Qualia Immune - The Science Behind The Formula & Immune System Intelligence

Qualia Immune - The Science Behind The Formula & Immune System Intelligence

QUALIA IMMUNE KEY BENEFITS & FEATURES

Qualia Immune combines 19 carefully selected ingredients for premium immune support. We think of it as being training for the immune system; a formulation designed to challenge the immune system in ways that will help it be fitter and perform more intelligently. 

It supports immune system fitness and intelligence by combining herbal immune adaptogens, superfood extracts, probiotics, beta glucans, algae extracts, polyphenols, trace minerals, and vitamin D. Qualia Immune is the complete solution for year-round and healthy aging immune support.*


WHAT DOES QUALIA IMMUNE DO?

  • Supports general immune health & wellness*

  • Supports a healthy immune system during aging*

  • Supports year-round immune health at all ages*

  • Supports seasonal health and well-being*

  • Supports key immune cells*

  • Supports the body’s natural defenses*

  • Supports the immune system during periods of intense exercise and training*

  • Supports healthy working days and work productivity*

  • Supports digestive tract health*

  • Supports respiratory tract health*


HOW DOES QUALIA IMMUNE DELIVER ADVANCE IMMUNE SUPPORT?

  • By supporting a “youthful” immune system, i.e., countering immunosenescence*

  • By supporting immune system intelligence, i.e., immuno-learning and memory*

  • By supporting recognition of new antigens*

  • By supporting immune tolerance, i.e., appropriate non-reactivity to self*

  • By supporting mucosal immunity. i.e., barrier immunity*

  • By supporting gut microflora, i.e., gut-immune intelligence*

  • By supporting hematopoietic stem cell function, i.e., generation of immune cells*

  • By supporting immune system fitness, i.e., trained immunity*

  • By supporting immune system communication*

  • By supporting dendritic cell (DC) number & function*

  • By supporting toll-Like receptor (TLR) expression/function

  • By supporting natural killer (NK) cell function*

  • By supporting macrophage function*

  • By supporting microglia function i.e., the brain’s immune system*

  • By supporting neutrophil function*

  • By modulating mast cell, basophil, and eosinophil responses

  • By supporting gamma delta T cells (γδ T cells)*

  • By supporting naïve T cells*

  • By supporting CD8+ T cell function*

  • By supporting antibody response to new immune challenges i.e., B cell function*

  • By supporting Nrf2 i.e., a master regulator of cellular defenses

  • By supporting healthy mitochondria i.e., immune cells need & use energy

  • By supporting healthy cortisol and testosterone levels*


WHAT IS A SMARTER IMMUNE SYSTEM?

WHAT IS THINKING?

Why develop an immunity product? And why are terms like “intelligence,” “smart,” and “fitness” relevant to the immune system? Neurohacker Collective started as a cognition company (our first product was a nootropic supplement for brain performance). You might say that optimizing thinking is built into our corporate DNA. So, to answer these questions, let’s start with the brain and thinking.

The brain’s primary function is to take in, process, transmit, and use information. Collectively these can be summarized in one word—thinking. The brain thinks by using cognitive skills, which allow it to perceive, reason, understand, learn, and remember.

Specific cognitive skills—the subtasks that allow for thinking—include (1) being alert and paying attention, (2) focusing on some things while being able to ignore others, (3) quickly responding to and processing new information, (4) using reasoning to find patterns and solve new problems, (5) staying flexible when circumstances change or unanticipated challenges arise, and (6) storing and retrieving relevant information.

In the best-selling book Thinking, Fast and Slow, Daniel Kahneman introduces a two character model of how the brain “thinks.” He calls these characters System 1 and System 2. System 1 is the “fast thinker.” This character is instinctive and quick to act. The “slow thinker” is System 2. It’s slower to act and involved in more complex computations. 

If a friend told us we were about to get hit with something that was thrown at us, System 1 response—the instinctive thinking that is going to cause us to immediately duck—is a good enough solution. But if we want to be an expert on catching things, or telling the difference between all types of objects that might hit us, we’ll need System 2. 

It makes sense to have these different systems of thinking. Some types of brain problems require speed. If there’s something unsafe in the environment that could harm us unless we respond immediately, it doesn’t make sense to spend time trying to figure out what the best thing to do might be. Other types of problems require precision; it’s worthwhile to trade speed for accuracy. The brain can take more time to learn and come up with solutions tailored more specifically for the task.

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“Immunity is not merely a reflex to a foreign presence, but an act of cognition.”

Irun R. Cohen and Sol Efroni from The Immune System Computes the State of the Body

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DOES THE IMMUNE SYSTEM "THINK?"

From birth till death, the immune system must stay constantly alert, sensing what is going on inside and outside the barriers of the body. And, it is involved in an ongoing process of making decisions, determining what to pay attention to (non-self) and what to safely ignore (self and helpful organisms like commensal bacteria in the gut microbiome).

To do its job the immune system needs to be able to recognize and respond to new information. Molecular patterns are information in the immune system’s world. Processing speed, the ability to rapidly recognize and respond to minor differences in molecules, is essential.

The immune system is brilliant when it comes to recognizing patterns. It’s ability to detect and recognize patterns, figuratively searching for and finding needles in haystacks of molecules—self molecules far outnumber non-self—allow it to quickly identify molecular situations that require its attention, while ignoring all the molecules that don’t.

Dealing with change, meeting unanticipated challenges, and remaining flexible as circumstances evolve … if there were a job description for the immune system, these would be essential requirements.

Over the course of a lifetime the immune system must learn and be able to store and recall information about millions of different molecular patterns. And it will remember what it learns for decades, still being able to recall and use information in old age that it learned in early childhood. 

If these characteristics of the immune system sound similar to what the brain does, it’s because they are. While there’s no one central “brain” in charge of the immune system, there’s no question that the immune system behaves intelligently.

Similar to the brain, the immune system has to also make speed versus accuracy trade-offs. It does this in an analogous manner to Kahneman’s System 1 and 2 characters.

The “fast thinker” in the case of the immune system is called innate immunity. This is made up of the nonspecific (i.e., generalized) immune responses we inherit. This instinctive immunity activates within minutes to hours, sending waves of healing agents to solve problems.

The “slow thinker” is adaptive immunity. These are the immune responses that require more complex computations. They take time to deploy as the immune system learns how to specifically deal with new molecular patterns. This learned immunity takes days to weeks as unique solutions are crafted to solve each new problem.

So, does the immune system “think?” The answer is yes. The immune system will spend every moment of every day through a person’s entire lifetime “thinking.” It just uses a different kind of intelligence than the type most of us equate with being smart. 

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“It can be no accident that the evolution of immunity precisely parallels the evolution of the higher nervous system. ... Even among vertebrates, the diversity of the antibody repertoire is proportional to the size of the brain.”

Frank T. Vertosick, Jr, from The Genius Within: Discovering the Intelligence of Every Living Thing

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WHAT IS IMMUNE SYSTEM INTELLIGENCE?

The immune intellect, like all intelligence, solves problems. It does this by using innate and acquired knowledge, which in the case of the immune system are called innate and adaptive immunity. Like other forms of intelligence, it has the ability to store past experiences and use that information to solve future problems.

When it comes to being smart, most of us think of the brain. Brain intelligence arises from the competition, cooperation and communication between communities of neurons. It’s designed to solve certain types of problems.

The “neurons” of the immune system are white blood cells. They compete, cooperate, and communicate in order to solve a different, but equally important category of problems—a category that can be broadly described as recognizing self and non-self in the microscopic realm. The immune system is able to solve new problems, evolving its strategies over time, because it is a complex adaptive system.

Complex systems science is an approach to scientific understanding that focuses on relationships between members in a group, and how these interactions give rise to collective behaviors that are more complex, richer, and usually “smarter” than what could have been guessed by studying the members of the group in isolation.

Immune intelligence is an example of a type of intelligence that has been a main focus of complex systems science—network intelligence, the intelligence that emerges from a large group of interacting agents. In the case of the brain the interacting agents are neurons. In the immune system, the agents are immune cells.

Social insects, ants and bees, are an example of network intelligence. Individual ants or bees, the agents acting out their roles in isolation, aren’t capable of behaving as intelligently as a community of them—an ant colony or beehive. The collective intelligence of the colony or hive superorganisms emerge from the interactions of the agents. And it is this collective intelligence that solves problems, adapting to and learning from new environmental challenges.

Network intelligence is widespread in nature. Social insects, the brain, and the immune system rely on the complex adaptive intelligence that emerges from the interactions of agents. This type of swarm intelligence or crowd wisdom results in a tremendous ability to get things done quickly. It also allows for redundancy. Since the intelligence is not centralized—there’s literally no one in charge—the system is resilient to shock … it is robust.

