Autoimmune disease & the Th1/Th2 paradigm - The Functional Naturopath // Dan Sipple (2022)

During my pre-university days of research and trying to bio-hack my way out of the autoimmune conundrum, I became fascinated by an area of research that was gaining momentum in the world of functional medicine and how chronic inflammatory illnesses were treated. It highlighted the importance in re-establishing “Immune balance” when treating autoimmune disease in order to re-balance all arms of the immune system to break the cycle of damage.

My aim with this post is educate you with an overview of immune system function, what goes wrong in autoimmunity and how botanical medicine can modulate and help restore immune balance!

The immune system is such a vast area it requires hours of discussion, but for the purpose of this blog piece, we will focus on the role of T Helper cells. There are various subdivisions of T Helper cells, with each group containing different “cytokines”. Cytokines are hormonal messenger proteins triggered in response to different sources of stimulation and communicate to other cells of the immune system. Cytokines are stimulated in response to viruses, bacteria, fungus, parasites, and as part of environmental and food allergies.

In an ideal scenario, a person’s immune system responds appropriately through exposure to stimulation and cell memory is gathered throughout life to form “antibodies” for future reoccurrence. A proper functioning immune system will deploy its troops appropriately and rein them in when the enemy is dealt with, and return to regular surveillance. Most importantly, the difference between a legitimate foreign threat and it’s own host is well established and distinguished by a proper functioning immune system.

In any autoimmune condition, this innate ability known as “self-tolerance” becomes lost. The immune system loses its ability to distinguish between friend and foe. In continuing to respond against actual foreign threats, it mistakenly attacks various proteins of the body. This phenomenon is known as “molecular mimicry”. It is thought that certain proteins in the body may resemble proteins of pathogens so closely that the immune system creates antibodies (or auto-antibodies) and launches an inflammatory attack against both the threat as well as the tissue resembling the threat – as it views them as one the same. Depending on what tissue or organ is targeted distinguishes one autoimmune disease from the next.

For example:
*Hashimotos thyroiditis (Auto Antibodies progressively destroy the thyroid gland resulting in hypothyroidism)
*Systemic Lupus Erythematosus (Auto Antibodies progressively destroy connective tissue eg. Joints, skin, organs)
*Coeliac disease (Auto antibodies progressively destroy the epithelial tissue of the small intestine causing malabsorption)

The below image displays the various arms of immunity along with their various cytokines
Autoimmune disease & the Th1/Th2 paradigm - The Functional Naturopath // Dan Sipple (1)

The crucial point here is this – in any autoimmune disease state, there is ALWAYS immune dysregulation in the subdivision of T-Helper cells (TH1, TH2, TH3, TH17). This results in an exaggerated pro-inflammatory response of one subdivision (varies with each individual) and usually an inverse deficiency in another. This results in immune dysfunction and leads to unchecked inflammation throughout the body.

So then what?

Well… The modern medicine REACTIVE strategy to many autoimmune conditions is to use steroids and immunosuppressants. These pharmaceuticals tend not to discriminate, and their role is reduce ALL immune activity to squash any areas of inflammatory response in the process. Theoretically this might help to alleviate autoimmune symptoms, but hey – we still need our immune system right? We still need to defend from pathogens and keep cancer cells in check?

Time and time again we see autoimmune sufferers on prescription immunosuppressant medications whom experience not only minimal relief, but usually fall prey to repeat infections, increasing the need for antibiotics due to their completely reduced immune response. This can lead to a perpetual cycle, which over time not only opens the gates to viruses, bacteria and fungi, but reduces commensal gut bacteria (the good guys) whom have been shown to protect us from developing autoimmunity in the first place!

Take a second to read that again!

Additionally, the causative factors (which are becoming more and more well established in peer reviewed research as contributors to the evolution of autoimmunity) are not even considered or dealt with by the Western approach.
Such factors include;

  • Physiological and emotional stress & trauma
  • Intestinal permeability; allowing for the escape of undigested proteins and pathogens through gut wall and directly into the blood stream evoking prolonged inflammatory immune responses
  • Alterations in gut microflora
  • Hormonal imbalances
  • Diet & nutritional deficiency
  • Genetics
  • Heavy metal toxicity

Each of these concepts deserve their own blog entry, but for the sake of this piece, lets keep going.

