Balancing Th1 and Th2 Immune Responses
Innate immunity is the body’s first line of defense. It is a rapid response system that does not involve antibodies but relies on cytokines produced from . Cytokines are the hormonal messengers that are responsible for cell mediated immunity and , and Th1 and Th2 are both prolific producers of cytokines. Cytokines are inherently inflammatory, which is a good thing when needed for the right purpose. But imbalance in cytokines can lead to too much inflammation and the potential to signal the immune system to attack either a harmless substance (allergies) or self (autoimmunity).
Back in the late 1980s, in vivo research revealed that T-helper cells express different cytokine pathways and as a result, Th1 and Th2 cells initiate different immune responses. Th1 cells drive innate (cell-mediated) immunity while Th2 cells drive humoral (antibody) immunity. Balance between the two pathways is critical to a healthy immune response. For example, when Th2 cells are overactive, Th1 cells can be suppressed and vice versa. It’s a delicate balance that can be addressed in clinical practice, because inflammation and are two of the biggest drivers of imbalance.
In 2003, studies looking at the effects of Th1 and Th2 cells and their role in immune function eventually led to theories of immune dysfunction as a result of either Th1 or Th2 dominance. This idea became popular, leading people to associate auto-immune disorders (solely) with Th1 dominance. However, there was a flaw in the theory. In 2005, a groundbreaking study identified another type of cell separate from either Th1 or Th2 cells – Th17 cells. Studies eventually revealed that the actual driver of autoimmune cell damage is Th17 cells. Th1 response inhibits Th17 activation, while Th2 response increases Th17 activation.
When Th1 and Th2 are balanced, so is the immune response. A healthy immune system easily switches back and forth between Th1 and Th2 responses. However, the immune system can become somewhat “stuck” in one of these responses, leading to excessive production of certain cytokines over others. This can be problematic because these two components of the immune system function in a delicately balanced relationship.
There are many reasons why immune imbalance occurs – improper diet, lifestyle factors, high stress, medications and genetics are all factors – but patients with chronic illness often present with one or all of these things in common: , dysbiosis and stress. These conditions all contribute to suppression of innate immune status through Th1 suppression.
Supporting Th1 Status
When innate immune status (Th1 status) diminishes, patients may experience higher incidence of infection, especially in the “hollow spaces” of the body which have some direct contact with the external environment. GI dysbiosis, sinus infection and bladder infections are a sign of depressed Th1 status because the overall pathogen load becomes greater than the immune system can handle. In turn, increased infection drives increased , which drives Th1 suppression even lower in a continuing cycle.
stress or dysbiosis, and thus Th1 suppression, may experience a variety of health challenges including organ-specific autoimmune conditions, (Hashimoto’s thyroiditis, diabetes) delayed food sensitivities, (Crohn’s or celiac disease), psoriasis, fatigue, brain fog, and other immune-related conditions. The key then becomes supporting a healthy level of Th1 activity while modulating Th2 activity. When it comes to Th1 support, it is critical to balance cytokine production to help promote Th1 differentiation. Lifestyle factors are key: , adequate sleep and rest, exercise, clean, healthy, nutrient dense diet, avoidance of toxins, and microbiome balance, are all critical to supporting balanced immune system function.
Nutrients and botanical extracts that have been shown to help balance cytokine production and support Th1 differentiation, include:
- Berberine
- Broccoli sprout extract
- Chinese skullcap
- Ginger
- Sulphoraphane
- Zinc
The Th2 Allergy Pathway
Because Th2 activates antibody-mediated immunity, it’s not surprising that when Th2 dominates, there is an excess production of antibodies. The Th2 pathway is related to allergies and IgE-based issues. Typical signs that a patient is Th2 dominant include having seasonal allergies, allergic rhinitis, food allergies, eczema and asthma. Because of the potential for inflammation and excess mucus production, this active and increased Th2 status can suppress the Th1 driven innate immunity and impact the health and function of the sinuses, respiratory, gastrointestinal and urinary systems.
The development of Th2 immune overactivity has many different points of origin. Exposure to environmental toxins and heavy metals, microbial exposures, alteration of the microbiome (from pathogenic infection or from antibiotic use) and thus, alteration of GI integrity, nutritional deficiencies and of course, genetic variability are just a few of the many predisposing factors. The epigenetic influences of stress, diet, exercise and other lifestyle components, contribute to greater or lesser balance of this pathway. Moderate exercise has been shown to support Th1/Th2 balance. Since stress negatively impacts Th1 and Th2 balance, working with patients on and rest and on effective is important. Obviously, a nutrient dense, anti-inflammatory diet is also an important foundation.
Botanicals and nutrients which may support healthy modulation of Th2 cytokines include:
- Astragalus
- N-Acetyl-L-cysteine
- Glutathione
- Perilla extract
- Luteolin
- Quercetin
- Probiotics
- Licorice root
Other nutrients shown to support Th1/Th2 immune balance include vitamin A, vitamin D, turmeric/curcumin, trans-resveratrol, zinc, and . Optimal modulation of Th2 activity can be supported through an integrative approach that includes a healthy anti-inflammatory diet, lifestyle factors such as stress management, and exercise, and key immune modulating nutrients and herbs.