Presentation is loading. Please wait.

Presentation is loading. Please wait.

Regulation of Human Immune System by TMED7 Christs College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry.

Similar presentations


Presentation on theme: "Regulation of Human Immune System by TMED7 Christs College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry."— Presentation transcript:

1 Regulation of Human Immune System by TMED7 Christs College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry

2 What is Biochemistry?

3 PROTEINS!

4 Immunity Germs!!! Bleurgh.. Innate immune response Adaptive immune response Vaccination Antibodies Specific Outside Inside Physical and chemical barriers e.g. skin, mucous membrane

5 Immunity Germs!!! Bleurgh.. Innate immune response Non-specific Acute response Requires pattern- recognition receptors (PRRs) Adaptive immune response Outside Inside Physical and chemical barriers e.g. skin, mucus membrane

6 Innate Immunity Outside of cell Cell surface

7 Members of Toll-like receptor family in human Kanzler et. al., Nature Medicine Vol. 13, No. 5, May 2007

8 Birth of proteins Nucleus DNA RNA Protein Golgi apparatus Rough Endoplasmic Reticulum Mature proteins

9 Receptor signalling Signal Receptor, e.g. TLR4 Message is relayed involving many proteins Nucleus Output: production of certain proteins in response to the signal Information arrival Information detection

10 TLR4 signalling There are two distinct pathways TLR4 Mal-MyD88 NF-κB transcription factor Inflammation TLR4 TRAM-TRIF IRF3 transcription factor Antiviral response Plasma membraneEndosomes

11 11 Toll-like receptor 4 signalling TLR4 CD14 MD2 Early endosome Antiviral response Inflammation Cell surface LPS

12 How do you control TLR4 activity? TMED7? Control their production?Control their activity once they have been produced and activated? Pre-activation Post-activation

13 What is TMED7? GOLD domain Coiled-coil region for binding to itself Membrane The tail contains a post code information

14 Results

15 TMED7 makes a physical contact with TLR4 GOLD domain Coiled-coil region for binding to itself Membrane Surface where the contact is made

16 How does TMED7 control TLR4?

17 Experiment #1 TMED7 sends TLR4 to the correct place

18 Inflammation

19

20

21 Antiviral

22 Summary Increasing TMED7 on its own can elevate both the inflammation and antiviral responses without signal from LPS But this has very little/ no effects on LPS- stimulated activations of both pathways Hypothesis: TMED7 sends TLR4 to the correct places, therefore increases the availability of TLR4

23 TMED7? Hypothesis Protein productionMessage relay process

24 Experiment #2

25 Endosome/ ER lumen Cytoplasm Full length (TMED7) GOLD domain + coiled coil domain (CC) GOLD domain (GOLD)

26 Antiviral

27 Inflammation

28

29 Inflammation response Without signal from LPS

30 Hypothesis Protein productionMessage relay process

31 ??? Postcode-less TMED7 (CC)

32 Summary TLR4 is important for detecting attacking pathogens by recognising bacterial components Signal from LPS leads to rapid innate immune responses such as inflammation, redness, fever This activity can be controlled pre- or post- LPS signal TMED7 makes a physical contact with TLR4 TMED7 acts as a birth controller/ chaperone of TLR4 and hence regulating TLR4s activity pre-LPS signal

33 Relevance? Innate immunity is a bridge to adaptive immunity Hey, I just met you, and this is crazy. But heres a germ, so kill it in the future, maybe? Sure! Innate immunityAdaptive immunity

34 Relevance? Inflammation versus antiviral responses How much inflammation do we need? – Septic shock – Autoimmune diseases Exploiting the pathways so we can get a more favourable outcome?

35 Thanks for not falling asleep! Questions?


Download ppt "Regulation of Human Immune System by TMED7 Christs College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry."

Similar presentations


Ads by Google