Understanding autoimmune diseases

Surely we have all heard about nasty diseases where our own body turns against us and slowly kills us. They are autoimmune diseases and only 5% of the population are likely to develop them. Autoimmune diseases develop only when the tolerance mechanisms fail and the strongly autoreactive immune cells and antibodies are generated, leading to destruction of our own healthy tissue. Interestingly, they tend to affect women more than men.

A low level of autoreactivity is required to have a healthy immune system. Autoantigens play a role in the maturation of lymphocytes, as well as the survival of naive T cells and B cells on the periphery. Multiple tolerance mechanisms exist to restrict autoimmune attacks.These are like a chain of checkpoints, cooperating to detect and remove very strong anti-self immune cells without compromising the immune response to pathogens.

Strongly autoreactive lymphocytes are usually detected and cleared as soon as they are synthesised by central tolerance mechanisms occurring in the thymus and bone marrow. If they manage to escape this checkpoint, they will have another barrier to cross at the secondary lymphoid organs: the lymph nodes and spleen. Regulatory T cells induce inactivation or deletion of these potentially dangerous immune cells.

Regulatory T cells play a crucial role in controlling self-reactive leukocytes, but lymphocytes also have intrinsic mechanisms to limit their proliferation and survival. Autoreactive cells are generated frequently, but a healthy immune system will be able to control them and eradicate them by apoptosis- programmed cell death.

These successive checkpoints are a more refined mechanism of autoimmunity control than a strong singular process, so immunity is not impaired. However, they are susceptible to failure, and nobody knows exactly how to restore this immunological tolerance once it is lost.

Autoimmune diseases can go from organ-specific diseases – such as autoimmune thyroiditis and type I diabetes – to systemic diseases, as atherosclerosis and systemic lupus erythematosus. The specificity of the disease depends only on the natural distribution of the antigen that is being recognised by the immune system. If the antigen is restricted to the thyroid epithelial cells, then only thyroid is going to be affected and slowly destroyed. If, on the other hand, the antigen is a nuclear antigen, then every cell of the body with a nucleus will be affected.

Treatment for autoimmune diseases remains a challenge. Common approaches are to manage the outcome of the disease, for instance supplying insulin therapy for type I diabetic patients, or to suppress general immunity, which greatly increases susceptibility to pathogenic infections.

Animal models of autoimmunity – both induced and spontaneously developed autoimmunity – have been studied deeply to further our understanding of what triggers anti-self attacks. But how easy is to translate animal model studies to humans? How accurate is the modulation of a human disease in a mouse?

It is also  known that genetics play a role, but the environment seems to be slightly more important. It seems that 35% of autoimmunity disease is inherited, still leaving  65% unaccounted for…

Much has still to be done to understand how to manage autoimmune diseases without compromising the whole immune system. In the meantime, we must be aware that bugs and accidents are not the only things that harm us. Some attacks come from within.

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