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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. Louise Henningsen, PhD-student. The immunologists on the 5th floor . Hanne Frøkiær, Professor Stine Metzdorff, Assistent Professor

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Louise Henningsen, PhD-student

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  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. 3. Activation 1. Recognition and internalisation 2. Interaction Martien L. Kapsenberg, Nature Reviews Immunology 3, 984-993(December 2003) 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. Araki et al. Journal of Cell Science 116, 247-257 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. DNA Transcription Translation The central dogma of molecular biology Protein mRNA

  16. When we stimulate a cell we get mRNA and protein Protein

  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

  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- β response Illustration by: Julie la Cour Karottki

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

  24. Thank you for your attention 

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