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The Immune System
Studying effects on the immune system is an attractive approach to natural products research.
The immune system is dynamic and rapidly changing, it contains many cell types, each with many ways to respond to a complex natural product.
The effects may show unexpected synergy between ingredients that tap into separate signaling pathways.
- Synergy between ingredients… 1+1=37?
Innate Immunity
The innate (=immediate) immunity involves the recognition that something is wrong, and that bacteria or viruses have entered the body.
- Immediate killing of bacteria
- Immediate killing of virus-infected cells
- Communication via cytokines
Innate immune cells react instantly to some types of natural products – examples include soluble and insoluble fibers, such as apple pectin and beta-glucans. They are the immediate responders.
Innate immune cells communicate with each other, and also with cells from the adaptive immune system. The innate immune cells are the instigators of initial immune alertness and activation.
Without the innate immune response, we would not be able to mount an adaptive immune response for long-term protection.
The gut mucosa is densely populated with innate immune cells. This includes dendritic cells, macrophages, natural killer cells, and gamma-delta T cells. When we consume a natural product, the dendritic cells sample the product with tentacles, while communicating with the other immune cells on the inside of the gut barrier.
Adaptive Immunity
Innate immune cells communicate the threat to cells in the adaptive immune system (B cells and T cells). While innate immune cells work on containing the initial infection, the adaptive immune cells begin their work to generate a highly efficient elimination through antibodies. The adaptive immune system also generates memory cells that can activate much quicker if the same infection comes around in the future.
The effects of a natural product on the adaptive immune system are best studied:
- In vitro: Cell cultures that contain both innate and adaptive immune cells are used for this testing. Many natural products affect the innate immune cells, that then communicate with the adaptive immune cells, so it is ideal to co-culture both types of cells. The effects of a natural product on cell proliferation and antibody production are measured.
- Clinical: Since the adaptive immune response happens over 1-2 weeks after an immune challenge, this is an example where the study design requires a longer time. Typically, such a study involves a loading phase, an immune challenge (such as a vaccine), and a phase to allow the adaptive immune system to produce antibodies directed at the vaccine. The generation of memory B cells can also be measured.
Studying the immune system’s response to natural products.
When we study the effects of natural products on the immune system, it is beneficial to combine three different methods:
In vivo: In the body. Studying events as they happen in the participant, that we can measure in blood samples. Such events include changes to cytokine levels and immune cell alertness.
Ex vivo: Outside the body. We take blood samples into the lab to evaluate the immune cells’ responses to bacterial and viral stressors. The changes reflect re-programming of the cells inside the body after consuming a product, prior to a challenge in the laboratory. Changes demonstrate rapid re-programming of the immune system.
In vitro: In test tubes. The natural product is added to immune cells in the laboratory. The direct effects of the natural product on immune cells are documented in detail, including time- and dose-curves. This testing elucidates specific mechanisms of action.
Immune Modulation
Consuming a single dose of a natural product triggers synchronized waves of changes to immune alertness and surveillance. In this 3-hour study, the early initiating events included changes to the chemokines IP-10 and MCP-1 and reduced levels of pro-inflammatory cytokines.
The early events also included increased migration of monocytes, cells belonging to the innate immune system, and pivotal communicators to cells from the adaptive immune system.
These early events were transient, indicating that the effects are a temporary enhancement of the body’s normal healthy routine, and not a disturbance. Later events include increased immune surveillance by specific types of killer cells.
Sequential Waves of Immune Effects
Consuming different types of natural products can trigger highly selective effects on immune cell behavior. A natural product may trigger increased surveillance activity of monocytes and natural killer cells but have no detectable effect on T cell numbers in the blood circulation. When we interpret the results, we need to be reminded that possibly, the migration of T cells was also affected, but the number of cells leaving the blood and entering the blood may have been similar, so the total number seems constant.
We test for markers of immune alertness on cells in the blood circulation. For example, CD69 is a marker that reflects NK cell alertness. If in a quiet Study we see more NK cells with the CD69 marker on the cell surface, this suggests that NK cells of a higher state of alertness have entered the blood circulation.
Consuming a Natural Product
When we consume a natural product, the immune-modulating effects start at the gut/immune interface in the gut mucosa. The cells lining the gut bind to components in the product and communicate to immune cells inside the gut lining. This triggers a nerve signal to the brain, and the brain orchestrates the symphony throughout the body. The exact tune varies between different natural products.
Typically, immune cells responsible for immediate action are affected, and are encouraged to travel through the body, looking for invading bacteria and viruses. Cytokine levels in the blood also show waves of change, with initial, often transient, signals to encourage immune surveillance, followed by waves of cellular trafficking.
Mucosal Immunity
Immune cells actively protect our skin and mucosal barriers from attacks from pathogens. Some immune cells reside in skin and mucosal tissue, and other cells migrate between locations as part of our normal healthy immune surveillance.
In a Quiet Study we can detect rapid changes in the movements of monocytes, NK cells, and gamma delta T cells, to mention a few cell types of pivotal importance for the innate and adaptive immune defense systems.
Cytokines
The immune system communicates via small proteins called cytokines (cyto: cell, kine: movement). This communication also involves communication to and in the brain, and in various metabolic functions. They are present at picomolar concentrations and affect the entire organism. Therefore, cytokine testing is a pivotal part of Quiet Studies, to evaluate initiating signals that trigger downstream cascading effects on cells and cytokines.
An interesting group of cytokines are called chemokines, because they are involved in initiating cellular movements by attracting immune cells into tissue as part of immune surveillance. Since the Quiet Study design incorporates changes to immune cell movements (immune surveillance), the connection between cytokine changes and cellular behavior often reveals key roles of specific cytokines early on, within an hour after consuming a natural product.
Some cytokines, such as interferon-gamma, are also anti-viral peptides. Interferon-gamma has multiple roles, including support of natural killer cell activity and inhibiting viral replication in virally infected cells.