How does the immune system function, and how does it deal with unwanted guests?

We started to look at youtube videos on the immune system to start our research. We found a science based youtube channel named: Kurzgesagt – In a Nutshell. At the end on the video we watched he was selling a book about the immune system. The book had everything in the video and a whole lot more. We both got the book and that's were we got 90% of our information. The book and souces too, and we went into those and got more on the information there. We wrote down our information and research in a google doc, then transfered the information to canva and made our trifold. 

From now on we will call “unwanted guests” their more scientific name, pathogens. A pathogen is anything that will challenge your immune system. Not all bacteria are bad. Some are good and help you out. Same with viruses. But we will get more into that later. Just know if you see the word pathogen, we’re talking about a harmful “thing” that will give your immune system a run for its money, and wants to steal your body's precious resources. Most pathogens can fall under the umbrella of bacteria, viruses, parasites, and cancer. For the majority of this project we will talk about your most common invader, bacteria. And after explaining how your body deals with bacteria, then we’ll go onto your second most common invader viruses.

The immune system is the most complex thing besides the human brain in the whole known universe that we know of right now. It has been on this earth since the beginning of multicellular life, which arrived around 600 million to 1.5 billion years ago. The main point of your immune system is to kill all pathogens, and sometimes your cells, if they mutate into cancer. All animals and things alive that are a form of multicellular life, have some sort of immune system. But by far, ours is the most complex.

Now where is your immune system? It is you. Maybe not the answer you were looking for, but it is everywhere inside you. It has hundreds of tiny organs, around 600 of them throughout your body. These are the lymph nodes, and are your factories that make some of the cells for your immune system. It’s also a meeting point for cells navigating your lymph vessels, which acts as a superhighway for your immune cells. It also reabsorbs your blood, and redistributes it back into your bloodstream, and debris from a surrounding area. Along with your lymph nodes, your body has multiple large organs for the immune system. These are your spleen, and thymus. Your spleen is kind of a warehouse, having as much as 33% of all your immune cells there as back up, as well as around a pint of blood. So it’s like a large lymph node, and does everything a normal lymph node would do, as well as clean your blood in the lymph vessels. Your thymus is a mix of a nursery and a murder school. Its main purpose is to train and kill unworthy T cells, one of the most important immune cells, as well as other immune cells. Also you have your bone marrow, which trains and kills B cells, and many more of your immune cells. And protecting your mouth and what comes in is the tonsils. This controls what goes into your body, and was used to think by scientists and doctors that the tonsils were useless. Now that we know that they aren’t useless, doctors take more precaution before removing them for a variety of reasons. 

 

Cells are the smallest unit of life, and they are what make up you. Your cells are made up of proteins. (Cells are made up of many other things like water molecules, but proteins are the most important part of the cell for this project.) Proteins are like a 3D puzzle piece. The shape of a protein determines what other proteins it can connect with. A series of these connections is called a pathway. Proteins are made up of amino acids. If you get 50-2000 amino acids to connect, you get one protein. Get a couple million proteins to connect with each other and with things such as water molecules, and we have a new cell. Every cell has millions of “noses” called receptors. These “noses” pick up a special protein called cytokines. All this protein is meant to do is carry information around. These cytokines are released by dying and wounded civilian cells at the start of the battle. They are also released by the innate immune cells if they need backup, and many other immune cells for many reasons. What is the innate immune system? Let's learn about that.

 

Even though your immune system is very complex, it has two major parts to it. The Innate immune system, and the adaptive immune system. These aren’t organs or anything, but two different groups of cells that work together. The innate immune system is not specialized towards any pathogens, but the adaptive side does. The innate immune system is ready from birth, the adaptive part needs a few years to grow. This is why babies need vaccines of some dangerous pathogens at weeks old. 

 

Your innate immune system is the part of your immune system that does most to all of the fighting in most cases. Your innate immune system has two killers, a macrophage and neutrophil. A macrophage is the first one to make an encounter with the enemy patrolling all entrances to your body, and every inch underneath your skin. When it recognizes a pathogen, it pulls it into the membrane of its body, like a little prison. When fully inside, it opens the pathogen to acids and proteins, which pulls apart the pathogen, and sorts the parts of the now dead pathogen. The macrophage uses what it can, then it recycles the rest. A macrophage can kill around 100 pathogens before getting tired, and needs a break. Then it releases cytokines that it needs back up. Soon, thousands of neutrophils come rushing from the surrounding blood vessels. If a macrophage is a soldier following orders, a neutrophil would be a rebel agent going against orders, and not using normal protocol, but still working towards the same goal. Neutrophils love to kill and will do almost anything to make sure the enemy is dead. They love to kill so much that they will explode themselves and cover the enemy in its DNA and RNA, which kills almost any pathogen. As well as vomiting deadly chemicals at surrounding pathogens. They also injure your own cells, but collateral damage is not their problem. 

 

Now to talk about one of the more important parts of defending enemies: inflation. Inflation is when an immune cell orders surrounding blood vessels to open up and let fluid flow onto the battlefield. This is what causes swelling and redness to an infection. This is very hard on the body as it causes a lot of stress on the surrounding tissue. Inflation brings in new soldier cells and another killer called compliments. But we will go more in depth about compliments later. Like many parts of the immune system, there are some no go areas in your body. Like your gut, lungs, eyes, liver, and brain, and other vital organs. These areas are very sensitive and have a really good chance of killing you if they get inflamed. Chronic inflammation is related to 1 out of every 2 deaths. Most of these deaths happen when cancer and some diseases orders inflammation in the no go areas.

