Our immune system handles our body’s security. It’s equipped with the resources necessary to deal with different levels of security threats. This system walls off the body, but also has the equipment to hunt down any intruders. We can think of our immune system as a game of strategy, where defensive and offensive maneuvers are equally important. This game is not a simple, single-session one. It involves constant information gathering, weapon developing, and soldier training. In short, it involves constant change.

The body’s general defense mechanisms, called the innate immune system, can be considered the first line of defense, aimed at preventing bacteria or other pathogens (sickness-inducing factors) from entering the body in the first place. These include the skin (the walls of the castle), as well as mucus, tears, saliva, and acids (the boiling oils of the castle). Vulnerable entry points such as the respiratory system are covered with thick, sticky mucus, which traps pathogens and then disposes of them by way of sneezing or coughing. Other sensitive spots such as the eyes are constantly washed with tears. Tears are produced on top of the eye and drain into the bottom, near the nose, ensuring sterility.

The innate system also uses a mechanism called inflammation to handle pathogens that manage to breach the outer defenses. The main goal of inflammation is to prevent the pathogens that enter through the skin from reaching the blood. Inflammation is initiated by immune cells that are found within the injured tissue. These immune cells can be considered “patrol cells” and are found everywhere in the body, not just the blood. The moment these cells come across a foreign antigen (the molecular fingerprint of a cell or virus), they sound the alarm, triggering inflammation. Inflammatory precautions include blood clotting, macrophage migration, and increased blood flow to the area. Blood clotting occurs relatively quickly, since inactive clotting factors are already present and only need to be activated. This seals off the security breach, preventing more pathogens from entering. Macrophages are very large immune cells that migrate to the scene and capture any bacteria they encounter. Increased blood flow to the area both eases and accelerates the entrance of reinforcements, such as antibacterial proteins and other white blood cells. This is the reason for the swelling we see.

If all fails and the pathogens manage to enter the bloodstream, the body has no choice but to pull out the big guns: the adaptive immune system. The adaptive immune system is unique in that it knows its enemy and adapts accordingly, hence the name. Each type of pathogen has strong and weak spots. Some are resistant to antibacterial proteins, while others are resistant to being phagocytosed (being eaten alive!) by macrophages. During the first encounter, the adaptive immune system tries different methods of destroying the pathogen, and “records” the most effective method. It then stores the antigen of that specific pathogen. So, during the second encounter, the adaptive immune system already “knows” what to do and eliminates the pathogen almost immediately.

Now, let’s get into some detail.

There are many types of cells in the adaptive immune system. Each has a very specific role to play. Cytotoxic T cells are the ones responsible for destroying bacteria. One feature that distinguishes these cells from macrophages is the method of activation. Unlike macrophages, cytotoxic T cells only kill after being activated by another type of cell, the helper T cell. The helper T cells’ main purpose is to activate or suppress the immune response, like an on-off switch. They are so effective that without the secretions of these helper T cells, the adaptive immune system literally shuts down. The cytotoxic T cells also need a means of recognition. This role is fulfilled by antigen-presenting cells (APCs). When APCs find foreign antigens left behind in the blood by bacteria, they stick them on their own membranes. Then, they start handing them around to cytotoxic T cells, like police identifying bandits from WANTED posters. After obtaining these outlaws, cytotoxic T cells kill any of those bacteria they encounter.

A second difference between cytotoxic T cells and macrophages is how they kill. Rather than phagocytosing (eating alive) bacteria, they shove a tube-like protein into their membrane, allowing its insides to flow out and ultimately deflating and killing it.

After the body recovers from the sickness, most of the outlaws are destroyed. But a few are kept and stored in memory B cells. Memory B cells are like the immune system’s archives, in that they have long lifespans and are kept safe deep in the bone marrow. The file of each bacterium is kept in these cells, with its poster on the front for quick identification. Therefore, if the body encounters the bacteria again in the future, the immune system loses no time trying to identify them. The elimination process starts promptly, even before any signs of illness. This mechanism is, in fact, what makes vaccination possible. Dead or harmless pathogens are injected into the body so that their files can be created in our archives without the hassle of illness.

