Immunologia – Cellule Dendritiche

Cellule Dendritiche e Cellule Natural Killer:

le fasi iniziali della risposta immune

Prof. Guido Ferlazzo

Università degli Studi di Messina Corso di Laurea in Medicina e Chirurgia

6 Aprile, 2006

Innate

Adherence to epithelium

MacrophagesDendritic Cells

Innate

Local infection, penetration of epithelium

MacrophagesDendritic CellsNatural Killer Cells

Adaptive

Local infection of tissues

T cellsB cells

Protection against infections

Antigene e costimolo sono necessari per l’attivazione dei T linfociti

Malignant tumor cells expressing TRA but no co-stimulatory molecules

Naive CD8T cells specific for TRA cannot be activated by the tumor cells and may be rendered anergic

Tumor grows progressively

Transfect tumor cell with B7

Tumor cells expressing B7 can activate TRA-specific CD8 T cells

Activated CD8 T cells eliminate tumor

Mouse can now reject parental B7-negative or GM-CSF-negative tumor

Transfect tumor cell with GM-CSF

GM-CSF recruits dendritic cells, which can present tumor antigens to T cells

INDUCING FACTORS

• GM-CSF
• IL-3
• IL-4
• Viruses

pathogens, e.g. LPS, bacterial DNA

cytokines, e.g. TNF, GM-CSF

T cells, e.g. CD40L

viral dsRNA

PROPERTIES

DC PRECURSOR

IMMATURE DC

CYTOKINE RELEASE

• IFN alpha
• TNF
• IL-1

ANTIGEN CAPTURE

• High intracellular MHC II
• Endocytosis
• Phagocytosis
• High CCR1, CCR5, CCR6
• Low CCR7
• Low CD54, 58, 80, 86
• Low CD40
• Low CD83, No DC-LAMP

MATURE DC

ANTIGEN PRESENTATION

• High surface MHC II
• Low endocytosis
• Low phagocytosis
• Low CCR1, CCR5, CCR6
• High CCR7
• High CD54, 58, 80, 86
• High CD40
• High CD83, high DC-LAMP, high p55

Chemokine Receptors on Dendritic Cells

B cell receptor

Membrane-bound IgM (mi gM)

recognition

light chain

heavy chain

IgB lgx

signaling

T cell receptor

TCR

recognition

CD3

α β

ε δ

γ ε

ITAMs

ζ

signaling

Class I MHC

IR

No lysis

Normal cell

AR ligand

AR

NK cell

IR

Lysis

Neoplastic cell

Virus infected cell

AR ligand

AR

NK cell

Class I MHC

Meccanismi di citotossicita' dell'immunita' innata

• Enzimi litici
• Perforina
• TNF
• Granzimi

Neutrofilo

Cellula NK

Eosinofilo

Cellula bersaglio

Antigene di superficie (Ag)

Ag legato all'Ab legato al recettore per l' Fc

Recettore per Fc

Macrofago

NK limit viral load and tumor burden prior to the initiation of the adaptive immune response

• Production of IFN_α, IFN_β, TNF_α and IL-12
• NK cell mediated killing of infected cells
• T cell mediated killing of infected cells

Virus titer

Time after viral infection (days)

Janeway and Travers, 1994

NK burst precedes T cell activation during viral infections