The Importance of Achieving a Balanced Immune Response

by Dr. Susan Tanner, MD

The topic of immunity is vast and complicated for patients and practitioners alike. We use many terms to describe different parts of the immune system and how they impact the body as a whole. We strive for a balance in the immune system; one that is protective against infection and not overly activated to cause massive inflammation and self-attack or autoimmunity. The impacts of the environment with special recognition to mold as well as to certain illnesses (COVID 19 being one) combine with individual genetics to have both temporary and long-lasting effects on immune balance–it is a nuanced and complicated subject. Thus, while there are many ways of discussing immune balance and response, I decided to rely heavily on the work of Dr. Robert Rountree to help me with this article. Dr. Rountree was the 2015 recipient of the Linus Pauling Award, and his definitions of different types of immunity have a way of making this extremely complex subject both understandable and sensible. Additionally, each of Dr. Rountree’s explanations of immunity can be impacted and modified by a person’s environment, diet, and specific nutraceuticals, making his approach valuable for the reader.

Immunomodulation

Many immune-related conditions are on the rise. As clinicians, we see more allergies, asthma, recurrent infections, and autoimmune diseases than ever before. We also see resistant infections and a rise in certain types of cancer, like non-Hodgkin’s lymphoma. And, unfortunately, these problems seem to only be getting worse.

Different immune-related conditions have different mechanisms at play, but they also have a common thread: None develop overnight. There are pathophysiologic mechanisms in place that persist for years or even decades before the condition fully presents. That begs the question: Is there a rational and systematic approach that we can take to support the immune system in becoming stronger and healthier to thwart exterior and interior threats and breakdowns?

That’s where the concept of immunomodulation comes in.

When we talk about immunomodulation, we aren’t talking about treating a specific disease or symptom. Rather, we’re talking about regulating, balancing, and supporting a healthy immune response. If we can succeed in doing this, then we may be at a lower risk of developing immune-related conditions and will be able to enjoy a better quality of life.

Barrier Integrity

Let’s start with barrier integrity. A critical determinant of health is that microbes stay in the right place. Some of the healthiest microbes in the gut become deadly if they enter the bloodstream. If the gut barrier is compromised, fragments of microbes cross into the bloodstream and activate an immune response.

A good example of barrier compromise can be illustrated with lipopolysaccharides (LPS), fragments of the outer membrane of gram-negative bacteria. Also known as endotoxins, LPS are widely present in the lumen of the intestines. If a large amount breaches the gut barrier, it causes endotoxic shock. Endotoxemia from LPS is similar to what happened years ago when tampons caused toxic shock syndrome; tampons irritated the vaginal mucosa enough to create a breakdown of barrier function and allow innocuous vaginal bacteria into the bloodstream, where the bacteria then could become deadly. With LPS, if a small amount crosses from the gut into the bloodstream, it activates an inflammatory response. When this situation becomes chronic, it is called “metabolic endotoxemia”. Metabolic endotoxemia is thought to be one of the primary instigators of inflammatory disorders, including obesity, metabolic syndrome, and type II diabetes.

Barrier function is important not only for the gut and vagina but also for the sinuses and skin. At all of these barriers, immune cells such as dendritic cells, macrophages, and natural killer cells lie just at the surface. Collectively, these immune cells are called sentinel cells, and they extend tendrils through the barriers so that they can continually sample the microbial mix on the other side. It’s where they monitor for pathogens and other threats. In situations of moldy environments, the inhaled mold spores are the invaders. And just as tampons were able to create a storm of inflammatory devastation secondary to an infection, so can mold and mycotoxins do the same upon entry to the body.

Priming of Innate Immunity

The second immune mechanism is the “priming of innate immunity”. The dendritic cells and other sentinel cells that patrol the barriers of the body have receptors called toll-like receptors (TLRs) on their surfaces. These receptors recognize two types of molecular patterns on other cells: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs).

Think of PAMPs as the “stranger” and DAMPs as “danger” signals. Here’s how the process works.

