insorgere di mutazioni. I melanociti si possono identificare nello strato basale, e infatti possiamo mettere in evidenza la presenza dei melanociti con dei marcatori (come, per esempio, le tirosinasi che formano la melanina), che sono localizzati nello strato basale. In questo caso possiamo vedere, nell’epitelio della cornea, la presenza dell’immunofluorescenza, dei melanociti marcati con questo marcatore specifico del melanocita (e che quindi sono proprio nello strato basale). Quest’ultimo in particolare è positivo alla p-caderina che è quindi un marcatore del melanocita della cellula nello strato basale. Mentre la cheratina/la pan cheratina marca gli strati superiori. Cosa succede se abbiamo una iperplasia del melanocita? A cosa ci si sta predisponendo? Al melanoma. Quindi sotto un punto di vista medico istologico, prima di avere la trasformazione tumorale, i melanociti diventano più abbondanti e di dimensioni più irregolari. In particolare li troviamo anche negli strati superiori e non solo nello strato basale quando viene effettuato l’esame istologico. Cellule di Langerhans Le cellule di Langerhans sono delle cellule del sistema immunitario, che derivano dalla famiglia dell’ovocita dei macrofagi, troviamo cellule derivate da questa famiglia in diversi tessuti, e nell’epidermide si differenziano nelle cellule di Langerhans. Per esempio nell’osso differenziano nell’osteoclasto, oppure nel connettivo in macrofagi. Quindi sono tutte cellule che derivano dall’ovocita (da questa famiglia), e che hanno delle caratteristiche comuni, come la capacità di fagocitare, o di presentare l’antigene. Sono marcate ad esempio dall’antigene Cd1, e sono la prima sentinella dell’epidermide per i noxa patogena. Ovvero possono fagocitare e possono attivare la risposta immunitaria in caso di patogeni. Qui possiamo vedere una cellula di Langerhans, all’interno di uno strato spinoso, con questi lunghi processi citoplasmatici, che caratterizzano la cellula di Langerhans, ma anche le altre cellule della stessa famiglia. Cellula di Merkel Infine abbiamo la cellula di Merkel, che è responsabile della percezione sensitiva, quindi tramite il tatto, è più abbondante in alcune zone anatomiche, come ad esempio i polpastrelli e le labbra. In questa microscopia elettronica a trasmissione, possiamo vedere, la cellula di Merkel sopra al nucleo, è presente nello strato basale, perché subito sotto dal tessuto connettivo arrivano le terminazioni nervose, che prendono contatto diretto con la cellula di Merkel. Quindi la cellula di Merkel funziona da meccanorecettore, che trasmette direttamente al sistema nervoso la percezione meccanica. E qui possiamo vedere la giunzione con una cellula nervosa e la presenza delle cellule di Schwann, che sono delle cellule di sostegno associate al neurone, che stabilizzano le giunzioni con le sinapsi dei neuroni, e hanno poi la funzione di formare la guaina mielinica lungo l’assone. Non esistono solo le cellule di Merkel come recettori del tatto associati alla cute (lo vedremo poi con anatomia), esistono terminazioni nervose libere, corpuscoli dei bacilli e altre strutture. Abbiamo poi gli epiteli pluristratificati pavimentosi. Ma abbiamo la distribuzione limitata anche degli epiteli pluristratificati cubici (in foto a dx), che sono presenti in alcuni solchi maggiori e in alcune ghiandole esocrine (la funzione è sempre quella di trasporto). Lo stratificato colonnare, che è molto raro nei mammiferi (in foto a sx), presenta sempre alcuni dotti di alcune ghiandole esocrine. È caratterizzato di solito da due strati: uno di cellule cubiche e uno superiore di cellule cilindriche o colonnari. Infine abbiamo l’epitelio di transizione, che a seconda dello stato rilassato o disteso dell’organo, ha una conformazione differente. Quando la vescica è rilassata, abbiamo un maggior numero di strati, le cellule superficiali hanno questa forma a cupola; quando, invece, la vescica è piena l’epitelio/il tessuto si distende, e questo anche grazie alla presenza delle giunzioni tra una cellula epiteliale e l’altra, le cellule cambiano di forma e ci appaiono più schiacciate, ad esempio negli strati più superficiali (quindi diminuisce il numero di strati). Questa caratteristica permette una grande capacità di distensione. Cosa intendiamo con Metaplasia? Intendiamo un processo che è ancora reversibile, dove la cellula epiteliale passa da un tipo di epitelio a un altro, perché sottoposta, ad esempio a stress, o costante infiammazione o infezione virale. Quindi la metaplasia è il primo passo della trasformazione carcinogenica a cellule squamose o ad adenocarcinoma. Per esempio in foto è presente la cervice uterina, dove l’epitelio colonnare semplice converte, quando abbiamo metaplasia, in epitelio squamoso stratificato, che è ovviamente disfunzionale. Per esempio se si prendesse la trachea di ratto, esposta o meno al fumo di sigaretta (ovvero un fattore stressogeno), le cellule sono sottoposte continuamente a sostanze infiammatorie, che possono causare la mutazione dell’epitelio della trachea, che è pseudostratificato ciliato, ad un epitelio che invece è stratificato. Quindi ovviamente, in questo caso si ha una perdita di funzione dell’epitelio della trachea. Renew Capital Policies & Administrative Updates Why and How Managers Plan Importance of planning The planing process Benefits of planning Planning and time management Types of PLans used by managers Long term and short term plans Strageic and tactical plans Operational plans Planning Tools and Techiqunes Forecasting Contrigency planning Scenario planning Benchmaking Use of staff planners Implementing Plans to Achive Results Goal