So what can we do about this?

This is where naturopaths and doctors practicing functional medicine have their advantages. There are many constituents found in herbal medicine as well as some nutritional medicine supplements, which have been shown to favourably skew and re balance ones dominant T-cell pathway. This allows us to be more selective, discriminate and not affect the remaining arms of immunity, as we see can happen with immunosuppressant medications.

Functional diagnostics allow us to be able to use “Cytokine panel testing” as well as symptomatology to work out what ones dominant division is expressing, further guiding treatment. Occasionally, one may be expressing more than one dominant pathway, or both the TH1 and TH2 can be hypo or hyper functioning. This highlights the valuable role of testing and takes out the guess work.

TH17 – The new kid on the block

For years autoimmune dysregulation was put down purely to imbalances in just the TH1/Th2 cytokines and compounds that stimulated a TH1 dominant condition would theoretically worsen a TH1 drive condition, butrelieved by those stimulatingTH2 cytokines, by balancing the “see saw” (and vice versa with TH2 dominant conditions responding to TH1 stimulating compounds). This hypothesis was challenged as new research evolved over recent years confirming the prevalent role of TH17 cytokines and their strongpro-inflammatory associationtoautoimmune conditions. This discovery doesn’t discredit the previous hypothesis, but more so enhances a practitioners understandingof the conundrum and allows for a more fine tuned approach. The good news is, many natural compoundshave been shown to down regulate TH17 cytokine expression. Herbal medicineto the rescue once again

“REGULATORS, Mount up!”

Lastly, the TH3 arm of the immune system which govern “T regulatory cell” function is without doubt a vital area to target when treating autoimmunity in addition to balancing ones dominant pathway and reducing Th17 cytokine expression. T regulatory cell function helps prevent excessive immune responses from rogue cytokines (eg TNFa, Interleukin 6, NF-kB) and is the immune systems own tool to help maintain balance and “immune tolerance” – which we highlighted earlier, becomes lost in autoimmunity.

Below is a brief overview of both herbal & nutritional compounds shown to promote each subdivision of T helper cells.

TH1 promoters
Medicinal mushrooms, Astragalus membranaceus, Echinacea purpurea, Panax ginseng, Chlorella, Vitis vinifera

TH2 promoters
Curcuma longa (turmeric), Camellia sinensis (green tea), Centella asiatica (Gotu kola), Quercetin, Resveratrol, Caffeine

TH3 promoters
Cod liver oil, Vitamin A (animal source), Vitamin D, Colostrum, Essential Fatty Acids from cold water fish), as well as certain probiotic strains such as;
Lactobacillus rhamnosus (LGG) & Lactobacillus plantarum (LP-33)

Autoimmune disease are currently in the top 10 world leading causes of death. Establishing the root causes of an autoimmune disease (or any chronic illness) is absolutely paramount for remission or recovery. Functional diagnostics allows practitioners to go deeper and look for imbalances in nutrients, gut flora, hormones and much more to work out what tailored approach an autoimmune sufferer requires to correct the causes and begin healing.
If you’re reading this and suffer from a chronic illness, don’t hesitate, come and see me at Endeavour student clinic and I can help you locate the hidden causes of your condition and treat it right at its roots.

REFERENCES:

http://www.ncbi.nlm.nih.gov/pubmed/17127149
http://www.ncbi.nlm.nih.gov/pubmed/21248165
http://www.ncbi.nlm.nih.gov/pubmed/18950596
http://www.ncbi.nlm.nih.gov/pubmed/26703710
http://www.ncbi.nlm.nih.gov/pubmed/15585788
http://www.ncbi.nlm.nih.gov/pubmed/26300591
http://www.ncbi.nlm.nih.gov/pubmed/27051079
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1480569/
http://www.ncbi.nlm.nih.gov/pubmed/25652649

FAQs

What is the Th1 and Th2 paradigm? ›

The classical view of the Th1/Th2 paradigm posits that the pathogen nature, infectious cycle, and persistence represent key parameters controlling the choice of effector mechanisms operating during an immune response.

