'SELF' TISSUE & MOLECULAR MIMICRY IN AUTOIMMUNITY
AUTOANTIGEN - AUTOREACTIVE CELLS - AUTOANTIBODIES - AUTOIMMUNITY
An effective immune system must efficiently recognise and eliminate foreign antigens (pathogen, toxin or allergen) to protect the host. However, it is important that an immune system can distinguish ‘self’ from ‘non-self’, so that it does not attack its own body tissues. This is called immune tolerance and Autoimmunity occurs when there is a loss of oral, central, and/or peripheral tolerance.
The adaptive immune system has evolved with specificity for foreign antigens. This means that T cells and B cells have antigen-specific receptors expressed on their surfaces. These receptors are encoded by genes and form a diverse repertoire allowing the immune system to recognise foreign antigens effectively in the body. Everyone has a different repertoire based on their genetics and influences.
As the immune system matures, various tolerance mechanisms develop to stop the body from attacking 'self'. T cells & B cells with receptors to 'self' autoantigens (autoreactive T & B cells) will undergo apoptosis within the thymus, lymph nodes or peripheral circulation or are suppressed by Regulatory T cells. However if these tolerance mechanisms do not work, autoreactive T and B cells that survive due to failure of apoptosis or a process called molecular mimicry may result in the destruction of self-tissue by both autoantibodies and/or autoreactive T & B cells.
MOLECULAR MIMICRY
Molecular mimicry has been linked to the pathogenesis of many Autoimmune diseases. The term molecular mimicry was originally defined as “the sharing of antigens between parasite and host”. In simple terms, molecular mimicry can be explained as the immune system getting confused between an external antigen (eg a pathogen) and the body's own tissue because they may for whatever reason share the same molecular protein structure (see diagram below). For example molecular mimicry between viral pathogens (such as Coxsackie virus) and beta cell proteins in the pancreas has been a popular theory to explain loss of tolerance in type 1 diabetes.
The mechanisms associated with cross-reactivity via molecular mimicry are complex and integrate genetic and environmental factors. It is also not only pathogens that can cross react with host antigens.
Autoantigens known to be involved in Autoimmune diseases have been found to share sequence homology with food items proteins/peptides such as wheat and milk. This is why gluten and dairy removal become so important in Autoimmunity. The failure of oral tolerance triggers immune reactivity against dietary antigens and this can cause food sensitivities and even lead to Autoimmunity. Furthermore when chemicals bind to proteins and produce haptens, cross-reactivity can also occur.
