Immune Tolerance Mechanisms and the Effects on Autoimmune Diseases

Elrashdy Shakya^*
*Correspondence: Elrashdy Shakya, Department of Biological Chemistry, Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia, Email:

Introduction

The immune system is a complex network of cells and molecules that protect the body against foreign invaders such as pathogens. However, in some cases, this system can malfunction and attack the body's own healthy cells and tissues, leading to autoimmune diseases. The development of autoimmune diseases involves a breakdown in immune tolerance, which refers to the ability of the immune system to recognize and tolerate self-antigens while mounting an immune response against foreign antigens. Understanding the mechanisms of immune tolerance and their implications for autoimmune diseases is crucial for developing effective treatments and interventions. In this article, we will explore the various mechanisms of immune tolerance and their significance in the context of autoimmune diseases. Developing targeted therapeutics can benefit from an understanding of the precise mechanisms underlying immunological tolerance breakdown in various autoimmune disorders. For instance, methods designed to improve regulatory T cell functionality or reestablish central tolerance mechanisms are being researched as prospective anti-autoimmune therapies. Therapies that alter immunological checkpoints or make use of chemicals that promote immune tolerance may also be effective in restoring immune tolerance and preventing autoimmune reactions [1,2].

Description

One of the fundamental mechanisms of immune tolerance is central tolerance, which occurs during the development of immune cells in the thymus and bone marrow. In the thymus, T cells undergo a process called thymic selection, where immature T cells that recognize self-antigens with high affinity are eliminated through a process called negative selection. This prevents the development of T cells that could potentially target self-antigens. Similarly, in the bone marrow, B cells that recognize self-antigens with high affinity are eliminated or undergo receptor editing to prevent the production of autoantibodies. Failure in central tolerance mechanisms can result in the escape of autoreactive T and B cells, leading to autoimmune diseases. While central tolerance plays a critical role in preventing autoimmune responses, additional mechanisms of immune tolerance operate in the periphery to maintain self-tolerance. Peripheral tolerance mechanisms act on mature lymphocytes that have left the thymus and bone marrow and are present in the circulation and peripheral tissues. One such mechanism is anergy, which refers to the state of functional inactivation of selfreactive T and B cells [3]. Energy can be induced by antigen recognition in the absence of co-stimulatory signals, leading to the suppression of the immune response. This mechanism prevents autoreactive lymphocytes from mounting an immune response in the absence of appropriate activation signals.

Another important peripheral tolerance mechanism is regulatory T cells (Tregs). Tregs are a specialized subset of T cells that actively suppress the activity of other immune cells, including autoreactive T cells. They maintain immune homeostasis and prevent excessive immune responses by secreting anti-inflammatory molecules and inhibiting the activation of other immune cells. Deficiencies in Treg function or numbers have been associated with the development of autoimmune diseases, highlighting their importance in maintaining immune tolerance. Furthermore, peripheral tolerance is also achieved through the process of clonal deletion or clonal anergy. In clonal deletion, self-reactive lymphocytes are eliminated through apoptosis, ensuring that they do not cause damage to self-tissues. Clonal anergy, on the other hand, renders self-reactive lymphocytes functionally inactive, similar to anergy mentioned earlier. The breakdown of immune tolerance plays a crucial role in the development of autoimmune diseases. When self-tolerance mechanisms fail, autoreactive lymphocytes can recognize self-antigens and mount an immune response against them. This immune response leads to chronic inflammation and tissue damage, resulting in various autoimmune conditions [4,5].

For example, in type 1 diabetes, there is an autoimmune destruction of insulin-producing beta cells in the pancreas. The failure of central tolerance mechanisms allows autoreactive T cells specific to beta cell antigens to escape thymic selection and attack the beta cells in the periphery. Similarly, in rheumatoid arthritis, autoreactive B cells produce antibodies that target self-antigens, leading to inflammation and joint damage. Understanding the specific mechanisms underlying immune tolerance breakdown in different autoimmune diseases can help in developing targeted therapies. For instance, strategies aimed at enhancing the function of regulatory T cells or restoring central tolerance mechanisms are being investigated as potential treatment options for autoimmune diseases. Additionally, therapies that modulate immune checkpoints or utilize immune tolerance-inducing molecules show promise in restoring immune tolerance and preventing autoimmune responses [5].

Conclusion

Immune tolerance is a complex and dynamic process that involves multiple mechanisms to prevent the immune system from attacking self-tissues. Central and peripheral tolerance mechanisms work together to ensure self-tolerance and prevent the development of autoimmune diseases. Dysregulation or failure of these tolerance mechanisms can lead to the breakdown of self-tolerance and the initiation of autoimmune responses. Advances in our understanding of immune tolerance mechanisms have provided valuable insights into the pathogenesis of autoimmune diseases. This knowledge paves the way for the development of novel therapeutic strategies that aim to restore immune tolerance and halt or even reverse the progression of autoimmune diseases. By targeting the mechanisms underlying immune tolerance, we can hope for more effective treatments and improved outcomes for individuals affected by autoimmune diseases.

Acknowledgement

We thank the anonymous reviewers for their constructive criticisms of the manuscript.

Conflict of Interest

The author declares there is no conflict of interest associated with this manuscript.

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