Cholesterol boosts the memory of the immune system
December 24, 2012 in Immunology
In a naive cell (left), the receptors (blue) on the membrane are arranged individually. Pathogens (yellow) must bind to many receptors in order to activate the immune defense. In a memory cell (right), the receptors are joined together by cholesterol (red). When a pathogen binds one receptor of a cluster, all of the receptors within the cluster are activated. © Schame
The memory of the human immune system is critical for the development of vaccines. Only if the body recognizes a pathogen with which it has already come into contact in the case of a second infection, the immune system can combat it more effectively than it did the first time. The Freiburg immunobiologist Prof. Dr. Wolfgang Schamel from the Institute of Biology III of the University of Freiburg and his colleagues have succeeded in demonstrating how the memory of the immune system functions. Their findings have now been published in the journals Immunity and Journal of Biological Chemistry (JBC).
The immune system becomes acquainted with a pathogen during an initial infection and understands that it must be combated. When the T cell receptors of the immune system come across the same pathogen a second time, they are much more sensitive toward them than during the first encounter, and it thus takes less pathogens to activate the immune system. It was previously unclear why the receptors become more sensitive.
In 2011, Schamel's research group and a team led by Prof. Dr. Balbino Alarcon from the Autonomous University of Madrid, Spain, found the answer to this fundamental question. In a publication in the journal Immunity, they showed that the increased sensitivity is caused by a clustering of the T cell receptors: In a naive cell that has not yet met the pathogen, the receptors are arranged individually on the cell membrane, each fending for itself. A large number of receptors thus needs to be confronted by a large number of pathogens in order for the immune system to react. In a so-called memory cell, which remembers the pathogen, the receptors are arranged in groups on the membrane. When a pathogen binds to a receptor from a cluster, all of the receptors within the cluster are activated at once. This makes the immune system more sensitive.
Now, as reported in the journal JBC, a team of researchers in Freiburg under Schamel and Prof. Dr. Rolf Schubert, professor for pharmaceutical technology and biopharmaceutics at the Institute of Pharmaceutical Sciences of the University of Freiburg, have succeeded in demonstrating how a cell forms these receptor clusters. The critical factors for the success of this endeavor were Schamel's expertise in biochemical research on T cell receptors and Schubert's expertise in the production of liposomes. The collaboration between the two teams was made possible by a project funded by BIOSS Centre for Biological Signalling Studies, a Cluster of Excellence at the University of Freiburg.
Dr. Eszter Molnár, a postdoctoral researcher in Schamel's team, and Dr. Martin Holzer from Schubert's research group isolated the receptors and reconstructed them in a synthetic membrane. After one and a half years of work, the scientists achieved a breakthrough: They discovered that the composition of the lipids of a membrane is responsible for the clustering of the receptors. The lipid composition of a naive cell differs from that of a memory cell. Cholesterol is the key factor in this process, as it is present in higher concentrations in a memory cell. This higher concentration of cholesterol leads to the aggregation of receptors, because the cholesterol joins them together like glue.
Schamel and Schubert are members of the Freiburg Cluster of Excellence BIOSS Centre for Biological Signalling Studies. Schamel is also a member of the Spemann Graduate School of Biology and Medicine and the Center for Chronic Immunodeficieny of the Freiburg University Medical Center and director of the EU network SYBILLA, which also supported this project.
More information: Increased Sensitivity of Antigen-Experienced T Cells through the Enrichment of Oligomeric T Cell Receptor Complexes, Immunity, Volume 35, Issue 3, 375-387, 08 September 2011, www.cell.com/immun… 761311003566
Cholesterol and Sphingomyelin Drive Ligand-independent T-cell Antigen Receptor Nanoclustering, First Published on October 22, 2012, doi: 10.1074/jbc.M112.386045 December 14, 2012 The Journal of Biological Chemistry, 287, 42664-42674. http://www.jbc.org/cgi/doi/10.1074/jbc.M112.386045
Journal reference:
Immunity
Journal of Biological Chemistry
Provided by
Albert Ludwigs University of Freiburg
-
One lock, many keys
Oct 06, 2010 |
not rated yet |
0
-
Blood cancer cells initiate signalling cascade
Aug 13, 2012 |
not rated yet |
0
-
A crucial link in immune development and regulation unearthed
Oct 13, 2010 |
not rated yet |
0
-
Researchers discover a new basic principle of the mitochondria architecture
Sep 14, 2012 |
not rated yet |
0
-
The connection between a cell's cytoskeleton and its surface receptors
Mar 06, 2011 |
not rated yet |
0
-
Motion perception revisited: High Phi effect challenges established motion perception assumptions
Apr 23, 2013 |
3 / 5 (2) |
2
-
Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update)
Apr 02, 2013 |
4.5 / 5 (11) |
5
-
The visual system as economist: Neural resource allocation in visual adaptation
Mar 30, 2013 |
5 / 5 (2) |
9
-
Separate lives: Neuronal and organismal lifespans decoupled
Mar 27, 2013 |
4.9 / 5 (8) |
0
-
Sizing things up: The evolutionary neurobiology of scale invariance
Feb 28, 2013 |
4.8 / 5 (10) |
14
-
Magnetic field lines through copper
4 hours ago
-
Lagrangian of object with air resistance
7 hours ago
-
Does electromagnetic waves are generated by dc current?
7 hours ago
-
Please check what's in the Ulaby book regarding reflection.
11 hours ago
-
Question in reflection and transmission at oblique incidence.
15 hours ago
-
Is this plasma (picture in thread)
16 hours ago
- More from Physics Forums - Classical Physics
More news stories
Pollen count apps for smartphones are nothing to sneeze at
Kate O'Reilly's spring allergy survival kit includes the usual stuff - nasal sprays, allergy pills and a box of tissues. This season, she's added a new weapon to her line of defense: an app on her smartphone.
Immunology
19 hours ago |
not rated yet |
0
Going live: Immune cell activation in multiple sclerosis
Biological processes are generally based on events at the molecular and cellular level. To understand what happens in the course of infections, diseases or normal bodily functions, scientists would need to ...
Immunology
22 hours ago |
5 / 5 (5) |
0
|
Vaccine blackjack: IL-21 critical to fight against viral infections
(Medical Xpress)—Scientists at Emory Vaccine Center have shown that an immune regulatory molecule called IL-21 is needed for long-lasting antibody responses in mice against viral infections.
Immunology
May 23, 2013 |
5 / 5 (2) |
0
|
Fast-acting mothers' milk for healthier babies
Human breastmilk responds quickly to protect the child when there is an infection in mothers or babies, according to new international research led by The University of Western Australia.
Immunology
May 23, 2013 |
5 / 5 (1) |
0
New immune system discovered
(Medical Xpress)—A research team, led by Jeremy Barr, a biology post-doctoral fellow, unveils a new immune system that protects humans and animals from infection.
Immunology
May 20, 2013 |
4.8 / 5 (29) |
9
|
First drug to improve heart failure mortality in over a decade
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
Heart failure accelerates male 'menopause'
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
Hormone levels may provide key to understanding psychological disorders in women
Women at a particular stage in their monthly menstrual cycle may be more vulnerable to some of the psychological side-effects associated with stressful experiences, according to a study from UCL.
Feds fight morning-after pill age ruling in NY
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
Death highest in heart failure patients admitted in January, on Friday, and overnight
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
Researchers identify first drug targets in childhood genetic tumor disorder
Two mutations central to the development of infantile myofibromatosis (IM)—a disorder characterized by multiple tumors involving the skin, bone, and soft tissue—may provide new therapeutic targets, according to researchers ...