Unfortunately, bacteria also have a few tricks up their sleeves. Bacteria are single cells, and this enables them to change their genetic material without major consequences. These genetic changes also cause structural changes. Even though each bacterium is individual and independent, they get their strength from their large numbers. For example, imagine a population of 100 bacteria, all with different genetics. During an infection, our immune system uses a special tactic – for example, phagocytosis – to get rid of the bacteria. But one of these bacteria has a genetic feature – say, a strong cell wall – that gives it immunity from this tactic. So, while the other 99 bacteria get eradicated, this one bacterium survives. This bacterium then multiplies into 100 new bacteria with strong, phagocytosis-resistant cell walls. This forces our immune system to find new strategies to overcome the bacteria’s new defenses. Resistance in bacteria only gets stronger if provoked. This is the reason why excessive use of antibacterials is not recommended. While they may give temporary relief, they cause the bacterial population to grow more resistant.

Even though bacteria are skilled in the art of genetic mutation, there is another pathogen that is undoubtedly the master: The Virus.

Viruses are so tiny that it has been debated whether they should be considered living creatures or just molecular structures. They contain very little genetic material, which makes them extremely prone to mutation. They mutate so rapidly that it is impossible for our body to create files for them. Moreover, they do not need provocation to mutate, since mutation is a part of their life cycle. This is the reason why immunodeficiencies (weaknesses of the immune system) are one of the most notorious disease types. Most immunodeficiencies are genetic and/or viral. The immunodeficiency with probably the worst reputation is AIDS. AIDS stands for “acquired immune deficiency syndrome,” and is caused by the human immunodeficiency virus (HIV). The thing that makes this particular virus so notorious is the fact that it targets the very cells that allow the immune system to operate, the helper T cells. Without the secretions of the helper T cells, the entire adaptive immune system virtually shuts down. After that, even the simplest illness can lead to serious consequences.

The HIV virus is an external threat, whereas another immunodeficiency, multiple sclerosis (MS), is an internal one. MS is a disease where our immune system sees our own cells (especially nerve cells) as enemies. This results in the destruction of cells by none other than our very own immune system. Destruction of the nerve cells may cause various neurological symptoms such as weakness, visual problems, or even psychiatric issues. Although the exact mechanism causing this deficiency is unknown, genetics is thought to play a big role. As a result, there is currently no known cure for MS.

In sum, our immune system continuously plays an extremely sophisticated, microscopic strategy game, of which we are observers more than we are players. Even as observers, we cannot entirely understand the battle at center stage, let alone the struggle going on in the game’s dark corners. Our immune system develops new strategies to keep us safe from thousands of daily attacks on the body. We are not even aware of all these strategies and defenses, unless they fail and we fall sick. There is no apparent winner or loser of this ongoing game, which requires extensive knowledge, intelligence, and uninterrupted adaptability, alertness, and creativity. As fantastic as observing this collective performance is, one cannot also help but ask whether each and every one of these players (our immune system, bacteria, viruses, etc.) a master strategist, owning all of these wondrous attributes, or are they directed to make their moves by the same One Master Strategist, for us to watch in awe and reflect upon?

Nigella sativa, commonly known as black cumin or black seed, is native to the Mediterranean region, but has also been grown on the Arab peninsula, Africa, and western Asia. It belongs to the Ranunculaceae family and is one of the numerous plants from this family that has been shown to have great potential for therapeutic use. With more than 100 nutrients and compounds, black cumin is rich in unsaturated fatty acids and essential oils (about 0.4%), including but not limited to thymoquionone and carvacrol. The antioxidants in black cumin attributed to the compounds in the essential oil relieve oxidative stress by scavenging activity through free radicals. Other nutrients include proteins, carbohydrates, and many, many vitamins. The plant can grow up to 30 cm and have white flowers with black seeds no more than 3 mm in length.

Historically, black cumin has been used for two different purposes: as a seasoning and flavoring in foods, and as a medicine for the treatment of ailments. Ibn Sina (980-1037), also known as Avicenna, refers to black cumin as stimulating the body’s energy and helping it recover from fatigue. Recent research shows that if it’s taken over time, black cumin can greatly boost the immune system. Another report from the Prophet Muhammad, peace be upon him, similarly puts emphasis on consistent use of black cumin with the phrase, “hold onto the use of the seed.”

Research highlights

Recent research highlights the benefits of black cumin in the induction of apoptosis (cell death) in cancer cell lines and in decreasing blood sugar levels, which can help limit complications from diabetes. Numerous medicinal properties of black seed extracts and oil have been shown to strengthen the immune system, radioprotectivity, antihistaminic, antihypertensive (reduces high blood pressure), analgesic (pain reliever), anti-inflammatory (reduction of swelling/inflammation), hypoglycemic (suffering from an abnormally low level of sugar in the blood), antibacterial, antifungal, antitumor and protective effects against oxidative stress, hepatotoxicity (toxicity to liver) and nephrotoxicity (damage to the kidneys). Black cumin seed extracts also inhibits NO production. Thymoquinone found in black seed improves liver antioxidant capacity while increasing expression of antioxidant genes. Black cumin reduces the risk of various other maladies such as respiratory disorders, skin disorders, and allergies.

