APC抗原递呈细胞

Extracellular/Vesicular Ags
Antigen-presenting Cells (APC)
APCs: Specialized cells that present Ags to CD4+ T cells
Ag-presenting Cells
1. Activate naï ve or effector T cells.
Name Conventional dendritic cell (cDC) Description Most similar to monocytes. Secretion Toll-like receptors
IL-12
TLR 2, TLR 4
Plasmacytoid dendritic cell (pDC)
Immunologist’s dirty little secret
Ag-presenting Cells
1. Activate naï ve or effector T cells.
2. Present Ag to T cells and provide the 2nd signal. 3. Microbial products enhance the antigenpresenting function of APCs. 4. Bidirectional interaction between APC and T cells.
Look like plasma cells, but have certain characteristics similar to conventional dendritic cells.
Can produce high amounts of interferonalpha and thus became known as IPC (interferon- TLR 7, TLR 9 producing cells) before their dendritic cell nature was revealed.
Innate Recognition (PAMP and PRR)
Conserved, essential, characteristic molecules, absent in the host
PAMP
PRR
Toll-Like Receptors (TLRs)
PAMP Enhances Antigen-presenting functions of APCs
2. Present Ag to T cells and provide the 2nd signal. 3. Microbial products enhance the antigenpresenting function of APCs. 4. Bidirectional interaction between APC and T cells.
The Nobel Prize in Physiology or Medicine 2011
Bruce Beutler
Ralph Steinman
Jules Hoffmann
Dendritic cells
• Conventional DC • Plasmacytoid DC
cDC vs. pDC
抗原提呈细胞和抗原提呈
Antigen-presenting Cells (APC) and Antigen Presentation
Kill
Activate macrophages
Produce Abs
T Cell Functions
• CD8+ Cytotoxic T cells, CTL Eliminate virusinfected cells • CD4+ Helper T cells, Th Activate macrophages and B cells
How do T cells recognize Ag?
The T-cell receptor resembles a membrane-associated Fab fragment of immunoglobulin
T cell Repertoire
The T-cell receptor resembles a membrane-associated Fab fragment of immunoglobulin
• CD40(APC)-CD40L(T) • IFN-γ • Positive feedback to maximize the immune responses
Dendritic Cells
Dendritic Cells
1973, Ralph.M.Steinman, Rockfeller University Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. J Exp Med.
• MHC class I contains alpha 1-3 domains and Beta 2-microglobulin • MHC class II, alpha chain and beta chain • Binding of MHC is restricted to appropriate T-cell co-receptors (CD4 or CD8)
Immune Synapse
Ag-presenting Cells
1. Activate naï ve or effector T cells.
2. Present Ag to T cells and provide the 2nd signal. 3. Microbial products enhance the antigenpresenting function of APCs. 4. Bidirectional interaction between APC and T cells.
• Peptide-MHCI CD8+ T Cells • Peptide-MHCII CD4+ T Cells
Peptide-MHC I CD8 T cell
Peptide-MHC II CD4 T cell
The TCR binds to the peptide:MHC complex
Hale Waihona Puke Epithelial Langerhans Cell
• Ag-specific T cells are rare. • Infection may occur at any site in the body. • Antigen-presenting cells (APC) capture, present antigen and activate T cells.
Naï ve T cell activation requires 2 signals
Signal 1 = MHC-AgTCR Signal 2 = Costimulators B7(CD80/86)CD28 CD40 CD40L Signal 3 = Cytokines, IL-12
Naï ve T cell activation requires 2 signals
Challenges for T cells to overcome
• Ag-specific T cells are rare. • Infection may occur at any site in the body. • Antigen-presenting cells (APC) capture, present antigen and activate T cells.
MHC I and MHCII (Review)
The two classes of MHC molecule have similar three-dimensional structures
• MHC class I contains alpha 1-3 domains and Beta 2-microglobulin • MHC class II, alpha chain and beta chain • Binding of MHC is restricted to appropriate T-cell co-receptors (CD4 or CD8)
Every TCR is specific for a combination of a peptide Ag and parts of MHC (MHC restriction).
MHC cell surface expression
• All nucleated cells express MHC Class I, presenting Ag to CD8+ T cells. • Antigen-presenting cells (DC, Mac, B) display Ag in MHC Class II to CD4+ T cells.
Ag-presenting Cells
1. Activate naï ve or effector CD4+T cells.
• Express MHCII
• DC naï ve T cells • Mac, B activated T
Ag-presenting Cells
1. Activate naï ve or effector T cells.
Cytotoxic T cell (CTL, CD8+) Directly kill virus-infected cell
Helper T cells (Th, CD4+) Activate Macrophages and B cells