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The Wheat Series Part 4: Home Invasion

Nothing is scarier than someone invading your home. You’re nearly asleep when you hear the sound of something rustling downstairs. Instantly you’re awake and your internal alarm bells go off. You grab the phone. Fortunately the police are nearby and arrive almost instantly. They’ll catch the invader. You have nothing left to fear. Or do you?

The police enter the darkened house to a confusing scene. Your teenage son, sneaking home from the party you told him not to go to, has stumbled into the unknown invader. Meanwhile, your partner has entered the other side of the room carrying a baseball bat. The police can just make out three figures in the dark. Several seem armed and one may be a hostage. An officer draws her gun, but who does she point it at?

Sadly, it’s not always a happy ending. Innocent people are killed in their own homes all too often.

While a home invasion is something most of us will hopefully never experience, dealing with invaders is something our bodies have to handle thousands of times each day. And just like a thief entering your house, it would seem the job of identifying the invader – bacteria and viruses – should be a simple task. But it’s not.

The immune system – the police of our bodies – has to deal with equally dark and confusing scenarios as it tries to differentiate dangerous invaders from our own cells, beneficial microflora, and food.1-3

Fortunately, it has evolved remarkably complex systems that make it very good at determining which is which.

One food however is even better at breaking in, turning out the lights, and making the police point the gun in the wrong direction. Wheat.

In Parts 1, 2, and 3 of this series on wheat, we talked about how wheat affects the three things that can cause the digestive immune system to dysfunction. The first was increased permeability (Part 2), the second was excess bacterial stress (Part 3). The third is the subject of this post – harmful dietary antigens.

Antigens – Identifying the invader

Antigens are critically important to our immune defenses. In fact, without them, most of our immune system wouldn’t be able to function. Which begs the question – what exactly are antigens?

They are just molecules. And not really any special type of molecule. Antigens exist in everything – bacteria, viruses, our food, even our own cells. As long as our immune cells can bind to it and identify it, it’s an antigen.4

Certain cells in our immune system, called antigen presenting cells (APCs), travel around our bodies “sampling” everything they encounter. They aren’t particular – they’re just as likely to check out our own cells as a foreign bacterium. They chew everything they sample into small molecules and present these antigens to the brains of our immune system – T Cells.4

T Cells are trained from birth not to respond to our own unique self-antigens which makes them remarkably good at identifying anything foreign. Together, T Cells and APCs determine when an antigen isn’t self and more importantly if it’s something to be worried about.5

Think of an antigen as an ID card. APCs and T Cells are the police hunting through the house for anyone who doesn’t belong. The more hot-headed APC likes to slam anyone it encounter up against the wall and takes their ID. It’s the T Cell who looks over their identification and decides if they belong or not. It’s the misfit buddy cop movie of our bodies.

The problem is, just like in the movies, ID cards are easy to fake. Some viruses have evolved the ability to mimic our own antigens in an attempt evade detection.6, 7

And like your daughter’s boyfriend who tends to sneak through the window at night, not everything from outside is bad (though some fathers reading this may be thinking “shoot him.”) Beneficial bacteria in our gut are foreign, but we’ve learned to live in synergy with them.2, 3, 8 Likewise, all food is technically foreign, but an immune response to what we eat would lead to debilitating allergic reactions and worse.9-11

To deal with this extra level of complexity, our immune systems have developed two sophisticated “interogation” techniques – co-stimulation and oral tolerance.

Co-stimulation (or the second signal)

Just identifying an antigen as foreign actually isn’t enough for a T Cell to start an immune response. The T Cell must also receive an activating signal from the APC as it presents the antigen. The APC gives this second signal when it has been exposed to a large amount of the antigen or if the body is in an inflamed state.5, 12-15

It’s the equivalent of the T Cell asking the APC “I don’t recognize this guy, should I draw my gun?” Surprisingly, the tough guy APC generally replies “What this wimp? Nah I can take him.”