Supportive role in the immune system

Studies done decades ago suggested that the use of black cumin on regular basis enhances human immunity, especially in immune-compromised patients. In the 80s and 90s, different studies done on human volunteers show that black cumin acts as a natural immune enhancer. Use of black cumin for this purpose has been patented as well. These findings suggested that black cumin could play an important role in the treatment of cancer, AIDS, and other diseases associated with immuno-deficiency.

In 2010, Xuan and colleagues at University of Tubingen, Germany conducted a study on thymoquinone, a component of black cumin, to test its effect on dentritic cells, which take key role in the innate and adaptive immunity. By using mouse bone barrow derived dentritic cells as model, they showed that thymoquinone cooperate in the maturation, cytokine release and survival of dentritic cells.

Black cumin also has radioprotective effects. A study by Assayed in 2010 on rats aimed to investigate the radioprotective potential of black seed oil against exposure to radiation. Gamma irradiated rats fed black seed oil demonstrated that black seed oil is a promising natural radioprotective agent against the immunosuppressive and oxidative effects of ionizing radiation. Those findings suggest that black cumin might be used as protection against the adverse effects of radiation in the case of a nuclear leakage from nuclear plants, such as the one that happened in Japan following the massive earthquake in March 2011.

Reducing blood sugar in diabetes

A study performed in Japan by Fararh and colleagues on the hypoglycemic effect of black cumin oil in streptozotocin-induced diabetic hamsters showed that treatment with black cumin oil has both a regulatory role in blood glucose levels and an immunopotentiating effect. In this study, black cumin oil decreased blood glucose from 391+/-3.0 to 179+/-3.1 mg/dl after the fourth week of treatment. Hepatic glucose production from gluconeogenic precursors (alanine, glycerol, and lactate) was also lower in the treated hamsters. In addition, they showed that black cumin has an immunopotentiating effect through inducing the phagocytic activity of macrophages and lymphocyte count in the blood. Approaches for the treatment of diabetes using black cumin are noteworthy, including patented ones (US Patent No 6042834).

Studies on inflammation, cancer, and oxidative stress

Black seed oil has an anti-inflammatory effect and it could be useful in relieving the effects of arthritis. Thymoquinone, an active ingredient of black cumin, shows a remarkable anti-inflammatory potency. Research on thymoquinone also demonstrates that it increases T cells and natural killer cell-mediated immune responses.

Moreover, black cumin is known to show protection against cancer growth due to the induction of cellular death. A study on mice back in the 90s showed that fatty acids derived from black cumin could inhibit the various cancer cell lines, including Ehrlich ascites carcinoma and Dalton’s lymphoma ascites. This study concluded that black seeds contain a potent anti-tumor agent, and this could be long chain fatty acids.

Another study also found that black cumin oil could inhibit eicosanoid generation; thus, black cumin demonstrates anti-oxidant activity. This inhibition of eicasanoid production, however, was higher compared to thymoquinone alone, suggesting the presence of other compounds within the oil that increases anti-inflammatory reactions.

A model based on experimental autoimmune encephalomyelitis (EAE) done by researchers at Gaziosmanpasa University in Turkey showed that black cumin may be protective against oxidative stress in the brain. Black cumin also regulates tissue NO levels, at least to some extent.

Black cumin as an anti-histamine agent and a fighter of bacteria

Bronchial asthma is associated with allergic reactions, and sometimes this could arise from the production of histamine from bodily tissues. Back in the 60s, it was shown that dimer dithymoquinone (nigellone) from black seed oil suppressed symptoms associated with bronchial asthma. In 1993, Chakravarty demostrated that nigellone inhibits histamine through the inhibition of protein kinase C, a protein known to induce the release of histamine. A clinical trial on 152 patients with the allergic disease done in 2003, in Germany, also demonstrated that black seed oil is an effective agent for the treatment of allergic diseases. These studies offered alternative treatments using black cumin to people who suffered from bronchial asthma and other allergic diseases.

Studies in Bangladesh showed that black cumin extracts exhibit anti-bacterial and anti-fungal properties as well. A study comparing the volatile oil of black cumin with five antibiotics (ampicillin, tetracycline, cotrimoxazole, gentamicin, and nalidixic acid) demonstrated that black cumin oil is effective against various strains of bacteria, including V. cholera, E. coli (a common infectious agent), and strains of Shigella.

