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:
Regulation of Human Immune System by TMED7 Christs College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry
What is Biochemistry?
Immunity Germs!!! Bleurgh.. Innate immune response Adaptive immune response Vaccination Antibodies Specific Outside Inside Physical and chemical barriers e.g. skin, mucous membrane
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
Innate Immunity Outside of cell Cell surface
Members of Toll-like receptor family in human Kanzler et. al., Nature Medicine Vol. 13, No. 5, May 2007
Birth of proteins Nucleus DNA RNA Protein Golgi apparatus Rough Endoplasmic Reticulum Mature proteins
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
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
How do you control TLR4 activity? TMED7? Control their production?Control their activity once they have been produced and activated? Pre-activation Post-activation
What is TMED7? GOLD domain Coiled-coil region for binding to itself Membrane The tail contains a post code information
TMED7 makes a physical contact with TLR4 GOLD domain Coiled-coil region for binding to itself Membrane Surface where the contact is made
How does TMED7 control TLR4?
Experiment #1 TMED7 sends TLR4 to the correct place
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
TMED7? Hypothesis Protein productionMessage relay process
Endosome/ ER lumen Cytoplasm Full length (TMED7) GOLD domain + coiled coil domain (CC) GOLD domain (GOLD)
Inflammation response Without signal from LPS
Hypothesis Protein productionMessage relay process
??? Postcode-less TMED7 (CC)
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
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
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?