Immunity Switch: Innate/Acquired
Specialists of the Curie Institute and Dynavax Technologies (California), working under the guidance of Dr. Vassili Soumelis, have identified a previously unknown mechanism that provides the right choice between activating the mechanisms of innate and acquired immunity.
The authors found that the activation of the PI3 kinase enzyme is a necessary condition for the normal functioning of innate immunity. The action of this protein triggers mechanisms that ensure the synthesis of type 1 interferons – the first link in the protection of innate immunity, destroying foreign agents that have entered the body. This discovery provides new therapeutic opportunities, because it indicates possible ways to normalize the functions of innate immunity, overly activated in autoimmune diseases and suppressed in many types of cancer.
The body often faces attacks from the outside (viral and bacterial infections) and sometimes from the inside due to a malfunction of its own cells (cancer) and is protected by activating the immune system. There are two types of protection. The first type – innate immunity – is always on guard, recognizing and destroying abnormal, malignant and virus-infected cells immediately upon their appearance, but is not capable of learning and acts instinctively. Acquired immunity is capable of both "learning" and storing the memory of antigens for years, but it takes more time to launch it, which is necessary for "familiarization" (sensitization) with the enemy of immune cells and the formation of a population of lymphocytes aimed at a specific target.
The first intruders into the body of strangers are recognized by dendritic cells, which, depending on the situation, trigger the mechanisms of innate or acquired immunity. When encountering a foreign agent, dendritic cells either synthesize a large number of interferons that trigger rapid immune reactions aimed at destroying viruses, or "specialize" and set up the immune system to fight a certain pathogen.
Scientists have deciphered the mechanism by which dendritic cells regulate the launch of two types of immune response. First, regardless of the situation, the presence of the pathogen stimulates the TLR receptor located inside the dendritic cells. After that, depending on the nature of the pathogen, the cell makes a choice. When it is necessary to trigger the mechanisms of the innate immune response, the PI3 kinase enzyme is activated, which stimulates the activity of a cascade of proteins inside the cell. Thus, information about the presence of a pathogen in the body is transmitted to the "destination" – the cell nucleus – where the transcription factor IRF-7 modifies the expression of certain genes that change the functioning of the cell. In this case, IRF-7 induces the synthesis of type 1 interferons (including interferon-alpha) that destroy viruses and activate various immune cells.
In autoimmune diseases, such as systemic lupus erythematosus, excessive stimulation of the innate immune response leads to damage to cells, tissues and organs of the body itself. In some malignant diseases, on the contrary, innate immunity practically does not work, which may be due to the suppression of the PI3-kinase-mediated signaling mechanism. The authors hope that over time they will be able to develop methods for the treatment of autoimmune and malignant diseases by changing the activity of PI3 kinase.
Portal "Eternal youth" www.vechnayamolodost.ru based on the materials of ScienceDaily
29.02.2008