Final remarks

It has been suggested that black cumin could support metabolism, improve digestion, and drive out worms and parasites from the intestines. It could also be used for soothing coughs, stimulation of menstrual periods, the promotion of lactation (the flow of breast milk), increasing sperm count and hair growth, and perhaps even more.

Modern technology and studies based on synthetic compounds for new therapeutics have diverted the attention of researchers to where they could seek cures that already exist in the natural world. Pharmaceutical drugs show a lot of benefits to human well-being, and have cured a number of diseases, but they also have unwanted side effects.

Black cumin could be a treasury for medicine. Research findings and historical practices shed light on the curative aspects of black cumin. However, the quantity, quality, and extent of studies on black cumin are not comparably high. This urges researchers to put more, and more intense efforts into understanding and discovering treatments for diseases that we are facing today by using black cumin – a natural cure that people have been using for 1400 years.

References

• Xuan et al. (2010) Effect of thymoquinone on mouse dendritic cells. Cell Physiol Biochem. 2010;25(2-3):307-14. Epub 2010 Jan 12.
• Assayed ME. (2010) Radioprotective effects of black seed (Nigella sativa) oil against hemopoietic damage and immunosuppression in gamma-irradiated rats. Immunopharmacol Immunotoxicol. 284-96.
• Abdel-Zaher AO et al. (2010). Blockade of nitric oxide overproduction and oxidative stress by Nigella sativa oil attenuates morphine-induced tolerance and dependence in mice. Neurochem Res. 2010 Oct;35 (10):1557-65.
• Butt MS and Sultan MT. (2010) Nigella sativa: reduces the risk of various maladies. Crit Rev Food Sci Nutr. 2010 Aug;50(7):654-65.
• Salem ML. (2005) Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. Int Immunopharmacol. 2005 Dec;5(13-14):1749-70.
• Kalus et al. (2003) Effect of Nigella sativa (black seed) on subjective feeling in patients with allergic diseases. Phytother Res. 2003 Dec;17(10):1209-14.
• Fararh et al. (2004 ) Mechanisms of the hypoglycaemic and immunopotentiating effects of Nigella sativa L. oil in streptozotocin-induced diabetic hamsters. Res Vet Sci.:123-9.
• Schleicher, P., and M. Saleh (2000) The Magical Egyptian Herb for Allergies, Asthma, and Immune Disorders. Rochester, VT: Healing Arts Press.
• Luetjohann, S. (1998) The Healing Power of Black Cumin. Twin Trees, WI: Lotus Light Publications
• M. Ali Albar. The Revival of Prophetic and Herbal Medicine. Fountain Magazine. Issue 14 April – June 1996.
• Ziya Aydin. Asirlarca Once Mujdelenen Sifali Bitki: Corek Otu. Sizinti Dergisi.
• Nigella sativa. http://en.wikipedia.org/wiki/Nigella_sativa
• Research. http://www.blackcuminseedoil.org/research.php
• US Patent No 5482711 and 6042834.

These findings might help researchers to design more effective drugs for various human infections by focusing on the minimization of the inflammation. Moreover, bats are capable of sustained long flights, as some bat species can fly more than 1,000 km in a single night. With such intense physical activity, cells often produce high levels of toxic (free radicals) that would usually damage DNA sequence.

This study also found that bats are equipped with a highly functional set of genes that mediates DNA repair in response to DNA damage, thus bats are protected from toxic cellular waste with this advanced mechanism. Aging, cancer and infectious diseases are the three major issues medicine is facing today and biological abilities granted to bats seem to provide important clues for us to discover new ways to combat these big health problems