Oral tolerance

This is a fancy term for not reacting to food. A special type of APC, called dendritic cells (DCs), specializes in reaching into the gut to sample food particles and microflora. Most of the time it presents the antigens with the message: “This is food. Don’t do anything.”1, 12, 14 DCs work in conjunction with a special T cell called T Regulatory (Treg) cells that respond to self-antigens instead of foreigners. But unlike other T cells, when activated, Treg cells suppress the immune system.12, 16-18

These two cells are the police movie equivalent of the by-the-books pencil-pushers who constantly tells the loose cannon to holster his gun. Fortunately, in our bodies, the pencil-pushers are in control most of the time.17

The image below shows the antigen identification system in action. Plasma cells, macrophages and DCs are all APCs. As you can see, in the healthy gut, Treg cells dominate:19

Wheat: The master criminal

For the rest of this post we’ll talk about how wheat is essentially a “master criminal” able to flip our antigen identification system on its head. But unlike a virus, wheat doesn’t break the system to try to evade detection. Instead it intentionally sets off the alarms and provokes the immune system to draw its guns. Tragically it’s also very good at getting immune cells to fire on the wrong target.20

The lock-picker

Part 2 of this series explained how wheat effectively opens the tight junctions of our gut allowing bacteria, large molecules and gliadin from wheat itself to enter the body.21-24

But that’s not the only way wheat breaks in.

A protein in wheat called Wheat Germ Agglutinin (WGA) is very good at binding to the cells in our digestive tract and passing right through them into our blood stream.13, 25, 26 WGA can also bind other particles. So not only can it gain entry into circulation, but it can carry antigens from the gut with it.27, 28

The police-provoker

Above, we discussed how the immune system doesn’t automatically respond to foreign antigens. It first needs a co-stimulation before drawing its guns. We also covered the two things that cause APCs to provide this second signal.

The first was exposure to a large quantity of antigens. By “picking the locks” to the house, wheat essentially flings open the doors allowing a huge flow of antigens from the gut into the body.

The second thing that gets APCs to provide the co-stimulation is inflammation. In Part 3 of this series, I explained how wheat tricks the body into believing it is under perpetual bacterial stress.29-33 This creates a constant inflammatory state that causes the once suppressive DCs to flip and start activating the immune system.34, 35 Other APCs follow suite.30, 32, 36-39

In other words, the once tolerant “pencil-pusher” cops of the immune system become gun happy in a way that would make Arnold Schwarzenegger cringe.13

In short, wheat ensures there’s a co-stimulation. Wheat also breaks tolerance:

WGA is able to enter the body bypassing all the mechanisms of oral tolerance.25, 28 So, the first time WGA and the food antigens bound to it are exposed to the immune system is in circulation where the response is almost always inflammatory.

Worse, in multiple studies of wheat’s effect on mice and humans, wheat reduced the levels of Treg (the immune suppressors) in favor of a type of T Cell called Th17.29, 34, 40 We’ll explore this shift in greater detail in Part 5. All you need to know for now is Th17 is the loose cannon cop who shoots first, asks questions later.41-43

The red herring

This is the definition of an autoimmune disease. It is a condition where the immune system identifies self-antigens as foreign and attacks its own body.44 In other words, the police accidently shoot the residents.

One popular theory of how autoimmune disease comes about is the viral mimicry theory. A virus enters the body that mimics self-antigens.14 In the process of fighting the virus, the immune system ends up identifying the mimicked self-antigens as foreign.6, 7, 45

For this to happen, the body has to be in an inflamed state. That way APCs provide the co-stimulation required and they also suppress Treg cells which would otherwise prevent a reaction to self. This is why the theorists looked at viruses. Not only would they mimic self-antigens, they’d also create the necessary inflammation.7, 45

However, we’ve just seen that wheat does an equally good job of providing the co-stimulation and shutting down Treg cells. And wheat may provide the mimicry as well, so forget the virus.20, 44, 46-48

Of the over 100 autoimmune conditions identified, the trigger has been discovered for only a handful. One of those is celiac disease. In this condition, gliadin from wheat binds a protein in the body called tissue transglutaminase (tTG). The immune system reacts to tTG-gliadin antigens causing it to attack the digestive tract.39, 49, 50

Gliadin may also cross-react with neural components of the brain and contribute to conditions like multiple sclerosis, gluten ataxia, and autism.46, 47, 51 Similarly, WGA is able to bind to many different cells once inside the body.20, 26, 31 While responding to WGA, the immune system will sometimes also react to its binding tissues.20, 52

What all of this amounts to is the ending to that home invasion story none of us want to hear. Wheat and the police end up in a tense standoff and guns are drawn. Tragically your son gets mistaken for one of the invaders and gets killed in the cross-fire.

Fortunately, while wheat can dysregulate the immune system in all of us, not everyone who eats it develops an autoimmune disease. In the final part of this series we’ll talk about how genetic susceptibility is required for disease.


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Trevor Connor, M.S.

Dr. Loren Cordain’s final graduate student, Trevor Connor, M.S., brings more than a decade of nutrition and physiology expertise to spearhead the new Paleo Diet team.

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