Nav: Home

A new model for activation of the immune system

January 23, 2017

By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated. The activation of the C1 protein is a fundamental mechanism in immunology, and therefore the new research results also have medical potential.

An important part of the immune system is the so-called complement system. When the immune system detects a microorganism or other signs of danger, the complement protein C1 is converted into an active enzyme which can cleave other proteins, thus initiating a chain reaction. The end result of this reaction is that, for example, invading pathogenic microorganisms are ingested by our immune cells, and an inflammatory response which leads to the elimination of the microorganisms is triggered. In the past few years, there has been increased focus on the C1 protein, since -- in addition to its function in the immune system -- it has been shown to be closely involved in the development of the nervous system and neurological disorders.

Textbooks in immunology claim that the C1 protein is activated when a very complicated change in the structure within each C1 molecule takes places when it recognises, for example, a pathogenic organism. The new research results from Aarhus University discard this dogma by showing that activation of the complement system occurs when two C1 proteins are located sufficiently close to each other, which is a much more simple and general mechanism.

Close collaboration led to results

The new results were achieved through a close collaboration between four research groups at Aarhus University. First, Postdoctoral Fellow Simon A. Mortensen isolated a special version of the C1 complex with Professor Steffen Thiel from the Department of Biomedicine. Also Professor Jens Christian Jensenius and Laboratory Technician Annette Hansen participated in this work. These samples were analysed with electron microscopy where individual C1 molecules could be identified in collaboration with Associate Professor Bjørn Sander and Associate Professor Monika Golas at the Department of Biomedicine.

"I had carefully optimised my protocol for the preparation of the C1 complex, and it took a long time -- at least a year -- to make the right sample," says Simon A. Mortensen. "But the first time I saw the C1 molecule clearly with Bjørn and Monika, I was so excited, and it was definitely worth the hard work."

In parallel with this, PhD Student Rasmus K. Jensen used X-rays to examine the structure of Simon's C1 protein in solution under the guidance of Professor Gregers Rom Andersen from the Department of Molecular Biology and Genetics with the assistance of Professor Jan Skov Pedersen from the iNANO Center. Jan and Simon made the first measurements in Aarhus with X-rays, while Simon, Rasmus and Gregers collected the best data on the PETRA III Synchrotron in Hamburg, and Rasmus then spent months analysing this data.

"The C1 complex was actually too big and complex for our computer programs to calculate its structure," says Rasmus K. Jensen. "So I obtained a special version for this task. Then I went through many cycles of calculations, and each took two weeks, despite the fact that I used powerful computers."

"The C1 complex is the largest and most complicated protein that I have ever worked with for nearly 30 years. Its structure is very unusual so it has been challenging but also really interesting," adds Professor Gregers Rom Andersen.

The results showed that the old model for the activation of the C1 protein had to be discarded because it was simply physically impossible.

"During the past four to five years, we had the feeling that the old model was not correct," says Professor Steffen Thiel. "Also, three years ago, we demonstrated that a corresponding protein with a similar function in another branch of the complement system was activated in the same way. Therefore, with the new results for the C1 protein, we feel confident in suggesting a general model for activation of complement. Thus, we now have a better understanding of how our immune system works," concludes Steffen Thiel.

The research has been published in the renowned journal Proceedings of the National Academy of Sciences USA (PNAS).
-end-
For further information, please contact

Professor Gregers Rom Andersen
Department of Molecular Biology and Genetics
Aarhus University, Denmark
gra@mbg.au.dk - +45 3025 6646

Professor Steffen Thiel
Department of Biomedicine
Aarhus University, Denmark
st@biomed.au.dk - +45 2927 0890

Aarhus University

Related Immune System Articles:

