Identification of the First Direct Interaction between Trypanosomes and the Host Immune System...
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Transcript of Identification of the First Direct Interaction between Trypanosomes and the Host Immune System...
![Page 1: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/1.jpg)
Identification of the First Direct Interaction between
Trypanosomes and the Host Immune System
Olivia Macleod
![Page 2: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/2.jpg)
![Page 3: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/3.jpg)
African sleeping sickness
Endemic to sub-Saharan Africa
Caused by the parasite Trypanosoma brucei
Transmitted by the tsetse fly
Lives in the bloodstream of humans and livestock
Ineffective treatments
Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen
![Page 4: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/4.jpg)
African sleeping sickness
Endemic to sub-Saharan Africa
Caused by the parasite Trypanosoma brucei
Transmitted by the tsetse fly
Lives in the bloodstream of humans and livestock
Ineffective treatments
Photos: Brun et al. (2010); Prof. Michael Duszenko, Universität Tübingen
![Page 5: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/5.jpg)
How does the parasite avoid detection in our bloodstream and
destruction by our immune systems?
![Page 6: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/6.jpg)
Avoiding the immune system
Immune attack 1 Immune attack 2
Grey destroyedYellow survive and multiply
Yellow destroyedRed survive and multiply
Process continues for many
years
The parasites constantly change their surface coat
![Page 7: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/7.jpg)
How, then, can we target these parasites?
![Page 8: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/8.jpg)
Close-up of parasite surface
Parasite surface: a weak spot
Known surface proteins that take
up essential nutrients from the
bloodstream
Unknown surface proteins
![Page 9: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/9.jpg)
Known surface proteins that take
up essential nutrients from the
bloodstream
Unknown surface proteins
Close-up of parasite surface
Parasite surface: a weak spot
![Page 10: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/10.jpg)
Aim of PhD
To determine the function of these surface proteins in order to obtain a complete understanding of the molecular interaction between the parasite and the host
![Page 11: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/11.jpg)
Identifying novel surface proteins
Human and cattle bloodstream Tsetse fly
Factor H
![Page 12: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/12.jpg)
Importance of discovery
Factor H-binding protein is the first discovery of a direct interaction between the host immune system and this parasite
Blocking the interaction between Factor H and the parasite may prevent its survival in the host
Two additional surface proteins have been discovered that bind components in the bloodstream
Factor H
![Page 13: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/13.jpg)
Commercial application
Progress with company in Cambridge
Producing monoclonal antibodies against two trypanosome surface proteins
Could lead to a targeted treatment against African sleeping sickness
![Page 14: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/14.jpg)
Commercial application
Progress with company in Cambridge
Monoclonal antibody competes/interferes with Factor H binding
Parasite death
Factor H
![Page 15: Identification of the First Direct Interaction between Trypanosomes and the Host Immune System Olivia Macleod.](https://reader030.fdocuments.net/reader030/viewer/2022032523/56649d775503460f94a58c8c/html5/thumbnails/15.jpg)
AcknowledgementsCarrington Lab Members Lab Funding PhD Funding
Magdalene CollegeUniversity of Cambridge
Cambridge Society for the Application of Research