setting Goal management Goal alignment Participation and involvement Planning Def: The process of setting objectives and determining how best to accomplish them Planning at Eaton Corporation “Making the hard decision before events force them upon you, an anticipating the future needs of the market before the demand asset itself Objectives and goals Identifity the specific results or desired outcomes that one intends to achieve Plan Def: A statement of action steps to be taken in order to accomplish the objectives (goals) Steps in the planning process: Define your objectives Determine where you stand vis-a-vis objectives Develpo premises reagrdsing future conditions Analyze alternatives and make a plan Implement the plan and evaluate results What are the benefits of planning Improves focus and flexibility Imporves action orteitation Imporves coordination and control Imporves time management Time Managment Personal time management tips Do say “no” to request that distract you form what you should be doing Dont get bogged down inn details that can be addressed later Do screen telephone calls, emails and meeting request Dont let drop in visitors, text messaging use up your time Do prioritize your important and urgent work Dont become calendar bound by letting other control your schedule Do follow priorities; do most important and urgent work first Some 77% of mangers in one survey said that digital age has increased th number of decisions they have to make 43% said there was less time available to make these decisions Types of plans used by Managers What is teh time horizon Long term vs Short term Long term Look three or more years into teh future Short term plans Typically cover one year or less However: the increasing environmental complexity and dynamism of recent years has severely tested the concept of “long-term” planning Plans are subject to frequent revisions Most executives would likely agree that these complexities adn uncertainties challenge how er actually go about planning and how far ahead we can really plan At the very least we can conclude that there is a lot less permanency to long term plans today and that tey are subject to frequent revision Managment reaeracher Eillot Jaques believes tha people vary in their capability to think with different time horizons Types of Plans used by Managers (3 of 5) Strategic plans Set broad, comprehensive and linger term action directions for teh entire organization or major division Vision Clarifies purpose of the organization and what it hopes to be on the future Typical plans Specify how the organizations resources are used to implement strategy Tactical plans in business often take the form of functional plans Functional plans Incidate how different component within the organiztion will help accompnlish the overall strategy Production plans Finacial plans Facilites Plans Logisitc plans Marketing plans Human Resource Plans Operation plans Describe short-term activities to implement strategic plans Policies: Are standing plans that communicate guidelines for decisions Ex: Policies on office romances: The media is quick to report when a top executive or public figures runs into trouble over an office affair. Are there ant policies on office romances? Employer polices on office raltioshiis vary. One survey find teh following: 24% prohibit relationships among employees in the same department 13% prohibit relationships among employees who have the smae supervisor 80% prohibit relationships between supervisors and subordinates 5% have no restrictions on office romances Procedures: Are rules that describe actions to be taken in specific situations Budgets: are single use plans that commit resources to projects or activities Zero based budgets: allocate resources as if each budget were brand new There is no guarantee that any past funding will be renwer. All propsales, old and new, must compete for available funds at teh start of each new budget cycle Forcasting Attempts to predict the future Qualitaive forecasting uses expert opinions Quantitative forecasting uses mathematical models and statiscal aanylsis of historical data dna surveys Contingency planning Identify alternative course of action to take when things go wrong Anticipate changing conditions Contain trigger points to indicate when to activate plan (or a specific course of action) Scenario planning A long term version of contingency planning Identifying alternative future scenarios Plans made for each future scenario Increases organizations flexibility and preparation for future shocks Benchmarking Use of external and internal comparisons to better evaluate current performance Adopting best practices: things people adn organization do that lead to superior performance Staff Planners Experts who assist in all steps of the planning process They help bring focus and expertise to a wide variety of planning tasks Important: Communication between staff planers landline managers is essential for teh success of teh planning process Goal Setting - Always set SMART goal The solution: Goal Aligment Between Team Leader and Team Member Jonintly plan: Set objectives, set standards, choose actions Individually acy: Perform tasks (member), provide support (leader) Jointly control: Review results, discuss implications, renew cycle x4 Collective effort and commitment Participatroy planning Includes in all planning steps that people who will be affected by the plans adn askedd to help implement them Unloacks motivational potential of goal setting Management by objective (MBO) promotes participation Participation increases understanding and acceptance of plan and commitment