The immune system may explain skepticism towards immigrants
There is a strong correlation between our fear of infection and our skepticism towards immigrants.
New insights on how pathogens escape the immune system
The bacterium Salmonella enterica causes gastroenteritis in humans and is one of the leading causes of food-borne infectious diseases.
Understanding how HIV evades the immune system
Monash University (Australia) and Cardiff University (UK) researchers have come a step further in understanding how the human immunodeficiency virus (HIV) evades the immune system.
Carbs during workouts help immune system recovery
Eating carbohydrates during intense exercise helps to minimise exercise-induced immune disturbances and can aid the body's recovery, QUT research has found.
A new model for activation of the immune system
By studying a large protein (the C1 protein) with X-rays and electron microscopy, researchers from Aarhus University in Denmark have established a new model for how an important part of the innate immune system is activated.
Guards of the human immune system unraveled
Dendritic cells represent an important component of the immune system: they recognize and engulf invaders, which subsequently triggers a pathogen-specific immune response.
How our immune system targets TB
Researchers have seen, for the very first time, how the human immune system recognizes tuberculosis (TB).
How a fungus inhibits the immune system of plants
A newly discovered protein from a fungus is able to suppress the innate immune system of plants.
A new view of the immune system
Pathogen epitopes are fragments of bacterial or viral proteins. Nearly a third of all existing human epitopes consist of two different fragments.
TB tricks the body's immune system to allow it to spread
Tuberculosis tricks the immune system into attacking the body's lung tissue so the bacteria are allowed to spread to other people, new research from the University of Southampton suggests.

Related Immune System Reading:

How the Immune System Works (The How it Works Series)
by Lauren M. Sompayrac (Author)

How the Immune System Works has helped thousands of students understand what’s in their big, thick, immunology textbooks. In his book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject.

In fifteen easy-to-read chapters, featuring the humorous style and engaging analogies developed by Dr. Sompayrac, How the Immune System Works explains how the immune system players work together to protect us from disease – and, most importantly, why they do it this way.

Rigorously updated for this fifth... View Details


The Immune System Recovery Plan: A Doctor's 4-Step Program to Treat Autoimmune Disease
by Susan Blum (Author), Mark Hyman (Foreword), Michele Bender (Foreword)

One of the most sought-after experts in the field of functional medicine shares her proven four-step program to treat, reverse, and prevent autoimmune conditions and repair your immune system.

• Are you constantly exhausted?

• Do you frequently feel sick?

• Are you hot when others are cold, or cold when everyone else is warm?

• Do you have trouble thinking clearly, aka “brain fog”?

• Do you often feel irritable?

• Are you experiencing hair loss, dry skin, or unexplained weight fluctuation?

• Do your joints ache or... View Details


The Immune System, 4th Edition
by Peter Parham (Author)

The Immune System, Fourth Edition emphasizes the human immune system and presents immunological concepts in a coherent, concise, and contemporary account of how the immune system works. Written for undergraduate, medical, veterinary, dental, and pharmacy students, it makes generous use of medical examples to illustrate points. This classroom-proven textbook offers clear writing, full-color illustrations, and section and chapter summaries that make the book accessible and easily understandable to students.

The Fourth Edition is a major revision that brings the content... View Details


Basic Immunology: Functions and Disorders of the Immune System, 5e
by Abul K. Abbas MBBS (Author), Andrew H. H. Lichtman MD PhD (Author), Shiv Pillai MBBS PhD (Author)

In this updated edition of Basic Immunology, the authors continue to deliver a clear, modern introduction to immunology, making this the obvious choice for today's busy students. Their experience as teachers, course directors, and lecturers helps them to distill the core information required to understand this complex field. Through the use of high-quality illustrations, relevant clinical cases, and concise, focused text, it's a perfectly accessible introduction to the workings of the human immune system, with an emphasis on clinical relevance.... View Details


The Immune System, 3rd Edition
by Peter Parham (Author)

The Immune System, Third Edition emphasizes the human immune system and synthesizes immunological concepts into a comprehensible, up-to-date, and reader-friendly account of how the immune system works. 

Written for undergraduate, medical, veterinary, dental, and pharmacy students in immunology courses, it makes generous use of medical examples to illustrate points. 

