Takeaways Hail to the Immune System
“The most powerful therapeutic in the world is our own immune system.”
—Francis deSouza, American entrepreneur
Remember, the mouth is the gateway to the entire gastrointestinal tract. It’s the front entrance. You don’t leave your front door unlocked, do you? You need protection at the front of your home so that only people you choose can enter. Likewise, the mouth is equipped with defenses to protect the body from potentially harmful outside invaders. However, most of what comes into the mouth is not dangerous: It’s mainly food, water, pollen, friendly bacteria, friendly fungi, etc. So, the immune system has to figure out who is a bad guy and who is a good guy.
An Epic Game of “Where’s Waldo?”
The immune system is incredible. I liken its job to the Where’s Waldo? book series. The exercise in these books was to comb through huge crowds of people to find Waldo, a single quirky guy wearing red-and-white stripes and a hat. Likewise, the immune system has to find Waldo, in this case a pathogenic “bad guy,” and make sure all of the defenses are up wherever Waldo may try to gain entry. On the other hand, the immune system has to ignore everyone else who is totally harmless—the good and neutral microbes. And the immune system has to remember who is who, over time, without making mistakes. This is no easy job.
There are two major branches of immune function at the mucous membrane, and they have to work together. The first line of defense is called the innate immune system because humans have evolved it over millennia. The second branch is the adaptive immune system (also called the acquired immune system). As the name implies, this is the part of the immune system that can learn as it goes. It has a memory. When you get exposed to a new thing, your adaptive immune system can remember whether it is a good guy or a bad guy.
Your immune system operates within an infrastructure of base camps and superhighways that make up the lymphatic system. Lymph tissues include lymph nodes, tonsils, and other tissues and organs that fight infections in the body. This is how the body delivers immune-fighting cells from the tops of our heads to the tips of our toes. Mucosa-associated lymphoid tissue (MALT) is the immune system network that monitors and protects the mucosal surfaces of the body. If the mouth lining, or epithelium, is the frontline of the battle, the MALT act as the headquarters where immune “soldiers” congregate, get their orders, and head back out to battle. The tonsils, salivary glands, and adenoids are the principal MALTs in the oral cavity.30 In the gut, these headquarters are called gut-associated lymphoid tissue (GALT), and in the nose it is called naso-pharynx associated lymphoid tissue (NALT).31 Lymph nodes are other major basecamps in the infection-fighting network. They are knots in the net of lymphatic vessels. Each lymph node is filled with immune cells called lymphocytes. They act like filtering stations to purify the lymph before it enters the bloodstream. Lymph nodes are the prime sites where immune cells congregate, get orders, grow their armies, and head back out to the tissues to continue protecting and defending. Lymph is a clear fluid that irrigates our bodies, supplying us with immune fighter cells and keeping our body fluids in balance.
The Innate Immune System and the Barrier
The innate immune system is somewhat straightforward, perhaps because it is so ancient. It has evolved over millennia. It acts as the first line of defense against threats and recognizes foreign invading microbes and destroys them. But before we get into how the innate immune system eliminates the enemy, let’s take a minute to recognize the physical barrier itself.
The first part of our innate immune defenses in the mouth is the physical barrier itself, the oral mucosa. The mucosal barrier has to keep bad stuff out but let the good stuff in. For instance, it is responsible for keeping disease-causing microorganisms out but letting food and nutrients in. It also has to let beneficial microbiota hang around. This is a delicate balance to uphold. As we discussed in Chapter 3, the cells in the oral mucosa are flattened and lined up, one over another, to form a continuous sheet of tissue that is hard to penetrate, yet porous. It is thicker and denser that the gastrointestinal mucosa but nevertheless still permeable and fragile. The mucous membrane is also coated in a dense layer of mucin, or snot. The barrier is also covered with saliva, which contains immunoglobulins, antimicrobial proteins, and enzymes that can ward off bad guys.32
Meanwhile, the innate immune system is ready to pounce. It uses proteins called Toll-like receptors to look for unwelcome microorganisms. Toll-like receptors stick out of the epithelial lining into the mouth and fish for suspicious foreign invaders. Dendritic cells, a type of immune cell, sit on the oral mucosa and project their little fingers, called dendrites, into the oral cavity. Dendritic cells take samples, recognize microbes, and report them back to headquarters (launching an immune response through the adaptive immune system’s T cells, which we will discuss next).33 Other innate immune cells include natural killer cells, macrophages, neutrophils, eosinophils, and basophils. These cells basically eat the bad guys or release toxic bombs to destroy them.
