Natural Killer Cells: the James Bond of your immune system

Natural Killer Cells: the James Bond of your immune system

Author: Liliana Sánchez Rocha 

Read time: 6 minutes   

 

Your body’s army is divided into two major forces that work hand in hand to keep you alive. The “frontline defenses” (innate immunity) are always on high alert and quick to react at the first sign of trouble. Then, there’s the “strategic defense unit” (adaptive immunity), a team of highly trained operatives that plan and execute precise strikes against specific enemies. But between these major forces lies a special subdivision: the “secret agents”, experts in bridging the gap between the innate and the adaptive forces. Though originated as part of the strategic units, these secret agents belong to the frontline defenses, operating independently, equipped with high-tech gadgets, and masters in uncovering hidden dangers. Not only that, but just like James Bond these cells are licensed to kill. Their name? KILLER... NATURAL KILLER CELLS 

 

Are natural killer cells innate or adaptive? 

By origin, Natural killer cells (NK) are lymphocytes (specialized immune cells like B-cells or T cells), however, they are separate from the strategic defense unit (adaptive immunity). Instead, they belong to a special group called the “immediate licensed commandos” or ILCs. This group shares valuable characteristics with T cells, but not the complexity of their arduous training or exceptional skills. Members of the ILCs are dispatched to the frontline defenses (Innate immunity) for more refined support. NKs are in charge of eliminating any cell that has been invaded, is “defective” or does not belong to the body. No questions asked! 

 

What stimulates NK cells

To perform this crucial task, NK cells are armed with a highly advanced radar system, imagine it as a network of tiny “antennas” (receptors) scattered all around the surface of their slightly irregular spherical body. This system is vital to understand the surroundings of the field, but also the insides of other cells. Is there an innocent civilian taken hostage by evil invaders? Or perhaps there are conspiracy “thoughts” nesting in the core of a rebellious cell? The radar system is critical to detect and neutralize these threats. But these high-tech antennas are not exclusive to NK cells. In fact, all cells in your body display some type of receptors with different functions, some are designed for a group of cells with specific missions. NK’s special receptors turn ON or OFF their assassin mode, but to effectively work, they need direct contact with the suspicious cell’s receptors, especially with the “master receptor”. 

This master receptor shared among all of your cells (except red cells) is the “Resident HoLA health card” or HLA. This is like a resident permit that identifies your cells as your own and allows them to live and work in your body. On a biological level, this card/receptor holds your unique identity, it is what defines you as YOU. This HLA card also provides deep information about the cell health situation or any “suspicious activities” going on inside. HLA is vital to uncover dangerous intruders, and it is especially critical to survive any encounter with NK cells. This friendly “HoLA” might be the only reason to turn off their killing “mode”, if this is missing and the receptors capture “ON” signals, the assassination has no turnback. 

 

Natural Killer cells function

How do natural killer cells work? Imagine you’ve just returned from holidays in a beautiful tropical country, there you got infected with dengue virus. This virus forced itself inside one of your precious cells turning it into a mere slave. From the outside an inexperienced soldier passes by, oblivious to the misery unfolding inside. However, for the highly trained eye, the surface of this infected cell displays discrete SOS messages, just perceptible by the antennas… or the lack of them.  

The virus “knows” that the immune alarms will eventually go off and the strategic defense units will be mobilized. To avoid the risk of being spotted and eliminated, the virus dismantles the resident HLA system, leaving almost no identity receptors. Now the cell has been silenced and it is virtually invisible to some immune cells. But this strategy does not fool the NKs, NKs are trained to sniff out danger and act fast! Driven by their insatiable need to kill, NKs corner each cell they come across, when they are face to face, they aggressively demand to see their HLA card. NK gets close enough to the scared innocent cell, which desperately displays all possible antennas that might turn OFF the NK killing mode. If the number of OFF signals outnumbers the ON ones, the cell is safe, NK detaches, and unapologetically moves on, as cold and indifferent as ever.  

 

What is the mechanism of action of natural killer cells?

