Scientists used these blocking antibodies to successfully treat mice suffering from chronic lymphatic leukemia. Note: Content may be edited for style and length. Science News. Interrupting the cycle of self-destruction These new findings will help treat autoimmune diseases and lymphatic leukemia in the future: Therapeutic antibodies which block the interaction of RANK receptors and RANKL ligands were originally developed and used to treat osteoporosis: Here the objective is to counteract the deterioration of bone tissue, which is also triggered by hyperactive RANK receptors.
ScienceDaily, 2 February When hyperactive proteins trigger illnesses: Researchers find trigger for autoimmune diseases and cancer of the lymph node. Retrieved November 12, from www. To protect healthy body cells from its own immune system, they have developed a protective shield: the protein CD47 is a so called 'don't eat me' Scientists have now identified a receptor on murine immune cells Stimulating these protective cells could lead to new therapies for Current studies, such as those of Michael Reth, for example, indicate that these antennas are not randomly distributed over the surface of the cell.
Instead, they are bundled together in organized protein islands that coalesce as soon as a foreign substance is bound to a B cell receptor. Minguet and her team have discovered that the protein Caveolin-1 regulates this organization, making it the key to activation of the B cells and the triggering of an immune response.
Without Caveolin-1, the binding of viruses or bacteria to the B cell results in a reduced activation signal, which leads to a weakened immune response. In the body, developing B cells are educated to distinguish the body's own substances from foreign ones.
This process is based on the efficient signal transfer of the B cell receptors. B cells that do not produce Caveolin-1 cannot properly organize the receptor on the cell membrane and as a result, efficient signal transfer fails. It is then that B cells emerge that recognize the body's own tissues. Yet they classify them as foreign, which leads to activation of the B cell and an undesirable immune response which can result in triggering autoimmune disease. The researchers demonstrated this by conducting experiments on mice.
The team's results have the potential to improve the current understanding of autoimmune disease and its treatment -- also because up to now, science has lacked suitable animal models that present the same immune deficiencies that are observed in humans. Note: Content may be edited for style and length. Science News. There they act as homing beacons for specialized assassins called cytotoxic, or killer, T-cells. These cells are the actual agents of destruction, so scientists investigating autoimmunity look for these T cell—autoantibody pairs.
What scientists have recently learned is that although the killer T cells and autoantibodies are signs of an autoimmune problem, their location seems more important than the mere fact of their existence.
Healthy people can have these T cells in their blood, for example, without becoming ill. In immunologist Roberto Mallone of INSERM in France and his colleagues published a study that compared people with type 1 diabetes, others with the type 2 version of the disease a nonautoimmune disorder in which insulin is produced but works badly , and people without either disease.
The levels of killer T cells in the bloodstream were remarkably similar across all three groups, including the nondiabetic people. Everyone had them. But it was a different story in the pancreas.
There, Mallone and his colleagues found, autoreactive T cells were present at much higher levels in people with the type 1 version of the disease. Mallone, like Eizirik before him, suspects that they are there not coincidentally but because of a problem with the target tissue, the beta cells.
Another reason researchers are considering target cells as major players in autoimmune diseases comes from genetic studies, which have shown that genes influencing these diseases are expressed not just by immune cells but also by target cells. Starting in the early s, the complete sequencing of the human genome made it possible to do genome-wide association studies GWAS , which revealed many genes that, when mutated, were linked to higher risk of autoimmune disorders.
And those genes turned up not just in Bcells or T cells but also in cells that were not part of the immune system, Sharma says. For example, nonimmune cells have genes that allow them to release cytokines and chemokines, chemical messengers that summon an immune response.
This activity is quite important for cellular health. All cells are susceptible to transformation into cancers, for instance, or to infection. When such harmful changes happen to cells, Sharma explains, they need to be able to tell the immune system that they are in trouble. But mutations in those genes may create apparent distress signals when the cells are not really damaged. The immune system will react as if they are and swoop in. A study by Eizirik and his colleagues published this past January in Science Advances provides examples of misleading target cells in multiple autoimmune diseases.
The scientists examined published genome association research and found that more than 80 percent of identified genetic variants were expressed by target cells in type 1 diabetes and three other autoimmune diseases: multiple sclerosis, lupus and rheumatoid arthritis. The study showed not only that target cells contain disease-related genes but also that in people with disease, they make more of those proteins than in healthy people.
Eizirik and his colleagues mined genetic databases created from biopsies of affected tissues from people with autoimmune disease: pancreas cells of people with diabetes, joint tissue from people with rheumatoid arthritis, kidney cells from those with lupus and even autopsy samples from the brains of people with multiple sclerosis. Their analysis showed that many candidate genes were exceptionally active in the targeted tissues, and many of these active bits of DNA appeared in multiple diseases, pointing to common threads.
Among the top genes showing extra activity were those related to interferons, a class of proinflammatory cytokines that cells release to flag down immune cells when there is a problem such as a viral infection. Many of the target cells in autoimmune disease also share nongenetic features that make them exceptionally vulnerable to assault.
Second, the cells secrete hormones and other peptides directly into the bloodstream. A third weakness for target cells is that they are penetrated by lots of blood vessels, making them easily accessible.
On top of those vulnerabilities, target cells may react to an outside threat—damage from a virus, for example—in ways that bring on a strong immune response. Some cells self-destruct when infected by a virus, taking themselves out before the harm can spread and before immune system intervention is needed.
But certain cells afflicted in autoimmune diseases, such as neurons and beta cells, are in limited supply. Simply dying off after a viral infection is not an option for them, Eizirik says. Instead they stick around, and the immune system starts interpreting the molecules they release as signs that all cells of that class are in trouble. Then an autoimmune attack ensues.
One striking example of a weakness in target cells that leads to an immune response comes from the blood vessel disease vasculitis.
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