regulation of human immune system by tmed7
Download
Skip this Video
Download Presentation
Regulation of Human Immune System by TMED7

Loading in 2 Seconds...

play fullscreen
1 / 35

Regulation of Human Immune System by TMED7 - PowerPoint PPT Presentation


  • 313 Views
  • Uploaded on

Regulation of Human Immune System by TMED7. Christ’s College ERSS 4 th September 2012 Ardi Liaunardy-Jopeace Prof. Nick Gay Lab Department of Biochemistry. What is Biochemistry?. PROTEINS!. Immunity. Physical and chemical barriers e.g. skin, mucous membrane. Adaptive immune response

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' Regulation of Human Immune System by TMED7' - makala


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
regulation of human immune system by tmed7

Regulation of Human Immune System by TMED7

Christ’s College ERSS

4th September 2012

ArdiLiaunardy-Jopeace

Prof. Nick Gay Lab

Department of Biochemistry

immunity
Immunity

Physical and chemical barriers

e.g. skin, mucous membrane

  • Adaptive immune response
  • Vaccination
  • Antibodies
  • Specific
  • Innate immune response

Germs!!! Bleurgh..

Outside

Inside

immunity1
Immunity
  • Innate immune response
  • Non-specific
  • Acute response
  • Requires pattern-recognition receptors (PRRs)

Physical and chemical barriers

e.g. skin, mucus membrane

Adaptive immune response

Germs!!! Bleurgh..

Outside

Inside

innate immunity
Innate Immunity

Outside of cell

Cell surface

members of toll like receptor family in human
Members of Toll-like receptor family in human

Kanzler et. al., Nature Medicine Vol. 13, No. 5, May 2007

birth of proteins
Birth of proteins

Mature proteins

Rough Endoplasmic Reticulum

Golgi apparatus

Nucleus

DNA RNA Protein

receptor signalling
Receptor signalling

Information arrival

Signal

Receptor, e.g. TLR4

Information detection

Message is relayed involving many proteins

Output: production of certain proteins in response to the signal

Nucleus

tlr4 signalling
TLR4 signalling

There are two distinct pathways

TLR4

Mal-MyD88

NF-κB transcription factor

Inflammation

TLR4

TRAM-TRIF

IRF3 transcription factor

Antiviral response

Plasma membrane

Endosomes

slide11

Toll-like receptor 4 signalling

CD14

LPS

MD2

Cell surface

TLR4

Early endosome

Inflammation

Antiviral response

slide12

Pre-activation

Post-activation

How do you control TLR4 activity?

TMED7?

TMED7?

Control their production?

Control their activity once they have been produced and activated?

what is tmed7
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
TMED7 makes a physical contact with TLR4

GOLD domain

Coiled-coil region for binding to itself

Surface where the contact is made

Membrane

summary
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
slide23

Hypothesis

Protein production

Message relay process

TMED7?

TMED7?

slide25

Endosome/ ER lumen

Cytoplasm

GOLD domain + coiled coil domain (CC)

GOLD domain (GOLD)

Full length (TMED7)

slide29

Inflammation response

Without signal from LPS

slide30

Hypothesis

Protein production

Message relay process



slide31

???

Postcode-less TMED7 (CC)

summary1
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 TLR4’s activity pre-LPS signal
relevance
Relevance?
  • Innate immunity is a bridge to adaptive immunity

Hey, I just met you, and this is crazy. But here’s a germ, so kill it in the future, maybe?

Sure!

Innate immunity

Adaptive immunity

relevance1
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?
ad