(i) Cell battle on the front-line: Phagocytes & NK cells



Phagocytes
They break up the pathogens (dead bacteria or viruses) and present the pieces to the second-line T cells, while activating the adaptive immune response. The adaptive immune response initiates antibody production and T cell memory function. T cells are able to memorize invading bacteria, microbes or viruses in order to accelerate immune response upon future encounters. They act just like a country’s patrol police, who not only seize fugitives, but also report back to the strategic commanding unit the characteristic features of the fugitives.


If phagocytes function poorly, the hosts lose their strong first-line defense, become prone to infections caused by foreign bacteria, pathogens and moulds. Cancer patients undergoing chemotherapy or radiation therapy are a good example. Their blood-cell maker, the bone marrow, is damaged by the side effects of their therapy, and they suffer from a decreasing number of immune cells (leukocytes). In order to boost their immune system, doctors might suggest an injection of GM-CSF (granulocytes – macrophage colony-stimulating factor) to increase the number of phagocytes two weeks after the injection. This type of medicine is a costly cytokine, and the high cost of treatment shows the important role phagocytes play in the immune system.


Efficacy of Ganoderma on Phagocytes
Many researchers have reported that ganoderma, as well as its polysaccharides, are able to stimulate macrophages to secrete cytokines. The most important is the study on suppressing tumor cells conducted by the research team led by Professor Sheng-Yuan Wang of Taiwan Yang Ming University. They found a pure ganoderma polysaccharide could stimulate marcopahges and lymphocytes to secrete Tumor Necrosis Factor (TNF- ∝), increasing concentration up to 9.8 times.



In 2004, a similar study was published by the research team of Taiwan’s Academia Sinica under the direction of Prof. Chi-Huey Wong. The results demonstrated the anti-tumour activity mechanism for a ganoderma polysaccharide. Through the combination of the polysaccharide with the TLR4 receptors on the macrophage membrane, the secretion of various tumour-resistant cytokines was induced, thereby fulfilling its anti-tumour role.

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Natural Killer (NK) cells

They deal specifically with normal cells parasitized by germs or newly-established cancer cells, both of which are mutated cells that may cause further harm in the body, so they must be destroyed immediately. If the nucleus of a cell is invaded or even worse, the DNA in the nucleus is replaced by a virus, this will eventually die since the virus will use the host as nutrients and become a hotbed for tens of thousands of viruses, including mutations. Worse still, the parasitized cells are the cancer cells, those cells which people fear most. The best strategy to combat these is to remove them at the onset of their development into a minimum observable tumor, namely at the zero stage. NK cells are in charge of terminating mutated/ cancer cells before these cells turn into malignant tumors.



NK cells have drawn much attention from the immunologists in recent years; they seem to exist for cancer cells. It is interesting to discover that in an in vitro test when NK cells are added into a solution containing cancer cells, they will start to approach them, then stretch out a pipe-shaped object to bite on the cancer cells like a serpent, and inject venom (e.g. cytotoxin) to destroy them. Thus some scholars allude to NK cells as ‘God-given’ anti-cancer cells. Several clinical studies show that the severity of cancer is inversely proportional to NK cell activity. The less active the NK cells, the more active and serious the cancer progression.



Efficacy of Ganoderma on NK cells

The earliest clinical study on the effect of ganoderma on NK cell activity was conducted by Prof. Da-Cheng Dong at Taipei Medical University. Healthy adults were given ganoderma hot-water extract (at a dose of 2g which was extracted from 40g of the dry ganoderma fruiting-body). After two weeks, a significant increase in the NK cell activity was found. A similar in vitro study was carried out by following the official validation method for immune modulation established by the Department of Health of Taiwan. Mice were administered with a commercial ganoderma product and the results were the same: increased NK cell activity. This result was validated by a committee comprised of physicians, nutritionist, chemists and toxicologists; a total of 17 experts. A consensus was reached within the validation committee after a review of the research work that the ganoderma product was capable of increasing NK cell activity in-vivo. The amount of ganoderma product administered to the mice was 0.005g/d (grams per day), corresponding to 4.31 capsules (450mg/capsules) for human use. This suggests that the NK cell activity in the human body may be enhanced on the basis of long-term consumption of a dose of 4.31 capsules/day.



(ii) Cell battle on the 2nd line: T cells & B cells



T cells, the main player of the immune cells, undertake many tasks such as receiving messages, eliminating enemies, storing information etc. They are divided into two types: cytotoxic T cell (Tc) and helper T cell (Th). Once T cells receive the information sent by phagocytes on the characteristics of the pathogens, they will begin to propagate so that Tc cells are ready to mount a strong response should they encounter the same pathogens. Helper T cells, however, a type of “information cell”, will start to engage in a task unique in the human body – key-in the received information from the encountered pathogens to the “pathogen database” and familiarize other phagocytes and B cells with information on the invader. The immune war then enters a stage of unprecedented intensity.



Helper T cells have to differentiate into two types of Helper cells, namely, Th1 and Th2, each in charge of different types of immune responses, in order to accomplish the numerous tasks. It is for them to decide what kind of weapons to employ so as to destroy the enemies in this immune war. In the process of Th cell differentiation there must be an optimal proportion Th1 and Th2 cells, the proportion usually referred to in immunology as the Th1/ Th2 balance. Th1 cells assist Tc cells, and therefore, are considered a great help in the immune war. Th2 cells, however, help B cells in producing antibodies, especially in producing a particular type of allergy antibody called lgE (a kind of immunoglobulin) that plays an important role in the allergic asthma reaction. Allergy jeopardizes healthy cells, but a well-balanced distribution of Th1 and Th2 cells helps to maintain strong resistance as well as prevent unnecessary harm. The optimal proportion of Th cells in an immune battle is more Th1 cells than Th2 cells, so reaching a “balance”.



Efficacy of Ganoderma on T cells & B cells

In animal tests on the use of a specific ganoderma product, the analytical results for some cytokines suggested that the mice taking ganoderma had more Th1 and less Th2 cells, indicating a positive effect on the Th1/Th2 balance. Rises in Th1 cell activity help to “strengthen immunity” while declines in Th2 will assist in modulating immunity and avoiding allergic reactions. So, the impact of the effect of ganoderma in T cells is bi-directional – serving to strength immunity in times of low immunity and to lower immunity in times of over-reaction.



To determine which part of ganoderma plays this mediating role in T cells, the National Taiwan University conducted experiments in mice on T cells by using two main components, high molecular polysaccharide-peptides and crude triterpenoids, separated from a specific strain of G. tsugae (YK-01). The findings show a stark contrast in the roles of these two substances, with polysaccharide peptides encouraging the differentiation of Th1 and with triterpenoids inhibiting the differentiating of Th2. This is an interesting finding showing that two substances with contrasting mechanisms exist in the same ganoderma. The two substances work together simultaneously, helping both Th1 enhance immunity and Th2 prevent allergy. Ultimately, the better proportion of Th1 and Th2 takes the immune battle forward.

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B cells are regarded as soldiers; antibodies can be considered their weapons. The key to victory in an immune war is that the reinforcements supply sufficient troops and firepower in the shortest time possible. T cells and B cells serve as these reinforcements in the human body. As B cells increase, the number of antibodies (ammunition) also increases. The number of B cells is maintained at a certain level and they cannot proliferate limitlessly. However, the number of antibodies can grow over millions or tens of millions, packing blood with their presence likened to an interlaced fire-net that is used to attack large numbers of pathogens and immobilize foreign bodies.