What are the risk factors that cause the loss of immune tolerance?

Immune tolerance refers to the ability of the immune system to recognize self-antigens and not attack them. This is critical for preventing damage to healthy tissues. Loss of immune tolerance can lead the body to develop an autoimmunity against its own cells and tissues, resulting in autoimmune disease. 

Risk factors that cause the loss of immune tolerance include a combination of environmental and genetic factors. These are some of the more common risk factors for loss of immune tolerance: 

• Genetic predisposition: Individuals with a family history of autoimmune diseases are more likely to inherit certain genetic variations that increase their likelihood of losing immune tolerance and developing autoimmune conditions. About 50% of genetic predispositions are caused by the human leukocyte antigen (HLA) gene family. 
• Impaired Treg response: Regulatory T cells (Tregs) play a crucial role in maintaining immune tolerance by suppressing inappropriate immune responses. A deficiency or dysfunction in Treg activity can lead to the breakdown of self-tolerance and the onset of autoimmune disorders.
• Female gender: Several autoimmune disorders are more commonly observed in females of childbearing age, which suggests that higher estrogen levels contribute to the loss of immune tolerance.  
• Infection: Infections can trigger autoimmune diseases through various mechanisms, including molecular mimicry. In this phenomenon, the immune system mistakenly targets self-antigens because of its inability to differentiate the self-antigens from foreign antigens that have a similar structure. This can lead to a loss of immune tolerance and the initiation of autoimmune disorders.