Is Th1 or Th2 inflammatory? ›

Thus Th1 cells cause rubor (redness), tumor (swelling), dolor (pain), and calor (warmth), the 4 cardinal signs of inflammation. Th2 cells, conversely, stimulate high titers of antibody production. In particular, IL-4, IL-10, and IL-13 activate B cell proliferation, antibody production, and class-switching [ 56–58 ].

What is the difference between Th1 and Th2 immune response? ›

Definition. TH1 immune response refers to the cytokine-mediated immune response generated by TH1 cells against intracellular parasites such as bacteria and virus, while TH2 immune response refers to the cytokine-mediated immune response generated by TH2 cells against large, extracellular parasites such as helminths.

What is Th1 disease? ›

Th1 Spectrum Disorder refers to the group of chronic inflammatory diseases, which are hypothesized to be caused by the Th1 pathogens, a microbiota of bacteria which include L-form, biofilm, and intracellular bacterial forms.

Are allergies Th1 or Th2? ›

Th1 cells (secreting interleukin (IL)-2 and interferon (IFN)-γ) lead to cell-mediated responses, whereas Th2 cells (secreting IL-4, IL-5 and IL-13) mediate for humoural immune responses 2. Accordingly, allergy results from an imbalance in favour of a Th2 response, and is negatively regulated by Th1 cells.

What do you understand by Th1 Th2 balance? ›

One theory of immune regulation involves homeostasis between T-helper 1 (Th1) and T-helper 2 (Th2) activity. The Th1/Th2 hypothesis arose from 1986 research suggesting mouse T-helper cells expressed differing cytokine patterns.

How do you know if you are Th1 or Th2 dominant? ›

One trick is to discover which side of your immune system is more active — the side that deploys natural killer and cytotoxic T-cells, or the side that deploys B-cell antibodies. Are you producing too many natural killer and cytotoxic T-cells, the ones responsible for killing invaders? If so, you are TH-1 dominant.

What do Th1 and Th2 do? ›

Th1 and Th2 cells play an important role in immunity. Th1 cells stimulate cellular immune response, participate in the inhibition of macrophage activation and stimulate B cells to produce IgM, IgG1. Th2 stimulates humoral immune response, promotes B cell proliferation and induces antibody production (IL-4).

What is an example of a Th2 immune imbalance? ›

For example, some researchers regard allergy as a Th2-weighted imbalance–and allergic reactions are known to be inflammatory [49]. People with Th2 dominance may produce more antibodies and instant food allergies might be more likely to occur, according to limited data [49, 1].

What do Th2 cells activate? ›

Th2 cells mediate the activation and maintenance of the humoral, or antibody-mediated, immune response against extracellular parasites, bacteria, allergens, and toxins. Th2 cells mediate these functions by producing various cytokines such as IL-4, IL-5, IL-6, IL-9, IL-13, and IL-17E (IL-25).

What induces Th2 response? ›

Administration of antigen–IgE immune complexes induces TH2-type responses both through the FcεRI-mediated activation of basophils and the targeting of antigen to these cells, promoting their role as APCs29.

What is the Th2 response? ›

Th2 responses.

Th2 cells are involved in type 2 immune responses, which are important for eradication of extracellular parasites and bacterial infection. They produce IL-4, IL-5, IL-10, and IL-13, which are important for the induction and development of humoral immune responses.

What triggers Th1 response? ›

Interferon-γ (IFN-γ) and interleukin (IL)-12 induce JAK1/2 and STAT1/3/4 to stimulate T-bet and further IFN-γ production, resulting in a T helper type-1 (Th1) response, whereas IL-4 triggers JAK1/3 and STAT6 to activate GATA-3 and a T helper type-2 (Th2) response.

