Essence and biological significance of the phenomenon
One of the main functions of the human immune system is reliable protection against various pathogens. However, any powerful protective response must be strictly controlled. If this process is left unchecked, there is a high risk of severe damage to the body's own tissues.
This is precisely why immunological tolerance exists. Essentially, it is a state in which an immune response to a specific, targeted antigen simply does not develop. The cornerstone of this phenomenon is the immune system's ability to flawlessly distinguish between "self" and "non-self". When this fine line is blurred and the ability to differentiate is impaired, the immune system begins to attack its own cells. Such a breakdown underlies the development of severe autoimmune diseases.
Acquired tolerance
Tolerance is not only directed against self-tissues but can also be acquired during life. Acquired tolerance is absolutely essential to prevent destructive hypersensitivity reactions upon initial contact with any environmental antigen.
A classic and most understandable example is the absence of an immune reaction to dietary proteins. The formation of tolerance to them prevents undesirable and dangerous reactions during all subsequent exposures to food. Without this acquired property, normal nutrition would be impossible, as every meal would be regarded by the body as a massive antigenic attack.
Mechanisms of tolerance induction
To maintain a state of unresponsiveness to specific antigens, the immune system utilizes several complex pathways. In pathomorphology and immunology, three key mechanisms are distinguished:
- Clonal deletion. The essence of this process is the physical absence of self-reactive (autoreactive) T lymphocytes and B lymphocytes. Cell clones potentially capable of attacking the body are simply eliminated.
- Clonal anergy. Under this mechanism, lymphocytes persist but undergo prolonged or completely irreversible functional inactivation. This deep "hibernation" is triggered by specific contact with the antigen, after which the cell loses its ability to respond.
- Peripheral suppression. This is a mechanism of active suppression. It involves specialized suppressor T cells. They purposefully inhibit autoreactivity by secreting specific molecules called cytokines. These cytokines effectively reduce the overall intensity of the developing immune response.
Autotolerance
Special attention in the study of immunology is paid to autotolerance—that is, tolerance exclusively to the body's own antigens. It is important to understand the hierarchy of the defense mechanisms described above.
Of the three pathways listed, clonal deletion and clonal anergy act as the primary mechanisms of autotolerance. They ensure the baseline safety of self-tissues, guaranteeing that lymphocytes capable of triggering an autoimmune process will be either eliminated or permanently disabled.
Briefly: answers to topical questions
In which organs does clonal deletion of autoreactive T lymphocytes take place?
Clonal deletion of autoreactive T lymphocytes takes place in the central organ of the immune system, the thymus. This process is a crucial mechanism of central tolerance (negative selection), in which autoaggressive lymphocyte clones are destroyed via apoptosis. The interaction of Fas receptors on self-reactive T lymphocytes with Fas ligands triggers their programmed cell death pathway.
Specifically, what cytokines do suppressor T cells secrete to suppress the immune response?
Suppressor T cells (regulatory T cells) secrete suppressive cytokines IL-10 and TGF-$\beta$. The release of these substances reduces the intensity of the immune response and inhibits autoreactivity, ensuring peripheral tolerance to self-antigens. In addition, the suppression of the T-cell response can also occur through direct contact-dependent inhibition, independent of cytokines.
What types of immunological tolerance exist based on their origin?
Based on origin, there are two main types of immunological tolerance:
- Natural tolerance — forms during ontogenesis and represents the physiological absence of an immune response to the body's own tissue and cellular antigens (autotolerance).
- Acquired tolerance — necessary to prevent hypersensitivity reactions upon primary and subsequent contacts with a foreign antigen (e.g., the absence of adverse reactions to dietary proteins).
What markers are expressed on the surface of suppressor T cells?
Natural regulatory T cells (suppressor T cells) express $CD4^+$ and $CD25^{hi}$ (high expression of CD25) markers on their surface. In addition to surface receptors, they intracellularly contain the transcription repressor protein FOXP3, which is a key factor for their suppressive properties. The full phenotype of such cells is designated as $Foxp3^+$ or $CD4^+CD25^+Foxp3^+$.
How can you easily remember the three mechanisms of tolerance? Use the acronym DAS: Deletion (absence of cells), Anergy (inactivation of cells), Suppression (cytokine-mediated suppression).
Class and exam questions
What happens if the body loses the ability to distinguish "self" from "non-self"?
Impairment of this crucial recognition ability underlies the development of autoimmune diseases, in which immunity begins to destroy its own tissues.
What is the purpose of acquired tolerance?
It is necessary to prevent hypersensitivity reactions upon primary contact with an antigen. For example, the lack of a reaction to dietary proteins protects us during repeated meals.
Which mechanisms of autotolerance are considered primary?
The primary (baseline) mechanisms of tolerance to self-antigens include clonal deletion and clonal anergy.
What else to study on this topic
- The role of suppressor T cells and the cytokines they secrete
- Differences between clonal deletion and clonal anergy
- Pathogenesis of autoimmune diseases upon the breakdown of tolerance
- Mechanisms of acquired tolerance induction to dietary proteins
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