• Issue 114 / November - December 2016

    The Strategy Game of Our Immune System

    Brian Turk

    The organs and systems of the human body work together in perfect harmony. If kept in optimal condition, they function for many years. Our body is the perfect environment for life, but not necessarily just for our own cells. There are thousands of different types of microorganisms living mutually with our cells. Unfortunately, not all microorganisms have good intentions. Harmful bacteria and viruses could damage our body without much effort, if it weren’t for one thing: our immune system.

    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?


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