Lecture 14 - Antigen-Presenting Cells Flashcards
What do T cells do in a naive state?
Circulate between lymphoid organs and tissues in lymph.
Can’t elicit effector function
Time taken for a naive T cell to mature
~2 days
Where do most pathogens reside?
The periphery
What is an APC versus a professional APC?
APC is any cell with MHCI
Professional APC is a cell with MHCII (EG: dendritic cell)
Dendritic cell life 1) 2) 3) 4)
1) Grows in the bone marrow
2) Travels to tissue
3) Stays in tissue for several days, picks up antigens
4) Takes antigens to lymph node, presents them, dies
Dendritic cells in epidermis
Langerhans cells
How do dendritic cells enter a lymph node?
Through the afferent lymphatics
Types of dendritic cells
1) a, b
2)
3)
1) Conventional dendritic cell
a) CD8+
b) CD8-
2) Inflammatory dendritic cell
3) Plasmacytoid dendritic cell
Why doesn’t the spleen receive dendritic cells?
The spleen receives no lymph
What do CD8+ conventional dendritic cells arise from?
CD24high progenitors in the spleen
What do CD8- conventional dendritic cells arise from?
CD24low progenitors in the spleen
CD8+ cDC
Cross-presentation
CD8- cDC
Best at presenting on MHCII
Best DC at presenting on MHCII
CD8- cDC
Types of conventional DCs (apart from CD8+/-)
1)
2)
1) Peripheral tissue-resident –> present in most peripheral tissues, but different tissues have different DC types.
2) Lymphoid-tissue resident –> Two types - CD11blo, CD11bhigh
Inflammatory DC
1)
2)
3)
1) Non-existent in healthy state
2) Differentiate from monocytes under inflammatory conditions
3) Antigen presentation to tissue effector cells
Why are inflammatory DCs important in inflamed tissue?
Tissue CD4 T cells need MHCII presentation
iDCs do this
Plasmacytoid DCs 1) 2) 3 4)
1) When inactive, look like plasma cells
2) When activated, look like dendritic cells
3) Good at secreting IFN1, IFN2
4) In blood and tissues
DC activation
1)
2)
1) DCs circulate in immature state, with high phagocytic activity and poor antigen-presenting capacity
2) When a PRR is stimulated, DC matures, begins antigen presenting
Way for DCs to recognise intracellular bacteria
Inflammosomes
Why don’t dendritic cells activate T cells against self antigens?
If a DC begins presenting a self antigen but there are no PAMPS, it will not mature, and therefore not be able to stimulate T cells with self antigen
Cytosolic PRRs
NLRs
Inflammosomes
How does a DC encounter a virus?
Very rare to encounter virus in extracellular fluid
Phagocytoses a dead cell, viral antigens are detected by TLRs in endosome
Most important antiviral cytokines
IFN type I, II
TLR9 stimulation effect
1)
2)
3)
1) IL12 (Th1)
2) CD40 (B cell activation)
3) CD80, 86 expression (T cell activation)
RIG-like helicase ligand
dsRNA
RIG-like helicase receptor
RIG-1
RIG-like helicase location
cytosolic
RIG-like helicase stimulation effect
IL-6
IFNa, b expression
NLRC4 ligand
Flagellin
NLR location
Cytosolic, coupled to inflammosome
NLR stimulation effect
1)
2)
3)
1) IL-1b
2) IL-18
3) IL-33
TLR-9 ligand
cPgDNA
