The human immune system consists of cells spread throughout the body, and these cells need to interact and communicate with each other to function properly. Despite their potential for medical treatments, understanding of these cell interactions on their surfaces was still incomplete.
Now, in a scientific breakthrough, research from the Hull York Medical School and led by the Wellcome Sanger Institute, has mapped the human immune system for the first time.
The research has shed light on the intricate web of interactions that occur on the surface of immune cells, providing a molecular understanding of how these cells communicate with each other.
This breakthrough in mapping the human immune system's interactions opens the door to the development of targeted therapies and medicines for a wide range of conditions, including cancer treatment, infectious diseases, and autoimmune disease.
A physical wiring diagram for the human immune system. Image courtesy of Nature.
A physical wiring diagram for the human immune system. Image courtesy of Nature.
The human immune system is a complex network of approximately 40 different cell types, collectively known as white blood cells, each with distinct functions. These migratory cells are distributed across various areas of the body including the spleen, bone marrow, lymph nodes, and tonsils, working together to create effective immune responses against pathogens such as viruses, bacteria, and cancer cells.
The key to a well-functioning immune system lies in the coordination of these diverse cells. This communication primarily occurs through proteins present on the surface of the cells. These proteins play a pivotal role in recognising and responding to different environmental cues, helping the immune system distinguish between healthy and harmful cells.
Professor Gavin Wright, Professor of Microbial Biochemistry at Hull York Medical School and co-lead of the study, has a long-standing interest in the mechanisms of cellular communication.
He explains, "One of the ways that cells interact with each other is through direct interactions with proteins that are displayed on the surface. Those proteins are the ones that I'm really fascinated with, and particularly the interactions that they form with other similar proteins on the surface of other cells."
Potential future clinical benefits
The discovery has shed light on many previously unknown interactions between immune cells across the body, and an insight into the organisation of the body's immune defences.
The knowledge gained from mapping these interactions has significant potential in medicine. One of the most promising applications is for the development of therapeutic monoclonal antibodies which can target cell surface proteins and their interactions.
Professor Wright acknowledges that having this knowledge about the immune system opens up exciting possibilities for clinical benefits by targeting specific cell surface receptors.
"It's a significant advancement in the medical industry" Pictured: Professor Gavin Wright
"It's a significant advancement in the medical industry" Pictured: Professor Gavin Wright
He explained, “The technology to create therapeutic monoclonal antibodies is well-established. By identifying the interactions between cell surface receptor proteins and using monoclonal antibodies to target them, we have the potential to develop new medicines.”
Therapeutic monoclonal antibodies can treat various diseases, including cancer and autoimmune disorders, by modulating immune responses.
Next steps
Professor Wright and his team are now expanding their library of proteins to further investigate host-pathogen interactions, particularly with infectious agents like the malaria-causing Plasmodium parasites.
Professor Wright explained, “These parasites can persist in the body for a long time, evading the immune system by displaying their own proteins on infected cells, which then interact with surface proteins on white blood cells. This interaction can dampen the immune response or even switch it off.
“Understanding how parasites dampen the immune system could offer valuable insights into developing treatments for autoimmune diseases"
"We aim to decipher the mechanisms behind this process to find ways to modulate the immune response in a controlled manner, just as the parasite does."
The research team has secured a grant to expand their collection of proteins for further study. In their previous research paper, they explored approximately 600 different proteins present on the surface of white blood cells. However, they are aware that there are numerous other proteins of this type encoded in the human genome, and these proteins are also found in various cell types, including neurons, skin cells, and muscle cells.
With the newly acquired funding, the research aims to broaden their library of proteins over the next few years. The primary objective of this expansion is to investigate how pathogens, responsible for causing diseases and infections, interact with human cells. The researchers seek to understand the mechanisms through which these pathogens recognise specific cell types and, in certain cases, invade host cells.
Collaborating with experts in virology, bacteriology, mycology, and parasitology, the team aims to gain comprehensive insights into host-pathogen interactions. By delving into these interactions, they hope to identify potential targets for combating infectious diseases and enhancing our understanding of pathogen behaviour.
Making the research open to all
Professor Wright’s vision for this research is to make it accessible to all and contribute to the development of novel therapies for a range of diseases.
Although the majority of this groundbreaking work was carried out in his previous role at the Wellcome Sanger Institute, Professor Wright, along with first author and collaborator Dr Jarrod Shilts from the Institute, hopes that their efforts will pave the way for a more comprehensive understanding of the immune system and its potential for medical advancements.
"We want this to be accessible to everybody, so that everyone no matter where they live in the world can benefit from our research"
Professor Wright said, “This is the start of a new era of developing new, targeted medicines."
A physical wiring diagram for the human immune system is published in Nature. The research was funded by Wellcome and the Swiss National Science Foundation.
For more information about the study, please contact Professor Gavin Wright. Professor Wright is a member of the Experimental Medicine and Biomedicine research group.