Lecture 15 - APCs II Flashcards
What is important about the generic sort of signals that stimulate DCs?
Danger signals: exogenous AND endogenous
Not solely pathogens signals
What happens when mitochondria become damaged?
Cell automatically undergoes apoptosis
Mitochondrial DNA that leaks out binds PRRs in the cytosol
Describe the sequence of events that occur when the DC experiences LPS
- LPS binds TLR 4 on DC surface
- Induction of a signal transduction pathway involving MyD88
- NFKB activated
- NFKB translocated to nucleus and turns on gene expression
- IL-6 production
Where are the different locations of TLRs?
Cell surface
In endosomes
i.e. must be associated with a plasma membrane
Describe how DCs recognise viruses and bacteria
Viruses: the DNA / RNA stimulates PRRs
Bacteria: flagella, LPS etc stimulates PRRs
Which PRR recognises LPS?
TLR 4
Describe the adherence of DCs in tissues before maturation
DCs (e.g. Langerhans cells) present in epidermis; weaved into the keratinocyte network
Adherence through various molecules:
• E-cadherin
- experience of antigen -
Down regulation of E-cadherin
Upregulation of CCR7
Describe migration of DCs to the lymphoid organs
DCs become unstuck
Lymphoid organs release chemokines, creating a gradient
• CCL19
• CCL21
Chemokines specifically
DCs follow a gradient towards the lymphoid organs
• CCR7
• receptor on DCs that allow them to recognise the chemokines being released by lymphoid organs
Where are T cells found in lymph nodes?
Paracortex
Through which structure do DCs get into the lymph nodes?
What else comes through in this way?
Afferent lymphatics
Whereas naïve T cells come in via HEV
Where do DCs specifically go in the lymph node?
Paracortex: i.e. where the T cells are
Describe cross presentation
Compare with direct presentation
MHC I presenting peptide from an exogenous source
- Extracellular antigen translocated into the cytosol, where it is loaded onto MHC class I
- We now have exogenous peptide on MHC I for presentation to CD8+ T cells
In direct presentation cytosolic peptide binds to MHC I while it is still in the ER
NB This is thought to be an artificial system
Why is cross presentation so important?
DCs can present viral peptides on MHC I without being infected
Can present peptides from viruses that circumvent DCs
What happens if a pathogen does not infect DCs?
Potentially, the antigen won’t be presented to T cells
Describe antigen presentation for HSV
• HSV only infect the epidermis
• DCs sit next to the infected keratinocytes
• DCs present viral peptide on MHC I
etc.
Which path of antigen presentation is best for extracellular bacteria?
Why?
MHC Class II
Primes CD4+ T cells:
• ‘helper’ T cells release cytokines to kill the bacterium
• help for B cells to produce Ab
Which path of antigen presentation is possible for soluble antigens or virus particles?
MHC Class II
and
MHC Class I (via cross presentation)
How are soluble antigens & virus particles taken up by APCs?
Macro-pinocytosis
How are extracellular bacteria taken up by APCs?
Receptor mediated phagocytosis
Which path of antigen presentation is best for viruses?
MHC class I pathway
Which path of antigen presentation is best for extracellular viruses particles?
MHC II
What are the different mechanisms for viral antigen presentation on MHC I?
- Cell is infected
• Protein being made in the cell - Cross presentation
• Phagocytic / macropinocytic uptake of virus
• Degraded
• Presented in MHC I - Transfer from incoming DC to resident DC (in LN)
Describe antigen presentation of intravesicular pathogens
- In intracellular vesicle
- Degraded in vesicle
- Loaded into MHC II (in MIIC)
- Presented to CD4+ T cells
Describe the three signals required for antigen presentation
Signal 1: TCR-MHC interaction
Signal 2: Co-stimulation
• CD80, CD86 and CD28
Signal 3: Release of soluble factors from DC (e.g. cytokines)
