Question

Explain how tolerance to self-antigens may be produced. Also, give two examples of autoimmune diseases and explain their possible causes.

Short answer

Tolerance to self-antigens is produced through central and peripheral tolerance mechanisms. Central tolerance occurs in primary lymphoid organs, where immature lymphocytes undergo apoptosis or receptor editing to prevent maturation. Peripheral tolerance occurs in peripheral tissues, involving anergy, suppression by regulatory T cells, and activation-induced cell death to maintain unresponsiveness. Two examples of autoimmune diseases are rheumatoid arthritis, where synovial membranes in joints are targeted, and systemic lupus erythematosus, which affects multiple organ systems. Causes of autoimmune diseases may include genetic predisposition, environmental factors, and hormonal imbalances, leading to the loss of tolerance to self-antigens.

Step-by-step solution

Define Self-Antigens and Immune Tolerance

Self-antigens are molecules produced by the body's own cells that can potentially trigger an immune response. The immune system is supposed to recognize and tolerate these self-antigens to avoid attacking normal, healthy cells. Immune tolerance is the process by which the immune system becomes unresponsive to specific antigens, preventing an immune response against these molecules.

Discuss Mechanisms of Tolerance to Self-Antigens

There are two main mechanisms through which tolerance to self-antigens may be produced: central tolerance and peripheral tolerance. 1. Central tolerance: This process occurs within primary lymphoid organs (like the thymus for T cells and the bone marrow for B cells) during lymphocyte development. Immature lymphocytes encounter self-antigens, and those that strongly bind to these antigens undergo apoptosis (cell death) or receptor editing. This prevents them from becoming mature lymphocytes, reducing the likelihood of them attacking the body's own tissues. 2. Peripheral tolerance: This process occurs outside primary lymphoid organs in peripheral tissues. Even after central tolerance, some self-reactive lymphocytes can escape and remain in circulation. Peripheral tolerance mechanisms, including anergy (functional inactivation), suppression by regulatory T cells, and activation-induced cell death, help maintain the immune system's unresponsiveness to self-antigens.

Briefly Describe Two Autoimmune Diseases

1. Rheumatoid arthritis: This autoimmune disease occurs when the immune system mistakenly targets the synovial membranes in joints, causing joint inflammation, pain, and eventually joint damage. The precise cause of rheumatoid arthritis remains unknown, but a combination of genetic and environmental factors may contribute to its development. 2. Systemic lupus erythematosus: Another autoimmune disease, lupus affects multiple organ systems, resulting in a range of symptoms including inflammation and damage to the skin, joints, heart, lungs, and kidneys. The causes of lupus are not entirely understood, but genetic, hormonal, and environmental factors may all play a role in its development.

Explain Possible Causes of Autoimmune Diseases

Autoimmune diseases arise when the immune system loses tolerance to self-antigens, resulting in an attack against the body's own tissues. Several factors can contribute to this loss of tolerance: 1. Genetic predisposition: Certain genes may predispose individuals to develop autoimmune diseases by influencing the regulation of immune tolerance mechanisms. 2. Environmental factors: Infections or exposure to certain substances can trigger an autoimmune response by promoting molecular mimicry, where foreign antigens resemble self-antigens, or by causing the release of sequestered self-antigens that the immune system has never encountered. 3. Hormonal factors: Hormonal imbalances, particularly those involving sex hormones, may influence immune responses and contribute to autoimmune disease development. Overall, the process of tolerance to self-antigens is essential for maintaining a properly functioning immune system. The malfunction of these tolerance mechanisms can lead to autoimmune diseases, with various factors contributing to their development.

Key concepts

Self-Antigens

In our bodies, self-antigens are simply molecules that are part of our own cells. Usually, these molecules go unnoticed by the immune system. However, they have the potential to cause an immune response if not appropriately regulated. The immune system's role is to differentiate between harmful invaders, like bacteria and viruses, and these self-antigens. If it fails to do so, it may attack its own cells, leading to autoimmune diseases. Developing immune tolerance to self-antigens is crucial. It ensures that the body doesn't accidentally harm itself, maintaining a balanced and healthy state.

Autoimmune Diseases

Autoimmune diseases arise when your immune system mistakenly targets your own body. These diseases occur as a result of the immune system's failure to maintain tolerance to self-antigens. Let's look at a couple of examples:

• Rheumatoid arthritis: This disease leads to swelling and pain in the joints. Genetic and environmental factors, like smoking or infections, can increase the risk. The immune system starts attacking the lining of your joints, causing inflammation and damage.
• Systemic lupus erythematosus (Lupus): Lupus targets multiple body systems, from the skin to the kidneys. Like rheumatoid arthritis, it may arise from genetic, hormonal, and environmental influences. In lupus, the immune system attacks healthy tissues, leading to a variety of symptoms depending on the affected organs.

Understanding the causes and mechanics of autoimmune diseases is essential for formulating effective treatments.

Central Tolerance

Central tolerance occurs in the early stages of immune cell development. The process takes place in the primary lymphoid organs:

• Thymus for T cells
• Bone marrow for B cells

During this stage, immature immune cells (lymphocytes) that bind strongly to self-antigens undergo apoptosis, a form of programmed cell death. This ensures that potentially harmful cells that could attack the body are eliminated before they mature. In some cases, B cells may undergo receptor editing, which is a mechanism that changes their antigen receptors to non-reactive versions. This step is crucial for preventing autoimmune reactions at the very foundation of immune cell development.

Peripheral Tolerance

Peripheral tolerance acts as the immune system’s safety net, catching potentially self-reactive lymphocytes that escape central tolerance. It operates in the body’s peripheral tissues and employs several strategies to maintain self-tolerance:

• Anergy: When self-reactive lymphocytes become functionally inactive without being eliminated.
• Suppression by regulatory T cells: These specialized cells help control immune responses and maintain tolerance by suppressing potentially harmful lymphocytes.
• Activation-induced cell death: This process leads to the elimination of any self-reactive cells that become activated in the peripheral tissues.

If these peripheral mechanisms fail, the risk of developing autoimmune diseases significantly increases. Together, central and peripheral tolerance are vital processes that protect the body from self-inflicted harm, ensuring a balanced and effective immune response.