# Part I of Article on What's Happening with the Immune System with Hahsimoto's



## Marc Ryan (Mar 22, 2013)

Hello, people. Here's Part I of a 2 part article on what is happening with the immune system in Hashimoto's. I'll post Part II as a reply. Thought it might make for some interesting discussion.

Hashimoto's is the most common autoimmune disease in the United States, but very few doctors, alternative practitioners or patients understand what is happening to the immune system or what to do about it.

As a result, treatment largely ignores the autoimmune part of the disease. In this post, I break down the basics of the immune system, explain how it affects people with Hashimoto's and why it matters.

The Immune System Is Supposed to Protect Us

The immune system protects us from foreign invaders. Its like our body's military. It finds the bad guys (like bacteria, fungus, parasites and viruses) and it kills them. It also cleans things up by destroying our own dead and dying cells. This is called cellular apoptosis, and if this process stops working, cancer develops.

In addition, the immune system creates inflammation as part of the process of healing after an injury. Recent research has shown that immune system has the ability to communicate with the nervous system, the endocrine system and digestive system and that it is actively modulating and influencing the body all the time.

The Immune System Has Different Parts

The immune system has many different parts, but the 2 important parts are called non-specific and specific immunity.

Non-Specific Immunity

The non-specific immune system is our immediate attack response. These are the front line soldiers that hang out in our borders (the mucous membranes of our lungs, digestive tract, skin and brain) and kill invaders.
This part of our immune system is called the T-Helper 1 (or TH-1) response. These are the macrophages (the Pac-man cells) and Killer T cells, the elite squads that are pathogen killing machines.

TH-1 is also broken down into messenger proteins like Interleukin-12 (IL 12), Interleukin 2 (IL-2), Interferon Gamma (IFN) and Tumor Necrosis Factor (TNF). These are the bad ass cells that get the job done.

IL-12 is a commander and facilitator that is responsible for helping cytotoxic lymphocytes, natural killer cells mature and it also supplies growth factor to help certain cells grow into the killers that they are.

It is also involved in turning on genes that result in attacks on specific organs and has been implicated as an important player in Hashimoto's.
IL-2 is synthesized by CD 4 T cells, it increases antibody production, improves bone marrow responses to other immune cells and is used in the treatment of HIV.

A close relative of IL-2, IL-15, has been shown to be low in Hashimoto's and treatment with levothyroxine increases IL-15 levels, as do some Chinese herbs.

Here is a perfect example of the contradictory nature of the immune system. Increasing IL-15, some theorize, may reduce the destruction of thyroid cells in Hashimoto's.

Interferon Gamma is another commander that fights viruses and prevents their RNA from passing on genetic information, it activates the pacman cells (macrophages) to destroy organisms that get inside of cells and it kills tumor cells.

Tumor Necrosis Factor (alpha) also kills tumor cells, it turns on angiogenesis (the hallmark of malignant tumors), promotes fibroblasts and is involved in wound healing.

TNF (beta) is another commander who helps kill tumor cells, activates genes, and it helps instruct CD8 T cells, NK cells, and helper-killer T cells to induce them to fatally injure their targets.

A TNF receptor called CD95, which is responsible for cell death, has been found to be very high in patients with Hashimoto's.

Specific Immunity

The specific immune system produces antibodies that label the bad guys. This part of the immune system is like the C.I.A., it gathers intelligence on the invaders and it labels them with an antibody. Once a foreign invader has been labeled by an antibody, its much easier for the killer cells to destroy it.
And like the C.I.A., it takes a while for them to gather the intelligence, so this process is usually delayed for a period of time. This part of the immune system is called T-Helper 2 (or TH-2).

These cells also do more than just labeling, they also attach themselves to certain cells like viruses to keep them from entering into our cells. This is important because once they are in our cells, they are much harder to kill and they can replicate more quickly.

TH-2 is also broken down into interleukins. IL-10 and IL-4 being 2 important ones.

IL-10 has been implicated in numerous autoimmune disease such as type I diabetes and multiple sclerosis. But it is another perfect example of the unpredictability of the immune system. It turns on some immune functions and shuts off others. It can block IL-1, IL-6 and TNF alpha, but turns on IL-2 and IL-4.

IL-4 is produced by CD 4 T cells and activates IgE, an immunoglobin important for creating immunity to parasites and involved in allergies.

Complicated, But Really Cool

To further complicate matters we have other parts of the immune system driving the immune attack and this is the family of interleukins that belong to IL-1. IL-1 is released by the pacman cells that are the front line attackers.
IL-18 belongs in this family of cells and there is a lot of it in Hashimoto's patients, especially those with severe symptoms that don't respond to levothyroxine treatment.

