n.b. of course, all of the components of the immune system are important as without any one of them infection, inflammation and cancer may be a problem.
However, about three years ago I was ruminating on how important the immune system was in almost all diseases including inflammation, cancer and infection after another doctor quoted his relative as saying “all diseases are allergic in nature”.
After some initial reading it seemed that almost all if not every disease is associated with immunological abnormalities.
One of the earliest recent medical breakthroughs in this regard was the realization that if a substance released by the immune system called TNF was blocked in it`s actions there was clinical improvement in some inflammatory diseases e.g. rheumatoid arthritis and Crohn`s disease.
These relative primitive awakenings of the importance of the immune system in disease have led onto further increasingly more sophisticated immune treatments for cancer. Unfortunately the new treatments are very expensive and not available to everyone because of this.
Trying to understand the immune system.
The immune system is both simple and complex. One of the simplest approaches is as follows:
1. The immune system is exposed to a substance which may be
a) An immunogen e.g. food, bacteria, chemicals, drugs.
b) An auto-immunogen e.g. cancer cells, mutant enzymes and their products.
2. The immune system`s macrophages, dendritic cells or microglia devour the substance (phagocytosis) and become antigen presenting cells (APC).
3. Some of the substance is revealed to the rest of the immune system on the surface of the APC on MHC II complexes.
4. White cells called helper T-cells connect to the complexes.
5. White cells called regulatory T-cells (TREGS) either permit or prohibit the next stage of the immunogenic response.
6. If permitted the helper T-cells activate killer T-cells and antibodies to destroy the substance.
7. Substances called cytokines such as TNF are released which cause tissue damage.
Early on, I wondered if the macrophages were more important than the TREGS or vice-versa. I thought that three years ago the TREGS were more important in the control of the immune system even though history and research suggested that macrophages were.
George Bernard Shaw in his play, A Doctor’s Dilemma, honoured the concepts of phagocytosis (large-particle endocytosis) and opsonisation (antibody/antigen binding) described by Metchnikoff and Ehrlich, winners of the 1908 Nobel Prize in Medicine with the phrase “stimulate the phagocytes”.
However over the past three years it does appear that TREGS are more of a controlling influence than the macrophages.
We are now discovering TREG abnormalities in almost all diseases studied.
Generally speaking if
1. TREGS are too low the immune system is more active and inflammation occurs.
2. TREGS are too high the immune system is less active and infection and cancer occur.
Doctors are now on the verge of deliberately reducing TREGS in cancer and infection to enhance the immune response and increasing TREGS in inflammatory diseases in order to reduce the immune response.
Already some patients with non-responsive cancer have responded to TREG deletion treatment.
Perhaps all diseases should be regarded as “allergic in nature” as the doctor`s relative described.
A suitable title may be “TREG syndrome” which is described as “TREG abnormalities resulting in an excessive or impaired immunogenic response to an immunogen or auto-immunogen in a genetically predisposed individual resulting in inflammation, infection and/or cancer”.
One of my other fields of interest is in the immuno-genetics of psychiatric disease where immunological abnormalities are now being regarded as characteristic. Many doctors now regard psychiatric disease as neuro-inflammatory in nature in common with most other diseases which were previously of unknown cause e.g. coronary artery disease, peptic ulcer etc.
At present a lot of research attention is focused on the brain macrophages known as microglia and nerve cell death or neuronal apoptosis.
However it is now realised that most of the time the nerve cells are still alive but in a state of inflammation in psychiatric disease. This inflammation is also reversible. This has been demonstrated with the use of TNF-blockers in Alzheimer`s disease. (see the Youtube video below)
I anticipate that brain TREGS will be found to be in control of microglial activity in the future.
Who knows, perhaps psychiatric and neurologic disease will be treated with
1. TREG enhancement (for most neuro-inflammatory psychiatric and neurological diseases)
2. TREG deletion (for brain tumors and infections)
therapy in the future?
Youtube of The TREG syndromes