What is Th1 inflammation? ›

Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses. Interferon gamma is the main Th1 cytokine.

Do people with autoimmune diseases have more T cells? ›

However, it must also be recognized that patients with systemic autoimmunity develop more inflammation and T cell autoreactivity than patients with atherosclerosis (125).

How do I lower my Th2? ›

Glycyrrhizin increases IFNy and decreases the Th2 response [17, 18]. Gynostemma [19]. This is a Th1 immune stimulant and reduces allergies. Gynostemma is recommended also because it's a powerful mitochondrial enhancer.

What do Th1 cells do? ›

Th1 cells play important roles in the identification and eradication of intracellular pathogens such as viruses and bacteria, including Mycobacterium tuberculosis, Mycobacterium leprae, and Leishmania.

Is asthma a Th2 disease? ›

Asthma has been considered a T helper 2 (TH2) cell-associated inflammatory disease, and TH2-type cytokines, such as interleukin-4 (IL-4), IL-5 and IL-13, are thought to drive the disease pathology in patients.

What is TH1 to TH2 shift? ›

The TH1/TH2 cytokine ratio in T cells of women during pregnancy and after delivery was significantly decreased. In contrast the TH1/TH2 ratio was elevated to near normal in women with recurrent spontaneous abortions, indicating a marked shift towards TH1 immunity.

Is Hashimoto's Th1 or Th2? ›

Consequently, if viewed from the perspective of thyroid-specific autoantibodies, Hashimoto's thyroiditis is both a Th1- and Th2-associated disease.

What happens after T cell activation? ›

Following activation, T cells expresscytotoxic T lymphocyte antigen-4 (CTLA4) on their surface, which also binds B7-1 and B7-2 on the antigen-presenting cell and with stronger affinity than CD28. This interaction sends a negative signal to down-regulate the T cell response after its initial activation.

What is helper T cells function? ›

Helper T cells are arguably the most important cells in adaptive immunity, as they are required for almost all adaptive immune responses. They not only help activate B cells to secrete antibodies and macrophages to destroy ingested microbes, but they also help activate cytotoxic T cells to kill infected target cells.

What is the difference between TH1 and TH2 T cells? ›

The main difference between TH1 and TH2 helper cells is that the TH1 helper cells generate immune responses against intracellular parasites, including bacteria and viruses, whereas the TH2 helper cells generate immune responses against extracellular parasites including, helminths.

What is the difference between type 1 and type 2 inflammation? ›

For most infections, save those caused by large eukaryotic pathogens, type 1 immunity is protective, whereas type 2 responses assist with the resolution of cell-mediated inflammation.

When do helper T cells develop into TH1 or TH2 cells? ›

After activation CD4+ helper T cells differentiate into T-helper (Th) 1 or Th2 effector cells. These two subsets are characterized by their distinct cytokine expression pattern and the immune function they mediate.

What is a Th1 response? ›

Th1 cells generate an immunologic response that provides an effective defense against viral infections and other intracellular pathogens and that depends on T cell and monocyte or dendritic cell interactions.

What is produced by Th2 cells? ›

Th2 cells. Th2 cells produce IL-4 and IL-13 and contribute to humoral responses but are also involved in allergic reactions. They require the transcription factor GATA binding protein 3 (GATA3) and STAT6 for their differentiation. Th2 cells also produce IL-5 and IL-10.

What is a type 1 immune response? ›

Type I hypersensitivity is the most common type of hypersensitivity reaction. It is an allergic reaction provoked by re-exposure to a specific type of antigen, referred to as an allergen. Unlike the normal immune response, the type I hypersensitivity response is characterized by the secretion of IgE by plasma cells.

Is Th2 response anti inflammatory? ›

In summary, our data show that activation of Th2 responses inhibits inflammatory arthritis. Mechanistically, IL-4/IL-13-STAT6 signalling pathway induces macrophage polarization into anti-inflammatory macrophages into the joints. In addition, eosinophils are activated and further contribute to the resolution of disease.