to success Participatory planning - Number of people involved in teh decision making process Amazon is intensely focused on what it does. It believes in creating tight single-threaded teams, also known as “2 pizza team.” Data and Decision Making What are some of the important competencies managers must have today? Delegate Marketing and technology Manager must have Technological competency Ability to understand new technologies and to use them to their best advantage Information competency Ability to locate, gather, organize and display information for decision-making and problem solving Analytical competency Ability to evaluate and analyze information to make actual decisions and solve real problems What is the difference between Data and Information Data Raw facts and observation Information Data made useful and meaningful for decision-making Important concepts Big data Exists in huge quantities and is difficult to process without sophisticated mathematical and analytical techniques Data production today Bernard Marr is an internationally best-selling author. He helps organizations improve their business performance, use data more intelligently Data mining The process of analyzing data to produce useful information for decision-makers Management Analytics The systematic evaluation and analysis of data to make informed decision Information drives management Bad Data Refers to information that can be erroneous, misleading, and without general formatting The challenge: Can er use the data that is available in the “Big Data” Needs to be valid Can not trust everything out there Being ethical Look at the trends Data is structured and unstructured Data BIg Data = Structured + Unstructured Information Drive Management decision making What are the characteristics of useful information Easy to access If its credible Accurate Characteristics of useful information: Timely High quality Complete Relevant Understandable What about bad data It's not credible Miss information If it is not structured/ organized Bias based on opinions Confusing If its updated Bad data Refers to information that can be erroneous miss What are some examples of Management information system Business intelligence -BI Information systems to extract and report data in organized ways that are useful to decision-makers Executive dashboards Visually update and display key performance metrics (or Key Performance Indicators -KPIs) and information on a real-time basis Information needs in organization External Environment Information exchanges with the external environment Gather intelligence information Provide public information Information needs within the organizations (internal Enviroement) Information exchange within the organization Facilitate decision making Facilitate problem-solving Managers as information processors Continually gather, share and receive information Now as much electronic as it is face-to-face Always on, always connected How many people telecommute at least once a week 70% of people globally work remotely at least once a week, Work at home after covid 19 our forecast Our best estimate it that 25-30% of the workforce will be working form home multiple days a week by the end of 2021 As of 2023, 12.7% of full time employees work from home, while 28.2% work a hybrid model Managers as problem solvers Problem-solving The process of identifying a discrepancy between actual and desired performance and taking action to resolve it Ishikawa Fishbone diagram To identify the cause of problems Decision A choice among possible alternative courses of action Performance threat Something is wrong or has the potential to go wrong Performance opportunity The situation offers the chance for a better future if the right steps are taken Problem-solving approaches or style - from textbook Problem avoiders Inactive in information gathering and solving problems Problem seekers Proactive in anticipation of problems and opportunities and taking appropriate action to gain an advantage Problem solvers Reactive in gathering information and solving problem Managers - can approach problems in a systematic or intuitive manner Systematic thinking approaches problem in rational, step-by-step and analytical fashion Intuitive thinking approaches problems in a flexible and spontaneous fashion Multidimensional thinking- applies both intuitive and systematic thinking Managers face structured and unstructured problems Structure problems Are ones that are familiar, straight forward, and clear with respect to information needs Program decisions apply solutions that are readily available from past experiences to solve structured problems Know how to solve them Familiar Know what we are dealing with Unstructured problems Are ones that are full of ambiguities and information deficiencies Nonprogrammed decisions apply a specific solution to meet the demands of a unique problem Commonly faced by higher-level management Crisis decision making A crisis involves an unexpected problem that can lead to disaster if not resolved quickly and appropriately Ruled for crisis management Figure out what is going on Remember that speed matters Remember that slow counts, too Respect the danger of the unfamiliar Value the skeptic Be ready to “fight fire with fire” Managers make decisions with various amounts of information Certain environment Offers complete information on possible action alternatives and their consequences Risk environment Lacks complete information but offers probabilities of the likely outcomes for possible action alternatives Uncertain environment Lacks so much information that it is difficult to assign probabilities