Give an example of how autoimmune disease breaks tolerance
Give an example of how autoimmune disease breaks tolerance Autoimmune diseases are a complex group of disorders where the body’s immune system mistakenly attacks its own tissues, leading to chronic inflammation and tissue damage. Under normal circumstances, the immune system can distinguish between the body’s own cells (self) and foreign invaders like bacteria and viruses (non-self). This ability to discriminate is known as immune tolerance. When tolerance is broken, the immune system begins to target self-antigens, resulting in autoimmune pathology. Understanding how this breakdown occurs can be better illustrated through specific examples, such as the development of Type 1 diabetes mellitus.
Type 1 diabetes is an autoimmune condition characterized by the immune-mediated destruction of insulin-producing beta cells in the pancreatic islets. In healthy individuals, immune tolerance prevents immune cells from attacking these self-cells. However, in genetically predisposed individuals, certain environmental factors—such as viral infections—may trigger a failure in this tolerance. During this process, autoreactive T lymphocytes, which normally remain in a state of unresponsiveness or are deleted during immune development, become activated against beta-cell antigens. This activation leads to an inflammatory response targeting the pancreas, culminating in the destruction of insulin-producing cells.
The breaking of tolerance in this context involves multiple mechanisms. Central tolerance, which occurs during immune cell development in the thymus, normally eliminates T cells that strongly recognize self-antigens. However, some autoreactive T cells escape deletion. Peripheral tolerance mechanisms—such as regulatory T cells (Tregs) that suppress autoreactive immune responses—are crucial for keeping these potentially harmful cells in check. In autoimmune diseases like Type 1 diabetes, these peripheral tolerance mechanisms may become compromised. For instance, a deficiency or functional impairment of Tregs can allow autoreactive T cells to proliferate and attack pancreatic cells.
Furthermore, molecular mimicry plays a role in breaking tolerance. Certain viral proteins share structural similarities with self-antigens, leading to cross-reactivity. An immune response initially directed against a pathogen inadvertently targets similar self-proteins, initia
ting an autoimmune attack. In the case of Type 1 diabetes, viruses such as enteroviruses have been implicated in triggering the autoimmune process through this mechanism.
Once tolerance is broken, autoreactive immune cells infiltrate the pancreas, releasing inflammatory cytokines and recruiting other immune cells like macrophages and B cells. The resulting inflammation damages the beta cells, decreasing insulin production and causing the hallmark hyperglycemia of diabetes. This example demonstrates that a breakdown in immune tolerance—whether through failure of central or peripheral mechanisms, molecular mimicry, or environmental triggers—can initiate and perpetuate autoimmune disease.
In summary, autoimmune diseases exemplify the loss of self-tolerance through complex interactions between genetic susceptibility, environmental factors, and immune regulation failures. The case of Type 1 diabetes highlights how immune cells that should normally be kept in check can become destructive agents, attacking the body’s own tissues and leading to chronic disease.
