A Loss of Tolerance

1 Comment2 December 2019

I had the pleasure of attending 15 hours of post graduate education on autoimmunity treatment applications and clinical strategies by the Kharrazian Institute earlier this month and I wanted to write a few blogs over the coming months with some bite size pieces of information to help any of you that follow me. 

This post is on the very important area of losing tolerance - and I’m not talking about with your children or partner! 

Autoimmunity is highly complex and multi-faceted, with many overlapping possible causes (I purposely say “possible” as autoimmunity is not a one cause one treatment condition). As a functional health practitioner, with a particular interest in best supporting clients with autoimmunity to lessen symptoms and reduce  “flares”, a fundamental factor to try and manage initially is the area of “Immune Tolerance”.  

The body has three key mechanisms of protection against food reactivity and autoimmunity:

  • Oral tolerance

  • Central tolerance

  • Peripheral tolerance 

In this blog I will explore oral tolerance in more detail, and show how when this is “lost”, foods, chemicals and antigens-bacterial, viral and stealth can induce autoimmunity, and play a significant contributing factor. 

What is Oral Tolerance

Oral tolerance is the state of preventing and inhibiting immune system reactions and responses through the oral route.  Researchers use the term oral tolerance to explain whether a person’s immune system can tolerate acceptable foods while responding appropriately to bacteria or other harmful compounds. Technically, it is referred to as dietary protein tolerance, but I will call it oral tolerance for the sake of simplicity.

There are other types of tolerance:

  • Chemical tolerance is the ability to appropriately tolerate the many chemicals in our environment. People with loss of chemical tolerance have chemical sensitivities, such as to gas fumes or perfumes.
  • Self-tolerance is the immune system’s ability to respond appropriately to the body. The immune system must remove dead and dying cells and repair areas of injury, but in loss of self-tolerance it attacks and destroys healthy tissue, thus creating autoimmune disease.

How Oral Tolerance works 

I want to take you on a journey of parts of the immune system to better explain how a loss of tolerance occurs and then what steps we can implement to work at restoring tolerance.  

A large and significant part of the immune system resides in the mucosa (innermost layer) of the small intestine in the gut. This mucosal lining is made up of the largest collection of lymphoid tissue and lymphocytes - white blood cells.  

Firstly Dendritic cells:

Dendritic cells are immune cells that roam the small intestine. These cells have have long arms that sample different proteins (viruses and bacteria have protein structures on their cell membrane too) and determine whether the immune system should react to them.

A key component of loss of oral tolerance and multiple food sensitivities is over reactive dendritic cells.

So what causes dendritic cells to become overly reactive? Proteins that aren’t thoroughly digested due to deficiencies in stomach acid and pancreatic enzymes is one cause. Low SIgA -antibodies that are a first line of defence in the gut (more on this in a minute), are another. We can address hyper-reactive dendritic cells by a) improving breakdown of proteins and b) increasing SIgA levels. 

A. Improve breakdown of proteins

We need sufficient levels of hydrochloric acid (stomach acid) and adequate pancreatic as well as brush border enzymes to properly break down proteins so they become single amino acids, as the immune system doesn’t react or respond to these. It responds to peptides, which are proteins that aren’t broken down properly. 

Hydrochloric acid (HCl) is the stomach acid vital for digestion of proteins and activating the release of digestive enzymes. Enzymes are necessary to break apart these chains of amino acids called peptides and so the dendritic cells don’t become overactive.

It is also important to avoid artificial food colourings. Artificial food colourings have been shown to bind to proteins, thus preventing their breakdown. Avoid artificial food colouring for this reason.


B. Boost SIgA level

Immunoglobulin A (IgA) is an antibody, and in its secretory form, SIgA is the main immunoglobulin found in mucous secretions, such as the small intestine. SIgA is the first line of defence against bacteria, food residues, yeast, parasites and viruses, and imbalances may provide the link between gut imbalances and systemic illness. SIgA is also an important part of intestinal immune health by keeping pathogens from attaching to the intestinal lining and plays a vital role in preventing over triggering dendritic cells by surrounding immune reactive proteins and degrading them. I describe sIgA as a form of antiseptic paint that lines the small intestine. This form of protection if you like, keeps the dendritic cells from becoming overstimulated due to constant bombardment.

Low SIgA levels are common with high levels of stress, chronic infection, hydrocortisone or other steroid medications, or vitamin A deficiency.

Ways to boost low SIgA include addressing the underlying cause and this infographic, adapted from Thomas Guilliams, Ph.D. shows beautifully how a functional approach is required as addressing “stress” is not a quick and easy fix. All these factors will chronically tax the immune system and cause a low SIgA.





Secondly Regulatory T cells:

Regulatory T cells (T reg cells) are somewhat like a gatekeeper or peacemaker helping to keep the immune system in check so it doesn’t go on the rampage at every opportunity and cause out-of-control inflammation. Poor T reg responses are a primary factor in all autoimmune conditions.

We can significantly influence T reg cells to dampen the inflammatory response and therefore modulate the immune system away from a far more aggressive immune response or reaction - the ultimate of which is autoimmunity. Compounds that act on T cells to dampen inflammation include glutathione, vitamin D, omega 3 fatty acids, short chain fatty acids (SCFA), colostrum and endorphins (from exercise, laughter, positive relationships, etc.).

Thirdly Liver function plays a key role in oral tolerance: 

The dendritic cells also carry proteins to the liver. There, immune cells called  “Kupffer cells” can trigger inflammation if the liver is overloaded or has poor detoxification function. Supporting liver function and liver detoxification pathways is helpful. 

Finally, research has shown a rich diversity of gut bacteria is essential to maintaining oral tolerance with the main body of research is centring around short chain fatty acids (SCFA’s).

SCFAs are molecules produced by bacteria when they ferment dietary fibre and also plant polyphenols inside the colon. Some of these molecules stay close to home in the gut, but others travel far and wide throughout the body, taking part in complex interactions that produce various effects on health and are the subject of active scientific study. SCFAS (in particular, the SCFA butyrate) have anti-inflammatory effects and seem to play a part in kick-starting the differentiation (that is, specialisation) of immune cells that help ‘keep the peace’, called regulatory T cells.

Many factors can sabotage this homeostasis such as peritoneal and gastrointestinal  infection, chemicals, medication, dietary proteins and peptides, chronic stress, hormonal imbalances - especially thyroid and  blood sugar imbalances can definitely also weaken digestive health and function. This in itself highlights the beauty of applying a functional approach to best supporting autoimmunity, as there can be, and are many contributing factors to autoimmunity and there isn’t one single magic bullet. 

However, I do hope this information gives you another puzzle piece to fit into your overall health journey. 


In health, Tanya x