The muscle cells are responsible for the strength and tone of the vessels. Today, we know that the role of the endothelial layer goes beyond a simple physical barrier. In addition, there are twenty-five different substances secreted by the endothelial cells that play a role in blood clotting, cell proliferation, the regulation of vessel permeability, and the functioning of the immune system. The endothelial cells are 10-15 &μm wide and 20-25 μm long. They are located in the inner vessel wall in a single-cell layer. The total endothelial area in the body of an adult is around 5000-6000 m², and it weighs around 2.5 kg. Endothelial cells during inflammation Capillaries consist of an endothelial structure; they can only be seen under a microscope, but their total length is nearly 96,000 km. The blood brought by the arteries is conveyed to the vein through capillaries. At this stage, the gas, liquids, and nutrients are brought out through the vessels and the cells and tissues around are supplied with oxygen and nutrients. In return, the liquids that they discharge and other waste matter are conveyed to the vein through capillaries. This matter-exchange, which occurs both inside and outside of the capillaries, is regulated thanks to the permeability of the endothelial cell layer and the pressure balance of the capillary system. During cardiac failure and inflammation, liquid release is increased due to a pressure imbalance and the liquid retrieval is not sufficient to make up for the amount lost. This results in swelling in the area in question. Here, we need to underline that inflammation, which appears with symptoms such as edema, redness, fever, and pain, is not a harmful process. On the contrary, it is a miraculous defensive mechanism granted to our body; inflammation protects the body against serious damage. For instance, the inflammation that forms around a bee sting prevents the venom from spreading throughout the body. The endothelial cells are given an important role in the inflammation as well. The chemical molecules secreted by the endothelial cells in the inflamed spot cause the vessels to react by enlarging and thus perfusion is increased. Later, the endothelial layer becomes ready for leukocytes to settle; these are used in neutralizing the substance that caused the inflammation in the first place.

Balancing blood pressure

The layer of smooth muscle cells is stimulated with chemicals secreted by the endothelial cells and the tone of the vessels are controlled through the constriction and relaxation of the vessels. Therefore, an important duty in the regulation of blood pressure is given to these cells. During aninfection, bacteria circulate in the blood stream and the blood pressure falls extremely low. Tissue nutrition is upset (septic shock) and an excess of muscle-relaxing substance is released by the endothelial structure. Veins and arteries become too relaxed and there is a considerable drop in blood pressure (hypotension). On the other hand, with problems like atherosclerosis, the endothelial cells cannot fulfill their duty and due to a deficiency in nitrogen oxide, they become immune to the stimulus to relax the muscles. The resulting problem in this situation is hypertension.

Endothelial cells prevent hemorrhage

In order for a hemorrhage to stop the vessels that are bleeding need to narrow down. This is very important in the first stages of blood loss, particularly when there is a problem with blood clotting. When a hemorrhage begins, the endothelial cells are ordered to excrete a substance called endothelin. This starts the narrowing down of the bleeding vessels. Endothelin is not excreted in normal vessels. When the umbilical cord of a newborn is cut, it prevents the baby from losing blood.

Endothelial cells in blood clotting

The duty of endothelial cells can prevent or facilitate blood clotting, depending on the situation. First of all, they prevent the blood cells from adhering to the vessel walls and prevent clotting inside the vessels. Imagine water flowing through a pipe. The speed of the flow is greater in the center and lower at the periphery. Therefore, in the long run, some residue forms inside the pipe. In the veins and arteries, the flow of blood near the walls is also slower. To prevent the formation of any residue, both the endothelial cells and the blood cells are created with negative loaded surfaces and the blood cells are pushed towards the center. In addition, a substance called prostocyclin (PGI2) is excreted and the thrombocytes change their structure. As a result, residue formation and clotting is prevented along the vessel walls. In a case of any long term damage to the endothelium (e.g. due to smoking, diabetes, or hypertension), the relevant protection mechanism fails, and clotting inside the vessels results in thrombosis. Some serious cases can even necessitate the amputation of a limb. The endothelial cells can also facilitate clotting when necessary. In case of bleeding due to a wound, they function contrarily and help the blood to clot to prevent blood loss.

Endothelial cells in the bone marrow, the liver, and spleen

As a divine blessing, the endothelial cells form a looser layer in these organs and vessel permeability is increased. Thanks to this increase, matter Exchange with blood is easily realized; blood reaches these organs, which are responsible for the constant control of the contents of the blood, easily.

Endothelial cells in the brain and eyes

The endothelial cells in organs like the brain and eyes are very closely integrated forming a barrier between the blood and the organs. This is to such an extent that the major nutrients of the brain, like glucose and oxygen, pass without any obstacles, but several chemicals, including medication, are blocked by the selective-permeability of this protective mechanism. Research has proven that various substances injected into the bloodstream reach almost all the tissues except for the brain. Thanks to the efficient protective mechanism that has been given to these minute cells, the brain is saved from a great deal of negative effects. Even a single cell is not left to chance and nothing happens randomly. As can be seen throughoutthe universe, opposites are made to work hand in hand in the human body as well in a splendid harmony for the continuation of life.

References

• Vinay Kumar, Abul K. Abbas, Nelson Fausto, Richard Mitchell, Robbins Basic Pathology, W.B. Saunders; 8th edition, 2007. Hall, John E., Arthur C. Guyton, Textbook of Medical Physiology,