Immune cells teach each other to distinguish pathogens from body’s own cells

A team of scientists from the Institute of Molecular Genetics of the CAS has succeeded in identifying one of the principles by which our immune cells distinguish pathogens from the body’s own cells. The distinction is made by way of a system that scientists have likened to a “mail order service”. Teaching cells intentionally transfer information to those cells learning how to recognise safe molecules. The study was published in the prestigious eLife scientific journal.

The properly functioning immune system of a living organism requires balance. White blood cells, specifically T lymphocytes, must protect it from pathogens, but at the same time they must avoid triggering harmful reactions and attacking the body itself. Such aggressive reactions can manifest in a number of autoimmune diseases, such as type 1 diabetes, multiple sclerosis, or various types of allergies.

In order for T lymphocytes to reliably distinguish pathogens from the body’s own cells, they undergo a training of sorts. This occurs in the thymus gland. In this small but important organ located between the sternum and the lungs, it is the thymic epithelial cells and dendritic cells which are mainly responsible for the training process. These cells present the white blood cells with various molecules, called antigens, that originate from within the body. Through this process, the T lymphocytes learn to recognise and not attack them.

Dominik Filipp, Head of the Department of Immunobiology, Institute of Molecular Genetics of the CAS (CC)

The delicate relationship between dendritic cells and a functioning immune system is well-known to scientists. “The surface of thymic cells is covered with special receptors that recognise bacterial and viral components. We switched these off in mouse models and observed what happened,” Matouš Vobořil from Dominik Filipp’s team notes, describing the research in the Czech-language AΩ / Věda pro každého magazine. “They became very sick and more prone to develop inflammatory bowel disease, diabetes, and other autoimmune diseases.”

Immune cell packages have their recipients
To molecular geneticists, it's also no secret that these dendritic cells interact with each other and exchange their own antigens. The system functions on the basis of the training cells already possessing some type of antigens. These distributor cells then transfer the antigens to other cells (the recipients). Antigen distribution thus resembles a delivery or file transfer service for the immune system.

A team of scientists led by Dominik Filipp from the Institute of Molecular Genetics of the CAS has succeeded in proving that this distribution is by no means random. In fact, certain cells intentionally decide where and to whom to send the antigens and who will be the recipient, living up to its delivery service analogy.

The moment of antigen distribution from training cells (orange) to recipient cells (green). Fig. 1: active communication between cells. In Fig. 2, the training cell dies and breaks down into small parts containing antigens that are gradually distributed and absorbed by the recipients, as shown in Fig. 3.

In their study, the researchers pointed out that the training of T lymphocytes is significantly influenced by which cells distribute and which receive the antigens in every case. “Using mouse models, our team was able to demonstrate that in antigen transfer, preferential pairing occurs between certain thymic cell populations,” Dominik Filipp explains the study’s conclusions. “In addition, we were able to identify a population of activated dendritic cells that are most efficient at receiving antigens from thymic cells.”

Molecular geneticists have thus succeeded in clarifying how exactly the cell training process occurs and how certain relationships work within the distribution network. They have also proven that a single dendritic cell can acquire antigens from two or more thymic epithelial cells and, conversely, that two dendritic cells can function as both distributor and recipient within a single antigen transfer. The findings of their study represent the next step in the research of immune system functions and may contribute to the understanding of the formation of autoimmune diseases.

Text: Jan Hanáček, Division of External Relations, CAS
Photo: Shutterstock; Institute of Molecular Genetics of the CAS
Texts and photographs labelled (CC) are released for use under the Creative Commons license.

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