PAMPs are the first molecular signal, and they’re ubiquitous. The resident microbes of the gut, sinuses, and other barriers all have PAMPs on their cell surfaces. Our dendritic cells sample those patterns and begin to recognize them as pathogens, but don’t mount a full-on immune response. The PAMPs simply prime innate immunity so that the response will occur when the need arises.

DAMPs are the second molecular signal. DAMPs are molecular fragments that are released when cells have been damaged. For example, if the gut lining erodes from taking medications or drinking too much alcohol, the damaged cells release fragments of mitochondria or nuclear DNA—both of which are recognized by sentinel cells as DAMPs. If the sinus lining is damaged by the presence of molds and mycotoxins, a similar situation arises.

The presence of DAMPs alerts the innate immune cells to danger. It switches the primed cells from quiescence into action. Now they’re on fire. They start to program lymphocytes, which differentiate into either regulatory or inflammatory T cell lines and activate B cells to produce antibodies. Physically this can result in allergies and in reactive tissues. When the damage continues, so does the inflammatory response to the point where it can affect every system of the body.

Redox Balance

Finally, we have redox balance. Redox balance means the balance between free-radical and antioxidant activity inside cells. Environmental toxins are some of the biggest offenders when it comes to disrupting redox balance. A good example of this is mycotoxins produced by molds. Because we breathe in over 3,000 gallons of air per day, you can easily see how moldy air inside your home can disrupt redox balance quickly and drastically.

Dendritic cells are exquisitely sensitive to intracellular redox balance. If redox balance is disrupted, dendritic cells can become either underactive or overactive. This type of mechanism explains why too many free radicals can lead to immune-related problems. This also gives more insight into why certain antioxidants, particularly vitamin C and glutathione, are so very helpful in treating mold-related illness. It is not just about detoxification of the liver but also about reestablishing the redox balance that is so heavily impacted.

Causes of Immune Problems

Malnutrition is much less likely to be the cause of immune problems in modern times. Environmental toxins, poor diet, sugar excess, and emotional stress are more likely to influence immune function today. For example, the number one risk factor for developing rheumatoid arthritis is smoking tobacco. Many different toxins and air pollutants have been implicated in other autoimmune diseases, most notable are mycotoxins from mold. The amount of autoimmune thyroid disease has risen exponentially as mold cases have been more and more prevalent. Other toxins (chemicals, pesticides) and stress are also major contributors to oxidative stress and immune cell damage.

Another theory as to why immune-related conditions are on the rise has to do with overly clean (and by this, I do NOT mean mold-free, but overly used cleaners and disinfectants) in our home environments and the overuse of antibiotics. People living in developed countries have significantly less diversity of their gut microbiomes than those who live closer to nature. According to Dr. Martin Blaser, author of Missing Microbes, each successive generation has less diversity than the one before. The microbes in the gut play such an important role in educating the immune system that their depletion compromises immune health. The molecular mechanisms of immune function become impaired.

Helping Our Immune Systems

What can we do to strengthen, and just as importantly, regulate and modulate our immune systems so that they are robust, protective, but not inflammatory? Besides starting with our “clean air, clean food, clean water” rule of eliminating or greatly reducing airborne toxins, food additives, and impure water, there are several helpful nutritional protocols to consider.

Probiotics For Barrier Function and Immune Programming

One of the obvious ones when it comes to barrier immunity is probiotics.

Probiotics are useful for supporting the barrier function of the gut, sinuses, and other body surfaces. But it’s important to understand that probiotic supplements don’t colonize. Instead, they make the mucosal environments more friendly for colonization with healthy microbes.

For instance, we see that if we supplement a single strain of probiotics (such as Lactobacillus GG) for a few weeks and then evaluate the microbiome, there’s an increase in the range of beneficial bacteria. What’s happened is that the probiotic supplement created an environment to support more diversity. This leads to improved barrier function.

Probiotics support barrier function, but they also interact with immune cells to support immune programming. The pathways are not entirely understood, but we see that probiotics program dendritic cells to turn naïve T lymphocytes into T regulatory cells, which keep the inflammatory response in check. This mechanism is especially evident in the developing immune system. When we give probiotics to infants, for example, it helps to program their immune systems and reduce the chance of the onset of immune-related issues.

