Immunological Tolerance

Another very interesting twist in Autoimmune disease is the concept of Immunological Tolerance. Earlier, in Autoimmunity, you found that autoimmune response generated by faulty recognition of own body parts.

But in IT, the twist is that body has ‘natural’ ability to ‘tolerate’ what you know as autoantigens or parts of body tissue. When this tolerance comes down, then we suffer from autoimmune disease.

Now autoimmunity results from partial or full absence of IT or its partial absence. This is something more obvious and clear.

Poor Immunological Tolerance = High Autoimmunity

So autoimmunity in this way is considered as a play-fight. It is good when autoimmune response is low. The common example is everyday protection of body from cancerous cells.

Some cells turn into cancerous cells each and every day. Body is able to get rid of them easily through good immunological tolerance or low level autoimmunity.

When IT comes down, autoimmune response soars and this ‘play-fight’ turns harmful to body as evidenced in all autoimmune diseases.

Scientific evidence in this direction is provided by Pioneering work by Noel Rose and Ernst Witebsky in New York, and Roitt and Doniach at University College London. They demonstrated that, at least in terms of antibody-producing B lymphocytes, diseases such as rheumatoid arthritis and thyrotoxicosis are associated with loss of IT. The defined immunological response as the ability of an individual to ignore ‘self’, while reacting to what is ‘non-self’.

How does Immunological Tolerance work in favor and against Autoimmune disease?

Actually 5 different theories are put forward to explain this. And the actual working might be a combination of one or more of them.

Frank M. Burnet and Peter B. Medawar were awarded Nobel prize in 1960 for putting this theory. They demonstrated that self-reactive lymphoid cells are destroyed during the development of the immune system in an individual as a mechanism of immunological response. (Clonal Deletion Theory)¹

Nossal proposed that self-reactive T- or B-cells become inactivated in the normal individual and cannot amplify the immune response. (Clonal Anergy Theory)²

Third concept asserts a network of antibodies capable of neutralizing self-reactive antibodies exists naturally within the body. (Idiotype Network theory by Jerne)³

Fourth theory suggests that bodyÂ’s immune responses are directed to ignore self-antigens. (Clonal Ingnorance Theory)⁴

According to Fifth theory – Suppressor population” or “Regulatory T cell” theories, regulatory T-lymphocytes function to prevent, downregulate, or limit autoaggressive immune responses in the immune system.

As mentioned earlier, evidence suggests the working of immunological response along all the five lines. These are not exclusive.

What are the different types of Immunological Tolerance?

Now, you can understand the role of immunological response in autoimmune disease. Immunological tolerance is grouped into three categories – central, peripheral and acquired.

Central Immunological tolerance develops where Thymus and Bone Marrow where respectively T cells and B cells are maturing and exposed to self-antigens.

The T Cells responsible for good immune response are selected and live on while those having poor immune response for antigens die.

Additionally T cells and B cells with good immune tolerance becomes regulatory cells that help to keep immunological tolerance.

Peripheral immunological tolerance develops in when T and B cells enter periphery and circulation.

Acquired or Induced Immunological tolerance is very important. It means that absence of immune response when it should have occurred otherwise.

The best and most important example is pregnancy where the fetus and the placenta are well tolerated by the immune system of mother.

Second best example of acquired immune tolerance is oral tolerance that evolved to prevent hypersensitivity reactions to food proteins and bacterial antigens present in the microbes living in mucus membrane of oral cavity or mouth. Failure of oral tolerance is believed to be associated with development of Inflammatory Bowel Diseases such Ulcerative Colitis and CrohnÂ’s disease.

Induced acquired immunity is very important in Organ transplant as it is important for the survival of transplanted organ. However, it is actually forced on the body using a variety of medical drugs for a long duration. ^5,6,7

Implication for Ayurvedic Treatment of Autoimmune Disorders:

For over several decades, Ayurvedic treatment for autoimmune disorders appeared to be contrary to medical treatment in concept and principles.

Corticosteroids and Immunosuppressive Drugs and Chemotherapeutic agents like Methotrexate are the mainstream of medical treatment. This paradigm and practice is governed by the concept of minimizing symptoms of autoimmune diseases through these drugs.

Ayurveda employs rejuvenative herbs or Rasayana herbs along with other groups of herbs that do provided symptomatic relief (anti-inflammatory herbs, regional or organ system health improving herbs or specific rejuvenative herbs).

Some medical doctors suggest their patients not to take herbs that might improve ‘immunity’. This really got down well with patients for whom their doctor is the ‘authority’.

Even doctor’s suggestion is naive and based on the textbooks that they had gone through and routine practices that they have seen and governed by the paradigm of medical community.

Their understanding and suggestion relied upon that herbs might interfere with drugs that they are prescribing for suppressing immunity of a person suffering from autoimmune disorders.

However, rejuvenative or Rasayana herbs of Ayurveda do positively affect immunity and have many benefits that is beyond the medical concept of immunity (Channel cleansing effect, Effect on Metabolism, Antioxidant, Adaptogenic, Nervine, Antistress, Herbal Nutrients) and might not be well understood by medical community because they are usually trained on analytic grounds.

And I am not saying this to lower their system or practices. Medicine really has done marvels in almost all fronts, at least in broadening the understanding. This concept of immune tolerability is entirely a medical concept.

But it very well fits in and might be helpful in describing how Ayurveda herbs and treatment might give benefit to patient without having immunosuppressive effects, and with their possible immune boosting effect.

Ayurvedic treatment for autoimmune disorders might benefit by improving immunological tolerance of body, and thereby, body could tolerate easily and its autoimmunity and autoimmune response might stay in ‘CHECKED’ or ‘CONTROLLED’ condition.

And it is really happening in all healthy individuals naturally!

Don’t you think that good and optimal immunological tolerance is safeguarding all otherwise healthy persons from autoimmune disorders?

I, Dr. Vikrama Aditya Tomar, believe so and hope that Immunological Tolerance might bridge the understanding of Ayurvedic Treatment for Autoimmune disorders in a better manner.

References:

1. Edwards JC, Cambridge G, Abrahams VM (1999). “Do self perpetuating B lymphocytes drive human autoimmune disease?”. Immology 97: 1868–1876.
2. Stefanova I., Dorfman J. R. and Germain R. N. (2002). “Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes”. Nature 420 (6914): 429–434. doi:10.1038/nature01146. PMID 12459785.
3. Pike B, Boyd A, Nossal G (1982). “Clonal anergy: the universally anergic B lymphocyte”. Proc Natl Acad Sci USA 79 (6): 2013–7. doi:10.1073/pnas.79.6.2013. PMC 346112. PMID 6804951.
4. Jerne N (1974). “Towards a network theory of the immune system”. Ann Immunol (Paris) 125C (1–2): 373–89. PMID 4142565.
5. Hurakadle, Kobkate Lalalpure (2011), Textbook bof Pharmaceutical Biotechnology, pp. 22–23, ISBN 81-312-2828-2
6. Mayer L, Sperber K, Chan L, Child J, Toy L (2001). “Oral tolerance to protein antigens”. Allergy 56 (s67): 12–5. doi:10.1111/j.1398-9995.2001.00904.x. PMID 11297999.
7. Wiener HL (October 2000). “Oral tolerance, an active immunologic process mediated by multiple mechanisms”. Journal of Clinical Investigation 106 (8): 935–7. doi:10.1172/JCI11348. PMC 314352. PMID 11032852.