to the likely outcomes of alternative Ex: Certain and uncertain environments: The worldwide Governance Indicators for over 200 countries, comparing distinct environments (Canada-Brazil) Step 1-Identify and define the problem Focuses on information gathering information processing and deliberation Decision objectives should be established What are some common mistakes in definding problems? Common mistakes in defining problems Defining the problem too broadly or too narrowly Focusing on symptoms instead of causes Choosing the wrong problem to deal with Step 2- Generate and Evaluate Alternative Courses of Action Potential solutions are formulated and more information is gathered, data are analyzed, the advantages and disadvantages of alternative solutions are identified Common mistakes: Abandoning the search for alternatives too quickly Step 3- Decide on a preferred course of Action Two different approaches Behavioural model leads to satisficing decisions Classical model les to optimising decisions Behavioural Model Rationality is bounded because: There are limits our thinks capacity Available information (incomplete) Time constraints Step 4-Implement the decision Involves taking action to make sure the solution decided upon becomes a reality Managers need to have the willingness and ability to implement action plans Problems: Lack of participation error should be avoided Step 5 - Evaluate Results Involves comparing actual and desired results The positive and negative consequences of the chosen course of action should be examined If actual results fall short desire results, the manager returns to earlier steps in the decision-making process At all steps, check ethical reasoning Ask these spotlight questions Utility Does teh decision satisfy all constituents or stakeholders Rights Does the description respect the rights and duties of everyone? Justice Is the decision consistent with the canons of justice Caring Is the decision consistent with my responsibilities to care? Issues in decision-making How do errors happen? Heuristics: are strategies for simplifying decision-making Availability Bias: Bases a decision on recent information or events Representativeness bias: Bases a decision on similarity to other situations Anchoring and Adjustment Bias: Bases a decision on incremental adjustment from a prior decision point Framing error: Tring to solve a problem in the context perceived, positive or negative Confirmation Error: Focusing on information that confirms a decision already made Escalating commitment: Continuing a course of action even though it is not working Creative Decision making Creativity is the generation of a novel idea or unique approach that solves a problem or crafts an opportunity Big C: Creativity occurs when extraordinary things are done by exceptional people Little C: Creativity occurs when average people come up with unique ways to deal with daily events and situations The three types of situational creativity drivers Chapter review What are objectives and goals? The specific results or desired outcomes What are the 5 characteristics of great (SMART) goals? Forecasting - Attempts Qualitative forecasting uses options Quantitative forecasting uses mathematical models and statistical analysis of historical data and surveys Scenarios-Oracle’s crystal ball combines qualitative and quantitative methodsThe Revolt of the Northern Earls (1569) Most people in the North remained loyal to the Catholic noble families who controlled the north and their Catholic faith. When Elizabeth came to power, she promoted ‘new men’ (Protestants) from the gentry and the powerful Catholic nobles lost their power and influence. This led them to organise the most serious rebellion of Elizabeth’s reign in 1569. Why did the Northern Earl’s revolt? The Earls had lost their power when Elizabeth became Queen (and wanted it back). They wanted Catholicism restored in England (and felt that ordinary Catholics would support it). Elizabeth was refusing to marry or to name an heir, causing uncertainty about England’s future. Mary Queen of Scots (if freed from prison) could replace Elizabeth and solve all these problems Who were the key players in the Revolt? Earl of Northumberland • A Catholic who had held an important position under Mary I. • He lost a lot of influence under Elizabeth (as she favoured Protestant gentry) • Elizabeth also took the rights to a valuable copper mine found on his lands Earl of Westmorland • From a rich Catholic family in the north Also the Duke of Norfolk’s brother in law Duke of Norfolk • England’s most senior Protestant noble, but he had very close links to old northern Catholic families, & was sympathetic to them & greedy for power. • He hated William Cecil & Robert Dudley, Earl of Leicester (Elizabeth’s favourite) who were Protestant and from the gentry • He planned to marry Mary QS, but later backed down and urged the earls to call off the rebellion. Mary also supported the plan to marry him What role did religion play? (7/10 – but only because it was linked to power) • Most northerners held onto their Catholic beliefs & although Elizabeth didn’t persecute them, they knew that she wanted their religion to gradually die out, so they supported the revolt. • In 1561 Elizabeth hired a strict Protestant as archbishop of Durham to promote Protestantism in the north, but he was unpopular & turned many northerners against the Protestant religion. What role did politics/power play? (9/10 – this was the most important cause of the revolt) • The Northern Earls lost a lot of their power/influence (even jobs/money under Elizabeth) • Northumberland was