How do you increase helper T cells? ›

Eat fruits and vegetables high in folic acid, vitamin B6, and thiamin. These vitamins and minerals can increase the number of t-cells in your body so try to include them in your daily diet. One of the best ways to get these nutrients is to eat a varied diet that includes fresh fruit and vegetables.

Which cytokine induces Th2? ›

The critical Th2-inducing cytokine is IL-4, which mediates its effects through the Stat6 signal transduction pathway (Wurster et al., 2000; O'Shea et al., 2002).

What is type 2 inflammatory disease? ›

Type 2 inflammation is a specific type of immune response pattern. It can have positive effects, like helping eliminate a parasitic infection. But it also plays a role in certain medical conditions, such as atopic dermatitis (eczema), allergic rhinosinusitis, and some types of asthma.

What causes type 2 immune response? ›

Type 2 immunity is characterized by the production of IL-4, IL-5, IL-9 and IL-13, and this immune response is commonly observed in tissues during allergic inflammation or infection with helminth parasites.

Which cytokines that are secreted by Th2 cells function to increase gut mucus production and gut motility? ›

IL-4, IL-5, IL-13, and IL-9 are the chief cytokines that are produced by Th2 cells, and their expression is under the control of GATA3.

Do Th2 cells activate B cells? ›

Th2 cells secrete cytokines such as interleukin (IL)-4, IL-5, and IL-13, which could promote development of B cells into antibody-producing plasma cells.

What cells do Th1 cells activate? ›

Th1 cells function to activate macrophages and neutrophils; and are critical for host defense against intracellular pathogens such as M. tuberculosis. In support of this, patients with defects in IL-12p40 production, IFN-γ production, or IFN-γ receptor signaling have an increased risk of TB.

Which cells are Th1 cells? ›

What are Th1 cells? As their name suggests, T helper (Th) cells provide helper functions to other cells of the immune system—especially the antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B cells—and are important for their activation and maturation.

What is a Type 3 immune response? ›

Type 3 immunity is characterized by the recruitment of neutrophils and the stimulation of epithelial antimicrobial defenses at infection sites. Type 3 immunity is often triggered by extracellular bacteria and fungi and seems to be particularly suited to defend epithelial barriers against these pathogens.

What are pro inflammatory foods? ›

The pro-inflammatory foods are red meats, processed meats, organ meats (i.e. liver, kidney, brain, heart), non-oily fish (i.e. white fish), eggs, sugar-sweetened beverages (i.e. soda), tomatoes, and refined grains (bread or pasta and white rice).

How do T cells cause autoimmune disease? ›

Those T cells with high affinity receptors for MHC plus self-peptides undergo clonal deletion which is also called negative selection through induction of apoptosis. Any disturbance in this process can lead to the escape of auto-reactive T cells that may trigger autoimmune disease.

Which type of T helper cell inhibits inflammation? ›

Abstract. CD4+ helper T type 1 (Th1) and Th2 cells are critical mediators of inflammatory diseases. Although T cells represent only a fraction of the leukocytes that are found in the lung during inflammation, they play a critical role in coordinating the immune response to infectious agents and allergens.

How do I calm my immune system? ›

Practice Relaxation

Deep and relaxed breathing can pacify your immune system and decrease inflammation by reducing the levels of stress hormones in your body, so consider making focused breathing exercises, meditation, yoga or tai chi part of each day.

What is the test for autoimmune disease? ›

The antinuclear antibody (ANA) immunofluorescence assay (IFA) is a first-line screening test for patients with a suspected autoimmune disease. This test is the gold standard because of its high sensitivity compared to other assays.

What is the role of Th2? ›

Th2 cells mediate the activation and maintenance of the humoral, or antibody-mediated, immune response against extracellular parasites, bacteria, allergens, and toxins. Th2 cells mediate these functions by producing various cytokines such as IL-4, IL-5, IL-6, IL-9, IL-13, and IL-17E (IL-25).

