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Infection, autoimmunity

Jon Trister MD

Humans and microorganisms have lived in reasonable harmony for many millennia.
Coevolution for so long has resulted in mutual benefit.
Humans accommodate vast numbers of microorganisms.
Evolution produced a wide variety of microorganisms well adapted to live harmoniously with their human partners. Microorganisms exist on all exposed body surfaces:skin,mucosal lining, gastrointestinal tract.
These microbes learned to avoid and suppress immune response of the host.
Humans have adapted mechanism to evade the harmful activities of the microorganisms.
This delicate coevolution produced stable microbial population-microbiota-which actually exceeds by 10-fold the numbers of cells that compromise human body.
This coexistence results in a homeostatic equilibrium advantageous for both.Members of the Microbiome have found a congenial environmental niche.
In turn, it benefit the human host by performing valuable physiologic reactions and generating needed nutrients.
The resident microbial population itself retards infection or overgrowth by potentially harmful microorganisms.
At times, the symbiotic relationship established between the microbial population and its human counterpart become unbalanced because both parties are constantly subject to change.
Aggressive microorganisms with overwhelming disease-induced properties may gain within microbiome.
Alternatively, the ability of human immune system to cope with microbial population may falter because of age, hormonal status, nutrition and lifestyle. This dysfunction interrelationship is a promotion of autoimmune disease as a consequence of infection.(N.Rose, 2015)

One of the classic example of dysregulated immune response is Rheumatic Fever-when particular infection ( Streptococcus pyogenes ) can induce autoimmune disease in human. Madeleine Cunningham showed that antibodies and T lymphocytes specific for epitopes on the streptococcal M protein cross-react with cardiac myosin of the myocardium and N-acetyl-beta-D glucosamine residues on the cardiac valve endothelium.(M.Cunningham , 2012).
Another example is a Guillain-Barre syndrome where antigen (GM1) from Campylobacter jejuni cross-reacts with similar antigen in human peripheral nerve axones causing acute motor axonal injury.(S. Kuwabara , 2013)
These are two examples where defined microbial antigen mimicking its counterpart in the human host and inducing immune response in human.

Mechanisms of autoimmunity:

-Molecular or epitope mimicry between a microorganism and a host constituent induces pathogenic autoimmunity following resolution of the infectious process. Molecular mimicry is a compelling theory to explain the association of infections with autoimmune disease.Sometimes the microorganisms involved have little or no clinical or epidemiologic association with the particular human disease but capable to induce autoimmune process. ( N.Rose,2000).

-Charles Gauntt suggests that when damaging cells, the invading microorganism may cause the expression of otherwise unavailable autoantigens , providing both a trigger and a vulnerable target for a pathogenic autoimmune response. Cell damage or “spillage” inflicted by the microorganism overcome “immunologic ignorance” of previously ignored antigen.(C.Gauntt, 1979). {examples: DM type 1, post-viral myocarditis ( Coxsackievirus B3), CMV}.

-Host antigen sometimes incorporated into an infecting virion and can induce an autoimmune response in the manner recalling classic hapten-carrier relationship.( N.Rose, 1990)

-Infecting microorganism may alter a host protein to the point where it is perceived by the host immune system as foreign