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“Why did Neurohacker Collective create Qualia Immune? We think there is a need to support people having smarter immune systems, and we felt like our expertise in complex systems science allowed us to contribute uniquely when it came to supporting an intelligent network in performing even more intelligently.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective

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The immune system is made up of many different types of cells—stem cells, dendritic cells, natural killer cells, neutrophils, macrophages, T cells, B cells, etc. Each cell type plays an important role, but smart behavior of the whole system, what’s generally called immunity, arises from the interactions of the community of white blood cells as a whole. It’s this community, not any individual cell, that absorbs information, learns from it, stores it, retrieves it as needed, and uses it to develop future strategies. This community has the collective capacity to think about vast amounts of 3-dimensional molecular data—the immune system can differentiate billions, perhaps trillions of different molecular patterns.

Learning is an essential feature of complex adaptation. The immune system will learn and commit huge numbers of molecular shapes to memory. But it does more than just rote memorization; it reasons. A cornerstone of biological reasoning is the ability to generalize past learnings to new situations that, while not identical, may be similar. The immune system uses this type of biological reasoning when it encounters new molecular shapes, starting from known best guess solutions and altering strategies to come up with much more perfected solutions.

Agents within an intelligent system must be able to detect what occurs in their environment and respond to it by changing behavior. Each immune system cell “perceives” the world around it by using external receptors, receiving whatever signals its receptors can detect. These receptors are figuratively speaking, the eyes and ears of immune cells. They allow individual immune cells to sense antigens, metabolic products, cell interaction molecules, and other chemical signals. Immune cells also send information; they “talk” with each other, using chemical signaling molecules called cytokines.

The immune ecosystem uses chemical trails in much the same way an ant superorganism does. By sniffing out chemical signaling molecules, figuratively speaking, individual immune cells navigate long distances in a highly complex microenvironment to travel to remote destinations. Immune cells are about a hundred times smaller than a millimeter and are able to travel distances of one or more meters to get to where they are needed. This would be the rough equivalent of a 6 foot human being able to sense something about 114 miles away and then walking there without getting lost.

As a result of communication, individual cells change their behaviors and the collective performs intelligently. The information each immune cell sends and receives are collectively used, locally and systemically, to maintain, heal, regenerate and surveil the body. By interacting with neighboring cells, a collective of immune cells together can do remarkable things … things that individual immune cells, one-by-one on their own, could not do.

Nassim Nicholas Taleb, author of the books Fooled By Randomness, The Black Swan, Antifragile, and Skin In the Game, came up with the term “antifragile” to describe anything that is the exact opposite of fragile. An antifragile system, not only withstands challenges or stressors, it benefits from them (provided the challenge or stress isn’t too much). Antifragility, as Taleb uses the term, is a nonlinear response—the type of response that characterizes complex systems. What are examples of these antifragile systems?

The brain and nervous system is an example; it is antifragile. When challenged to learn new information, the brain benefits; it gets smarter. Muscles and bones are antifragile. When challenged by exercise, muscles and bones do more than tolerate the stress, they get fitter and stronger. Like the brain and muscles, the immune system is antifragile.

The answer to the question of “What Is Immune System Intelligence?” is that it is the antifragile intelligence that arises because of the cooperation, competition and communication of immune cells. The immune ecosystem is an adaptive intelligence. When challenged, it behaves intelligently, but it does more than this: It can get smarter and fitter.

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“Antifragility is beyond resilience or robustness. The resilient resists shocks and stays the same; the antifragile gets better.”

Nassim Nicholas Taleb from Antifragile: Things That Gain from Disorder

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HOW DO YOU SUPPORT THE IMMUNE SYSTEM IN BECOMING SMARTER AND FITTER?

If we want muscles to get bigger, stronger, faster, or more skilled, we need to train them, challenging them in ways that cause them to adapt. Exercise training (and the recovery from it) does this; it enhances fitness. In a sense, the investment in exercise toughens up our musculoskeletal system, preparing it to work more efficiently if we need it to in the future.

The brain can be trained in ways that make it smarter. Enriching the environment, learning a language or a new skill, and specific cognitive training tasks are examples of challenges for the brain. These types of stimuli act like exercise for the brain, supporting it in becoming an enhanced thinker. 

Exercise training, and an opportunity to recover from it, are critical ingredients in the recipe for muscle fitness. Another ingredient in the recipe is the category of compounds called ergogenics—dietary supplements that support physical performance, strength, stamina, or recovery.

The same general recipe applies to supporting the brain in becoming smarter. Challenge it with stimuli, enhance recovery—much of this recovery occurs during sleep—and supplement it with compounds that support healthy brain function and mental performance, which collectively are called nootropics. 

The immune system follows a similar principle. If we want the immune system to be smarter and fitter, the goal is to challenge it, enhance immune recovery functions, and give compounds that support performance. But what exactly is a challenge, the immune equivalent of exercise or brain training, for immune cells? What is immune recovery? And, what is immune performance?

We’ve mentioned that molecular patterns are information in the immune system’s world. It turns out that some molecules act very much like a “workout” for the innate (i.e., fast thinking) immune system. When challenged by certain types of molecules—beta glucan as an example—innate immune system cells are trained. They get bigger, stronger, and more active, becoming capable of responding faster and more intelligently to the same and different molecules in the future. One part of the recipe for supporting a fitter and smarter immune system is to challenge it with molecules that act like exercise, promoting innate immune training. 

Immune cells spend most of their time in a quiescent state, becoming active when needed, and then recovering. In a simplified sense, some of the immune system is designed to turn off or turn down the rest. Supporting immune cells’ ability to transition back into the more quiescent recovery state, and functions such as immune balance and tolerance, are an important part of having a smart and fit immune system.

Substances that support recovery from, and a generalized ability to be more resilient to challenges are called adaptogens. Adaptogenic compounds can be used to support exercise performance. Adaptogens can also support mental performance. Not surprisingly, some herbal tonics, mushroom extracts, and plant compounds act as immune adaptogens, supporting the general ability of the immune system to recover and be resilient, performing at a high level when challenged. They are another part of the recipe for supporting a smart and fit immune system.

There are many other considerations in designing a formula intended to support a smart and fit immune system. Like the brain’s fast and slow thinkers, the immune system has fast and slow components, the innate and adaptive branches of immunity, respectively.  A comprehensive immune formula should support both fast and slow immune system thinking.

The immune system uses collective intelligence, which is produced by the interactions of many different immune cell types in the immune ecosystem. If we want the immune system to be smarter and fitter, it makes sense to support the entire immune ecosystem of cells, the local immune environments like the gastrointestinal tract, where a majority of immune cells gather, and the stem cell environment that gives birth to immune cells. 

The immune system practices many of the same types of skills used by the brain and nervous system. It must stay alert and pay attention ... focus on some things and ignore others … respond quickly when it needs to but turn off this response when it is no longer required … stay flexible through a lifetime to deal with novel challenges … get along socially with other immune cells (and the cells of the body and the microbiomes) … sense and perceive its environment … talk—communicate—with other cells ... learn constantly and remember for decades. If we want the immune system to be smart and fit, we should support all of these skills.

The immune system surveils the body looking for external molecules, but it also needs to be able to recognize and manage the many different commensal organisms that reside in microbiomes in the gut, skin, and other areas. It heals wounds and repairs injuries. It is involved in muscle repair, growth, and regeneration. It detects and destroys aged and stressed cells. It is responsible for neuroprotection and sensing the well-being of the brain and eyes. The immune system has a lot of jobs to do; it is working on our behalf all the time.

Qualia Immune is a new approach to immune support. It was developed to comprehensively support the immune system, so it will be able to work more efficiently in all the jobs it does. It is a formulation designed to support the immune system in behaving intelligently and being fit. After all, doesn’t it make sense to approach supporting the immune system in a way that would support the skills it needs to do its job? To enhance immune system thinking? To help it to be smarter and perform more intelligently? And to create the equivalent of fit immune cells that are stronger and able to do more work? But how would you go about doing this? To answer this it can be helpful to understand more about how the immune ecosystem behaves … how it works. 

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“I think of Qualia Immune as being like a nootropic and ergogenic for the immune system, a formula designed to support the immune system in being both smart and fit. It was formulated to support both fast and slow immune thinking, which are called innate and adaptive immunity, and to train the many different types of immune cells that collectively produce immune intelligence.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective

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HOW DOES THE IMMUNE SYSTEM WORK?

The immune ecosystem is the collection of white blood cells, tissues, and molecules that work together to recognize and tolerate the healthy cells that make up the body (i.e., self), clean up stressed cells (such as senescent cells), and stay alert for the unfamiliar (i.e., non-self).

