The results advance the current understanding of the way the body’s initial, vague reaction to any invading organism expands into a precise and massive counterattack. That expansion starts when a dendritic cell “swallows” a piece of any invader encountered, ferries it to the nearest lymph node and presents it there for notice by lymphocytes, the workhorse cells of the immune system.
According to the current model, dendritic cells first must encounter T lymphocytes in the paracortex, or T cell zone, within the node. Only there will the interaction enable lymphocytes to expand into an army of clones primed to attack the invader.
To the research team’s great surprise, the data showed that, although immune response works this way during viral flu infections, it is not always the case. When the body is infested with parasitic worms, for instance, dendritic cells link with T cells near B lymphocytes, under the control of B cell-related signals and outside the T cell zone.
“Considering that diseases from asthma to lupus can occur because the system mistakenly ramps up the same types of T cell responses it normally uses against worms, our finding that B lymphocytes control the T cell/dendritic cell interactions that trigger such responses has important, practical implications,” said Frances Lund, Ph.D., chair of the UAB School of Medicine’s Department of Microbiology and corresponding author. “The field now has cause to look at several experimental and existing drugs known to interrupt B cell signals as potential treatments for diseases driven by T cells.”
Before joining UAB in March 2012, Lund worked alongside Tim Mosmann, Ph.D., at the University of Rochester Medical Center. In 1986 Mosmann advanced his groundbreaking theory on the way the immune system decides which sets of immune cells are most effective against different invader types. According to his Th1/Th2 model, Th1 T helper cells were best against viruses because they helped invaded human cells self-destruct before viruses could turn them into virus factories. Th2 helper T cells were best against parasites because they helped the B cells mass produce antibodies that glommed onto and removed worms from the spaces between cells.
The current study found that B cells, as part of the Th2 response to worms, start pumping out a protein called lymphotoxin, which in turn signals nearby stromal cells to produce more of the chemokine CXCL13.
B cells are able to gather in B cell areas of lymph nodes in the first place because they express CXCR5 receptor proteins that sense and move toward higher concentrations of CXCL13. The team discovered that a set of dendritic cells also begins expressing CXCR5 during a worm infection.
With B cells and activated dendritic cells gathered near B cells, T helper cells next must join the party if the immune response is to expand. While T cells dump into lymph nodes at many points, only those that happen to enter near B cells, and to bump into CXCR5-expressing dendritic cells, drive the response to worms forward, according to the authors.
The authors also believe such interactions trap T cells near the B cell area and that proximity determines the kind of cells they becomes next. Those receiving the strongest signals become the T helper follicular cells that B cells must partner with to produce antibodies specific to the current pathogen. Those getting weaker signals become Th2 effectors that travel back to the infection site to cause the histamine release and intestinal muscle contractions that help to expel worms.
Though vital to effective immune responses to worms, T helper follicular cells and Th2 cells have a dark side. For example, T helper follicular cells in some cases inappropriately help B cells produce high affinity “auto” antibodies that recognize the body’s own cells as foreign and can destroy the kidneys of lupus patients and the joints of patients with rheumatoid arthritis.
In other cases, Th2 cells respond to allergens in the lung like house dust mites because the mites look like worms to the immune system and the confused Th2 cells respond to the allergen as they would to a worm. This mistaken recognition causes histamine release and bronchoconstriction in the lungs, two of the major clinical symptoms of asthma.
“We know of experimental biologics that interrupt the ability of B cells to give off lymphotoxin and prevent the development of helper Th2 cells and T helper follicular cells,” Lund said. “Could such antibody-based treatments be useful against some autoimmune diseases and asthma? We think so, but time and further studies will tell.”
Along with Lund, Troy Randall, Ph.D., the Claude Bennett Scholar in the UAB Department of Medicine’s Division of Clinical Immunology and Rheumatology, and UAB post-docs Beatriz León, Ph.D., and André Ballesteros-Tato, Ph.D., made major contributions to the work. Also making important contributions were Jeffrey Browning at Biogen Idec and Robert Dunn at the Pfizer Centers for Therapeutic Innovation (formerly at Biogen Idec). The study was supported by the National Institute of Allergy and Infectious Diseases.
Known for its innovative and interdisciplinary approach to education at both the graduate and undergraduate levels, the University of Alabama at Birmingham is an internationally renowned research university and academic medical center and the state of Alabama’s largest employer with some 18,000 employees and an economic impact of more than $4.6 billion on the state. UAB has been named to the President’s Higher Education Community Service Honor Roll for exemplary service to America’s communities, and in 2008 ranked nationally as one of the top 5 “Best Places to Work in Academia” in a survey published by The Scientist magazine. For more information, please visit www.uab.edu.
EDITOR’S NOTE: The University of Alabama at Birmingham (UAB) is a separate, independent institution from the University of Alabama, which is located in Tuscaloosa. Please use University of Alabama at Birmingham on first reference and UAB on all consecutive references.
VIDEO: www.youtube.com/uabnews TEXT: www.uab.edu/news TWEETS: www.twitter.com/uabnews
Greg Williams | Newswise Science News
Further reports about: > Asthma > B cells > Birmingham > CXCL13 > CXCR5 > Discovery > Immunology > Lupus erythematodes > T cells > T helper cells > T lymphocyte > UAB > autoimmune disease > dendritic cells > flu infection > human cell > immune cell > immune response > immune system > lymph node > muscle contraction > receptor protein
Diabetes mellitus: A risk factor for early colorectal cancer
27.05.2020 | Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg
Ultra-thin fibres designed to protect nerves after brain surgery
27.05.2020 | Martin-Luther-Universität Halle-Wittenberg
Two prominent X-ray emission lines of highly charged iron have puzzled astrophysicists for decades: their measured and calculated brightness ratios always disagree. This hinders good determinations of plasma temperatures and densities. New, careful high-precision measurements, together with top-level calculations now exclude all hitherto proposed explanations for this discrepancy, and thus deepen the problem.
Hot astrophysical plasmas fill the intergalactic space, and brightly shine in stellar coronae, active galactic nuclei, and supernova remnants. They contain...
In living cells, enzymes drive biochemical metabolic processes enabling reactions to take place efficiently. It is this very ability which allows them to be used as catalysts in biotechnology, for example to create chemical products such as pharmaceutics. Researchers now identified an enzyme that, when illuminated with blue light, becomes catalytically active and initiates a reaction that was previously unknown in enzymatics. The study was published in "Nature Communications".
Enzymes: they are the central drivers for biochemical metabolic processes in every living cell, enabling reactions to take place efficiently. It is this very...
Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.
researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
02.06.2020 | Power and Electrical Engineering
02.06.2020 | Architecture and Construction
02.06.2020 | Life Sciences