The adaptive immune system is responsible for eliminating bad bacteria, viruses, tumors, and parasites. It also tells the body to tolerate harmless foods and microbes, or see certain foods as dangerous (for example, food allergies). Adaptive immunity is a slower response than innate immunity but has the benefit of being able to adapt to whatever new and unusual threats come our way. Even better: It remembers its enemies, so if they try to come around again, they are easily eliminated.
The Immune System in the Mouth and in the Gut
So many things about the mouth and the gut are similar, including the architecture and the immune defenses. The epithelial lining of the intestines is nearly identical to that in the oral cavity, and since so much more is known about the gastrointestinal mucosa, it serves as a model to understand the mucosal lining elsewhere in the body, including the mouth.34 One slight difference is that the epithelial lining in the gut has only one layer of cells, whereas the oral mucosa has multiple layers. The MALT in the mouth is very similar to its corollary in the gut, the GALT. Have you heard that 70 percent of your immune system lives in your gut? They are talking about the GALT, or the immune system tissue found at the gut lining. So, everything that we discussed earlier regarding the innate immune system and the adaptive immune system in the mouth applies to the gut as well. The entire mucosal surface of the gastrointestinal tract, starting with the mouth, is heavily armed with infection-fighting superhighways and headquarters.
In the mouth, when foreign molecules (antigens) bind to the mucosa, they go through an assembly line–like process during which the adaptive immune system decides on a response. The immune system has three levels of staff: guards, headquarters, and combat soldiers. First, guards in the MALT such as dendritic cells or M cells sample all of the stuff coming into the mouth. Dendritic cells can either recognize a harmless outsider and tolerate it or they can recognize a harmful invader and launch an attack. If they detect a bad guy, dendritic cells at the headquarters of the MALT then tell the combat cells, T and B lymphocytes (T and B cells, for short), to replicate themselves, then stalk and destroy the antigens. T cells attack dangerous cells while B cells clean up the hallways and alleyways between cells. In other words, B cells help keep the space between cells clear of bad guys. B cells produce antibodies specific to each foreign invader. Antibodies are proteins that tag a harmful invader by perfectly binding to it like a lock and key. Once an invader is tagged, the immune system can neutralize or dispose of it. Antibodies help spread the word about bad guys far and wide. Immune cells can communicate all of this information with the help of proteins called cytokines, which can either encourage or discourage attack and inflammation.
In this way, the immune system records a biochemical memory, or imprint, that perfectly identifies the antigen and can be communicated throughout the body so that the antigen is destroyed and never allowed to enter the body—and if it does, it can’t get very far. This is a huge over-simplification of the immune system, so please do further reading on this fascinating topic if your interest is piqued.
As you can see, the immune system is armed and dangerous. And if the immune system unleashed its fury on the human body, it would be brutal. So, there are checks and balances in place to control the immune system. Regulatory T cells, sometimes called Treg cells, dampen the aggressive actions of the other T cells. They can even kill aggressive T cells. Treg cells actually calm down the immune system and teach it tolerance. This helps pull the reins on the innate and adaptive immune responses so they don’t overreact and harm the host.35 If Treg cells are defective, autoimmune diseases, allergic diseases, and inflammation can spiral out of control.36
Another important immune tool is found in your mouth. Your saliva is loaded with secretory IgA (sIgA), an immunoglobulin produced by B cells in the oral mucosa. It helps trap and eliminate foreign invaders by binding to them, and keeps them from penetrating the oral mucosa or getting into the bloodstream. When something new arrives in the mouth, this component of your adaptive immune system tells everyone else in the neighborhood. It even makes sure that signals are sent downstream so that the gut mucosa can make sIgA antibodies against the new foreigner, too—the oral mucosa helps inform the gut mucosa what is to come.37 This illustrates that the oral immune system is closely connected with the gut immune system. They are two stops on the same bus line, after all!