Immune intelligence is, in a sense, everywhere and nowhere. It dispersed throughout the body in an ecosystem composed of billions of white blood cells. There’s no group of immune cells that run the show or a central place in charge of things. The intelligence exists in the network and the patterns and relations stored in it. Immunity is essentially the output of this system; it is the collection of intelligent behaviors. But how does it work?


WHERE DO IMMUNE CELLS COME FROM?

Immune cells are white blood cells (WBC; also called leukocytes) and are created in bone marrow by a limited number of hematopoietic stem cells. Hematopoietic stem cells also produce red blood cells (RBC; also called erythrocytes) and platelets (also called thrombocytes).

Hematopoietic stem cells are capable of extensive self-renewal. The self-renewal occurs in the stem cell niche within bone marrow. So hematopoietic stem cells, bone marrow, and the environment of the stem cell niche where self-renewal occurs play important parts in giving birth to the cells of the immune ecosystem.

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Hematopoietic Stem Cell Supportive Compounds

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Echinacea purpurea Root Extract

Tinofend® Tinospora cordifolia Stem Extract

Wellmune® Baker’s Yeast Beta Glucan

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

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Hematopoietic stem cells give birth to many different types of white blood cells, with the cell lineages being somewhat akin to a family tree. The two major branches of the tree are called myeloid and lymphoid.

Myeloid means bone marrow tissue. Cells in the myeloid branch of the family tree come from common myeloid progenitor cells, are birthed, and receive what could be thought of as their basic immune education in the bone marrow.

Myeloid cells include mast cells, basophils, eosinophils, neutrophils, and monocytes. When monocytes move into tissues they become macrophages or myeloid dendritic cells (not shown in the family tree image). All immune cells in the myeloid lineage are part of the fast thinking innate immune system. 

Note: While not part of the immune system, red blood cells and platelets are from the myeloid branch of the tree. 

Lymphoid has to do with lymphatic tissue (e.g., lymph nodes, thymus, tonsils, spleen) and involves the subset of immune cells called lymphocytes. Cells in the lymphoid branch of the family tree come from common lymphoid progenitor cells, are birthed in the bone marrow, but their basic immune education is not completed until they’ve migrated to lymphatic tissue.

Some immune cells in the lymphoid lineage are fast thinkers (e.g. natural killer cells, lymphoid dendritic cells), and others are part of the slow thinking adaptive immune system (e.g., T lymphocytes, B lymphocytes).

Image: White Blood Cell Lineages (i.e., the Immune Cell Family Tree)

Image By A. Rad and M. Häggström. CC-BY-SA 3.0 license.


WHAT ARE THE INNATE AND ADAPTIVE IMMUNE SYSTEMS?

The immune system is divided into two major subsystems: the innate immune system (i.e., the fast thinker) and the adaptive immune system (i.e., the slow thinker) . 

The innate immune system (also called non-specific immunity) is the evolutionarily older immune subsystem—plants, fungi, and primitive multicellular organisms only have innate immune systems. It acts quickly (hence our description as the fast thinker) when it recognizes any of the molecular patterns it evolved to identify.

The innate immune system includes physical barriers that separate the inner from the outer world (e.g., skin, gastrointestinal tract, respiratory tract), secretions (e.g., mucous, gastric acid, saliva, tears, sweat), and other general barrier mechanisms. All white blood cells from the myeloid lineage are part of the innate immune system. And two lymphoid lineages—natural killer cells and lymphoid dendritic cells—are classified as part of innate immunity.

Innate implies being born with a capability, which is a good choice of names, because the innate immune system includes all of the immune resources we are born with and do not need to learn. In a sense, it is the inherited immune wisdom that all humans share. This wisdom allows the innate immune system to behave intelligently, but without an ability to craft specific solutions for new molecular information. 

The innate immune system engages in a number of intelligent behaviors. These include:

  • Recognizing general broadly shared molecular patterns that evolution has taught it that indicate something needs attention. 

  • Recruiting other immune system cells to help.

  • Identifying stressed cells that are missing self markers, essentially being able to recognize when a cell may not be showing friendly behaviors.

  • Presenting antigenic information to (i.e., teaching) cells of the slower thinking adaptive immune system.

  • Sensing the environment (i.e., listening) and signaling (i.e., talking to) other agents in the immune ecosystem.

  • Adapting to challenges and remembering some molecular information for short periods of time. 

There can be broad-based benefits to cells within the innate immune system when challenged by some molecules (such as beta glucan). This concept is called “trained immunity.” Trained immunity refers to the ability of certain lineages of innate immune cells—primarily monocytes, macrophages, and natural killer cells—to respond to specific molecular challenges by literally becoming bigger, stronger, and more active. In a real sense, the innate immune cells become more physically fit, capable of responding faster and more efficiently to subsequent challenges. This heightened functional state can persist for weeks or more, but is not permanent. Similar to exercise training, and what occurs if a person becomes sedentary, the immune fitness gained will go away if the immune system is not challenged. But when challenged consistently with compounds that support trained immunity, the cells of the innate immune system, and the stem cells that give birth to new generations of them, become fitter and stronger. 

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Trained Immunity Supporting Compounds

Wellmune® Baker’s Yeast Beta Glucan

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

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The adaptive immune system (also called specific or acquired) is evolutionarily newer—it is a type of immune system intelligence that took nature longer to figure out. It allows an organism to adapt its behaviors, creating highly specific solutions to novel molecular information called antigens. But the trade off for this precision is time: The adaptive immune system takes days to weeks to figure out solutions.

The adaptive immune system deals with three-dimensional molecular patterns called antigens located on the surface of our cells—both healthy and stressed—as well as antigenic molecules in the things we eat, drink, and breathe. Its ability to learn and store molecular shapes is both mammoth and precise. It will solve the shape of a novel antigen it encounters within days to weeks by starting from best guesses (i.e., the closest matches it has available in its repertoire of lymphocytes) and adapting until it creates a great solution. Once it's solved the antigen, it will commit the molecular shape to long-term memory.

There are two major lineages within adaptive immunity: T lymphocytes (T cells) and B lymphocytes (B cells). These cells receive several levels of immune tolerance education in lymphatic tissues—central tolerance and peripheral tolerance. 

Central tolerance can be thought of as early education; it occurs as these cells develop into immunocompetent cells in the thymus and bone marrow. Peripheral tolerance is an advanced degree; it takes place after T and B cells are mature and enter the peripheral lymph tissues and nodes. This education is designed to make sure immune cells learn about getting along with self and friendly molecules.

The immune system has to know what to respond to (some non-self molecules) and what to ignore (self molecules, food, gut microbiota, etc.). This ignoring is called immune tolerance, a state of indifference towards certain molecules. Immunological tolerance allows the host to adapt to molecular stimuli that will consistently be present instead of expending resources on them. It is analogous to what occurs with how the brain responds to sensory information. The brain does not respond to all auditory or visual stimuli: It intentionally chooses to ignore most of it.

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Immune Tolerance Supporting Compounds

Vitamin D3 (as cholecalciferol)

Selenium (as Se-methyl-L-selenocysteine)

Zinc (as Zinc Gluconate)

Polygonum cuspidatum Root Extract (95% Resveratrol)

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Panax ginseng Root Extract

N-Acetyl-L-cysteine

Broccoli Sprout Powder

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Echinacea purpurea Root Extract

Wellmune® Baker’s Yeast Beta Glucan

Tinofend® Tinospora cordifolia Stem Extract

Palmitoylethanolamide

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

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Adaptive implies flexibility, learning, and an ability to change based on the circumstances. And adaptation is exactly what the cells of this immune subsystem do. Cells of the adaptive immune system specialize in learning and remembering the shapes of antigens, a thinking process that takes between 4 to 14 days.

Some of the intelligent behaviors of the adaptive immune system include:

  • Learning to tolerate (or get along with) self.

  • Acquiring specific information about antigenic molecules.

  • Rearranging genes to solve problems; essentially starting from best guesses and rapidly fine tuning its genetic offspring to arrive at precise solutions.

  • Developing immunological memory; remembering antigenic information for decades.

  • Sensing the environment (i.e., listening) and signaling (i.e., talking to) the immune ecosystem.

Hearing sounds and understanding a language are a rough analogy for the differences between the two immune subsystems. Humans inherit an ability to detect and respond to sounds. We don’t need to learn this; we are born with this capability. We are also able to slowly learn a language; discriminating subtle differences in sounds that allow us to produce a rich vocabulary and understand the complexities of the spoken word.

Language ability is built on top of and relies on the innate sound abilities: Acquiring the advanced skill is dependent on the inherited. The immune system is the same. The adaptive immune system’s performance is built on top of and dependent on the innate immune system capabilities. These two systems specialize in different types of immune thinking, but neither is more or less important—we need both fast and slow thinking for the immune system to behave intelligently.


WHAT DO IMMUNE CELLS DO?

