1. PROFESSIONAL ANTIGEN PRESENTING CELLS
Express MHC class I and class II molecules
Express co-stimulatory molecules (CD40, B7)
Take up extracellular antigens
B cells – soluble proteins, toxins
ADAPTIVE – Ag specific
Macrophages – extracellular pathogens (bacteria, yeast)
Dendritic cells – viruses, apoptotic cells
INNATE

2. THE ROLE OF PROFESSIONAL ANTIGEN PRESENTING CELLS IN THE IMMUNE RESPONSE
Infectious diseases
Tissue transplantation
Elimination of tumors
Autoimmune diseases
Gatekeeper function
Sensing pathogens
Priming adaptive immune responses
Maintenance of self tolerance to self structures

5. Dendritic cells are sensors, gatekeepers and messengers
Activation induces a phenotype essential for
the initiation of the adaptive immune response
In these images of dendritic cells in peripheral tissue (top panels), lymph (middle panels) and lymph node (bottom panels), the left panels are fluorescent micrographs of several cells with MHC class II molecules stained green and a lysosomal protein stained red, and the right panels are scanning electron micrographs of single cells. The dendritic cell body is clearly seen in the top right panel, but in the top left panel the cell bodies are difficult to discern. The observed yellow staining shows endocytic vesicles within the dendrites that contain both MHC class II molecules and lysosomal proteins: the combination of the red and green stains gives the yellow color. On activation and passage to the lymph the morphology of the dendritic cell changes, as shown in the middle panels. Phagocytosis has now stopped, a change indicated in the middle left panel by a partial separation of the green MHC class II staining from the red lysosomal protein staining. This shows that peptide-loaded MHC class II molecules are moving out of the endocytic vesicles and onto the cell surface. On reaching the T-cell area of a lymph node (bottom panels), the now mature dendritic cells concentrate on antigen presentation and T-cell stimulation instead of the uptake and processing of antigens. Here the MHC class II molecules, which are at high density on the surface of the numerous dendrites, are completely separated from the lysosomal protein in the intracellular vesicles

6. CONTACT OF DENDRITIC CELLS AND T - LYMPHOCYTES IN LYMPHOID ORGANS
Activated dendritic cells act as professional antigen presenting cells
MHC-peptide complexes 1. signal STRANGER
Co-stimulatory molecule signal AMPLIFICATION
Cytokines 3. signal DANGER
They are in close contact with
specific T lymphocytes

7. INTERDIGITATING RETICULAR (MATURE DENDRITIC) CELL IN T CELL AREAS OF LYMPH NODES
NUCLEUS
T CELL
T CELL
CYTOPLASM

8. Cell-surface molecules of the immunoglobulin superfamily
initiate lymphocyte adhesion to professional
antigen-presenting cells B.
Transient interactions are stabilized by Ag-binding A.
Initial contact A
A) In the initial encounter of T cells with antigen-presenting dendritic cells, CD2, binding to LFA-3 on the antigen-presenting cell, synergizes with LFA-1 binding to ICAM-1 and ICAM-2. An interaction that seems to be exclusive to the interaction of naive T cells with dendritic cells is that between ICAM-3 on the naive T cell and DC-SIGN, a C-type lectin specific to dendritic cells, which binds ICAM-3 with high affinity. B) When a T cell binds to its specific ligand on an antigen-presenting dendritic cell, intracellular signaling through the T-cell receptor (TCR) induces a conformational change in LFA-1 that causes it to bind with higher affinity to ICAMs on the antigen-presenting cell. The T cell shown here is a CD4 T cell.

9. Monocyte
CHANGES OF TISSUE ENVIRONMENT INDUCES THE ACTIVATION OF MACROPHAGES AND DENDRITIC CELLS
Activated macrophage
Phagocytosis and degradation of backteria
(LPS, TLR) DANGER SIGNAL
Macrophage
Activated dendritic cell
Virus, extracellular pathogens, inflammatory cytokines (LPS, TLR)
DANGER SIGNAL
Dendritic cell
BLOOD
TISSUE
LYMPHOID TISSUE

10. ACTIVATION AND MIGRATION OF DENDRITIC CELLS
TISSUE LYMPH NODE TISSUE
Lymphatics
Effector and memory T cells
Activated DC
Inflammation
Pathogen
CIRCULATION
Naive T cells
Tissue DC
DC AND T CELLS
ENCOUNTER
T CELL ACTIVATION
ANTIGEN

11. Huang et al Immunity 2004 Rapid DC Migration in the Subcapsular Space
Capture of an Ag-Specific T Cell by an
Ag-Bearing DC
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
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. co-injection 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

12. Morphology of plasmacytoid dendritic cells
IPC/DC2
pDC
monocyte
Scanning EM Transmission EM

13. Plasmacytoid DCs control the function of many immunocytes
IFNα is impotant in
SLE pathology
HIV infects PDC
Role in immune response and in the pathogenesis of autoimmune
diseases and cancer

14. PLASMACYTOID DENDRITIC CELLS AS PROFESSIONAL TYPE I INTERFERON SECRETING CELLS
Enhanced NK cell cytotoxic activity
TLR4
Vírus infection
TRAM
TRIF
TLR7
TLR8
TLR9
TLR3
TRIF
MyD88
TANK
IRAK-1
Activation of  and γδ T cells
TRAF-6
RIG-1
IKKε
TBK1
IFN-β
IFN-α1
Cross-presentation by conventional dendritic cells is enhanced
IRF-3
IRF-5
IRF-7
IRF-7
Ig production by B cells is induced
Type I interferon receptor

15. Migration Pathways of PDC/IPC versus mDC into a
lymph node
mDC: afferent
lymphatics
IPC: HEV
Both migrate into the T-cell rich areas