Transcript Dendritic cells serve their purpose in our immune system by eating

Dendritic cells serve their purpose in our
immune system by eating and drinking
-phagocytosis versus macropinocytosis and the effect
on the immune response
Louise Henningsen, PhD-student
SEST October 7th 2011
Slide 1
The immunologists on the 5th floor
Hanne Frøkiær, Professor
Stine Metzdorff, Assistent Professor
Gudrun Weiss, post. doc.
Kristina M. Udsen, PhD-student
Dina S. M. Damlund, PhD-student
Lisbeth Drozd Lund, PhD-student
Mathilde B. Kristensen, PhD-student
Anita Nalla, PhD-student
Anni Mehlsen, Lab tech.
Marianne K. Petersen, Lab tech.
Sajeda Hamid Shaltagh, Lab tech. traninee
Eva Fuglsang, M.Sc.-student
Julie La Cour Karottki, B.Sc.-student
Kasper ..... , B.Sc.-student
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Slide 2
Dendritic cells have dendrites
Dendrites
The dendritic cell was
discovered and described by
Ralph M. Steinman in 1973
Fluorescent antibodies
He receives this years Nobel
Confocal microscope
Prize in Medicine.
= we can see the cells!
Sadly he passed away only a
few days before the
announcement 
Image by Julie La Cour Karottki
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Slide 3
When put on a glass slide they try to eat it
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Slide 4
...and 2 movies
What do they do?
•
•
Dendritic cells patrol our bodies to see if there is anything
we should activate our immune system against
They are very important in regulating our immune system
Dendritic cells
in the intestine
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Slide 5
They activate our immune system if needed
3. Activation
1. Recognition and internalisation
2. Interaction
Martien L. Kapsenberg, Nature Reviews Immunology 3, 984-993 (December 2003)
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My interest: 1. Recognition and uptake
Receptors on the surface of the cells recognise
conserved structures on viruses, bacteria, etc.
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Then the cells eat and drink
Phagocytosis = eating
Specific
Makropinocytosis = big gulp
Non-specific
Zipper-like mechanism
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Slide 8
Illustration by: Julie la Cour Karottki
Then the cells eat and drink
Phagocytosis = eating
Specific
Zipper-like mechanism
Araki et al. Journal of Cell Science 116, 247-257
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Slide 9
Makropinocytosis = big gulp
Non-specific
Hypothesis
Depending on the way bacteria is taken
up by the dendritic cell, different
immune responses are initiated
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Some stimuli trigger macropinocytosis
Laser
Macropinocytosis is measured by the amount of
small inert dextran particles the dendritic cells drink
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Illustration by: Julie la Cour Karottki
Some stimuli trigger macropinocytosis
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We can also see this in the microscope
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Now more on the immune response
in the dendritic cells
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Slide 14
The central dogma of molecular biology
DNA
Transcription
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mRNA
Translation
Protein
When we stimulate a cell we get mRNA and protein
Protein
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Slide 16
Kinetics in gene transcription
Interferon-β is a central signaling molecule in viral immunity
Lactobacillus acidophilus is a strong inducer of IFN-β
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Slide 17
Results: Gudrun Weiss
L. Acidophilus alone
...until we activate macropinocytosis before
adding the bacteria
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Slide 18
We can also measure the proteins produced
•
Protein signaling molecules (cytokines and chemokines) are
produced by the dendritic cells to tell the rest of the immune
system to activate or down-regulate
L. Acidophilus alone
Proinflammatory
cytokine
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Formation of signaling platforms
• To make the zipper-like movement many receptors are needed
in close proximity to the bacterium
• Sphingolipids in the cell membrane (ceramide) can form
rafts/domains
• Receptors can be concentrated in these domains
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Slide 20
Illustration by: Julie la Cour Karottki
Hypothesis
• Zipper-like mechanism (phagocytosis)
 A high receptor concentration which may allow
signaling platforms and strong immune responses
• Example: Lactobacillus acidophilus is normally taken
up by phagocytosis
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Slide 21
Illustration by: Julie la Cour Karottki
Hypothesis cont....
• If it it taken up by the macropinocytosis instead
 no concentration of receptors needed
 no signaling platforms are formed
 only a weak IFN- β response
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Slide 22
Illustration by: Julie la Cour Karottki
So this is where we’re at...
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Dendritic cells are very important for keeping a balance in
our immune system
•
To monitor what is present in our body they must eat and
drink what they encounter and respond appropriately to
alert and regulate the immune response
•
There are different ways of eating and drinking, but we
don’t really know what impact these different ways have
But it looks like they may play a very important role!
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Slide 23
Image by Julie La Cour Karottki
Thank you for your attention 
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