When the immune system is too incredible

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One of our previous articles on the immune system gave an incredibly detailed description of the immune system’s successes. However, one aspect not considered enough by us is just how annoying it can be. In killing invading pathogens, the body is often caught in the crossfire. Fever? It’s the immune system’s fault – by releasing prostaglandins, we’re made to feel hot and bothered. Itching? Again, the release of histamine (mediated by our immune system) causes itchiness. The list can go on but the point is that many of the symptoms of diseases are as a result of the immune response. This can be excused when we are kept alive every single day and these responses help to kill the pathogen. Sometimes, the immune system can go much too far and these responses present big clinical challenges.

The first of these challenges are autoimmune disorders – where an abnormal immune response affects body tissue. There are around 100 recognised autoimmune disorders so it is impossible to cover all of them in this article. One trait that they all share is that there is no defined cause – there may be an external trigger of some sort, but as of yet, scientists just don’t know. Many autoimmune diseases have been so deeply ingrained into today’s society that we barely consider them as autoimmune. One of the most prominent examples is type 1 diabetes mellitus (where the insulin-producing beta cells of the pancreas are destroyed by the immune system, which recognise them as foreign). The diseases considered below are also those that have been involved with important events and figures in society.

One of these autoimmune diseases is Addison’s disease, with the famous sufferer being John F Kennedy. This is an autoimmune disease of the adrenal glands (located just above the kidneys). Here the destruction of the adrenal gland is brought about by a ‘bad’ reaction to the enzyme 21-hydroxylase. Like Type 1 diabetes, the symptoms are caused by lack of hormones (steroid hormones) – clinically, this presents as abdominal pain, weakness and later on, darkening of the skin. Treatment of Addison’s is again similar to type 1 diabetes – the steroid hormone levels are kept up . This may seem like an odd choice for a socially important disease but in JFK’s era (and today), looking young was a crucial for a president. JFK managed to pull this off by his famous suntan but that was unfortunately a sign much worse than it appeared; a sign of Addison’s disease.

Another ‘autoimmune’ disease is multiple sclerosis, caused by the myelin sheath of neurons demyelinating. Consequently, nerve conduction is heavily impaired. Hallmark symptoms include double vision (as nerves controlling eye movement are inflamed) as well as muscle weakness as muscles are harder to move due to improper nerve supply. The autoimmune nature of this subject to debate (as can be seen at the research article attached at the end) – as there are other theories, however the symptoms are immune mediated. The reason I’ve chosen this is one of the symptom-relieving treatments suggested – going by the name of Sativex. This is a painkiller but more notably was one of the first drugs to incorporate cannabis – paving the way for many future debates regarding its use in medicine and to an extent, recreationally.

Autoimmune diseases cannot be cured as such as so far, as there has been no pinpointed trigger. Therefore, attempts to deal with autoimmune diseases either deal with symptoms (as above) or suppress the immune system, which is what the following sections will expand upon.

The immune system’s overzealous response also poses problems for transplants. Transplants are considered when an organ is completely failing at its job and the length of transplant lists is well-documented. However, when transplants are needed, it is not as simple as just taking out one organ and placing another one in.

Early attempts transplantation involved the most accessible organ – the skin. These were wildly unsuccessful and the man who found out why and provided a solution was Sir Peter Medawar. Among biologists, Medawar is held in great esteem as the ‘father of transplantation’ and for good reason. His research confirmed the ideas of acquired immunological tolerance, first hypothesised by Macfarlane Burnet (who shared the Nobel Prize in 1960 with Medawar). Burnet’s thoughts were that if introduced early enough in an organism’s life cycle, the embryo would recognise foreign tissue as its own. This was confirmed by Medawar’s experiments with mice, where injecting mice with the foreign tissue in the embryo ensured that if injected again later on in life, there would be no immune reaction. This paved the way for organ transplantation technique that still exists today.

Further developments by clinicians also established the need for immunosuppressive drugs. These inhibited the extreme reactions of the immune system, allowing transplants to go ahead. As with many medicinal discoveries, the drugs came from microorganisms. The figurehead immunosuppressive drug cyclosporine came about from a fungus, and is used extensively in many transplants carried out today. Its structure enables it to inhibit T cells (more specifically calcineurin in the calcineurin-phosphatase pathway). By doing so, a key signalling molecule (interleukin-2) is prevented from being released, meaning that our body’s leukocyte ‘army’ is not deployed.

Clinically, the immune system is a curse and a blessing. It saves doctors from having to deal with a pesky virus every single minute of their working day. But when it goes rogue, it can be a nuisance. From having to make drugs that suppress the immune system (potentially exposing the body to danger from the simplest infections) to dealing with incredibly debilitating diseases, it is clear a lot remains to be understood about the enigma that is our immune system.


References

  1. 2015 Apr 19; 370(1666): 20140382. Philos Trans R Soc Lond B Biol Scidoi: 10.1098/rstb.2014.0382 Medawar’s legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’
  2. https://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/autoimmunity/what-causes-autoimmune-diabetes/
  3. Autoimmune Dis. 2012; 2012: 969657. Published online 2012 May 16. doi: 10.1155/2012/969657 Is Multiple Sclerosis an Autoimmune Disease? Bharath Wootla, 1 Makoto Eriguchi, 1 , 2 , 3 and Moses Rodriguez
  4. https://www.healio.com/rheumatology/practice-management/news/online/%7B74059ff3-579e-4540-b20f-d496eec0a7f0%7D/all-the-presidents-secrets-john-f-kennedy-and-addisons-disease
  5.  Laupacis A, Keown PA, Ulan RA, McKenzie N, Stiller CR (May 1982). “Cyclosporin A: a powerful immunosuppressant”Canadian Medical Association Journal126 (9): 1041–6. PMC1863293PMID7074504.

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