The Third Edition has been extensively revised and updated and includes two new chapters on innate and adaptive immunity, which explore the physical, cellular, and molecular principles... View Details


The Immune System
by Peter Parham (Author)

The Immune System, Second Edition has been designed for use in immunology courses for undergraduate, medical, dental, and pharmacy students. This class-tested and successful textbook synthesizes the established facts of immunology into a comprehensible, coherent, and up-to-date account of how the immune system works, rather than presenting immunology as a chronology of experiments and discoveries. Emphasizing the human immune system the text has been designed to break down the barriers which often divide basic and clinical immunology. The reader-friendly text, section and chapter... View Details


The Immune System: A Dewey Decimal novel (Akashic Urban Surreal Series)
by Nathan Larson (Author)

"This final installment of the Dewey Decimal trilogy capably stands alone as a quirky, sparkly read that will embiggen your cerebellum."
--Library Journal

"Larson treats the English language as a sort of toy to play with and use for experimentation; language is not just used to tell the story, in other words, but is a part of the story, an extension of its narrator, Dewey Decimal, one of the more offbeat characters in fiction. A fitting conclusion to a unique and memorable trilogy."
--Booklist

"A sharp and satisfying conclusion to one of the... View Details


Immune System: 101 Natural Ways to Boost your Immune System, Fight Germs, and Live a Healthy Life
by Living in Health (Author)

BOOST YOUR IMMUNE SYSTEM! 101 NATURAL WAYS TO BOOST YOUR IMMUNE SYSTEM, FIGHT GERMS, AND LIVE A HEALTHY LIFE Your immune system is the body’s only line of defense against both foreign and internal threats. It is clear therefore that you must maintain your immune system in the best possible condition for optimal health. It is not a myth that some foods are better than others at boosting our immunity. If you were ever wondering what might be the best foods in the world to help keep your immune system in the best shape, then this book is simply the way to go. It really helps to have a great... View Details


The Immune System: A Very Short Introduction (Very Short Introductions)
by Paul Klenerman (Author)

The immune system is central to human health and the focus of much medical research. Growing understanding of the immune system, and especially the creation of immune memory (long lasting protection), which can be harnessed in the design of vaccines, have been major breakthroughs in medicine.

In this Very Short Introduction, Paul Klenerman describes the immune system, and how it works in health and disease. In particular he focuses on the human immune system, considering how it evolved, the basic rules that govern its behavior, and the major health threats where it is... View Details


The Immune System Cure: Optimize Your Immune System in 30 Days-The Natural Way!
by Lorna Vanderheaghe (Author)

What causes one person to catch a cold or flu and another to avoid it? Why do serious outbreaks of infectious diseases leave some individuals untouched? What allows someone to be incapacitated by allergies? The answer lies within nature itself-our immune system. The Immune System Cure provides simple techniques for supercharging your immune system to resist and prevent disease. Through diet, exercise, stress reduction and nutritional supplements, including plant sterols and sterolins, you can harness the power of your immune system in just 30 days and help it combat: Antibiotic-resistant... View Details

Best Science Podcasts 2017

We have hand picked the best science podcasts for 2017. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Simple Solutions
Sometimes, the best solutions to complex problems are simple. But simple doesn't always mean easy. This hour, TED speakers describe the innovation and hard work that goes into achieving simplicity. Guests include designer Mileha Soneji, chef Sam Kass, sleep researcher Wendy Troxel, public health advocate Myriam Sidibe, and engineer Amos Winter.
Now Playing: Science for the People

#448 Pavlov (Rebroadcast)
This week, we're learning about the life and work of a groundbreaking physiologist whose work on learning and instinct is familiar worldwide, and almost universally misunderstood. We'll spend the hour with Daniel Todes, Ph.D, Professor of History of Medicine at The Johns Hopkins University, discussing his book "Ivan Pavlov: A Russian Life in Science."