Breakdown of self-tolerance

BREAKDOWN OF THE SELF TOLERANCE

The breakdown of self-tolerance is a key concept in understanding autoimmune diseases. Self-tolerance refers to the immune system's ability to recognize and tolerate the body's own cells and tissues, distinguishing them from foreign invaders. When self-tolerance breaks down, the immune system mistakenly targets and attacks the body's own cells, leading to autoimmune diseases. Here's a breakdown of how self-tolerance can be compromised:

1. Genetic Factors:
• Genetic predisposition plays a crucial role. Some individuals may inherit genes that make them more susceptible to autoimmune diseases. These genes can influence the function of immune cells and the mechanisms responsible for maintaining self-tolerance.
2. Failure in Central Tolerance:
• Central tolerance occurs during the development of immune cells in the thymus and bone marrow. T cells and B cells, which are essential components of the immune system, undergo a selection process to eliminate those that react strongly against the body's own tissues. If this process fails, autoreactive cells may escape into the circulation.
3. Peripheral Tolerance Mechanisms:
• Even after central tolerance, additional mechanisms operate in the periphery (outside the thymus and bone marrow) to maintain self-tolerance. Regulatory T cells (Tregs) play a crucial role in suppressing potentially harmful immune responses against self-antigens. Dysfunction or a decrease in the number of Tregs can contribute to the breakdown of self-tolerance.
4. Molecular Mimicry:
• Infections or environmental factors may expose the immune system to substances that resemble the body's own tissues. If the immune system responds to these foreign invaders, it might also attack similar-looking self-antigens, contributing to autoimmune reactions. This phenomenon is known as molecular mimicry.
5. Loss of Immune Privilege:
• Some tissues in the body enjoy a state of immune privilege, meaning they are protected from immune attack. However, in autoimmune diseases, this immune privilege can be compromised, leading to immune cells attacking these tissues.
6. Inflammatory Signals:
• Inflammatory signals in the body can activate immune cells and promote an environment conducive to autoimmune responses. Chronic inflammation can disrupt the balance of the immune system and contribute to the breakdown of self-tolerance.
7. Environmental Triggers:
• Infections, exposure to certain chemicals, and other environmental factors can act as triggers, initiating or exacerbating autoimmune responses in individuals with a genetic predisposition.

Understanding the breakdown of self-tolerance is crucial for developing strategies to prevent or treat autoimmune diseases. Researchers are actively exploring ways to intervene in these processes and restore immune balance to mitigate the development and progression of autoimmune conditions.

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Key Elements

1.     Genetic Predisposition

2.     Immune System Dysfunction

3.     Loss in Immune Tolerance

4.     Triggering Events

5.     Molecular Mimicry

6.     Cytokine Imbalance

7.     Auto Antibodies

8.     Organ Specific vs Systematic Autoimmunity