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THE ROLE OF PROFESSIONAL ANTIGEN
PRESENTING CELLS IN THE IMMUNE RESPONSE
Gatekeeper function
Sensing pathogens
Priming adaptive immune responses
Maintenance of self tolerance to self structures
Infectious diseases
Tissue transplantation
Elimination of tumors
Autoimmune diseases
PROFESSIONAL ANTIGEN PRESENTING CELLS
Express MHC class I and class II molecules
Express co-stimulatory molecules (B7, CD40)
Take up extracellular antigens
B cells – soluble proteins, toxins (ADAPTIVE)
Macrophages
– extracellular pathogens (bacteria, yeast)
INNATE
– particles
Dendritic cells – viruses, apoptotic cells
PROFESSIONAL ANTIGEN PRESENTING CELLS
Express MHC class I and class II molecules
Express co-stimulatory molecules (CD40, B7)
Take up extracellular antigens
~25%
B cells – soluble proteins, toxins
ADAPTIVE – Ag specific
Macrophages – extracellular pathogens (bacteria, yeast)
3 – 6%
Dendritic cells – viruses, apoptotic cells
INNATE
~1%
CHARACTERISTICS OF PROFESSIONAL ANTIGEN PRESENTING CELLS
Macrophage
Ag uptake
phagocytosis +++
Dendritic cell B - lymphocyte
phagocytosis +++
virus infection ++++
Ag-specific mIg
++++
MHC expression induced +/+++
bacteria, cytokine
constitutive ++++
constitutive +++
immature/mature +++/++++ activation ++++
Pesented Ag
protein
virus protein, allergen
apoptotic cell
soluble protein
toxin
particulate Ag
intra/extracellular
pathogens
Co-stimulation
induced +/++
constitutive ++++
éretlen/érett +++/++++
induced +/+++
Localization
lymphoid tissue
connective tissue
body cavities
evenly
lymphoid tissue
connective tissue
epithelium
immature – tissue
mature – T cell area
lymphoid tissue
peripheral blood
Lymph node
follicles
CHANGES OF TISSUE ENVIRONMENT INDUCES THE ACTIVATION OF
MACROPHAGES AND DENDRITIC CELLS
Phagocytosis and degradation of backteria
(LPS, TLR) DANGER SIGNAL
Macrophage
Monocyte
Dendritic cell
Activated macrophage
Activated dendritic cell
Virus, extracellular pathogens, inflammatory cytokines (LPS, TLR)
DANGER SIGNAL
BLOOD
TISSUE
LYMPHOID TISSUE
ACTIVATION AND MIGRATION OF DENDRITIC CELLS
TISSUE
LYMPH NODE
Lymphatics
Activated DC
TISSUE
Effector and memory T cells
Inflammation
Pathogen
Naive T cells
ANTIGEN
Tissue DC
DC AND T CELLS
ENCOUNTER
T CELL ACTIVATION
CIRCULATION
Dendritic cells are sensors, gatekeepers and messengers
Activation induces a phenotype essential for
the initiation of the adaptive immune response
INTERDIGITATING RETICULAR (MATURE DENDRITIC) CELL IN T CELL
AREAS OF LYMPH NODES
NUCLEUS
T CELL
T CELL
CYTOPLASM
Cell-surface molecules of the immunoglobulin superfamily
initiate lymphocyte adhesion to professional
antigen-presenting cells
B.
A.
A
Initial contact
Transient interactions are stabilized by Ag-binding
Rapid DC Migration in the Subcapsular
Space
Bone-marrow derived DCs (either 5 µM CFSE,
green) or (50 µM Cell Tracker Blue, blue) were
injected into the footpad of a C57BL/6 mouse,
followed 18 hours later by intravenous injection
of freshly isolated polyclonal CD4+ T cells (5 µM
SNARF, red) and CD8+ T cells (5 µM CFSE and 5
µM SNARF, yellow). The draining LN was
removed 6 hours after injection
Capture of an Ag-Specific T Cell by an
Ag-Bearing DC
Bone-marrow derived DCs (yellow) were pulsed with
1 µM Ova 4 peptide and 10 µM Ova for 1 hour at
37oC, then injected into the footpad of a C57BL/6
recipient. This was followed 6 hours later by i.v. coinjection of OT-I CD8+ T cells (5 µM CFSE, green) and
OT-II CD4+ T cells (5 µM SNARF, red).
Huang et al Immunity 2004
CONTACT OF DENDRITIC CELLS AND T
- LYMPHOCYTES
IN LYMPHOID ORGANS
Activated dendritic cells act as professional antigen
presenting cells
MHC-peptide complexes
Co-stimulatory molecule
Cytokines
1. signal STRANGER
2. signal AMPLIFICATION
3. signal DANGER
They are in close contact with
specific T lymphocytes
Morphology of plasmacytoid dendritic cells
IPC/DC2
pDC
Scanning EM
monocyte
Transmission EM
Plasmacytoid DCs control the function of many
immunocytes
HIV infects PDC
IFNα is impotant in
SLE pathology
Role in immune response and in the pathogenesis of autoimmune
diseases and cancer
PLASMACYTOID DENDRITIC CELLS AS PROFESSIONAL TYPE I INTERFERON SECRETING
CELLS
TLR4
TRAM
TRIF
Vírus infection
Enhanced NK cell cytotoxic activity
TLR7
TLR8
TLR9
TLR3
TRIF
MyD88
IRAK-1
TRAF-6
TANK
Activation of  and γδ T cells
RIG-1
IKKε
TBK1
IRF-3
IRF-5
IRF-7
IFN-β
IFN-α1
Cross-presentation by conventional
dendritic cells is enhanced
IRF-7
Type I interferon receptor
Ig production by B cells is
induced
Migration Pathways of PDC/IPC versus mDC into a
lymph node
mDC: afferent
lymphatics
IPC: HEV
Both migrate into the T-cell rich areas
CO-STIMULATION IS ESSENTIAL FOR PRIMING OF NAIVE T
LYMPHOCYTES
The antigen-specific and the co-stimulatory signal has to
be induced in concert to induce T lymphocyte activation
The antigen-specific and co-stimulatory signals can be
delivered simultaneously by professional antigen
presenting cells, only
The antigen-specific and the co-stimulatory singnals has
to be delivered by the same professional antigen
presenting cell