While we don’t want to bog you down in all the details about the different types of immune cells, we do want to share some of their names and a brief bit about their main roles in immune system thinking and fitness.

We’ll start with neutrophils because they are the most abundant of all white blood cells—a healthy adult produces more than 100 billion neutrophils per day! Neutrophils (sometimes called polymorphonuclear leukocytes) are part of the fast thinking innate immune system. In fact, you might say they are the fastest thinkers, because they are the first responders of the immune system. Neutrophils migrate quickly to where they are needed, begin to deal with the situation, and recruit other immune cells to help. They are classified as phagocytes, because their solution for dealing with situations includes ingesting molecules—phago is from a Greek word that means to eat or devour.

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Neutrophil Supportive Compounds

Tinofend® Tinospora cordifolia Stem Extract

L-Theanine

N-Acetyl-L-cysteine

Wellmune® Baker’s Yeast Beta Glucan

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

Selenium (as Se-methyl-L-selenocysteine)

Zinc (as Zinc Gluconate)

Broccoli Sprout Powder

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Neutrophils are granulocytes. Granulocytes are a category of innate immune cells. This category is defined by how the cells look under a microscope—they contain protein and chemical particles on the inside (i.e., granules)—not by their job function. The other granulocytes are mast cells, basophils, and eosinophils. While mast cells, basophils, and eosinophils have somewhat different functional roles within immunity, they get grouped together because they: (1) share a similar appearance, (2) are involved with the histamine and immunoglobulin E (IgE) part of the immune response, and (3) evolved to recognize molecular patterns from things in the environment the immune system was challenged with … in the past. They represent aspects of immune wisdom that were the solution to a past problem that was considered important enough to pass down as part of the fast thinking innate immune system we inherit.

Mast cells, basophils, and eosinophils specialize in immune intelligence strategies that evolved based on what challenged developing human immune systems in the past, but rarely challenge immune systems today. They are part of the Hygiene (i.e., “Old Friends”) Hypothesis, which is the idea that if developing immune systems don’t get challenged by certain molecules, they might not learn important lessons in immune tolerance. This failure to learn results in a tendency to overreact to molecules that should be ignored. The goal with mast cells, basophils, and eosinophils is to help them to be more tolerant, supporting them in ways that allow them to become smarter when it comes to ignoring harmless molecules. 

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Mast Cell, Basophil, and Eosinophil Supporting Compounds

Tinofend® Tinospora cordifolia Stem Extract 

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Selenium (as Se-methyl-L-selenocysteine)

Palmitoylethanolamide

L-Theanine

N-Acetyl-L-cysteine

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Broccoli Sprout Powder

Polygonum cuspidatum Root Extract (95% Resveratrol)

Wellmune® Baker’s Yeast Beta Glucan

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Monocytes are the largest in size of the white blood cells (and are one of the lineages that can undergo trained immunity). They can differentiate into macrophages (another lineage that can undergo trained immunity) or dendritic cells, both of which are considered to be “Professional” antigen presenting cells (APC). Professional APC serve a unique role in displaying information to cells in the slower thinking adaptive immune system, so can be thought of as being akin to teachers or educators. We’ll cover macrophages first.

Macrophages—from Greek words that mean large eaters—are part of the fast thinking innate immune system. They arrive after neutrophils, both continuing the work neutrophils started and cleaning up after them. Like neutrophils they ingest molecules, so are phagocytes. But macrophages play a much more prominent role in repair and healing. In addition to their eating and janitorial roles, macrophages play a teaching role, facilitating the education of adaptive immune system T and B cells. They do this by “digesting” the proteins they ingest and then displaying smaller pieces of molecules—molecular fragments called antigens—to T and B cells. This presentation role helps the T and B cells learn about the shapes of the antigen molecules.

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Macrophage Supportive Compounds

Wellmune® Baker’s Yeast Beta Glucan

Maritech® Fucus vesiculosus Extract

 Maritech® Fucorich® Undaria pinnatifida Extract

Tinofend® Tinospora cordifolia Stem Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Palmitoylethanolamide

Broccoli Sprout Powder

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract 

N-Acetyl-L-cysteine

Polygonum cuspidatum Root Extract (95% Resveratrol)

Panax ginseng Root Extract

Selenium (as Se-methyl-L-selenocysteine)

Zinc (as Zinc Gluconate)

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Macrophages take different forms, with various names depending on where they are located in the body. The resident macrophages of the central nervous system are called microglia: They account for 10–15% of all cells found within the brain and are the main immune cells of the central nervous system. Similar to peripheral tissue macrophages, microglia migrate to the sites where they are needed, ingest molecules, and are part of the healing and repair response of the brain and nervous system.

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Microglia Supportive Compounds

Palmitoylethanolamide

Broccoli Sprout Powder

Polygonum cuspidatum Root Extract (95% Resveratrol)

Vitamin D3 (as cholecalciferol)

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Selenium (as Se-methyl-L-selenocysteine)

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Dendritic cells (DCs) are part of the fast thinking immune system, and like their siblings the macrophages—dendritic cells and macrophages are part of the monocyte cell lineage—are a critical bridge to slower thinking immunity. Dendritic cells are found in the blood and concentrate in areas of the body that are in close contact with the outside world. There are two subtypes of dendritic cells: conventional dendritic cells (cDCs) and a rarer type called plasmacytoid dendritic cells (pDCs). Conventional dendritic cells are phagocytes; they ingest molecules. One of their main jobs is to present the molecular information to T and B cells of the adaptive immune system. This allows T and B cells to learn the shapes of antigens and also educates them in immune tolerance. So, conventional dendritic cells can be thought of as playing a pivotal role in educating the slow thinking immune system. Plasmacytoid dendritic cells share these same jobs and are also interferon-producing cells: They produce far more type 1 Interferon than any other immune cells. Interferons are an immune system communication molecule. In a simple sense, plasmacytoid dendritic cells tell other cells in both the fast and slow thinking immune systems to wake up, serving as a bridge between innate and adaptive immunity. Collectively, dendritic cells can be thought of as playing a notification and teaching role, alerting and educating other types of immune system cells, essentially helping make many other cells smarter. Because of this they are an essential part of supporting a more intelligent immune system. 

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Dendritic Cell Supportive Compounds

Lactococcus lactis strain Plasma (heat killed)

Maritech® Fucus vesiculosus Extract 

Maritech® Fucorich® Undaria pinnatifida Extract 

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Wellmune® Baker’s Yeast Beta Glucan

Echinacea purpurea Root Extract

Tinofend® Tinospora cordifolia Stem Extract

Zinc (as Zinc Gluconate)

L-Theanine

Vitamin D3 (as cholecalciferol) 

**********************

Natural killer cells (also known as NK cells) are part of the fast thinking innate immune system (they are one of the lineages that can undergo trained immunity). They are a subcategory of lymphocytes, and similar to the T and B lymphocytes of the adaptive immune system undergo immune tolerance training in lymph nodes. NK cells are specialists in quickly finding and getting rid of stressed cells. They do this by recognizing molecular patterns that all stressed cells show on their surface ...no matter what might have caused the stress. And they are able to do this without being taught about any new molecules. In an immunological sense, this means NK cells are able to eliminate stressed cells without being “told” to do so by other parts of the immune system. NK cells are part of the innate immune system because their ability to recognize these molecular patterns is inherited (i.e., innate), not something that must be learned. Because it doesn’t need to be learned, they can respond quickly.

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NK Cell Function Supportive Compounds

Echinacea purpurea Root Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Wellmune® Baker’s Yeast Beta Glucan

 Broccoli Sprout Powder

Panax ginseng Root Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

L-Theanine

N-Acetyl-L-cysteine

Zinc (as Zinc Gluconate)

Selenium (as Se-methyl-L-selenocysteine)

Lactococcus lactis strain Plasma (heat killed)

Palmitoylethanolamide 

*******************************

So far the cells we’ve covered have all been fast thinkers—they belong to the innate immune system. They behave intelligently because of immune wisdom they’ve inherited. They are, in a sense, born ready to go to work. The immune cells we will be discussing next aren’t born ready; they need to acquire knowledge before being able to behave intelligently. 

The adaptive immune system—slow thinking immunity—crafts a unique solution to each new antigenic molecule it encounters. The two lineages within the adaptive immune system family tree are called T lymphocytes (T cells) and B lymphocytes (B cells). Antibody is the term commonly used to describe their solutions, though quite frequently antibody is used to only refer to B cell solutions. T cell solutions, more specifically, have solutions called T-cell receptors (TCR).

T lymphocytes (T cells) are part of the slow thinking adaptive immune system. While all T cells share the same original lineage, as they are educated, they learn specific jobs and develop ever increasing numbers of lineages (i.e., genetically distinct T cell offspring). Each T cell lineage has the potential to be directed against a specific molecular characteristic called an antigen.

