SEST October 7th 2011Slide 1

Louise Henningsen, PhD-student

Dendritic cells serve their purpose in our immune system by eating and drinking

-phagocytosis versus macropinocytosis and the effect on the immune response

SEST October 7th 2011Slide 2

The immunologists on the 5th floor

Hanne Frøkiær, Professor

Stine Metzdorff, Assistent Professor

Gudrun Weiss, post. doc.

Kristina M. Udsen, PhD-studentDina S. M. Damlund, PhD-studentLisbeth Drozd Lund, PhD-studentMathilde B. Kristensen, PhD-studentAnita Nalla, PhD-student

Anni Mehlsen, Lab tech.Marianne K. Petersen, Lab tech.Sajeda Hamid Shaltagh, Lab tech. traninee

Eva Fuglsang, M.Sc.-studentJulie La Cour Karottki, B.Sc.-student Kasper ..... , B.Sc.-student

SEST October 7th 2011Slide 3

Dendrites

Fluorescent antibodies

Confocal microscope

= we can see the cells!

Image by Julie La Cour Karottki

Dendritic cells have dendrites

The dendritic cell was discovered and described by Ralph M. Steinman in 1973

He receives this years Nobel Prize in Medicine.

Sadly he passed away only a few days before the announcement

SEST October 7th 2011Slide 4

When put on a glass slide they try to eat it

...and 2 movies

SEST October 7th 2011Slide 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

SEST October 7th 2011Slide 6

They activate our immune system if needed

Martien L. Kapsenberg, Nature Reviews Immunology 3, 984-993 (December 2003)

1. Recognition and internalisation

2. Interaction

3. Activation

SEST October 7th 2011Slide 7

My interest: 1. Recognition and uptake

Receptors on the surface of the cells recognise conserved structures on viruses, bacteria, etc.

SEST October 7th 2011Slide 8

Illustration by: Julie la Cour Karottki

Makropinocytosis = big gulpPhagocytosis = eating

Then the cells eat and drink

Specific

Zipper-like mechanism

Non-specific

SEST October 7th 2011Slide 9

Makropinocytosis = big gulpPhagocytosis = eating

Then the cells eat and drink

Specific

Zipper-like mechanism

Non-specific

Araki et al. Journal of Cell Science 116, 247-257

SEST October 7th 2011Slide 10

Hypothesis

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

SEST October 7th 2011Slide 11

Some stimuli trigger macropinocytosis

Macropinocytosis is measured by the amount of small inert dextran particles the dendritic cells drink

Laser

Illustration by: Julie la Cour Karottki

SEST October 7th 2011Slide 12

Some stimuli trigger macropinocytosis

SEST October 7th 2011Slide 13

We can also see this in the microscope

SEST October 7th 2011Slide 14

Now more on the immune response in the dendritic cells

SEST October 7th 2011Slide 15

The central dogma of molecular biology

Transcription TranslationDNA mRNA Protein

SEST October 7th 2011Slide 16

When we stimulate a cell we get mRNA and protein

Protein

SEST October 7th 2011Slide 17

Kinetics in gene transcription

Interferon-β is a central signaling molecule in viral immunity

Lactobacillus acidophilus is a strong inducer of IFN-β

Results: Gudrun Weiss

SEST October 7th 2011Slide 18

...until we activate macropinocytosis before adding the bacteria

L. A

cidophilu

s alo

ne

SEST October 7th 2011Slide 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. A

cidophilu

s alo

ne

SEST October 7th 2011Slide 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

SEST October 7th 2011Slide 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

SEST October 7th 2011Slide 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- β response

Illustration by: Julie la Cour Karottki

SEST October 7th 2011Slide 23

Image by Julie La Cour Karottki

So this is where we’re 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 don’t really know what impact these different ways have

But it looks like they may play a very important role!

SEST October 7th 2011Slide 24

Thank you for your attention