jealous of new Protestant families being given top jobs in the North • William Cecil & Robert Dudley were not from ancient noble families, but were very close to the Queen, so the northern Earls resented them getting top jobs in her Government • Elizabeth also confiscated large areas of land & the profits from their copper mines • It is possible, that had Elizabeth allowed the Catholic Northern Earls to keep their jobs, money and influence at court, they may have ‘tolerated’ her as a Protestant Queen (greedy/selfish). What role did Mary Queen of Scots and the Succession play? • Elizabeth was refusing to name an heir and it was becoming clear that she would not marry • If Mary Queen of Scots married the Duke of Norfolk, England would have an heir and England would be Catholic again. The country would be stable without people competing for power. • However, some of Elizabeth’s courtiers got worried that it might not work and that it might lead to charges of treason (punishable by death) • So by September 1569, Robert Dudley (Earl of Leicester) decided to tell Elizabeth about the plot. By this time it was much more serious than simply marrying Norfolk to Mary. • Mary QS had secretly asked Spain to send troops to help the rebellion & overthrow Elizabeth Plan for the Revolt of the Northern Earls (1569) • The Earls of Northumberland & Westmorland will raise rebel troops from their lands in the north and take control of Durham. • The rebels will then march south towards London to join with the Duke of Norfolk • 1000s of Spanish troops will land in England to support the rebel forces • The Duke of Norfolk & rebel forces will seize control of Government & overthrow Elizabeth • Mary Queen of Scots is to be freed, ready to marry the Duke of Norfolk Key Events of the Revolt • Once Elizabeth knew of the plot, Norfolk was arrested and sent to the Tower of London • The Northern Earls were worried they would be executed for their involvement and in a desperate attempt to avoid punishment, pushed ahead with the revolt • They raised an army of ordinary Catholics and took control of Durham cathedral • Catholic mass was celebrated across the north for 2 weeks. • They then headed south, to try and free Mary • Mary QSs was moved south to Coventry on the orders of Elizabeth, so she couldn’t escape • The rebellion failed as Spanish troops never arrived • Elizabeth’s friend (Earl of Sussex) had raised an army of 7,000 men to defend her throne. Results: • The rebellion was a serious threat to Elizabeth • She executed 450 rebels in the north • Northumberland was executed in 1572 & his head was put on a spike on the city gate • The Privy Council called for the Duke of Norfolk’s execution too, but Elizabeth released him. • Mary Queen of Scots was kept in prison for the next 14 years. • The failed plot also led the Pope to take action against Elizabeth • In 1570 he excommunicated Elizabeth from the Catholic Church • He also issued a Papal Bull (order) calling on all loyal Catholics to overthrow her hoping it would encourage another rebellion. • In 1571 Elizabeth called parliament to pass an Act making it treason to claim that she was not the rightful Queen and to bring in/print papal bulls in England. The Significance of the Revolt of the Northern Earls • It was the first and most serious rebellion by English Catholics against Elizabeth • Treason laws were made much harsher • It ended the influence of the powerful Catholic Earls in the North • It led to harsher treatment of Catholics, e.g. 1572 Elizabeth sent the Earl of Huntingdon (strict Protestant) to the north to carry out laws against Catholics (and suppress Catholicism). • Although Elizabeth’s brutal revenge on the rebels show how serious a threat it was, most Catholics in the north stayed loyal, but the Pope’s Papal Bull now put their loyalty in doubt There was little support for the revolt among the rest of the Catholic nobility and ordinary people. When faced with a choice between Elizabeth and their religion, most Catholics chose to support the Queen. 1569, was the last time English Catholics tried to remove Elizabeth by force. The future plots against her were always uncovered by Cecil & Walsingham, before they had a chance to get any public support. Despite this, the Northern Revolt & Papal Bull changed Elizabeth’s attitude towards Catholics who were now seen as potential traitors. From 1570, Elizabeth became less tolerant of recusants (people refusing to attend her church) & took increasingly tough measures against Catholics. The Ridolfi, Throckmorton & Babington plots • In the 1870s-80s, there were 3 Catholic plots to assassinate Elizabeth & replace her with Mary. • The plots were supported by France, Spain, the Pope and some Catholic nobles. • They reinforced the form Mary & from Catholics at home and abroad. Also the threat from Spain. The Ridolfi Plot (1571) • Ridolfi was an Italian banker living in England and a spy for the Pope. • He organised a plot to murder Eliz, marry Mary QS to the Duke of Norfolk & make her Queen. • The Pope & King Philip supported the plot & Philip told the Duke of Alba in the Netherlands to prepare 10,000 troops (but to only invade AFTER the English had overthrown Elizabeth). • The plot failed because Sir William Cecil intercepted coded letters & Norfolk was executed. • Mary was kept under closer watch. • Ridolfi was abroad when the plot was discovered and never returned to England. 