Immature T cells are produced from lymphoid progenitor cells in the bone marrow and migrate to the thymus, where these early thymic progenitors undergo multiple stages of education. This education of T cells, think of them as students, is designed to produce diversity, competence, and tolerance. Prior to this education, immature T cells lack the expertise to recognize anything in particular. By the end of their education in the thymus, they’ll be “book smart,” ready to go to work in the immune ecosystem.

T cell receptors (TCR) on the surface of T cells are used to recognize antigenic shapes. They determine the molecular patterns any individual T cell will be able to learn. The first stages of education in the thymus determines the type of TCR that will be on the surface of each individual T cell. This, in turn, dictates what shapes an individual T cell will be able to learn and the major career path it will follow. 

In the thymus, immature T cells undergo genetic scrambling of sorts, rearranging TCR genes, resulting in a huge diversity of TCR. This diversity is needed to create a T cell repertoire that has the potential to recognize vast numbers of different antigenic shapes. During this process, a majority of T cells develop TCR with alpha (α) and beta (β) chains. A smaller number will have TCR with gamma (γ) and delta (δ) chains. At this point in the educational process, the career path of αβ and γδ T cells branch.

We’ll discuss the γδ (gamma delta) T cells first because they have characteristics that place them at the border between innate and adaptive immunity. Like the αβ T cells we’ll discuss next, they’ll mature and receive immune tolerance education in lymph tissue. But γδ T cells are a distinct lineage, with different structure and functions.

γδ T cells tend to congregate at mucosal surfaces (e.g., intestine, lung). They are at their highest abundance in the gut mucosa and interact with gut microbiota. γδ T cells respond within hours to common molecules produced by gut microbes or found in some foods/beverages. This rapidity of response to general molecular patterns is a characteristic of the fast thinking innate immunity. γδ T cells can undergo trained immunity—another characteristic of innate immunity—when challenged by certain compounds, becoming capable of responding faster and more efficiently to challenges by different compounds. But γδ T cells can develop memory, which is a characteristic of slow thinking adaptive immunity.

While γδ T cells behave in ways that do not fit neatly into the innate or adaptive immune subsystems, they play an important role in the overall fitness and intelligence of the immune ecosystem, and may speed up learning for other T and B cell lineages within the adaptive immune system.

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γδ T Cell Supportive Compounds

Cranberry Fruit Extract

L-Theanine 

Polygonum cuspidatum Root Extract (95% Resveratrol) 

**********************

Αβ T cells, the T cells with αβ chains on TCR, proceed to the next step in their educational process, but only if they’ve also produced both cluster of differentiation 4 (CD4) and 8 (CD8) markers on their surfaces. These CD4 and CD8 markers determine an αβ T cell’s major job specialty (e..g., helping others, working alone), so T cells without these are figuratively speaking left behind. [Note: Left behind in immune cell education literally means being killed off.].

At this point, all the surviving αβ T cells still in thymus school have both CD4 and CD8 markers. The next part of the educational process forces them to choose to keep one or the other (but not both). This educational step is called positive selection and is designed to graduate competent T cells that are able to recognize antigenic shapes when they are presented. It also determines the type of work the T cell will be best suited to do. 

αβ T cells—we’ll leave off the αβ from here on and just call them T cells—don’t learn by themselves. They depend on other cells presenting antigen information to them. Dendritic cells, macrophages, and B cells are considered “professional” antigen presenting cells (APC), ingesting proteins and displaying fragments of them on cell surface proteins called class 2 major histocompatibility complexes (MHC 2). In addition to these professional APC, all cells, with the exception of red blood cells, can present antigenic information to T cells using class 1 MHC (MHC 1).

To be productive members of the immune ecosystem, mature T cells will eventually need to be able to interact with antigenic molecular information presented on either MHC1 and MHC 2. The positive selection educational step ensures they can do this. It also determines which type of teachers, professional or unprofessional, the T cell is best suited to interact with. T cells that are better in interacting with the information presented by the MHC 1 are selected to specialize in working alone and become CD8+ T cells. The T cells that interact better with MHC 2 information become CD4+ helper T cells.

During the positive selection process, self antigens, friendly molecular shapes produced by the host, are used. This makes sense in the same way it makes sense in team sports to practice with each other before playing against another team. A downside of this positive selection approach is that some of the selected T cells might be prone to overreact to self molecules. The next educational step is called negative selection; it screens out any T cells that react too strongly to self. This last educational step ensures that the T cells that graduate from the thymus meet at least a minimum threshold for getting along with self molecules. Keeping with the team sports analogy, T cells that practice too hard, ones that might hurt teammates, are removed from the pool.

The key point is that immature T cells enter the thymus for education and graduate as a diverse pool of competent and tolerant mature T cells, which is why they are referred to as immunocompetent (i.e., able to recognize molecular shapes and take smart actions).  

The different stages of thymus education create a vast repertoire of naïve T cells (many different lineages of immunocompetent T cells with differing TCR). Naïve implies lacking experience or wisdom, which is exactly the case with these T cells. Naïve T cells are antigen-inexperienced. An antigenic shape that is a match for a TCR is called its cognate antigen. A naïve T cell is one that has yet to encounter its cognate antigen. In a sense, a naïve T cell has passed all the tests needed to graduate from school and is ready to go to work, but has yet to find a job. It’s waiting for an antigenic opportunity that is a good fit for its particular TCR skills.

For any individual naïve T cell an opportunity to go to work may or may not ever come; it is literally a matter of chance. But whether an individual naïve T cell ever gets an opportunity is unimportant. For network intelligence, it’s the collective intelligence of the group, not the fate of individual agents that matters. A large diverse repertoire of naïve T cells means that the collective has greater potential to quickly learn to recognize unfamiliar antigenic shapes—having a diverse pool of naïve T cells literally means that the immune system will be better prepared to solve more types of new problems. In the case of T cells and the immune ecosystem, naïve does not mean stupid; it means potential to get to work quickly and behave intelligently.

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Naïve T Cell Supportive Compounds

LJ100® Eurycoma longifolia Root Extract

Zinc (as Zinc Gluconate)

Lactococcus lactis strain Plasma (heat killed)

Vitamin D3 (as cholecalciferol)

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Some naïve T cells specialize in helping. These are called CD4+ helper T cells (Th). Other naïve T cells have been selected to work alone as cytotoxic CD8+ T cells (Tc). No matter which functional role it may eventually play, individual naïve T cells spend their lifetimes waiting and searching for cognate antigen opportunities (i.e., antigens they can bind with). When T cells of either the Th or Tc type encounter their cognate antigen, they become activated. This starts a process of accelerated learning.

Even if there is a diverse population of naïve T cells, an exact match to a cognate antigen is unlikely. But many crude matches—naïve T cells with some but not perfect ability to bind to the antigen—will be common. All of these crude matches become activated, competing with each other in a race, where the winner will be the naïve T cell lineage that can adapt its TCR to recognize the antigen with near perfect accuracy (i.e., bind tightly) the fastest.

Adaption, what could be called learning, occurs genetically, with the activated naïve T cells proliferating, rapidly mutating TCR genes as they divide and produce offspring. Offspring that bind more tightly (i.e., have a higher affinity or better fit) proliferate more rapidly, edging out those that don’t. This process continues until eventually one lineage has figured out how to bind incredibly tightly. While many other naïve T cell lineages may have had some ability to recognize the antigen at the start, the process of T cells solving the binding problem is a winner take all situation. It is a Darwinian competition with the fittest, the lineage which recognizes the antigen the best, surviving and contributing its genes to the immune ecosystem genetic library. 

Ultimately, the CD4+ helper T cell clones that bind tightly will communicate with, recruit, educate, and stimulate other fast and slow thinking immune cells, while ensuring that immune cells behave appropriately. Activated CD8+ cells that are best able to recognize the antigen will be working on their own to deal with any stressed cells displaying these molecules. The CD4+ and CD8+ T cell behaviors will continue until there are no more antigens to bind. At which point, most of the clones won’t be needed (and will be eliminated), while a small subset of them will become permanent memory cells, remembering the exact solution to this antigenic challenge in case it’s ever needed again, and adding to the library of acquired immune knowledge. 

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T Cell Supportive Compounds

Lactococcus lactis strain Plasma (heat killed)

Wellmune® Baker’s Yeast Beta Glucan

LJ100® Eurycoma longifolia Root Extract

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

N-Acetyl-L-cysteine

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The development and initial education of B cells takes place in bone marrow, but is otherwise fairly similar to that of T cells. Like T cells, B cells graduate from bone marrow after receiving an education in diversity, competence and tolerance. After leaving the bone marrow, B cells migrate to the spleen to continue their education and complete their development into mature naïve B cells. The end result is a diverse pool of naïve B cells that give the slow thinking immune system billions of possibilities for recognizing antigens it may encounter.

