The Basis of Autoimmunity
Autoimmune diseases are a group of complex, heterogeneous diseases where the body’s immune system reacts inappropriately to self tissue. In effect, autoimmunity is a form of immune system hypersensitivity. Autoimmune diseases can be broadly classed into organ-specific (e.g., Hashimoto’s thyroiditis) and system-wide (e.g., Sjögren’s syndrome) diseases; however, this is a simple classification system and much overlap exists.
The immune system is designed largely to protect the organism from foreign proteins, with the assumption that these potentially could establish serious infection or disease. Why is it, then, does the immune system turn against its body? Is this a form of cellular ‘mutiny’? Probably not! The immune system is such a complex system of molecules and cells that there is bound to be problems at times. The immune system does not intentionally seek to destroy its own body, in other words; rather it is a product of the misguided process of creating immunity. A large part of autoimmunity results from the failure to keep the immune system in check, so this is analogous to a poor, frantic mother in the supermarket trying (but unsuccessfully) to tame her eight young children!
The molecular and cellular basis of this dysregulated immune system is the subject of intense research. Below, we will briefly visit some of the current overarching thoughts of why autoimmunity arises.
- Genetics – there is little doubt that genes play a significant role in autoimmunity. This can be seen with the tendency for inheritance in families. Many of these genes remain elusive; but scientists know that a large block of genes that encode a protein known as human leukocyte antigen (or HLA) is linked strongly with autoimmunity. These proteins affect the way and tendency for certain particles to be exposed to the immune system.
- Sex – females are more likely to develop autoimmunity than males. This has led some to speculate that hormones play a role in the disease initiation or process.
- Infections – significant infections with bacteria and viruses may trigger off autoimmune diseases; but the reasons for this are still not well understood. It could be a by-product of the inflammation to the original bug which triggers off the immune system (inappropriately) or the immune system accidentally cross-reacting with itself after encountering the bug.
- Environmental – this has become a term to include the miscellaneous external factors that seem to be associated with autoimmunity – the mechanism of how is very poorly understood. Smoking, certain drugs etc. seem to influence (trigger) the onset of autoimmune diseases.
- Immunodeficiencies – in rare instances of a severe depressed immune system, the immune system can be so dysregulated that, ironically, hyperactivity through autoimmunity can occur.
Future work in the area of autoimmunity would be to completely understand the triggers of autoimmunity and the mechanisms behind them. This would obviously be useful for the development of appropriate prevention and treatment strategies. Currently, a treatment strategy is to dampen down the immune system with non-specific anti-inflammatory drugs, and gradually, as we start to understand the disease mechanisms, these drugs are becoming more specific with (hopefully) less side-effects. Indeed, the future will undoubtedly start to see the introduction of management strategies at the genetic level, and this is the subject of ongoing research.
Future work in the area of autoimmunity would be to completely understand the triggers of autoimmunity and the mechanisms behind them. This would obviously be useful for the development of appropriate prevention and treatment strategies. Currently, a treatment strategy is to dampen down the immune system with non-specific anti-inflammatory drugs. Gradually as we start to understand the mechanisms, these drugs are becoming more specific with (hopefully) less side-effects. The future will no doubt start to see the introduction of management strategies at the genetic level.
Abbas, A.K., A.H. Lichtman, and S. Pillai, Cellular and Molecular Immunology. 6th ed. 2010, Philadelphia: Saunders Elsevier.
Kuchroo, V.K., et al., Dysregulation of immune homeostasis in autoimmune diseases. Nature Medicine, 2012. 18(1): p. 42-47.
This article is printed with permission from Adrian Lee, thanking Adrian for allowing us to share this article.
Adrian Lee, BMedSc (Hons), LMusA
Adrian is a medical student at the University of Tasmania with clinical and research interests in immunology, allergy and autoimmunity.
Copyright © A. Lee, 2014