The TIGER Protocol

CHAPTER 1

Overview—Immune Systems Gone Haywire

Does this sound familiar to you? Perhaps for years you have been struggling with similar symptoms, but none of the diagnoses you have received feel appropriate, and the medications you have been prescribed do not help, or else they cause unwanted side effects.

We will come back to Brenda’s case later in the chapter, to illustrate that there is often a lot you can do even when you have been told that “there is nothing you can do.” But first, let me tell you more about how common challenges with autoimmunity are, and teach you about the basics of the immune system.

As discussed, autoimmune disease rates are skyrocketing, making it the fastest growing category of disease. The incidence of type I diabetes has increased fivefold since 1950 in certain countries.¹ Rates of celiac disease, an autoimmune disease exacerbated by exposure to wheat, have also risen about fivefold in the past 50 years.² The growth of autoimmune diseases in children is especially worrisome, with some conditions growing tenfold in the past few decades.³ Almost all varieties of autoimmune conditions, numbering more than 100, are increasing.⁴

But why are autoimmune disease rates rising so steeply? To answer this question, we have to understand the perfect storm of risk factors that have come together to create this raging epidemic. But first, you need to know a bit about the basics of your immune system.

MEET YOUR IMMUNE SYSTEM

We live in a sea of microbes. They are within our body, outnumbering our human cells, and all around us, and your immune system is a sophisticated network of defense systems that protect you from these microbes. When your immune system is underactive, you become at risk for serious infections. When it is overactive, your risk of autoimmune diseases develops.

Your immune system is distributed throughout your entire body, including your thymus (a gland located in the upper chest), lymph nodes, spleen, bone marrow, liver, blood, and cells that sweep through and scrutinize every organ.⁵ At a basic level, it can be divided into the innate and adaptive components. The function of the immune system is incredibly complex; what follows is a simplified explanation so we can explore a few key concepts.

Innate vs. Adaptive

While there is often much interaction between them, the innate and adaptive branches can be thought of as the two main components of the immune system. The innate immune system is the first responder—it consists of white blood cells and all the proteins and messengers that trigger an immediate reaction when your body decides that it needs to defend itself against an invader. This response is instant and powerful, but nonspecific, and sometimes damages surrounding normal tissues in its haste.

The adaptive branch, a hallmark of more evolved animals, is slower but more targeted and precise; although its reaction may take days to weeks, it ensures a more accurate response, and preserves memory so that the immune system can respond more quickly the next time it encounters a specific pathogen.⁶ Memory from these immune cells can last for years or decades.

The adaptive response includes B cells and T cells, including a subtype of T cells called T regulatory cells. Considered the master regulators of the immune system, these cells are crucial for “keeping the peace” within the immune system and play a major role in the development of autoimmune disease, as we will see later.

Molecular Mimicry

The first mechanism through which autoimmune disease occurs involves a case of mistaken identity called molecular mimicry, in which a foreign protein—found on a bacteria, virus, or food—resembles a protein found within the human body. Our immune system generally produces antibodies, which, to review, are proteins that bind specifically to foreign proteins and mark them for attack and breakdown by immune cells.

Antibodies are used by the immune system to distinguish foreign invaders from the body’s own cells and should never bind to your own cells or tissues. However, the same antibodies produced against a foreign protein could mistakenly bind to a protein on one of your cells if there is a strong similarity between them—thus triggering the immune system to attack and destroy human tissues, while mistakenly thinking that it is attacking invaders. To use a military analogy, it is a case of “friendly fire.”

For example, a common virus known as Coxsackie B virus is implicated in type I diabetes. This is a condition in which the body attacks and destroys cells of the pancreas known as beta cells, which produce insulin necessary for regulating blood sugar. The virus contains a protein that strongly resembles an enzyme found in the pancreatic beta cells; when the immune system produces antibodies against the viral protein they may instead bind to the beta cells of the pancreas, triggering an immune system attack that is considered part of the process by which type I diabetes develops.⁷

Another example is Guillain-Barré syndrome, a disease affecting the nerves which causes weakness of the muscles and even paralysis in severe cases. Most of the time, a preceding infection is identified that triggers this condition. The most common offender is a bacteria called Campylobacter, which is the most common cause of bacterial diarrhea in the United States.⁸ Proteins in the outer cell wall of Campylobacter have a striking similarity to those found in human nerves, and the cross-reactivity of these antibodies is known to be one of the major causes of Guillain-Barré syndrome.⁹

Many such examples exist. However, it is important to know that the susceptibility of the individual makes a big difference. Not every person who gets Coxsackie B virus or Campylobacter will develop the associated autoimmune conditions. This illustrates the several-step process needed to develop an autoimmune disease, and why it is necessary to intervene with a multi-pronged approach to reduce autoimmunity, as we will be discussing in this book.

Bystander Effect

The second model of autoimmune development involves a case of “collateral damage” known as bystander effect.¹⁰ In this scenario, the immune system works hard to eradicate and destroy a foreign invader that has entered the body. However, in its overzealous efforts to destroy the pathogen, it may damage and destroy some of the surrounding human tissue as well.