While the education of T and B cells have many common themes, one main structural difference is that instead of having TCR that interact with antigens, B cells have B cell receptors (BCR). Another major difference is that B cells secrete immunoglobulins (commonly called antibodies) once they solve the molecular shape problem. A third difference is that B cells can present antigens. Like dendritic cells and macrophages, they are classified as professional antigen-presenting cells, so can play a role in displaying information to and educating T helper cells.

The B cell solution to recognizing antigens is to secrete antibodies. The process of creating specific antibodies to recognize novel antigens is a similar Darwinian competition to what T cells undergo. When challenged by novel antigens, naïve B cells with some ability to recognize the antigen (i.e., having a BCR that can bind it) produce clones that get progressively better and better able to recognize it. In most, but not all cases, interaction of the naïve B cell with a T helper CD4+ cell is necessary to produce full activation of the B cell. So T helper cells facilitate B cell learning, while B cells present the antigenic information to all T cells.

The lineage of naïve B cells that come up with the best solution, a lock and key antigenic match, stops proliferating and becomes a plasma cell (i.e., antibody factory) and rapidly produces and secretes antibodies to bind to the antigen—a single activated plasma cell can create several thousand matching antibodies per second.

B cell antibodies come in two basic types: binding and neutralizing antibodies. Binding antibodies act a bit like Velcro, attaching themselves to cells that are displaying the antigen, essentially marking it as something that requires attention by other cells in the immune ecosystem. Neutralizing antibodies, as the name implies, directly neutralize antigens on their own.

Similar to T cells, once there are no more antigens to bind, most of the plasma cells with the ability to recognize the antigen will no longer be needed, but some will be retained as memory B cells. These memory B cells will remember the antigen so the B cells can respond faster if they encounter it again. 

B cell antibodies (i.e., immunoglobulins) come in five isotypes—IgA, IgD, IgE, IgG, and IgM—that have varying functions and locations. For example, IgA is in higher amounts in the intestines and very involved in mucosal immunity, while IgM and IgG are much higher in the blood.

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B Cell Supportive Compounds

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

L-Theanine

Panax ginseng Root Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Lactococcus lactis strain Plasma (heat killed)

Vitamin D 3

Broccoli Sprout Powder

Selenium (as Se-methyl-L-selenocysteine)

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WHAT IS MUCOSAL IMMUNITY?

Mucosal immunity is the border patrol of the immune system; it is the collection of immune resources that gather in most of the places where our inner world comes into contact with the outer world. These include the gastrointestinal (GI), respiratory, and urogenital tracts. 

The mucosal immune system needs to behave intelligently, because, not only does it patrol the border to recognize non-self, but it must also be able to sort out friendly non-self (i.e., commensal microbes) from non-friendly molecules, tolerating the former but not the latter. And, mucosal surfaces need to have an additional layer of tolerance, making decisions about a vast array of foreign molecules in food, beverages, and air.

Mucosal immunity uses mucosa-associated lymphoid tissue (MALT) to store reserves of macrophages and lymphocytes (T cells and B cells). These MALT locations are situated to allow local parts of the immune system to respond quickly when needed and named for their locations. MALT in the GI tract is called GALT.

Because of its physiological function in food absorption, the GI tract is an Achilles heel, an area of vulnerability. Scientists estimate that more than half of all immune cells (maybe as much as 70%) reside in the GI tract within GALT. GALT relies on a large population of plasma cells—the antibody factories created from smart B cells—that produce immunoglobulins. Immunoglobulin A (IgA) plays a primary role in mucosal immunity in the oral cavity and gut mucosa: It is a way to intelligently deal with situations at the borders, so supporting IgA is a way to support mucosal immunity.

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Mucosal Immunity Supportive Compounds

Wellmune® Baker’s Yeast Beta Glucan

Vitamin D3

Cranberry Fruit Extract

Lactococcus lactis strain Plasma (heat killed)

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Echinacea purpurea Root Extract

N-Acetyl-L-cysteine

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

Panax ginseng Root Extract

Broccoli Sprout Powder

*********************

WHAT ROLE DOES THE GUT MICROBIOTA PLAY IN IMMUNITY?

Scientists estimate that between 50-70% of our immune cells are located in the gut. A significant part of the education and maturation of the local gut immune system is carried out by the contact and co-evolution with gut microbiota—the collection of mostly helpful organisms. But they have more than simply local actions. Gut microbiota play roles in immune tolerance and trained immunity. They influence B cell repertoires and influence immunity throughout the body. 

The human intestine hosts roughly 100 times more bacterial organisms than the number of cells in the body, and close to 1000 distinct species. The majority of bacterial species are members of either the Firmicutes or the Bacteroidetes phyla. 

The relationship between us and the gut microbiota is usually described as commensal, which means one organism benefits (i.e., us) and the other derives neither benefit nor harm (the gut microbiota), though there is likely a considerable degree of mutual benefit.

Some of the probiotic strains—both active and inactive—of commensal organisms support healthy gut immunity. This subset of probiotics are sometimes called “Immunobiotics,” because they are immune-supportive.

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Immunobiotic Compounds

Lactococcus lactis strain Plasma (heat killed)

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Some herbs, mushrooms, and superfood extracts contain prebiotic substances (typically as polysaccharides) and/or prebiotic-like substances (such as polyphenols) that support a more diverse and metabolically healthy gut microbiota. Some nutritional compounds (vitamins, minerals, amino acids) also have prebiotic-like qualities, supporting the richness of gut microbiota and the gut-immune axis.

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Gut Microbiota Supportive Compounds

Polygonum cuspidatum Root Extract (95% Resveratrol)

Cranberry Fruit Extract

Wellmune® Baker’s Yeast Beta Glucan

Vitamin D3 (as cholecalciferol)

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Panax ginseng Root Extract

Echinacea purpurea Root Extract

N-Acetyl-L-cysteine

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Maritech® Fucus vesiculosus Extract 

Maritech® Fucorich® Undaria pinnatifida Extract

Palmitoylethanolamide

Selenium (as Se-methyl-L-selenocysteine)

L-Theanine

Broccoli Sprout Powder

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HOW DOES THE IMMUNE SYSTEM LISTEN?

Immune system intelligence arises from the competition and cooperation of immune cells. It is a swarm intelligence or collective wisdom that resides in the network’s interactions. This type of dispersed intelligence relies on communication between the individual agents, which in this case are white blood cells.

The information each immune cell receives and sends are collectively used, locally and systemically, to maintain, heal, regenerate, and surveil the body. By interacting and communicating with neighboring cells, a collective of immune cells can together do remarkable things … things that individual immune cells, one-by-one on their own, could not do. This interaction and communication is a two-way street—white blood cells need to be able to listen and talk. Let’s start with listening. 

For complex adaptive intelligence to arise, a system of agents must be able to detect what occurs in their environment and respond to it by changing behavior. The brain solved this detection problem by developing sensory inputs—ears, eyes, etc. When hearing is impaired, as an example, the speed of response to auditory stimuli is impaired—we literally won’t be able to hear some of the sounds around us, and we respond more slowly to the ones we do detect. This impacts aspects of both Kahneman’s System 1 and System 2 thinking. In other words, all else being equal, the brain is able to think better when it hears better. An analogous issue faces immune cells—they need to be able to “hear” what is going on around them. Their solution is receptors.

Each immune system cell “perceives” the world around it by using external receptors, receiving whatever signals its receptors can detect. These receptors are figuratively speaking, the ears of immune cells, so spend their time listening for molecular signals. They allow individual immune cells to sense antigens, metabolic products, cell interaction molecules, and other signals. This sensory step is necessary for immune cells, and the immune ecosystem as a whole, to behave intelligently. If an individual (or many) immune cells is deaf to something (i.e., it’s receptors are figuratively hard of hearing), other cells can be shouting for attention, and the message will go unheard.

NKG2D is an example of an immune cell receptor. It’s found on NK cells of the fast thinking innate immune system, and natural killer T (NKT) and CD8+ T cells of the slow thinking adaptive immune system. It can also be found on subsets of γδ T cells—the group of immune cells that have functional characteristics of both fast and slow thinking. NKG2D plays an important role in the recognition of stressed cells—It detects markers on cell surfaces (called ligands) that indicate general cellular stress, which allows the various immune cells that rely on the NKG2D receptor to take intelligent actions. When NKG2D receptors are better able to sense their environment, the immune system’s ability to hear and respond to stressed cells is better.

Supporting immune cell receptors, including but not limited to NKG2D, is an important part of immune system communication. In the simplest sense, immune cells that can sense their environment better will think better; they are more aware of their environment, detect more information, and process it faster. Because they are able to respond to more subtle cues, they hear things early on and solve problems when they are smaller and more manageable.