1574: Catholic Priests and Priest Holes • From 1574 Catholic priests were smuggled into England to keep the religion alive. • They stayed with rich Catholic families, so Catholic families were kept under surveillance. • Catholic homes were raided – to find ‘priest holes’ where Catholic priests were hiding. • Catholic priests who were found could be hung, drawn and quartered (although not all were) • In 1581, Parliament also passed 2 new tougher laws against Catholics: • Recusants would be fined £20 (which would bankrupt most families) • Trying to convert people to Catholicism was now treason (punishable by death) The Throckmorton Plot (1583) • It aimed to assassinate Elizabeth and replace her with Mary. The French Duke of Guise (Mary’s cousin) would invade England with an army, funded by King Philip (Pope also supported it). • An Englishman, Throckmorton carried messages between Mary & Catholic plotters abroad. • Sir Walsingham (Secretary of State) uncovered the plot after his agents found the plans for the plot in Throckmorton’s house. Throckmorton confessed under torture and was executed. Significance: • The plots showed that Mary’s presence in England posed a serious threat • It also showed that France & Spain were a serious threat (& could invade) • Throckmorton’s papers showed a list of Catholic supporters in England, so the threat from English Catholics was also real • 1,000s of Catholics were imprisoned or kept under surveillance/house arrest • In 1585 another Act was passed to make helping Catholic priests punishable by death. • The Bond of Association was signed by the English nobles & gentry & forced them to promise to execute anyone who tried to overthrow the Queen. Weaknesses of the Plots The plots lacked public support & were uncovered by informers & spies before they had the chance to work King Philip was reluctant to destroy his alliance with Elizabeth (France was still a bigger rival) so is support for the plots was half-hearted, he rarely followed through on his promises to help the plotters or send an army The Babington Plot (1586) In 1586, Walsingham used his spy network to PROVE that Mary supported the Babington plot. His evidence persuaded Elizabeth to put Mary on trial & execute her for treason. • This was a plot to murder Elizabeth and put Mary on the throne • France would invade England with 60,000 men and Spain would also send an army • Babington was passing coded letters between Mary & her supporters in England & Europe. • But all of her letters were being intercepted and read by Walsingham. • Walsingham used his spies to follow every stage of the plot & had the letters decoded • One of Mary’s letters approved plans to murder the Queen and free Mary from prison • They also contained the names of 6 Catholics who planned to kill Elizabeth • They were arrested, hung, drawn and quartered for treason. • Mary had been implicated in plots before, but Elizabeth was always reluctant to execute her • But the proof found by Walsingham finally persuaded her to put Mary on trial • In October 1586, Mary was found guilty & was sentenced to death • But Elizabeth still hesitated, and did not sign the death warrant until February 1587. Significance 1) This plot was very significant because by 1585 England was effectively at war with Spain since Elizabeth had sent her army to help the Dutch Protestants fight the Spanish 2) This meant that Elizabeth’ situation was more dangerous than during previous plots. 3) Elizabeth’s government also became more determined to crush Catholicism 4) 1000s of recusants were arrested & 31 priests were executed 5) Mary’s execution removed the Catholic threat at home 6) English Catholics had no one to rally around, & lost hope of overthrowing Elizabeth 7) But Mary’s death increased the threat of a foreign invasion as England was at war with Spain and King Philip had been preparing an attack on England since 1585 8) Mary’s death made Philip even more determined to invade, Mary had left her claim to the English throne to King Philip upon her death Why was Mary Queen of Scots finally executed? 1 • A new Act in 1585 stated that in the event of Elizabeth’s assassination, Mary could be executed as long as she had been proved guilty & Walsingham had provided hard proof. 2 • Another reason was that by 1587, it was clear that Philip was planning to invade England • There were rumours that Spanish ships had landed in Wales & that Mary had escaped. This convinced Elizabeth that Mary had to be executed if she wanted to keep her throne. Walsingham’s Spy Network: • Walsingham (Secretary of State from 1573) had a network of spies all over England & abroad. He had spies in every English town, some were normal people paid to spy on neighbours. • He also had agents and spies in Spain, France, Germany and Italy • He hired mathematicians to crack written codes and people to open/seal letters secretly • He also pressured captured Catholic priests to spy on others for him in return for a pardon. • He used double agents to infiltrate Catholic networks - to help him discover traitors • But he only used torture against Catholic priests caught in England in the most serious cases • But 130 priests and 60 of their supporters were still executed during Elizabeth’s reign. Why did Relations with Spain get worse (1569-1588) • England had tried to stay on good terms with Spain, because Eliz wanted to avoid an expensive war that could lead to her being overthrown (English Catholics could support it) • But by the 1570s, Elizabeth wanted to have an empire of her own. • She also needed to make more money to defend her country and throne (by improving trade) • This religious, political and economic rivalry led to growing tensions between England & Spain Political and Religious Rivalry 1) Land abroad, gave countries wealth/power. By the 1580s, Eliz wanted an empire to rival Spain’s (especially as Spain had supported the Catholic plots against Eliz – even if it was half-hearted) 2) Religion was another cause of conflict. Philip opposed Elizabeth’s religious settlement 1559 3) Luckily for Elizabeth, in the 1550s Spain & France were competing to be the greatest European power and both wanted England as an ally against the other. 