Immune stimulation: Busting the myth

If you do a quick search on immune stimulation you will find thousands of sites claiming it to be a formula that might change health related problems such as chronic pain, an autoimmune disease or cancer. Imune stimulation refers to the stimulation of the immune system by an external source. The stimulation can act as a protective effect against microorganisms.

So what could immune stimulation be used for?

Today when antibiotic resistance bacteria is rising, scientist are trying to deal with it by stimulating the immune system rather than killing the bacteria. Since antibiotics only work for bacterial infections, immune stimulation can help to fight against viruses, chronic infections originating from protozoa, fungi and parasitic worms.

If one is able to control the immune response, then it is possible to both stimulate or to suppress its action. Cancer, auto-immune diseases may be eradicated by suppressing pathological immune responses. There is hardly any disease which do not have an immunological aspect to it. And, if not, then chances are that it can be attacked by using the weaponry of the immune system. This is in fact already happening in cancer immunotherapy.

The idea of using immune stimulation for curing disease has been more than a hundred years old, but its application has been used only recently.

The roots of the use of immune stimulation as a vaccine date back to the late nineteenth century. Then, William Coley, a New York bone surgeon, began treatments in which he injected cancer sufferers with a preparation consisting of dissolved Streptococcus pyogenes bacteria . Anecdotal evidence claimed remission of tumor growth in 40% of the treated patients. Then, in the 1980s, it was discovered that the observed anti-tumor activity of a bacteria known as Bacillus Calmette-Guerin was a property of the construction of the bacterial genetic material. Indeed, the bacterial genetic material is able to stimulate the immune system such that the target sequence of the bacterial gene is distinguished from the host genetic material. The resulting immune stimulation boosts antibody levels as well as another aspect of the immune system known as cell-mediated immunity .

Synthetic peptides have also proved useful as agents of immune stimulation. These compounds are made up of chains of amino acids. They are called synthetic because they are not naturally occurring, but rather are constructed in the laboratory. The peptide can contain amino acids in which a chemical group is oriented in a mirror image of that which is normally found in nature.

Danger Signals

Danger Signals are used by the immune system for detection of pathogens or cell damage. These molecules are usually bits and pieces from pathogens or debris left over after cell damage. Danger Signals are recognised by Pattern Recognition Receptors (1) of the innate immune system, which have been identified and characterised in the last 20 years. The discovery of these Danger Signal receptors gives us the opportunity to develop small molecule drugs that promote or inhibit the function of those receptors, effectively giving us the chance to control the immune response.

In terms of the military analogy of the immune system, scouts (Antigen Presenting Cells or APCs) collect intelligence (antigen) about the operations of invaders (pathogens) or the rebels (cancer) while patrolling the civil population (cells of the host). In this analogy, Danger Signals are a sort of evidence of threat that will alert the scouts (APCs get activated), who start to produce messages (cytokines) and will prompt them to bring back what they find to the Headquarters (Lymph node). There, the commanders of the immune response (T cells) receive the messages from the scouts, examine the intelligence and alert the troops.

At least this is how things should go, but as chronic/deadly infections and cancer do exist, it is evident that things do not always go that way. So, how is it that the “invaders” and the “rebels” can bypass the immune surveillance?

Alerting the Antigen Presenting Cells is so important that when it is absent[HM1] , curious things can happen, as was realised with cellular cancer immunotherapy. The main idea behind dendritic cell cancer immunotherapy (2) is to teach the immune system to attack cancer cells by training them to recognise cancer antigens on activated dendritic cells ( scouting Antigen Presenting Cell) to[HM2] T cells. A crucial step in the therapy is the activation of the dendritic cells (DCs) outside of the body in the presence of cancer antigens, which are then reintroduced to provoke an immune response. Importantly, without activation of the DCs, immunosuppressive regulatory T cells are produced and the immune system goes into complete standdown instead of attacking the cancerous cells (3). So, strangely, we could use Danger Signals to treat cancer.

But are danger signals  dangerous?

That is exactly the trouble: “native” Danger Signals from pathogens and damaged cells have a bunch of side effects. So, the trade- off is to find such molecules that do just enough to alert the immune system, but no more. Molecules with such a profile are few and far between and are still under development. The key to finding them is to understand the interactions of “real” Danger Signals with immune receptors at the molecular level and then design immune stimulators that do the right job. This is what I am working on too, but more about specific Danger Signals in the next post.

The original article was published in archive.yourformula