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Immune Cell Receptor Supportive Compounds

Polygonum cuspidatum Root Extract (95% Resveratrol)

Broccoli Sprout Powder

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Vitamin D3

Cranberry Fruit Extracts

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

*******************************

HOW DOES THE IMMUNE SYSTEM TALK?

In addition to listening, immune cells also send information; they “talk” with each other, using chemical signaling molecules called cytokines. The four main categories of cytokines are interleukins, interferons, chemokines and tumor necrosis factors. Immune cells make and use these communication chemicals to activate and recruit other immune cells, figuratively talking to each other, letting other cells know what is going on, where it is going on, and what assistance they’d like.

It can be useful to think about immune system communication using the principle of signal-to-noise ratio. The basal level of a molecule is the noise. An amount above this background noise level is the signal. The amount of background noise dictates how loud you’d need to speak in order to be heard. If the background is very noisy, one communication option is to speak a lot louder, shouting to be heard. There are several downsides to this approach.

What if you can’t raise your voice enough to be heard over the noise? Or what if, to be heard, you need to shout so loudly it might injure your voice or the listeners hearing? And what if background noise is not free, but has a cost—if on its own sustained louder noise damages hearing (by the way it does)? All of these are issues when it comes to communication at a cellular level.

Another option, and a physiologically more desirable one, is to dampen the background noise … to make things quieter. In immune system communication, this analogy means quieting the basal levels of cytokine molecules. That way, when it does need to talk, the immune cells in the immune ecosystem won’t need to shout so loudly to be heard. 

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Cytokine Quieting Compounds

Polygonum cuspidatum Root Extract* (95% Resveratrol)

Maritech® Fucus vesiculosus Extract 

Maritech® Fucorich® Undaria pinnatifida Extract

Broccoli Sprout Powder

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Panax ginseng Root Extract

Palmitoylethanolamide

Cranberry Fruit Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Wellmune® Baker’s Yeast Beta Glucan

N-Acetyl-L-cysteine

L-Theanine

Selenium (as Se-methyl-L-selenocysteine)

Zinc (as Zinc Gluconate) 

Vitamin D3 (as cholecalciferol)

**********************

WHAT ROLE DOES NRF2 PLAY IN IMMUNITY?

Nrf2—the abbreviation for nuclear factor erythroid 2 related factor 2—is a gene that regulates other genes. The Nrf2 signaling pathway is best known for being a master regulator of cellular defenses, including antioxidant defense, detoxification, cellular stress response, and cell repair genes. It also has a lesser known, but critical role in immune system performance. 

Nrf2 plays an important part in modulating aspects of the innate (i.e., fast thinking) immune system. In general, it supports the innate immune system’s role in teaching the slower adaptive immune system and shifts the immune system back into the quiescent surveillance mode where it spends most of its time. Nrf2 helps the immune system to perform at a high level when it comes to looking for and finding stressed cells and it is an important part of immune system recovery.

One of the specific roles of Nrf2 has to do with regulating dendritic cell function, which are the professional antigen presenting cells (APC) that teach the slower thinking adaptive immune system about antigens. Nrf2 also influences both the phagocytic and repair functions of macrophages (another professional APC).

Nrf2’s most important role in immune system function might be with communication. Nrf2 plays a large role in quieting the “noisy” state of cytokine communication after the need to talk loudly to other immune cells has passed. Returning the background noise to a quieter level ensures that the next time the immune ecosystem needs to communicate, individual immune cells won’t need to shout loudly to be heard. This quieting is a major part of immune system recovery functions.

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Nrf2 Supportive Compounds

Broccoli Sprout Powder

Polygonum cuspidatum Root Extract (95% Resveratrol)

Maritech® Fucus vesiculosus Extract

Maritech® Fucorich® Undaria pinnatifida Extract

Panax ginseng Root Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Cranberry Fruit Extract 

Echinacea purpurea Root Extract

Vitamin D3 (as cholecalciferol) 

Zinc (as zinc gluconate)

Selenium (as Se-methyl-L-selenocysteine)

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ARE THERE GENERAL PRINCIPLES OF THE IMMUNE SYSTEM I SHOULD UNDERSTAND?

Immunity is complex beyond imagination. But, oftentimes the ability to make predictions, to essentially make good choices will be furthered dramatically by understanding core principles about how something behaves. Exercise is an example. You don’t need to have a degree in exercise science or kinesiology, or to understand all the details about individual myocytes (i.e., muscle cells), never mind the mechanisms of competition and cooperation in the vast network of muscle cells, in order to understand how muscles as a whole adapt to stimulus. Understanding and applying core exercise principles will carry a person a long way on the road to producing great results. 

So, we want to share a few important immune system operational principles. Keep them in mind when considering what to do (or not do), how to do it, and what life circumstances might make supporting immune intelligence even more important.

1. Repetition is Important For Immune System Learning.

The brain learns through repetition. Whether called the “spacing effect,” “spaced repetition,” or “spaced learning,” if we want to learn discrete information, commit it to memory, and be able to recall it later, we’ll learn it better and faster if we are exposed to the information multiple times, with some time interval—a space—between them. The same principle applies to muscular fitness. It is the repetition of exercise over time (and the space between exercise sessions for recovery) that create fitness. This is exactly how the immune system learns. The best immune system learning occurs through spaced repetition. When it comes to recognizing and responding to molecular shapes, practice makes perfect, and spacing the information out over time can make a difference.

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“We’re often asked why we recommend taking a supplement for five days and then taking two days off … and to periodically take a week or so off. One reason for this is that complex adaptive systems get smarter when they are repetitively stimulated and have a space between stimuli to recover.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective

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2. The Immune System Learns By Being Challenged … Appropriately.

Exercise provides a challenge for muscles. In response to a challenge, and depending on the exact type of challenge, they get bigger, stronger, faster, or learn to excel at specific tasks or movements. Similar to exercise, the immune system thrives on challenges and learns by being placed under stress. Challenges can toughen it up, making it fitter and more antifragile.

Nassim Nicholas Taleb, author of the book Antifragile: Things That Gain from Disorder, came up with the term “antifragile” to describe anything that is the exact opposite of fragile. An antifragile system, not only withstands challenges or stressors, it benefits from them, provided the challenge or stress isn’t too much. 

The brain is an antifragile system. Bones and muscles are both antifragile. The same is true for the immune system; it learns by and thrives when challenged appropriately. But what is an immune system challenge?

Lifting weights is a type of muscular challenge. Muscles get bigger and stronger when challenged by lifting heavier weight, remodeling themselves, so that if they are faced with the same challenge in the future, they’ll be better able to handle the stress. This is exactly what the immune system does. But in the case of the immune system, the challenge is not weights, it’s molecular patterns … shapes.

Exercise can be used to create very specific types of adaptations, optimizing for strength, speed, endurance, or performance in any number of movement skills or sports. These are examples of creating specific fitness. Specific fitness allows us to perform at a high level but in a narrow range of exercise activities. When we encounter a challenge—a type of exercise stress—we’ve trained for, we handle it well. But if we encounter a type of exercise activity we are untrained for, some, perhaps most of the fitness benefits don’t carry over.

Exercise can also be used to create more generalized fitness. Instead of optimizing for strength or speed or endurance or a sport-specific skill, training can be designed to enhance fitness across many areas. This approach sacrifices some degree of specific performance for a more general ability to perform well in many different types of activities. General fitness also prepares us better should we encounter a challenge we haven’t been training for. The fitness benefits carry over into many areas. If the goal is to adapt quickly and overcome challenges outside of what we’ve been training for, general fitness trumps specific fitness. 

This idea of specific versus general fitness can be applied to the immune system. If we challenge it, but too narrowly, it will be creating fitness, but not the generalized fitness that allows it to recognize and adapt to unforeseen challenges. Conversely, if we challenge it with a broader range of molecules, we’ll be, in essence, putting it through more of a cross-training workout, toughening it up, producing general fitness.

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“One of our guiding principles when we designed Qualia Immune was to challenge the immune system in a way that would result in something akin to general fitness with exercise. This is part of the reason why there is such a range of ingredients from differing categories—algae, microalgae, herbal tonics, probiotic, beta glucan, mushroom, superfoods, etc. In a sense, we wanted to be giving the immune system the equivalent of a CrossFit workout.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective

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Depriving certain types of systems of vital stressors is not a good idea. In fact, it can be downright detrimental. Taleb makes this important point in Antifragile. Antifragile systems—the brain, bone, and muscles—suffer from disuse, lack of stimulation, and sedentary behaviors. Challenging an antifragile system can make it smarter, stronger or fitter, but failing to challenge it doesn’t leave it the same; it makes it dumber and weaker. 

