INFECTIONS & AUTOIMMUNITY

The link between Autoimmunity and infections has been researched extensively. Autoimmune conditions can either be induced or triggered by an infectious agent such as a virus, bacteria, fungi or parasite, particularly in genetically susceptible individuals. Quite often it is not just a single infection but a ‘burden of infections’ from childhood forming a ‘pathogen load’. Most Autoimmune diseases have been linked to one or more infectious agent, however infections can in certain people have no impact in Autoimmunity and in others suppress Autoimmunity altogether.

Infections can activate the inflammatory response, this can cause:

An increase in destructive T cell production and increased Autoimmune destruction.
Depletion of antioxidants and increase inflammation further.
Breakdown of immune barriers.

Infections can turn on Autoimmunity by:

Destroying tissue (DAMPS) causing self tissue proteins to enter the bloodstream. Antibodies are produced against this self tissue. For example, someone may get viral thyroiditis where they may have an upper respiratory infection which infiltrates and starts to destroy the thyroid gland. The proteins from the destruction get released into the bloodstream and the immune system makes antibodies to different subsets of those proteins and then the person who had a viral infection of the thyroid has now turned into thyroid Autoimmunity.
Some infections can invade the cell and the immune system activates destruction of that cell and antibodies form against those proteins causing Autoimmunity.
Pathogen antibody cross reactivity, where antibodies formed against a pathogen start to also attach to the body's own tissue. This happens if the pathogen protein, is very similar in amino acid sequences of protein structure to the body's tissue protein. T cells then start to target the pathogen as well as the body tissue.

Interplay of pathogenic and protective infections associated with autoimmune diseases.

'Different Autoimmune diseases (blue) might be caused by pathogenic infections (orange) or ameliorated by protective infections (green). Genetic susceptibility plays an important part in this wide array of interactions. Abbreviations: CJ, Campylobacter jejuni ; CP, Chlamydia pneumoniae ; HiB, Haemophilus influenzae ; HP, Helicobacter pylori ; NG, Neisseria gonorrhoeae ; SP, Streptococcus pyogenes ; RV, Rotavirus'.

Reference: (Shaye Kivity, Nancy Agmon-Levin, Miri Blank, Yehuda Shoenfeld, Yehuda Shoenfeld, 2009) doi.org/10.1016/j.it.2009.05.005

Mechanisms...

How Infections cause Autoimmunity?

A) Molecular mimicry model:

Characterised by cross-reactivity between epitopes (i.e. protein, carbohydrate, amino acid sequence or DNA) shared by the pathogen and the host's body tissue proteins. E.g.

Pathogen Protein Amino Acid Sequence - SNSSTLDLASINQRGRDHA

Human protein Amino Acid Sequence - TESSTLDFAPFQQFGRDHP

B) Bystander activation model:

Viral antigens stimulate receptors in the inflammatory environment causing the release of proinflammatory cytokines which can induce tissue damage and the release of hidden antigens which can activate autoreactive T cells that initially were not involved in the immune reactivity.

Epitope spreading sets up a vicious cycle in which newly created antigenic epitopes activate more lymphocytes of different specificities and recruit these cells into the reaction, leading to more tissue damage and the emergence of even more novel epitopes targeted by autoreactive lymphocytes.

Reference: (Smatti, M.K.; Cyprian, F.S.; Nasrallah, G.K.; Al Thani, A.A.; Almishal, R.O.; Yassine, H.M., 2019)

doi:10.3390/v11080762