It may be responsible for severe inflammation.
Both parts of the immune system are needed for certain types of invaders. For example, viruses are often very small and can sneak past the border security. Then the TH-2 system uses it's cellular informants to sniff them out and it tags them.

This can take several days to initiate and this is why it takes most people a few days to fight the common cold, which is caused by a virus.

In a general sense, the TH-1 system is considered inflammatory and the TH-2 system is considered anti-inflammatory. But in reality, they are both involved in the process of inflammation. And IL-12 and IL-18 are important drivers of inflammation in Hashimoto's.

New Research Has Revealed Other Parts of The Immune System

Recent research has shown that there are other parts of the immune system that play important roles in this process. T-Helper 3 (TH-3) cells are the regulatory part of the immune system. They help to orchestrate TH-1 and TH-2 cells and act as kind of cellular general to call off or calm the attack.
T-Helper 17 (TH-17) cells are instigators and they rev up the attack and can make the damage and the carnage much more intense. A delicate balance of all parts of the immune system is important and with an autoimmune disease, like Hashimoto's, this balance is lost.


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## Marc Ryan (Mar 22, 2013)

Here's Part II:

What Happens with Hashimoto's?

There are many possible reasons for the immune system to start labeling the thyroid as foreign tissue and create autoimmune thyroid conditions (including genetics, environment, endocrine imbalance, chemical exposure, responses to viruses and other antigens, stress responses and more).

It is probably some combination of those many factors that lead to the loss of self tolerance and the immune system attacking the body's own tissue.
In most cases of Hashimoto's, some combination of the factors mentioned above lead to a slow, gradual attack against the thyroid. This eventually leads to the loss of enough thyroid cells that the condition presents as primary hypothyroidism and is seen on a blood test as high TSH.

TSH becomes high because, when the thyroid is not working properly, the pituitary gland increases production of TSH to increase thyroid gland activity. For most people with Hashimoto's, the thyroid never develops overactive symptoms. Over time, they develop symptoms of low thyroid function and get put on thyroid replacement hormone.

The issue of the autoimmune attack is never addressed. Instead, they are considered to be properly managed by having normalized TSH.
In a sense, these patients are having their TSH managed, but they are not managing the underlying problem. Over time, they lose more and more thyroid cells and they need more thyroid replacement hormone.

The result, for many people, is that they continue to have all the hypothyroid symptoms (like fatigue, hair loss, depression, constipation, cold hands and feet, etc.) because the root cause has been largely ignored.

What Is Going On with the Immune System with Hashimoto's?

Since the thyroid is being destroyed, there is less thyroid hormone production. The immune system needs thyroid hormones to modulate TH-1 and TH-2 activity, so when this happens, the immune system can short circuit.

This leads to a larger number of TH cells, and autoantibody producing B cells. These cells accumulate in the thyroid and kill thyroid cells.

There are many possible scenarios that can lead to this outcome. For example:

* The T suppressor cells that regulate the immune response could be too few in number, and like a weak general that has lost control of his troops, this can lead to unchecked attacks by the immune system. And tissue like the thyroid becomes a casualty.

* TH-1 has a number of different soldiers, known as interleukins. These all have specific jobs. For example, interleukin 2 (IL-2) is a messenger chemical that sends out orders for the killer cells to start killing.

Some people make too much IL-2 and this creates a frenzy of destruction that can lead to the death of the thyroid cells. Chronic viral infections can cause too much IL-2 to be made and have been linked to the development of autoimmune thyroid disease.

* TH-2 also has lots of different soldiers. Interleukin 4 (IL-4) deploys B cells. Like some rouge C.I.A. agents, these cells can go crazy and tag the wrong proteins, and destruction of thyroid tissue is the result. Parasites and food allergies can cause too much IL-4 to be made.

* Too much sugar can cause the body to rapidly release insulin. These spikes in insulin can stimulate the production of too many B cells, they start tagging too many things, and this can lead to destruction of the thyroid.

And this is just the tip of the iceberg. In reality, there are many variables and many potential reasons for the immune system to short circuit. This is what makes treatment and management so challenging. And this is also why you must have a multi-pronged approach.

Which Parts of the Immune System are Out of Balance with Hashimoto's?

In most cases of Hashimoto's, researchers think TH-1 cells become overactive (but this is not true for everyone and is an oversimplification). It seems IL-18 and IL-12 also act together to throw a beating to the thyroid.
Look for development of drugs that inhibit these 2 interleukins. In the meantime, stay tuned to learn about herbs and foods that can accomplish that naturally!