If your immune system identifies a group of virus-infected cells, it recruits a strong inflammatory response and brings large white blood cells known as macrophages to the affected area. These cells release toxic compounds that kill the virus-infected cells but also damage the uninfected neighboring cells in the area.

The bystander effect is also thought to be one of the mechanisms by which toxins such as heavy metals trigger inflammation and autoimmunity, as we will discuss in chapter 2.¹¹

T Regulatory Cells

This type of immune cell plays a key role in the development of autoimmune disease; instability in these cells has been linked to increased risk of autoimmunity.¹² Conversely, interventions and factors that lead to improving the number and function of these cells are beneficial in autoimmune disease. They are the key regulators of the immune system, and they help to ensure normal activity and prevent autoimmunity.

This is one of the themes that we will be returning to frequently as we discuss strategies and treatments that favorably impact T regulatory cells. Emerging therapies that seek to reprogram T regulatory cells to treat autoimmune conditions are currently in clinical trials, as I will explain in chapter 12.

THE GUT IMMUNE SYSTEM

As you learn more about autoimmune disease, you will learn how fundamental the gut is to autoimmunity and, in fact, all chronic diseases. That’s why a focus on the gut is foundational to my approach. In terms of the immune system, the majority of it is actually located in what is called the gut-associated lymphatic tissue (GALT). It is estimated that upward of 70 percent of your body’s total immune system is present in GALT.¹⁷ This is because our gut, apart from our skin, is our primary source of exposure to the outside world and foreign material and microbes, and thus the highest level of surveillance is necessary there.

The Microbiome

Older estimates put the number of bacteria in humans at 100 trillion versus an estimated 10 trillion human cells, hence the inaccurate but often repeated slogan that we are only 10 percent human and 90 percent bacterial. Newer, more precise estimates are that human beings have around 38 trillion bacteria and about 30 trillion human cells—still, you are more bacteria than human.¹⁸ Anaerobic bacteria (which do not require oxygen for growth) may comprise more than 90 percent of the bacterial species, as we will discuss in detail in chapter 4.

We know that the microbiome (also known as “microbiota”—I will use these terms interchangeably) is complex and may contain hundreds (or even thousands) of different species in the average individual.¹⁹

A recent global study of people from 32 countries identified nearly 5,000 genetically distinct species that can be present in a human microbiome, with many of these species yet to be named; data from European and North American populations is plentiful, but South American, Asian, and African data is underrepresented and growing slowly (Data from these regions usually leads to the discovery of new species when included).²⁰ Our understanding of the microbiome is still in its infancy, although it is rapidly developing. There is much that is undiscovered and still unknown.

We know that gut bacteria play a critical role in many processes, including digestion, synthesis of vitamins and nutrients, metabolism, maintaining the health of intestinal cells, enhancing immune function, and protecting against pathogenic organisms. In addition, gut flora imbalance is implicated in various chronic illnesses including obesity, insulin resistance, and cardiovascular disease.

Some of the most exciting microbiota research involves autoimmune diseases. One of the key metrics to determine the health of the microbiome is diversity—tracking the number of different types of species in the ecosystem. Several distinct imbalances have been identified in the microbiome in various autoimmune disorders, but one of the most common findings is loss of diversity.²¹

In fact, studies show that the hallmark of the modern microbiome in almost all people today compared to the microbiome of our ancestors is a loss of diversity. Scientists have studied well-preserved stool samples from >1000 years ago and discovered dozens of bacterial species that are not found in modern microbiomes.²²

This loss of diversity and important bacteria from our microbiota is thought to be one of the key factors behind the dramatic rise in almost all chronic diseases in modern times.²³ A lack of diversity in the microbiome has been associated not only with autoimmunity but also systemic inflammation, obesity, diabetes, insulin resistance, elevated cholesterol, allergies, and asthma—so it has wide-raging health implications for most modern chronic illnesses.²⁴ This will be one of the central themes of this book, as I teach you how to improve the health and diversity of your microbiome, and heal your gut in order to address autoimmunity.

Loss of Diversity

Several factors have been shown to contribute to this reduction in diversity. These include reduced breastfeeding rates, the rise of C-sections, low-fiber diets, increased consumption of processed foods, widespread use of antibiotics, emotional stress, and environmental toxins. Over the years, increased use of antibiotics in livestock, overprescribing of antibiotics by physicians, sterilization of our drinking water, reduced exposure to farm animals and microbe-rich environments, increased use of antibacterial soap and cleansers, and improved sanitation of the environment have all led to dramatic decreases in the microbial diversity that we are exposed to while growing up.

This phrase “while growing up” is key because it appears that the exposure to key bacteria in the microbiome during the first few years of life is critical to the normal maturation and development of the immune system. Our gut bacteria play a key role in educating our immune systems during childhood. There is a key window of opportunity during the first year of life, especially during which breastfeeding and exposure to the right microbes can induce lifelong positive changes that reduce the risk of immune-mediated disorders.²⁵ A lack of this proper training of our immune cells by the microbiota can have long-term negative consequences for our health.