What is the role of Th1 cells? ›

Th1 cells play important roles in the identification and eradication of intracellular pathogens such as viruses and bacteria, including Mycobacterium tuberculosis, Mycobacterium leprae, and Leishmania.

What is the Th1 immune response? ›

Th1-type cytokines tend to produce the proinflammatory responses responsible for killing intracellular parasites and for perpetuating autoimmune responses. Interferon gamma is the main Th1 cytokine.

What is the meaning of Th2? ›

T helper 2 (Th2) cells. T helper 2 cells are known to have a significant role in humoral immunity and defense against helminth infections. Besides, Th2 cells play a principal role in a group of prevalent diseases that are allergies.

Do Th2 cells cause inflammation? ›

T Cells and Their Effector Functions

Th2 cells promote IgE production and eosinophil function, which are the key players in the pathogenesis of allergic inflammation and immunity against parasitic infections.

What activates Th2? ›

The most efficient way to stimulate Th2 cells to produce cytokines is through their TCRs or by chemicals such as PMA and ionomycin to mimic TCR-mediated signaling.

What is the difference between Th1 and Th2 cells? ›

Th1 and Th2 cells play an important role in immunity. Th1 cells stimulate cellular immune response, participate in the inhibition of macrophage activation and stimulate B cells to produce IgM, IgG1. Th2 stimulates humoral immune response, promotes B cell proliferation and induces antibody production (IL-4).

What triggers Th1 response? ›

Interferon-γ (IFN-γ) and interleukin (IL)-12 induce JAK1/2 and STAT1/3/4 to stimulate T-bet and further IFN-γ production, resulting in a T helper type-1 (Th1) response, whereas IL-4 triggers JAK1/3 and STAT6 to activate GATA-3 and a T helper type-2 (Th2) response.

Do people with autoimmune diseases have more T cells? ›

However, it must also be recognized that patients with systemic autoimmunity develop more inflammation and T cell autoreactivity than patients with atherosclerosis (125).

How do T cells cause autoimmune disease? ›

Those T cells with high affinity receptors for MHC plus self-peptides undergo clonal deletion which is also called negative selection through induction of apoptosis. Any disturbance in this process can lead to the escape of auto-reactive T cells that may trigger autoimmune disease.

What is an example of a Th2 immune imbalance? ›

For example, some researchers regard allergy as a Th2-weighted imbalance–and allergic reactions are known to be inflammatory [49]. People with Th2 dominance may produce more antibodies and instant food allergies might be more likely to occur, according to limited data [49, 1].

Is Hashimoto's Th1 or Th2 dominant? ›

Because Graves' hyperthyroidism is directly caused by thyroid-stimulating antibodies (TSAbs), it is logical to assume that the disease belongs to the Th2 category. Conversely, the dominance of cellular immunity and thyroid tissue damage in Hashimoto's thyroiditis implies a Th1 origin.

How do I lower my Th2? ›

Glycyrrhizin increases IFNy and decreases the Th2 response [17, 18]. Gynostemma [19]. This is a Th1 immune stimulant and reduces allergies. Gynostemma is recommended also because it's a powerful mitochondrial enhancer.

Where are Th2 cells located? ›

It has been shown that antigen-specific memory Th2 cells driving lung allergic responses reside within the lung tissue and that the Th2 memory response is dependent on IL-7 and IL-33-producing lymphatic endothelial cells (LECs) found within localized structures called inducible bronchus-associated lymphoid tissue ( ...

What is the type 2 immune response? ›

The T helper type 2 (Th2) immune response, characterized by the production of interleukin-4 (IL-4), IL-5 and IL-13, is a critical immune response against helminths invading cutaneous or mucosal sites. It also plays a critical role in the pathophysiology of allergic diseases such as asthma and allergic diarrhoea.

Which cytokines are secreted by Th1 cells? ›

Th1 cells are most often defined by their production of IL-2 and IFN-γ but have been reported to produce a number of cytokines including: TNF, lymphotoxin, and granulocyte-macrophage colony-stimulating factor (GM-CSF).

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