The Microbes and the Immune System Do a Dance
Remember the game of “Where’s Waldo?” that the immune system is so good at? Here is the other side of the coin. Aside from pinpointing, attacking, and eradicating the bad guys forever, the immune system has to identify and tolerate (or ignore) the good guys. Enter your normal, healthy oral microbiota. These are microbes that the immune system has worked out an agreement with. They are allowed to hang around. Some of the microbiota actually send signals that tell the immune system to calm down and look the other way. Others stimulate the immune system and help it improve its surveillance. Regulatory T cells are part of the adaptive immune system and promote tolerance, as mentioned earlier.
The oral microbiome can suppress the body’s immune reaction or stimulate and “prime” it. Microbial populations have also worked out ways to evade the immune system so that they can hang around without being bothered. It is generally believed that commensal bacteria keep inflammation in the gut and mouth to a minimum. In a healthy mouth, pro-inflammatory and anti-inflammatory mechanisms are kept in check. Certain oral commensal microbiota may affect this balance by decreasing inflammatory cell messages, promoting anti-inflammatory regulatory T cells, or activating immune cells.
Good bacteria can act like anti-inflammatory agents and can promote tolerance. We don’t fully understand all of the ways that they do this. However, one of the strongest lines of evidence is that when mice don’t have any good bacteria, they develop food allergies. Good bacteria, therefore, educate the immune system so that it doesn’t mistakenly attack harmless foods.38
Lactobacillus species, a friendly bacteria found in probiotic supplements, can calm down immune messages and ramp up anti-inflammatory chemical messages. Up to 30 to 40 percent of Streptococcus species from the tongue and dental plaque can “scare off” immune cells that are attracted to the gums, thereby protecting their communities from attack.39
All of this, and nothing to mention of their role in preventing invasion and infection! I think it’s fair to say that good bacteria are partners with the ”superorganism” immune system, if not officially part of it. As mentioned in Chapter 1, humans together with our microbial inhabitants are considered “superorganisms.” Good bacteria block out or prevent colonization by bad bugs for us each and every day. Remember, this is one of the most important services our little critters do for us.
All of these incredible mechanisms that defend and protect us contribute to our overall levels of inflammation. I think of it as chemical and biological warfare. Inflammation in small doses is very healthy and keeps us in tip-top shape. The immune response needed to kill a pathogen is vital to our survival. Yes, you feel bad when you get sick, but your immune system is going hog-wild eliminating the culprit. In the process, the immune system fires off ammunition to kill the enemy, which causes inflammation, pain, and fever, among other symptoms. But the result is to successfully get rid of the bad guy and never have trouble with him ever again (the immune system has a memory, as we discussed in The Adaptive Immune System starting on page 27).
When inflammation is excessive, however, we have a whole other type of problem. Chronic inflammation suggests that the immune system is overreacting. The innate and adaptive immune systems are super powerful and potent. They don’t mess around. So if they unleash their fury for the wrong reason or for an extended period of time, they are very harmful. Inflammation is a major feature of periodontal disease, heart disease, Crohn’s disease, ulcerative colitis, and more. We are going to talk more about inflammatory diseases in Chapters 6, 7, and 8. Just remember that chronic inflammation speaks to a problem with the immune system and the natural processes that are intended to defend and protect us from invasion.
Periodontal disease is an example of the immune system trying to aggressively eradicate certain oral microbiota, but in the process, it seriously damages the host. It unleashes all of its power in the form of tons of immune cells to the gums. Some of the microbes in periodontal disease have learned how to evade the immune system—it essentially stands around, huffing and puffing, trying to find the little buggers. But it never gives up, and eventually, all of the inflammation it has created trying to kill the dental plaque instead destroys the gums and bones surrounding the tooth. We will talk about periodontal disease and dysbiosis in Chapter 6.