If instead of challenging the immune system with molecular shapes, we try to shelter it, we can be in effect weakening it, forcing it to be “sedentary.” This is the premise behind what’s called the “hygiene hypothesis”— failure to appropriately challenge an immune system during the period of early childhood, when it’s learning rapidly, hinders immune system development, especially in areas related to establishing immune tolerance. 

A last point Taleb makes is that antifragile systems get better when challenged, provided the challenge is not too great. Exercise again provides a useful analogy. Going from being sedentary to even moderately active can be a large challenge. If a person new to exercise trains too hard—the challenge is too great—they will traumatize muscles, or worse, injure themselves. These are both counterproductive to creating fitness.

While the immune system is antifragile, it can be over-challenged. When encountering new molecules (a new food or supplement is an example), it’s better to start with less and work up, rather than overdoing things. Instead of exposing immune intelligence to large amounts of a new molecule (or molecules) all at once, present challenges in more manageable loads, taking advantage of principle 1, repetition, to create immune fitness gradually.

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“Difficulty is what wakes up the genius.”

Nassim Nicholas Taleb from Antifragile: Things That Gain from Disorder

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3. Antifragility Is Created In Advance; It’s About Being Prepared.

Being prepared implies always being ready, willing, and able to do what is necessary in any situation that comes along. This can’t be achieved by only putting attention onto something after it’s come along … or when its arrival is imminent. The effort, work, education, etc. that we put in in advance is what allows us to be better prepared no matter what the future may bring. Why is this important for immune intelligence?

The more prepared the immune system is in advance of when we need it to perform intelligently, the better it will be able to do what is necessary when we need it to. Supporting it in advance of when we need it, simply put, makes sense. The time to make sure it is smarter, stronger, and fitter, is before we need it to metaphorically do a lot of thinking or lifting heavy weights.

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“Some immune support ingredients fit into a “be prepared” category. Many others don’t. When Neurohacker Collective created Qualia Immune, we prioritized ingredient choices that support the immune system to be smarter and fitter … in advance of when we need it to be. This is a very different approach to how other immune system formulas are designed and used.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective

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4. Immune Thinking Takes Energy

Like all types of work, brain thinking requires energy. Pound for pound the brain uses the most energy of any organ: It’s been estimated that on a second by second basis, the human brain uses more energy at rest than a human thigh during a marathon. What’s all this energy used for?

The majority of the brain energy budget, between two thirds to three quarters, is used for remaining vigilant and communicating. Sensing the environment and signaling throughout the neural networks (i.e., neurotransmission) takes huge amounts of energy. Which other system spends an inordinate amount of its resources staying vigilant, surveilling its environment, and communicating, listening and talking, across the network?

Between one quarter to one third of brain energy is used by neurons and glial (non-neuronal) cells—which includes the resident macrophages of the nervous system called microglia. This energy is used for housekeeping, maintenance, and repair functions needed to keep the nervous system healthy and functioning. Which other system spends a lot of its resources on housekeeping and maintenance, on healing and repair?

Cognitively demanding tasks—System 2—including executive functions, social cognition, learning, and memory require more energy than simple tasks and are often the first to suffer when demands for energy exceed the amount available. Which other system, and in particular which subsystem of it, is involved in intensive computational tasks?

The answer to all of the above is the immune system. The immune system, both the fast and slow thinking subsystems, require energy to do work. And, the answer to the last question is the slow thinking adaptive immune system, which requires more energy—and changes its metabolism accordingly—as naïve or memory lymphocytes are activated, going from a quiescent state to actively being engaged in solving challenges. Like brain thinking, immune system computation costs effort and requires energy. Individually and collectively, immune cells will, after all, be working harder.

ATP is the primary chemical energy molecule of the body. It’s produced by mitochondrial networks, another example of swarm intelligence and collective wisdom. Like cells in the brain (or muscles), white blood cells have mitochondrial networks; they produce and use ATP. And, they use more of it when they need to do more work. Like brain thinking, immune work can be exhausting. If we want immune cells to be capable of doing more work, it's important to support mitochondrial health.

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Mitochondrial Network Supportive Compounds

Polygonum cuspidatum Root Extract (95% Resveratrol)

Broccoli Sprout Powder

Palmitoylethanolamide

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract  

Panax ginseng Root Extract

Cranberry Fruit Extract

Maritech® Fucus vesiculosus Extract 

Maritech® Fucorich® Undaria pinnatifida Extract

Vitamin D3 (as cholecalciferol)

Zinc (as zinc gluconate)

Selenium (as Se-methyl-L-selenocysteine)

N-Acetyl-L-cysteine (as a glutathione precursor)

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5. High Demands In Other Areas Of Life Place Greater Stress On Immune Intelligence.

The immune system is always on, but sometimes it has to do more work than other times. Intense exercise is an example of one of these situations. When we exercise, even moderately, immune cells of both the fast and slow thinking immune systems become more engaged in surveillance, moving from the bloodstream to mucosal areas of the lungs, digestive tract, and skin. Immune cells are also involved in healing processes, so have to do more work after a strenuous workout to remodel and repair muscles, helping in the recovery stage of exercise. And, the more intense and more frequent the workout, the more demands we'll be putting on the immune system. 

Exercise is not alone. Psychological stress, work demands, exams, and lack of sleep, are a few of the circumstances known to impact immune system performance. The key point is that when we are challenging the body more intensely, frequently, or both, no matter what the challenge might be, we are very likely to be placing greater demands on the immune system. For people who live high performance lives, who place outsized demands on themselves, which includes most of the biohacking community, the demands placed on the immune system are also greater.

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Immune Support For Intense Exercise and Greater Stress

Lactococcus lactis strain Plasma (LC-Plasma)

Wellmune® Baker’s Yeast Beta Glucan

Panax ginseng Root Extract

Reishi Mushroom (Ganoderma lucidum) Fruiting Body Extract

L-Theanine

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extract

Tinofend® Tinospora cordifolia Stem Extract

LJ100® Eurycoma longifolia Root Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

Zinc (as Zinc Gluconate)

Vitamin D3 (as cholecalciferol)

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6. The Immune System Needs Extra Support As It Ages

The development of Qualia Immune started from research we were doing into a hallmark of aging called cellular senescence. Senescent cells—a category of stressed cells—accumulate in tissues during age. But they do more than simply grow in number, they contribute to tissue aging and are part of the “Aging as Damage Accumulation” theory of aging. A main reason they accumulate is because an older immune system does a poorer job recognizing them compared to a younger immune system.

Like an older brain and muscles, where thinking and exercise performance change in predictable ways with aging, an older immune system’s thinking changes in very predictable ways—this is called immunosenescence. Some of these predictable ways include diminished self-renewal capacity of hematopoietic stem cells, involution of the thymus (the lymph organ that produces diverse, competent and tolerant T cells), and changes in gut microflora (and hence the gut-immune axis).

Some of the fast thinking immune system changes with older age include:

  • Slower phagocytes (e.g., neutrophils, macrophages)

  • Less active natural killer (NK) cells

  • Poorer antigen-presenting function (ie., teaching job) of dendritic cells 

While aging changes immunity as a whole, the slower thinking adaptive immune system is believed to be even more impacted than the faster innate immune system. Adaptive immune changes include:

  • Too much immune intelligence is devoted to memory (i.e., lots of experienced lymphocytes) but not enough is dedicated to recognizing new molecular shapes (a lack of naïve lymphocytes that are waiting for opportunities).

  • Literally and figuratively lymphocytes are more exhausted, which as a result causes them individually and collectively to respond slower, take more time to think, learn new lessons poorly, and produce solutions, which, simply put, often don’t work as well as the ones a younger immune system would have thought of.

  • Lymphocytes have to work harder just to survive leaving less energy available for them to do immune system work. 

In a nutshell, an older adaptive immune system loses diversity, competence, tolerance, adaptability, flexibility, robustness, and resilience: It becomes less antifragile. The same things that happen to our brains, bones, muscles, and skin happen on the inside to our immune ecosystem.

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Immune Rejuvenating Compounds

LJ100® Eurycoma longifolia Root Extract

Polygonum cuspidatum Root Extract (95% Resveratrol)

Lactococcus lactis strain Plasma (LC-Plasma)

N-Acetyl-L-cysteine

L-Theanine

Echinacea purpurea Root Extract

Spirulina (Arthrospira platensis) Protein and Nucleotide Water Extracta

Wellmune® Baker’s Yeast Beta Glucan

Zinc (as Zinc Gluconate)

Broccoli Sprout Powder 

Palmitoylethanolamide

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“Why did we develop Qualia Immune? The answer is straightforward; we think having a smarter, fitter, higher performing immune system is a foundational pillar of health.”

Gregory Kelly, ND, Director of Product Development, Neurohacker Collective


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