When NK corners the infected cell and orders it to show the HLA cards, the specialized receptors detect vital information: No HLA and many distress receptors. The silent SOS signals trigger an electric shock wave that runs through the NK body, moving their stored arsenal in direction of the targeted cell to prepare for execution. In a very specific and controlled attack; NK shoots a round of molecular bullets, punching mini holes in the membrane of the cell (the skin of a cell). This is already lethal, but NK doesn’t want a messy explosion that releases all the unharmed viruses. So, it follows with another round of special ammunitions, these go inside the cell through the mini holes and activate the programmed cell death. From now on EVERYTHING within the cell will be carefully destroyed and packaged using the cell’s skin, just as if it were wrapping paper, making beautiful gifts for hungry macrophages! NKs then send messages to attract other immune cells that can help clear up the dead body and will support the hunt for more threats. Sometimes, NKs take a more direct approach, activating the cell’s suicidal tendencies through direct contact with the “death” receptors, the type of attack will depend on the situation. Additionally, NK cells can also aid in the destruction of threats outside of the cell, as long as this has been tagged with antibodies; the “handcuffs” of the immune system. 

 

Natural killer cells and cancer 

Just as with a viral attack, NK cells are on high alert for cells that rebel against their natural fate. Those cells who refuse to perform their designated tasks and produce unusual substances, ignore the natural order of death when their time is up, and start multiplying like there’s no tomorrow. These are the seeds of cancer, and NK secret agents are experts at uncovering and eliminating them without a shred of mercy, in a very similar process as the one described above. NK may come across as brutal, but their mission is delicate and they can’t afford to hesitate. However, it is estimated that the human body is made of up to 36 trillion cells! This would be 4,500 times the current world population! With this immense ocean of cells to scan, NKs might miss a dangerous rebellious cell. The older we get, the more cells that may seek independence, making it harder for NKs to perform their surveillance with the same efficacy. If these cells are not caught on time; they can develop sneaky tactics to mess up with the radar system of the NKs to become undetectable, even for this experienced James Bond of immunity. With plenty of time and no one who can stop them, they can give rise to cancer. 

Conclusion 

NKs are fascinating cells that intensely spy to uncover hidden threats. Although they've been on the scene for over half a century, these lethal guardians continue to baffle and intrigue scientists. Recent discoveries hint that these NK cells might be packing more tricks and even a memory sharper than we thought.  Unraveling their covert operations is not just fascinating, it’s crucial. Mastering their deadly skills could be the key to empowering your body's natural defenses against one of the most formidable enemies: cancer. So, while these special agents keep your cells in check, science is working to turn their lethal precision into a powerful ally. The future? It’s one where your body’s James Bond might just win the war against cancer. 

 

Gameplay Guide: Defend with Natural Killer Cells in ImmunoWars   

 

Whether it's a ruthless bacterium or a cunning virus, NKs have your back and are ready to take out the trash! This Immunocard is played in two actions:  

First: Add this card to your immune army (place the card in front of you on the table) 

Second: Select one of its lethal abilities and pay the cost!    

You now have two options, choose wisely!  

1.- For 3 ATP (yellow hexagon) you will unleash the “cytotoxic sacrifice” Your NK will shoot ALL its cytokine arsenal to any 3-star bacteria or virus, BAM! The catch? this NK dies of exhaustion and must be discarded.  

2.- If you have been greedy and saved enough energy, for 8 ATP your NK will execute a full-blown attack, killing any 3-star bacteria or virus and still keeping some arsenal as backup. What’s even better is that you will keep this soldier ready for the next attack (although you still need to pay the price). Watch your opponent’s face crumble as their hand work goes straight down the drain, muahahaha!  

But be careful, this ace up your sleeve can be used against you during an autoimmune attack! Anything can happen in this immune-war. 

Think you’ve got what it takes to command this battlefield? Surprise a friend with an immune challenge! Get ImmunoWars here.   

 

 

References: 

  • Crinier A, Narni-Mancinelli E, Ugolini S, Vivier E. SnapShot: Natural Killer Cells. Cell. 2020 Mar 19;180(6):1280-1280.e1. doi: 10.1016/j.cell.2020.02.029. PMID: 32200803. 
  • Bianconi E, Piovesan A, Facchin F, Beraudi A, Casadei R, Frabetti F, Vitale L, Pelleri MC, Tassani S, Piva F, Perez-Amodio S, Strippoli P, Canaider S. An estimation of the number of cells in the human body. Ann Hum Biol. 2013 Nov-Dec;40(6):463-71. doi: 10.3109/03014460.2013.807878. Epub 2013 Jul 5. Erratum in: Ann Hum Biol. 2013 Nov-Dec;40(6):471. PMID: 23829164. 
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