4) But from 1567, Spanish ships were sailing to the Netherlands with money for the Alba’s army 5) This alarmed English Protestants and Elizabeth’s Privy Council who put more and more pressure on her to send an army to help the Dutch Protestant rebels (in the Netherlands). Economic (commercial) Rivalry: The New World, privateers and Sir Francis Drake • Under Elizabeth, English merchants wanted to make big profits in the New World (Americas). • However, trading in the New World was difficult because of Spain’s power 1) Spain controlled most of the New World where there were huge profits to be made and anyone who wanted to trade there needed a licence from Spain (which it would not give): 2) But the Americas had valuable crops like tobacco, sugar, and also silver and gold 3) Elizabeth secretly encouraged privateers to trade illegally & raid Spanish ports & ships 4) At first Elizabeth denied responsibility for their actions, which delaye war with Spain Sir Francis Drake: Elizabeth sends Drake to rob Spanish colonies and ships (which infuriates Spain) 1) Spain’s support for the Ridolfi plot (1571) made her more willing to support Drake • In 1572 Eliz hired Drake to sail to the New World & steal £40,000 of Spanish silver • In 1577 she sent Drake back again with a secret mission to rob Spain’s colonies/ships • Drake brought back £400,000 of Spanish treasure & claimed an area of California in Elizabeth’s name (New Albion). He gave a lot of this money to Elizabeth • He boosted England’s finances at a time of growing concern over Spain’s threat • He became famous as the first Englishman to circumnavigate the globe. • Eliz knighted Drake as a reward, which infuriated Philip (as he saw Drake as a pirate) • Drake’s actions & his claim to California made it clear that England did not accept Spain’s domination of the New World. Elizabeth’s Support for the Dutch Rebels led to War with Spain (1585-88) • By the 1580s, tension between England & Spain had reached boiling point • At first, Eliz refused to send her army to help the Dutch rebels, because she wanted to avoid a war with Spain. So she tried to get the Spanish to leave the Netherlands in other INDIRECT ways: 1) By allowing Drake (& other English privateers) to attack and rob Spanish ships and colonies 2) By encouraging others (the French heir/mercenaries) to fight the Spanish in the Netherlands • In the 1570s, Elizabeth promised to marry the heir to the French throne (the Duke of Alencon) so that he would take an army to fight the Spanish in the Netherlands The Spanish Fury (1576) and the Pacification of Ghent (1576) • By 1576, the Spanish Govt in the Netherlands was bankrupt (the war was expensive) • After months without pay, Spain’s soldiers violently robbed Dutch towns in the “Spanish Fury” Spanish troops rebelling and robbing cities in the Netherlands in 1576. This united the Dutch Protestants & Catholics against Spain. They drew up the ‘Pacification of Ghent’ (demanding that): • Spanish troops leave the Netherlands • Spain allows the Dutch to rule themselves • The persecution of Dutch Protestants stops What did Elizabeth do? • Elizabeth sent £100,000 to help the Dutch rebels • In 1577 King Philip’s brother, Don Juan agreed to the rebels demands (but this was a trick) as just 6 months later Philip sent an even bigger army to attack the Dutch. • Elizabeth then hired a mercenary army of 6000 English & Scottish volunteers to help the Dutch. • But her plan backfired because the mercenaries destroyed Dutch Catholic churches, which caused the Catholics to make peace with Spain. • In 1578, her Privy Council urged Eliz to send her official army to help the Dutch, but she refused. The Dutch were disappointed & turned to France for help. The French Duke of Alencon arrived with an army to fight the Spanish, but by 1579 Spain had taken control again. • In 1580 Spain got even stronger after Philip won control of Portugal & its empire. • So Elizabeth gave the Duke of Alencon £70,000 to help him fight the Spanish • In 1582, Alencon took his army the Netherlands but failed to defeat Spain. • Elizabeth’s foreign policy in the Netherlands had failed & she had only managed to annoy Spain 1585: Why did Eliz finally decide to send her army to the Netherlands? (she lost her 2 main allies) • 1584 the Duke of Alencon died (so he could no longer fight the Spanish in the Netherlands) • 1 month later, William of Orange, the leader of the Dutch Protestant rebels was assassinated. • In 1585, Spain signed the Treaty of Joinville with France, agreeing to stamp out Protestantism in France/Europe meaning France & Spain were now allies against Protestantism • Elizabeth now felt she had no choice but to send her official army to the Netherlands • She signed the Treaty of Nonsuch with the Dutch rebels which promised them military help 1585: Robert Dudley’s campaign in the Netherlands was unsuccessful She sent 7,400 man army to the Netherlands led by Dudley. But he accepted the title of ‘Governor General’. Eliz was angry as it suggested that she had deposed King Philip so she told Dudley to resign this position. His army was defeated by the bigger Spanish Army as Eliz had not provided him with enough money to win. In 1587 Dudley resigned and returned to England. At the same time, Eliz