The immunity buzz

T cells, turmeric and trained immunity – are there any correlations?

Writer: Shivaani Iyer
Editor: Deanna Mills
Artist: Vera Liu

Following Metchnikoff’s unveiling of the concept of cellular immunity in 1882, our understanding of immunity has expanded, to say the least. As a consequence of the COVID-19 outbreak, we are witnessing a renewed interest in immunity. To cover all the bases, a surge in research on alternative immune-mediated approaches has surfaced alongside the race to develop an effective COVID-19 vaccine. A key example is dexamethasone, a corticosteroid used for immunosuppression in severe COVID-19 cases. But notably, global populations outside of doctors and scientists are now asking some big questions. What is immunity? And what can I do to ‘boost’ my immune system?

First, it is important to understand how the immune system works. During the process of haematopoiesis, an artillery of immune cells are formed in the bone marrow before being transported via the blood and lymph throughout the body. Our immune system can be categorised into two distinct branches: the innate immune system and the adaptive immune system. The innate system utilises immune cells such as neutrophils, mast cells and macrophages to facilitate a rapid but non-specific response to a pathogen, whereas the adaptive system provides differential responses tailored to each pathogen, with specific immunological memory as a hallmark. Both immune responses involve a network of beautifully intricate yet complex mechanisms and interactions between cells.

When a pathogen infiltrates the body, the innate response triggers a rapid cascade in which mast cells secrete histamine to initiate inflammatory responses, opsonin molecules from the complement system attach to pathogens, and pathogen-associated molecular patterns mark cells for phagocytosis, which is carried out by neutrophils and macrophages. The chemotaxis and communication between immune cells can be effectively mediated by adhesion molecules and chemokines such as interleukin-8, which in turn recruit more neutrophils.

Comparatively, the adaptive immune response involves lymphocytes, specifically T and B cells. T cells have receptors for specific antigens on a pathogen, while B cells produce specific antibodies against particular antigens. When a pathogen causes infection, dendritic cells capture and display antigens on their surface, travelling to the lymphatic tissue to notify and activate certain T and B cells, thus triggering the secretion of cytokines. Memory B cells provide the immunological memory that is characteristic of the adaptive immune system ‒ this is what prevents us from getting sick from the same illness twice. Meanwhile, cytotoxic T cells kill cells infected by pathogens by granule exocytosis or by the activation of FAS molecules that cause cell apoptosis.

Paradoxically, the same mechanisms that protect us can kill us. Autoimmune diseases arise when mistakes are made in differentiating pathogens from our body’s own cells. A distinctive feature in the pathology of many autoimmune disorders is the action of self-produced autoantibodies that target and destroy vital cell structures such as nucleic acids, resulting in tissue damage. Our advancing understanding of autoimmune diseases has led to the further exploration of treatments that protect against the destruction of host cells, tissues and organs.

Enter the fascinating world of immunity boosters ‒ a potential way to attack that feeling of helplessness and take control of our health. While vaccinations have demonstrated resounding success in their immunity-boosting capabilities, natural approaches are still a somewhat murky topic in evidence-based research. The supplements on the market range from vitamins to antioxidants to probiotics, and have appealed to and been purchased by over 50% of individuals in the United States at least once.

Many of these supplements are present as factors in the biochemical pathways of the immune response. Vitamin C is a cofactor for mono- and dioxygenase enzymes, and can counteract the overproduction of reactive oxygen species (ROS) as well as promote the production of host peptides. The efficacy of vitamin C in alleviating oxidative stress in vitamin C-deficient patients has been demonstrated by many pre-clinical trials. To appeal to a wider audience, this supplement is commonly marketed to ‘prevent colds’ and ‘boost the immune system’. On a similar note, curcumin, the active component in turmeric, has promise in moderating an imbalance of ROS in the body by removing excess free radical species. These claims, applicable to other functional foods consumed for their antioxidant value such as peppers, are yet to be confirmed by any large randomised clinical trial, which could produce results that differ greatly from the success observed in in vitro studies.

On the other hand, the value of probiotics in treating infections and allergies has been substantiated by several studies, and it is estimated that global supplementation with probiotics could decrease annual prescription of antibiotics by 2.2 million.

It is important to note, however, that the overreaction of the immune system can be detrimental, as has been observed in the fatal ‘cytokine storm’ response in certain COVID-19 patients. This could prove to be a key consideration when prescribing natural supplements. Additionally, increased engagement with complementary medicine, and therefore promotion of natural supplements, has shown correlations with decreased vaccination administration. Therefore, though further research into natural ‘immunity boosters’ could prove to be beneficial, it is essential that we tread carefully.

A consequence of lockdown appears to be the broad prescription of the ultimate ‘immunity-boosting’ cocktail to the general public: sleep and exercise. Increasingly over lockdown, studies have investigated changing sleep patterns under the new restrictions and identified a positive correlation between sleep quality and duration of outdoor exercise. Studies also show that adequate sleep decreases levels of adrenal hormones in the body and therefore benefits immune function. Other studies have shown that the immune system is highly responsive to various levels of exercise. While exercise of high intensity can be associated with decreased immune function and metabolic capacity, moderate exercise at regular intervals improves circulation of immune cells and inhibits overactive inflammation. The takeaway message here is that while individual supplements may not directly influence the strength of the immune system, a combination of nutrition, exercise and sleep can work in summation to provide a type of ‘insurance’ for better overall health and decreased susceptibility to infection.

While we may not be able to train our immunity with zinc tablets or kombucha, scientists have made breakthroughs in the concept of ‘trained immunity’. The belief that immunological memory is only associated with adaptive immunity is now an outdated one. Research now shows that the innate immune response can demonstrate a form of immunological memory called trained immunity. Plants rely on the innate system alone for protection against pathogens, and have exhibited lower reinfection rates and protection against different pathogens. This idea was first introduced by the discovery that the BCG vaccination, primarily implemented for tuberculosis, could afford protection against malaria and yellow fever via the action of monocytes, a component of the innate response. As the most widely implemented vaccine globally, it is not surprising that use of the BCG vaccine to lessen symptoms in severe COVID-19 cases was looked into. The suggestion that the BCG vaccine can protect against COVID-19 via trained immunity mechanisms is yet to be proven in large clinical trials. Regardless, this opens up a thrilling investigation into the potential therapeutic targeting of trained immunity. There has even been tentative experimentation with the epigenetic programming of myeloid cells to promote trained immunity and increase cytokine production.

Will the future entail individualised workout programmes for our immune systems? Perhaps it will entail epigenetic alteration rather than ‘immunity-boosting’ shots. Perhaps it’s too soon to tell.