Delving deeper into the aging immune system

Scientists have managed to describe mechanisms of immune aging by studying the tonsils of people of different ages.

The research, carried out by specialists from the National Council of Scientific and Technical Research (CONICET) and the University of Buenos Aires (UBA), both entities in Argentina, focused on the aforementioned lymphatic organs, which are considered the first line of defense of the immune system. The advance will contribute to better understanding the differences in susceptibility to different pathogens between children and adults and also provides useful data for the development of vaccines.

Until now, the cellular mechanisms that determine why a marked decrease in the size of the tonsils begins at puberty, tissues considered “immune barracks” located at the intersection of the oral and nasal cavities that provide protection to the respiratory tract. high.

Now, the aforementioned study has managed to reveal cellular mechanisms that are determining factors in the changes that occur in these lymphatic organs depending on age.

“Our work helps understand the differences in susceptibility to pathogens between children and adults and also provides cellular and molecular information that could influence the development of oral and nasal spray-based vaccines intended to be applied to those mucosal sites (the tonsils). so that they act against different infections,” highlights Eloísa Arana, leader of the study and CONICET researcher at the Institute of Immunology, Genetics and Metabolism (INIGEM, CONICET-UBA) located at the Hospital de Clínicas José de San Martín – UBA.

According to the researcher, the information obtained in the new study improves the understanding of the variability in the symptomatic infection presented by different age groups to pathogens such as the Epstein Barr virus and/or the SARS-CoV-2 coronavirus. “For example, the tonsillar decay that we documented in adults may be an influential factor in the higher frequency of symptoms caused by SARS-CoV-2 in that age group compared to children. The route of infection of this virus is precisely the oronasopharyngeal mucosa (nose and mouth),” explains Arana, doctor in Biochemistry and Molecular Biology, director of the B lymphocyte Physiopathology Laboratory of the INIGEM and professor of Human Immunology at the Faculty of Medicine of the UBA.

Microscopy image of germinal centers (“factories” of B lymphocytes) that are located in the tonsils. (Photo: CONICET)

First line of defense of the immune system

The tonsils contain germinal centers that are “factories” of the body’s antibodies because they are sites of proliferation of B lymphocytes, cells responsible for identifying the presence of pathogens and responding accordingly.

Using complex immune techniques and other procedures, the research team analyzed cells isolated from biopsies of 95 tonsils from patients between 2 and 39 years of age treated in the Division of Pediatric Otorhinolaryngology of the Hospital de Clínicas (UBA) and in the Arauz Otorhinolaryngological Institute.

The main discovery of the work led by the team of scientists from CONICET and the UBA was the detection of a particular type of B cells, called “CD39highCD73+ B cells”, which accumulate with age and whose function has to do with the suppression of immunity. “They are B lymphocytes specialized in degrading inflammatory mediators and generating anti-inflammatory molecules,” explains Rocío Pastor, first author of the work and doctoral fellow at INIGEM.

“Likewise, we discovered a correlation between the accumulation of these cells that regulate immune function and the decrease in the size and number of germinal centers, an issue that we also characterized in the study as a manifest phenomenon after approximately 10 years of age,” Arana points out.

The research team showed that the tonsils are also sites of accumulation of “memory B cells” with age. “Memory B lymphocytes guarantee protection against known pathogens, that is, those that infected the body in the past. These immune cells are capable of ‘remembering’ that pathological agent and inducing a more rapid production of antibodies in future infections,” explains Juliana Puyssegur, who began this study for her degree thesis at the INIGEM and is currently a doctoral fellow at the Institute of Medicine. Experimental (IMEX, CONICET – National Academy of Medicine). And she adds: “This means that the greater susceptibility presented by adults is not for long-standing pathogens in the individuals’ environmental environment but for pathogens unknown to the adult individual.”

The ideal vaccines to prevent upper respiratory tract infections “would be those that can be applied to the entrance mucosa itself in the form of a spray, for example,” explains Arana. And he continues: “There have been attempts (with mixed results) of similar vaccines for the prevention of influenza. The results of our study also contribute to understanding the difficulty in achieving success by applying vaccines in adults by this route due to the decline in the local immune response capacity depending on age that we revealed in our work.”

The study is titled “Role of germinal center and CD39highCD73+ B cells in the age-related tonsillar involution.” And it has been published in the academic journal Immunity & Aging. (Source: Bruno Geller / CONICET. CC BY 2.5 AR)