had sent Drake to raid Spanish colonies in the New World to disrupt King Philip’s flow of money. Philip was furious and told the Pope he planned to invade England at the end of 1585. Drake singes the King of Spain’s beard 1587 • In 1587 Elizabeth ordered Drake to attack Spain’s most important port Cadiz • He destroyed 30 ships in 3 days – known as the ‘Singeing of the King of Spain’s Beard’ • He also stole lots of wood, meaning the Armada did not have quality barrels for food/water • Drake’s disruption delayed the Armada by a year (& meant that its food rotted in 1588). • This bought England more time to prepare for war. The Spanish Armada (1588) The Plan • By 1588, the Spanish Armada was ready to invade England • It had 130 ships with 8000 sailors & 18,000 soldiers • The Duke of Medina Sidonia would lead the Armada, but he had little experience at sea and didn’t want the job • The Armada would collect Parma’s army from France & sail to England under the protection of the Armada’s warships • Parma would march to London to depose Elizabeth & impose a Catholic government in England. 1) The Armada reached the English Channel The Armada set out in May 1588, but was delayed for a few weeks by bad weather In July the Armada was near England & signal fires were lit to warn Elizabeth English ships set sail to meet the Armada The Armada sailed up the channel in a crescent (half moon) formation, to use the large armed galleons to protect the weaker supply and army ships The English navy carried out a few minor raids, but did not inflict much damage Only 2 Spanish ships were lost (by accident) 2) The English attack the Spanish at Calais (with fire ships) and at Gravelines The Armada sailed up the English channel & anchored at Calais to wait for Parma’s army But Parma’s men didn't reach the coast in time (news had reached them too late) At midnight, the English sent 8 fireships into the Spanish ships causing panic They cut their anchors, broke formation & headed for the open sea (without Parma) The Spanish ships sailed to Gravelines, but bad weather stopped them returning to Calais The English attacked and the battle lasted many hours (5 Spanish ships were sunk) The rest were forced to sail away from France towards Scotland The English ships followed them to make sure they didn’t come back to collect Parma’s army 3) The Armada’s Journey back to Spain around Ireland was a disaster The Spanish called off the attack and returned to Spain around Scotland & Ireland Bad storms sank many ships and wrecked more on the Irish coast Many sailors died from starvation & disease – less than half the men made it back to Spain How did England defeat the Spanish Armada? !) Faster Ships • Years before the battle, England had started building smaller, faster ships (galleons) that could fire canon balls quicker & further than Spanish ships • Spanish ships were huge and slow to change direction. 2) Bad Planning & Communication (Spanish) • Philip’s plan to join with the Duke of Parma’s army in France was risky. • Parma had lots of small ships which took 48 hours to load, man and set sail. • It took too long (a week) for word to reach Parma that Medina was in the English Channel, by which time Medina had set sail to Calais. • Parma was not ready to set sail & the English were already ready to attack (leaving Medina with very little back up when anchored in France). 2) English Tactics were more effective • Spanish ships aimed to come alongside the English ones, jump on board & fight the enemy. But the English ships were faster & kept a safe distance. • They chased the Armada down the Channel, with heavy cannon fire, which forced the Spanish to arrive in France before Parma’s army was ready • As the Armada was waiting, the English sent fireships into the Spanish fleet. • This caused the Armada to panic, cut their anchors & sail away to the north • When the Spanish ships regrouped, the English attacked them in the Battle of Gravelines & the Armada was forced to sail north, chased by faster ships. 5) Bad Weather • Strong winds made it impossible for the Armada to return & pick up Parma’s army and storms wrecked or sunk Spanish ships as they tried to return home along the Scottish-Irish coasts. 2) Spanish Supplies • The Armada was not well supplied with food/weapons. Drake’s attack on Cadiz port in 1587 had destroyed food barrels. Delays in setting sail meant that by the time the English attacked the Armada it had been at sea for 10 weeks and had rotting food. 1000s died from starvation/disease. The consequences of the English victory? • Victory over the Spanish Armada gave Elizabeth a great propaganda victory • A new portrait was made, and a medal was made to commemorate her victory, it said “God blew and they were scattered”. • Elizabeth claimed that God was on the side of Protestantism • This led to a feeling of English pride and encouraged the Dutch rebels to renew their fight against the Spanish • The defeat of the Armada showed the strength of the English navy and gave England the confidence to trade and explore more widely at sea • Although Philip did not give up and continued the war for the rest of Elizabeth’s reign, the defeat had cost Spain dearly, both financially and in terms of its power • The Armada marked the start of a long decline in Spain’s power and fortunes. • English ships were sent on voyages of discovery and set up valuable new trade routes • By the end of Elizabeth’s reign, the navy was also trying to set up a new colony in Virginia • The English victory boosted Elizabeth’s popularity & strengthened the Protestant causeRene Magritte Quiz :)Rene Magritte Rene Descartes