The importance of the epithelium as a mechanical barrier between the outside and inside world cannot be overstated. A healthy mucosal barrier is absolutely vital for a healthy immune system. If you are interested in gut health, immune health, or the gut microbiome, then you have probably heard of the concept of leaky gut, or intestinal barrier permeability. This is a hypothesis that has come from medical research on the gastrointestinal mucosa.
Leaky gut is a central theory in certain medical and research fields that greatly contributes to our understanding of autoimmune and chronic inflammatory diseases. The gastrointestinal tract has a mucous membrane just like the one in the mouth. The gut mucosa serves as a barrier between the outside world and the bloodstream. Just like the mouth, it is populated with immune cells, immune tissue, and billions of microbes. When the barrier is broken down or damaged, it becomes permeable. Little nicks and holes form in that barrier and then foreign molecules can reach the bloodstream, where they don’t belong. This is called intestinal permeability. The reason leaky gut is such an important idea is because it represents a total breakdown of the barrier that protects a person from the outside world. The result is that food, bacteria, fungi, parasites, chemicals, and toxins can get into the bloodstream and set off an even worse kind of immune reaction. The immune system goes on hyperactive red alert and sometimes cannot calm down. Intestinal permeability can increase the risk of chronic inflammatory diseases or autoimmune diseases.40, 41, 42 Autoimmune diseases are often a case of the immune system getting confused and attacking the tissues of the body instead of the bad guys.
This concept applies to the mouth as well. Remember that the oral mucosa is not an iron-clad barrier. It is porous and selectively permeable. Even in healthy people, the oral mucosa is leaky enough to let bacteria enter the bloodstream, called bacteremia. As we will discuss more in Chapter 8, it means that high levels of bacteria flood into the blood even when we do simple activities like brush our teeth, eat, or get a dental cleaning.
If the barrier in the mouth gets worn down and damaged, then foreign invaders from the outside world would have even easier access to the bloodstream. Bleeding, sore gums, or loose connections between the gums and teeth are a sign of a weak barrier and a “leaky mouth.” Remember from Chapter 3 that the oral mucosa has another unique chink in its armor: Every tooth that penetrates the barrier leaves an opening for microbes to enter.
When I was interviewed by Dr. Kara Fitzgerald, a functional medicine practitioner, in 2015, I suggested the idea of leaky mouth. It seemed like a natural next step from leaky gut, which is widely taught in the field of integrative and functional medicine. (Functional medicine is a model of medical treatment that addresses underlying causes of disease to restore each individual to optimum wellness.) Later, I interviewed a functional dentist, Dr. Mary Ellen Chalmers, and learned that she had suggested the same phenomena years earlier. Though leaky mouth is not a recognized condition, it deserves consideration. Leaky mouth could significantly worsen bacteremia. This might explain why and how the health of the oral cavity is so intimately intertwined with the health of the whole body. Stay tuned for more on this in Chapter 8.
A constant stream of bacteria and their products makes the mouth vulnerable to invasion from pathogens. The immune system is an incredibly complex network of cells, transport systems, chemical messages, and biological weapons. It operates 24/7 in the background at each mucosal surface of the body. It is intelligent and has a memory. The microbes in the mouth can both stimulate the immune system and suppress it, meaning that the oral microbiome is critical for the development and fine-tuning of the immune system. One of the most important defenses in the mouth is the mucosal barrier itself, which prevents outside invaders from reaching the bloodstream—to a point. The oral mucosa is naturally porous. If this barrier is breached, such as in the form of bleeding gums, leaky mouth could spell trouble for the rest of the body. Lessons from the gut mucosa tell us that this could be the case.
Takeaways
• A constant stream of microbes, chemicals, and toxins make the mouth vulnerable to invasion.
• The oral mucosa is a protective barrier between your body and the outside world.
• The immune system is a complex network of cells, transport systems, chemical messages, and biological weapons that can sort out friend or foe and destroy enemies.
• The oral microbiome can ramp up or calm down the immune response, and is important for fine-tuning the immune system in the mouth.
• Uncontrolled immune reactions and barrier permeability can increase the risk of autoimmune and inflammatory diseases.
• Damage to the oral mucosal barrier, or a leaky mouth, could open up the body to harmful microbes and inflammation.