Inciting and Inhibiting Autoimmunity

"Immunity may be viewed as a dynamic system driven by opposite vectors...The sum of the vectors yields an equilibrium point which allows protective immunity when the vectors are equal" - Blanco et al.
...meaning: as long as there is a balance of DCs, T-cells, B-cells, Cytokines, TLRs and all things contributing to overall immunity will function normally . However if an imbalance occurs the system will not work. To date dendritic cells are the only antigen-presenting cells known to be able to both incite and inhibit autoimmune disease.

there are many ways a DC might cause autoimmunity:

Self-Antigen
Self-antigen is normal cell that DCs or T-cells mistakenly think are invading antigen.
Sometimes a DC's may be faulty and capture and present self-antigen to T-cells during periods of tissue infection or injury. This leads to the creation of auto-agressive T-cells (T-cells which attack cells from their body according to the proscribed self-antigen). Auto-antibodies are then created by B-cells. While often these misguided cells are deleted by functional DCs, occasionally some manage to survive undetected.
For example If an immune response was elected against beta cells in the pancreas, the production of insulin and sugars would be significantly damaged and cause a type of diabetes.
autoantibodies.jpg
Misguided T cells can attack insulin-producing cells of the pancreas, contributing to an autoimmune form of diabetes.

Such is is the cause with many other diseases including systemic lupus erythematosus (SLE).


Cytokine imbalance
Treatment with the IL-1 antagonist IL-1-RA show therapeutic benefits to many inflammatory autoimmune diseases such as systemic onset of juvenile idiopathic arthritis, gout, type II diabetes other diseases included in the umbrella 'familial auto-inflammatory syndromes'. Further more, MS sufferers have been found to have an increased number of IL-17.
Considering studies such as these it was discovered that an increased production of certain cytokine causes an immune imbalance. (Blanco et al)


Heritage
Genes also play apart in the development of auto-aggressive DCs. It appears that many people with autoimmune diseases have characteristic types of self-marker molecules that often causes these mistakes.

Inhibiting autoimmunity
DCs are responsible for both producing many cytokines and antagonist cytokines as well the destroying of cells that overproduce or misguide cells. And thus are key factors in inhibiting autoimmunity.






previous page: T-cells, B-cells and Cytokines / next page: Dendritic Cells as Natural AdjuvantsHomeContributed by Jess Youngberry