When the body's defense systems sacrifice the long term for short term victories
Even after we have overcome a viral disease, our immune system works at full strength to produce antibodies that give us protection against further exposure. But what happens if while we are recovering from the flu, or God forbid from Corona, we are exposed to another infection - let's say salmonella from the chicken soup we ordered on delivery? In a new study published today in the scientific journal Immunity, scientists from the Weizmann Institute of Science have shown that the immune system has a sophisticated way of determining priorities in the case of different infections occurring one after the other, and that it may "sacrifice" long-term immunity in favor of short-term gains. Understanding these priorities may help develop new treatments for autoimmune diseases.
Our immune system has two arms: the innate system and the acquired system. The innate system - the body's first line of defense - goes into action when it senses the invasion of viruses, bacteria or other pathogens, and quickly neutralizes them using cells and biological substances that provide the body with a broad protective sheet. The acquired system, on the other hand, sometimes takes several days to deploy its soldiers - dedicated cells and antibodies adapted to the various invaders with miraculous precision; These antibodies remain in the body for months and even years and give it long-term protection.
In other words, each of the systems takes center stage at different stages of dealing with the disease. But what happens when two different infections enter the body in close proximity, one after the other, and both arms are forced to be called to the flag at the same time? A research group led by Prof. Ziv Shulman from the institute's immunology department aims to find out how the immune system will deal with a situation where the innate system rolls up its sleeves to fight a new invader, while the acquired one produces antibodies against the previous invader. In a study led by research student Adi Biram, the scientists found that the overlap in the activity of the systems creates a conflict: when mice that had recovered from the flu were infected with salmonella - dealing with the bacterial infection disrupted the production of antibodies to the virus. That is, under a life-threatening threat, the immune system stops the mechanisms necessary for long-term protection and concentrates on the immediate danger.
The scientists discovered that the bacterial infection did not directly lead to the cessation of antibody production. When the salmonella penetrated the lymph nodes of the mice, an "alarm bell" was activated that resonated throughout the body and mobilized cells of the innate system located in the bone marrow and called monocytes. These cells flooded the lymph nodes in an attempt to land a blow on the salmonella, and in the process changed their environment: the antibacterial chemicals secreted by the cells led to conditions of oxygen deficiency.
The cells of the immune system usually know how to adapt to environmental changes of this type and change their metabolism so that they are not dependent on oxygen for energy production - but the researchers discovered that there is a certain subtype of B cells for which the lack of oxygen becomes fatal. These cells play a central role in the operation of the acquired system: they are the ones that produce the antibodies that are optimally suited to the invaders within microscopic structures in the lymph nodes called "germinal centers". These cells do not change their metabolism in response to the lack of oxygen, and as a result they suffocate and die. In the absence of these cells, the production of antibodies necessary for long-term protection against the influenza virus ceases.
"When you have to fight life-threatening bacteria, you don't deal with long-term protection," explains Prof. Shulman. "Overcoming salmonella takes priority because it's a matter of survival."
Beyond a better understanding of how the immune system works, the new findings may help us to help the body's defense systems. For example, it is known that in order to increase the effectiveness of certain vaccines given today, it is customary to add proteins derived from bacteria to them; Judging by the new findings, it is possible that this practice may harm the purpose for which the vaccine is given: the production of antibodies. In addition, if the research results are also demonstrated in humans, they may mark a new therapeutic direction in autoimmune diseases. In diseases such as rheumatoid arthritis or lupus, the incorrect production of antibodies causes the immune system to act against the body itself. Possible treatments may recruit the monocytes from the bone marrow, thus leading to the cessation of the production of the harmful antibodies.
Jingying Liu, Dr. Hadas Hatzroni, Dr. Natalia Davidson, Dr. Dominique Schmidel, Dr. Iman Khatib-Masalha, Montser Haddad, Dr. Amelia Granov, Prof. Zvi Lapidot and Prof. Stefan Jung from the Institute's Department of Immunology; Sasha Levon, Dotan Hoffman and Dr. Roy Avraham from the institute's biological control department; Dr. Tomer Meir Selma from the Department of Life Science Research Infrastructures; Dr. Neely Dzorla from the Department of Chemical Research Infrastructures; Paula Abu Kerem from the Department of Biomolecular Sciences; and Prof. Mark Bamark from Gothenburg University in Sweden.
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