Hashimoto's people also often have a weak TH-3 regulatory system and their TH-2 may or may not be out of control. TH-17 is also often wound up, making the attack more intense. And none of this happens in a vacuum.
This is all taking place in the context of the body where the immune system is interacting with the endocrine system, the digestive system and the nervous system. Further complicating the task of unwinding this mess. Its no wonder patients and doctors alike get frustrated and overwhelmed.

Your Hashimoto's Is Unlike Anyone Else's

The reality is that your Hashimoto's is not the same as anyone else's. You may have an overactive TH-1 system or you may not. You may also have a weak TH-2 system or you may not. TH-3 is probably weak and TH-17 is also probably revved up.

And you may have leaky gut, and/or blood sugar issues, and/or adrenal fatigue, and/or anemia, and/or some active parasite or latent viral infection. It goes on and on.

You need an individualized approach that will create a unique action plan for your unique set of circumstances.

Marc Ryan, L.Ac.


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## nvsmom (Sep 30, 2012)

I'm looking forward to the day when they can actually stop an autoimmune attack. Until then it's just like putting a banad-aid on a cut that won't heal.


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## CA-Lynn (Apr 29, 2010)

Marc Ryan,

You're a licensed acupuncturist?


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## Marc Ryan (Mar 22, 2013)

Yes, CA-Lynn, I'm a licensed acupuncturist and a Hashimoto's patient. Out of necessity and personal and professional interest, I have spent a lot of time studying this stuff. I agree, nvsmom, unfortunately I don't think we're close to that yet. So, we have to make do with the information and tools that we have.


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## sjmjuly (Mar 23, 2012)

Marc,
I go to an acupuncturist twice a month now. It used to be once a week but my crazy schedule doesn't permit it anymore. I find that it helps my hashimotos and wondered why? Since you have experience with this, can you please give me some insight why it helps?


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## hashimotocoaster (Mar 22, 2013)

Thanks for posting this--lots of information!

I wish there were some way to actually stop the crazy immune response.

I heard a story on NPR a while back about a woman who had an autoimmune disease that attacked part of her brain and gave her really terrible symptoms (I can't remember the name of it, but I think her book is called Brain on Fire) and they treated her with plasmapheresis to get rid of all the autoantibodies floating around in her blood. I've been wondering why they don't do this with other autoimmune diseases. It's not a cure, but it seems like a better approach than letting the immune system continue to wreak havoc.


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## Keba (Aug 11, 2012)

Thanks so much for posting.


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## Marc Ryan (Mar 22, 2013)

sjmjuly said:


> Marc,
> I go to an acupuncturist twice a month now. It used to be once a week but my crazy schedule doesn't permit it anymore. I find that it helps my hashimotos and wondered why? Since you have experience with this, can you please give me some insight why it helps?


Hi sjmjuly,

Great question. I think there are a couple of plausible answers. Firstly, acupuncture helps to modulate immune function. There are some studies that indicate that it can be helpful in modulating TH-1 and TH-2 in particular. Also, we know acupuncture releases endorphins and enkephalins, these are endogenous opiates. Opiates have been found to calm the autoimmune response (this is why LDN or Low Dose Naltrexone works for some people, it keeps the body from reabsorbing endogenous opiates). So, it's a natural way of accomplishing what LDN does.


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## Marc Ryan (Mar 22, 2013)

hashimotocoaster said:


> Thanks for posting this--lots of information!
> 
> I wish there were some way to actually stop the crazy immune response.
> 
> I heard a story on NPR a while back about a woman who had an autoimmune disease that attacked part of her brain and gave her really terrible symptoms (I can't remember the name of it, but I think her book is called Brain on Fire) and they treated her with plasmapheresis to get rid of all the autoantibodies floating around in her blood. I've been wondering why they don't do this with other autoimmune diseases. It's not a cure, but it seems like a better approach than letting the immune system continue to wreak havoc.


 Hashimotocoaster (I just like writing that!),
That's really interesting. I think plasmaphoresis is effective because, as you said, it helps to clear the circulating autoantibodies. Unfortunately, in the Western medical model no action is taken with autoimmune disease until 70 - 90% of the target tissue is destroyed. It makes much more sense to treat it earlier. This one area of research that I am fascinated by and I have some ideas about what may work, or what is alleged to work, but I still need to learn a lot more before I can make any recommendations. Anecdotally, I have also heard that Selenium can be helpful in reducing TPO antibodies.


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## Marc Ryan (Mar 22, 2013)

Keba said:


> Thanks so much for posting.


Hi Keba,

You're welcome! I think it's useful to help us to wrap our minds around wat's going on with us!


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