19 stud ro toleranta ii 2013
DESCRIPTION
Imunologie, tolerantaTRANSCRIPT
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Toleranta Imunologica II
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Obiective
• Definitie si clasificare – conditii de obtinere a tolerantei imunologice
• Mecanismele inductiei tolerantei imunologice a limfocitelor T – Toleranta innascuta centrala – Toleranta innascuta periferica – Toleranta dobandita
• Mecanismele inductiei tolerantei imunologice a limfocitelor B
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Toleranta centrala: Ag self
OLP
L imature
Innascuta
Toleranta periferica:
Ag self/non-self
OLS
L mature naïve/autoreactive
innascuta/dobandita
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TIMUS
Scapa Deletiei Clonale
Cel T Autoreactive (Naïve)
Ag Sechestrate
Ignoranta Clonala/ Imunologica
MHC/Ag + Costim.
MHC/Ag No Costim.
Autoimunitate Anergie Clonala
Toleranta Periferica a Celulelor T
Supresia prin Celule T reg
PERIPHERY
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APC TCR
T cell CD28
Activated T cells
APC TCR
Functional unresponsiveness
Normal T cell response
Anergy
Apoptosis (activation-induced cell death) APC
Deletion
APC
Block in activation
Suppression
Regulatory T cell
Off signals
Activated T cell
1st signal
2nd signal
Toleranta Periferica LT
I N N A T E
A C Q U I R E D
I N N A T E
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Mecanisme de Mentinere a Tolerantei LT
Deletia clonala
Supresia
Toleranta centrala
Toleranta periferica
T regulatory CD4⁺ CD28⁺ FoxP3⁺
T suppressor
CD8⁺ CD28⁻ FoxP3⁺
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Celulele T reg
• Generalitati
• Caracteristici
• Fenotipuri
• Mecanism de actiune
• Functii
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Markeri Fenotipici ai Tregs
Regulatory T cells Effector/Memory T cell
Surface markers CD25/IL-2Rα chain (high) CD127 (IL-7Rα chain) (low) CTLA4
CD25/IL-2Rα chain (high→medium) CD127 (IL-7Rα chain) (low: effector cells high: memory cells)
CK produced on activation (main)
TGF-β IL-10
TH1: IFNγ TH2: IL-4 & IL-5 TH17: IL-17
CCR CCR6 CXCR3
GF requirement IL-2 Effector: IL-2, IL-4 Memory: IL-7
Major transcript fact expressed
FoxP3, STAT-5 ≠ Effector subsets: GATA-3, STATs Memory: BLIMP-1
Dupa A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
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Clasificare T regs
• Clasificare subseturi • Functii • Fenotip • Foxp3
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Dezvoltarea celulelor
T reg
A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
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Tregs Timice
• Caracteristici
• Origine:
• Trigger:
• Localizare:
• Rol:
Tregs Periferice
A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
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Supresia raspunsurilor LT da catre Tregs
A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
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Treg Periferice (Adaptative, Induse)
Ch Janeway et al. Immunobiology. .
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Toleranta Celulelor B
• Ag self T-independente
(PZ self, lipide, acizi nucleici) → nu sunt recunoscute de LT→ necesar inducerea tolerantei LB
• Ag self T-dependente
(Proteinele) self → necesar inducerea tolerantei LTh & LB pentru a preveni producerea de AAc (auto-anticorpi).
• Dovezi experim arata ca P self induc toleranta si in LB.
• Boli asociate cu productia de Aac (LES) sunt rezultatul tolerantei defectuoase in LT si LB.
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Toleranta Celulelor B: Centrala & Periferica
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Mecanismele de inducere a tolerantei centrale pentru LB
Deletia clonala a LB Resintetizarea secventei receptorului in LB imature
A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
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Toleranta periferica dobandita a LB
Ag T-dependente: Ag T-independente:
Ch Janeway et al. Immunobiology
Conditii de obtinere a tolerantei LB in periferie
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Termeni Opusi Importanti
• Toleranta Centrala (self-toleranta) vs toleranta periferica • Toleranta Activa vs. toleranta pasiva
(ignoranta) • Toleranta LT vs. Toleranta LB
• Toleranta naturala vs. artificiala
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Bibliografie selectiva:
• Ch Janeway et al. Immunobiology. 2005, 2007. Garland Science .
• A Abas et al. Cellular & Molecular Immunology. 2012 (7th ed)
• C Bara. Esential de imunologie. 2002. Ed Bic ALL.