Louise Henningsen, PhD-student

1
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

2
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

3
Dendritic cells have dendrites
Dendrites
The dendritic cell was discovered and described
by Ralph M. Steinman in 1973He receives this
years Nobel Prize in Medicine. Sadly he passed
away only a few days before the announcement ?
Fluorescent antibodies Confocal microscope we
can see the cells!
Image by Julie La Cour Karottki
4
When put on a glass slide they try to eat it
...and 2 movies
5
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
6
They activate our immune system if needed
7
My interest 1. Recognition and uptake
Receptors on the surface of the cells recognise
conserved structures on viruses, bacteria, etc.
8
Then the cells eat and drink
Phagocytosis eating
Makropinocytosis big gulp
Specific Zipper-like mechanism
Non-specific
Illustration by Julie la Cour Karottki
9
Then the cells eat and drink
Phagocytosis eating
Makropinocytosis big gulp
Specific Zipper-like mechanism
Non-specific
10
Hypothesis

• Depending on the way bacteria is takenup by the
  dendritic cell, different immune responses are
  initiated

11
Some stimuli trigger macropinocytosis
Laser
Macropinocytosis is measured by the amount of
small inert dextran particles the dendritic
cells drink
Illustration by Julie la Cour Karottki
12
Some stimuli trigger macropinocytosis
13
We can also see this in the microscope
14
Now more on the immune response in the dendritic
cells
15
The central dogma of molecular biology
mRNA
Protein
16
When we stimulate a cell we get mRNA and protein
Protein
17
Kinetics in gene transcription
Interferon-ß is a central signaling molecule in
viral immunity Lactobacillus acidophilus is a
strong inducer of IFN-ß
Results Gudrun Weiss
18
...until we activate macropinocytosis before
adding the bacteria
L. Acidophilus alone
19
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

Proinflammatory cytokine
L. Acidophilus alone
20
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

Illustration by Julie la Cour Karottki
21
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

Illustration by Julie la Cour Karottki
22
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- ß response

Illustration by Julie la Cour Karottki
23
So this is where were at...

• 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 dont really know what impact these
  different ways haveBut it looks like they may
  play a very important role!

24
Thank you for your attention ?