How the Immune System can Control Your Behavior

If someone you love is experiencing depression or finding less pleasure in social activities, you might want to look deeper.   It is quite possible that hidden infection or inflammatory condition may be causing the changes you observe.  Have compassion...there is often more to it than meets the eye.  I have seen many relationships crumble when one person is suffering from immune dysfunction and social isolation and the other does not see the illness for what it really is.

Our immune system is a powerful force inside each one of us!  This protective system is charged with the job of responding to foreign invaders to keep us in optimal health.  Most of us don't think too much about this system until it is not working correctly.  I treat many patients that suffer from overactive or under-active immune systems due to chronic infections, like tick-borne diseases;  toxic exposures, like mold and mycotoxins; or autoimmune diseases, like multiple sclerosis, lupus or Hashimoto's thyroiditis.  Although many patients understand the important role of the immune system in protection and defense, few people know that it also controls our behavior.  A recent study in Nature discussed the role of cytokines activated when the immune system goes on red alert and the connection to social isolation and autistic behaviors.  It's even plausible that changes in immune function may lead to personality changes!

Sickness and Depression

Perhaps no connection has been more studied than that of immune activation and inflammation and the link to depression.  Systemic infections cause the patient to allocate limited resources, conserve energy and prevent spread of infection.  The resulting sickness behavior is common to most infections, including viruses, bacteria and multi-cellular parasitic infections.  There is a broad spectrum of symptoms – fever, nausea, decreased appetite, malaise, fatigue and achiness – all of which may aid in the fight to conserve resources and increase isolation-type behavior.  In animal models we see sickness associated with a decrease in time  seeking interaction with a other animals as a result of diminished motivation for social exploration.  Symptoms of depression appear after pro-inflammatory cytokines are produced by the body or if they are administered experimentally. The fact that inflammation often leads to later depression suggests a cause–effect relationship.  It indicates that immune activation can precipitate depression. Many symptoms of inflammation-induced depression overlap with sickness behaviors, including fatigue, changes in sleep pattern, lack of interest in daily or pleasurable activities (anhedonia), changes in appetite or body mass and unexplained aches and pains

Inflammatory Cytokines and the Brian

A recent article about inflammatory cytokines and brain signaling discussed inflammation and the brain:

When considering the pathological signaling cascades in immunological disorders of the brain, certain cytokines might be considered of key importance, with their presence determining the course of a particular disease. Interleukin-1 (IL-1), IL-6, IL-17, and TNFα are critical for the pathogenesis of inflammation in certain brain disorders. Targeting these cytokines or their receptors can alter the course of several neurological diseases, but the effects may be beneficial or harmful.

We understand from this article that the inflammatory signals of the immune system (cytokines) have a profound effect on the brain.  Many patients battling systemic inflammatory or autoimmune disorders suffer from an "inflamed brain" and all that goes with it... symptoms like depression, anxiety and insomnia.  The role of cytokines on behavior can be summarized by saying that TNFα (sickness and depression) and IL-1β (sickness) alter behavior by direct actions on neurons of the brain.

Gaba may affect the immune system too...

GABA, an inhibitory neurotransmitter in the brain, has a similar inhibitory effect on the immune system. Antigen presenting cells (APCs) of the immune system have gaba receptors and therefore, gaba can directly inhibit the function of these immune cells. What this means is the neurotransmitter from the brain may have a direct inhibitory effect on the body's immune system.  This article on Gaba and the immune system states....Intricate and reciprocal regulatory relationships exist between the nervous system and the immune system, mediated in part by chemical messengers.

 

Insults to the body, from the outside or from the inside, activate cells of the innate immune system. 

[PHOTO SOURCE HERE]

Low SIgA and why it matters to your gut health!

What is SIgA?

IgA is a type of antibody that protects against infections of the mucous membranes lining the mouth, airways, and digestive tract... it is your first line of defense on the mucosal lining and it makes up a majority of your entire immune system.

Some people have a genetic deficiency and present with low levels of SIgA and frequent infections.  Others acquire a low level after their intestinal tract becomes over-run with abnormal microbes.

SIgA helps to shape the composition of the microbes in your gut!

Extraordinary amounts of immunoglobulin A (IgA) are produced in your intestinal mucosa daily, it is known as SIgA and is secreted into the human gastrointestinal tract. SIgA production is driven largely in response to mucosal antigens (bugs or food) encountered by gut-associated lymphoid tissue (GALT).  It is clear that secretory antibodies are directed against at least two broad classes of antigens. The first is associated with enteric pathogens (the "bad guys" or infections) and their virulence factors, or things that the bugs secrete, like toxins.


The second broad class of antigens recognized by SIgA is associated with the intestinal microbes or commensal microflora (the "good" guys, like probiotics). In experimental animal models commensal bacteria are potent inducers of secretory antibodies; in humans, it is estimated that between 25 and 75% of intestinal bacteria are coated with SIgA.  This could explain why one of the most basic ways to improve levels of SIgA is to give a patient probiotics and saccromyces boulardii. 

There is also evidence from mice that secretory antibodies play an important role in shaping the composition of the intestinal microbiota, which in turn can influence your gut's defense against invaders and enhance resistance to the intestinal infections.
  
Profound Role in Intestinal Balance and Your Health

So because SIgA can neutralize the "bad guys" and shape the "good guys" SIgA plays a profound role in intestinal balance and health.  SIgA is the main immunoglobulin in mucus secretions. The intestinal cells produce about 2-3grams of SIgA every day!  And production tends to peak in childhood and start to decline after about sixty years old.

This is our first-line defense against gut pathogens like bacteria, food proteins, parasites, fungi, toxins and viruses. SIgA antibodies prevent micro-organisms, food proteins and cancer-causing substances from binding to the surface of absorptive cells. Effectively, they attach themselves to invading bugs and trap them in mucus to prevent them from going anywhere!

The antibodies also 'tag' foods as acceptable to the body and this suggests why low SIgA levels can be a factor in developing and progressive food allergy and intolerance. Intestinal permeability is also related since, if levels are low, repair of mucosal tissues can be compromised.  This is often referred to as Leaky Gut and can coexsist with low levels of SIgA.

Certain SIgA antibodies have been shown to directly quench bacterial virulence, whereas others help with uptake of SIgA–immune complexes by mucosal dendritic cells and result in down regulation of pro-inflammatory responses normally associated with pathogens and allergic antigens.

In fact it is becoming increasingly evident that human health is inextricably linked to the gut microbiota, intestinal homeostasis, and mucosal immunity. IgA is at the centre of this dynamic. 

Testing your SIgA

Secretory IgA is quite independent of blood IgA levels so just because one is normal, doesn’t mean the other is.   SIgA can be measured in different ways, including stool and saliva. Levels can turn out to be low or high. Stool measurements have traditionally been based on sample extractions from animal models – it is hard to ask a mouse to spit! Salivary samples provide a systemic overview of circulating SIgA.

Ongoing low levels can help to explain why people can’t shift an immune problem like allergies, chronic skin conditions or infections. It can also explain why they find it hard to get rid of a microbial infection, too. Celiacs and those with IBD can have low levels and chronic stress has a major effect on SIgA levels. Certain medications can lower levels – including anti-inflammatories.   Other factors  includeviral infections (like Epstein Barr viruses), poor nutritional status, food allergies, ongoing stress. Interestingly some studies have shown variations in levels with gender and age – male patients often have lower levels.

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