Zinc

We have all heard a lot lately about the use of zinc for immune function. Zinc is another nutrient to consider for barrier function. Zinc carnosine is often used for upper gastrointestinal support, but zinc picolinate is equally effective for general gastrointestinal barrier support as well as for the support of the mucosal membranes of the sinuses and respiratory passages. This gives a bit more specific reasoning to using zinc both for the prevention of COVID and other viral respiratory illnesses and for the treatment of allergies and overall immune reactivity.

Beta-Glucans, Medicinal Mushrooms, and Echinacea

Medicinal mushrooms have a similar proposed mechanism of action as probiotics. These mushrooms carry molecular structures on their surfaces, known as beta-glucans, that are similar to the PAMPs on yeast. The beta-glucans interact with the same TLRs on dendritic cells as yeast does. Reishi and other medicinal mushrooms that have been used for thousands of years carry these molecular markers. When consumed as a food or dietary supplement, they prime the innate immune cells and support a balanced immune response. Beta Glucans is a high-quality beta-glucans supplement that can be used for this purpose.

Echinacea species are similar to mushrooms, in that they contain compounds that interact with TLRs on immune cells to keep them primed. Some in vitro studies show that when you expose immune cells to echinacea or mushrooms, they start producing inflammatory cytokines. That has concerned some clinicians and scared them away from using these botanicals in certain patients. But modern immunology simply shows that mushrooms and echinacea have molecular structures that are priming immune cells, which explains the apparent paradox. What appears to be inflammatory in cell culture has a balancing and supportive effect on the human body.

Antioxidants and Other Supplements

Nutrition and supplementation can make a huge difference when it comes to antioxidant defenses. One simple intervention is supplementation with glutathione or glutathione precursors. Glutathione is a potent cellular antioxidant, and N-acetylcysteine (NAC) is its rate-limiting precursor. These compounds can be taken internally for systemic support.

Other antioxidant nutrients, like vitamins A, C, D, and E, can synergize to support redox balance. Many herbs also support redox balance—especially turmeric or its active compound, curcumin.

Many of the nutrients mentioned work via multiple mechanisms and support multiple pathways. L-glutamine is a good example. L-glutamine supports barrier function, serves as a fuel source for immune cells, and is a building block for glutathione.

There is another master immunomodulator that I must be mentioned: vitamin D. There are over two decades of research showing that vitamin D regulates immune cells and supports immune function. Something to keep in mind about Vitamin D is that the immune benefits seem to be greater with a daily dose rather than a large weekly or monthly dose of vitamin D. Also, bear in mind, this needs to be the activated form, Vitamin D-3, not D-2.

Immunomodulation has also been very positively impacted by the use of Sinus Defense, especially for mold-harmed patients. Sinus Defense is a homeopathic formula from Micro Balance, which balances both the impact of barrier and priming immunity. It contains homeopathic dilutions of transfer factors for a broad range of molds, allergens, and other environmental pathogens, which primes the immune system to recognize them and know how to react more efficiently and effectively when those same invaders are encountered in real life and circumstances. Many mold patients who normally would be debilitated after a subsequent mold exposure find that with regular use of Sinus Defense, they react less and recover faster.

An important note here:

Optimal health can’t all be about supplements. If a person is under a huge amount of stress, not exercising, or living in a polluted environment, supplementation will not be enough to turn things around. A vicious cycle can develop with illness from mold, for example, causing immense stress on so many levels. Studies have shown that stress hormones act as PAMPs, and further burden the immune system, increasing inflammation and lowering protection, and so it goes. I tell my patients to intervene on every level possible. Your air, water, and food are modifiable to a large extent. Techniques such as meditation, prayer, and EFT tapping cost nothing and can help with stress management. Similar to exercise, making these changes takes time, commitment, and discipline, but it is doable and certainly worth it in the long run for health and wellbeing.

(Note: Supplements mentioned here are available under many very good brand names on my practitioner page on Wellevate and at Micro Balance Health Products)