 

Let's talk about the killer that was briefly mentioned before, the complement system. The complement system is a mix of 30 complement proteins that work together by connecting with other complement proteins to cripple enemies. There are around 15 quintillion complement proteins in your body's fluids right now. The main 3 things the complement system does to cripple enemies, is: maims the enemy, it helps guide the immune system to the enemy, and rips holes in them till they die. How it does this is very complicated, and would be pages upon pages of information. The important thing is they connect with the pathogen specific proteins or receptors. Then it gets ready for more complement proteins to connect. After a few connections there is a little base on the surface of the pathogen, ready to wreak havoc. Soon there will be hundreds of bases on the pathogen. This works best for bacteria as they are bigger than viruses, so more bases can be built on them. They aren't pathogen specific, and sometimes don’t work on some involved pathogens, and these are the really dangerous enemies.

 

The thing about the adaptive immune system that is different from the innate immune system is it’s specific. So when activated it’s very effective. This happens though a dendritic cell. An intelligence officer that looks kind of like a ball with arms sticking out everywhere. While your macrophages and neutrophils are fighting, your dendritic cells are collecting pieces of dead pathogen, like a soldier covering itself in its enemies remains. They almost paint a picture in time, showing what happened. Since your dendritic cells are always doing this, the snapshots are always fresh. Now how does it activate the adaptive immune system? It does this by going to the nearest lymph node. As we know, they are meeting places for cells traveling the lymph vessel. This is where the dendritic cells will meet your T cells. To be more specific the helper T cell. Your T cells are the first adaptive immune cell to get activated. Your dendritic cell is looking for the T cell that has the weapon for that specific pathogen. Because cells are made up of proteins which are made up of amino acids, there can be really small differences from T cell to T cell. In this case it’s the pathogen it has the weapon for. So in your body there is a T cell with the power to help fight off every possible pathogen attack in the universe.

 

Now let's go back to the dendritic cell, who is looking for that specific T cell. Since T cells are very picky, the dendritic cell takes the remains of the pathogen and makes it into an antigen. This is like taking a raw turkey leg and cooking it and cutting it into very neat strips. Now the antigen is loaded into a MHC II molecule, which is then brought to the surface of the dendritic cell and is ready for presentation to the T cell. So for the next few hours your dendritic cell is rubbing the antigen on every T cell it sees. So when finally a T cell recognizes the antigen, it connects to the MHC II molecule on the dendritic cell. Now the T cell knows it’s needed, so it starts to clone itself. Within a couple hours you will have a couple thousand T cells. They split into 2 groups. One goes to the front lines, and the other group goes to activate more of the adaptive immune system. The group that goes to the front lines will be like a local commander. Even though they don’t do any of the fighting, they will request for back or more inflation if needed. They also are able to allow macrophages and neutrophils to go into full rampage mode. Even if they are beat and need to rest they will work harder than ever before in killing the pathogens. Now the other group of T cells goes to awaken another part of your adaptive immune system, the B cell.

 

The B cell is like an enemy specific complement system in a way. They produce antibodies. Antibodies are the most effective way your body has to deal with pathogens. But more on those later. In a similar way to the virgin T cells in your lymph node, your virgin B cells are also in your lymph node, but in a different part. They reside in the part of the lymph node where the stuff from the lymph vessels is floating through. As already mentioned, the lymph node absorbs almost everything around. Immune cells, red blood cells, and antigens. But B cells aren’t picky on antigens like T cells. It would be like a T cell only staying in a 5 star hotel and only eating from 5 star restaurants when traveling. Meanwhile, a B cells would stay in a motel and have Mcdonalds. So when it connects with an antigen, the virgin B cell turns into a normal B cell and starts to make copies of itself. Since sometimes the invasion of pathogens needs even more heavy weaponry. So a normal B cell can change into a plasma cell. A plasma cell wreaks havoc on pathogens as it can produce up to 2000 antibodies per second. For this to happen, the B cell needs to find a helper T cell to almost approved of this transformation.Since the B cell isn’t picky about antigens unlike a T cell, the B cell has to present the antigen in a MHC II molecule and presents it to the T cell. When the T cell recognizes the antigen, it gives the B cell “permission” to turn into a plasma cell. Now let's talk more about antibodies.

 

 

Antibodies like the complement system, its job is to assist the immune cells in killing pathogens. Antibodies are a clump of proteins that have two crab-like claws forking out on one end, and a roundish end on the other side. To make things let's call this a pincer. The crab claw is very good at connecting with the receptors of the specific pathogen they are hunting. While the roundish end is good at connecting with your immune cells. Specifically with bacteria, which are very slimy, it makes it easier for your immune cells to gobble up the bacteria. Now a problem that could be catastrophic, is if your immune cells just grab onto antibodies and are just floating around. So when an antibody attaches with its target, its roundish end changes so the immune cells know to grab on those antibodies. 

 

There are four classes of antibodies. (Technically there are five classes of antibodies, but IgD is not relevant to anything we are going to talk about.) The four classes of antibodies are IgM, IgG, IgA, and IgE. These all do different jobs, and a different number of those pincers attached to one another. For example IgM and IgE only have one pincer, but IgM has 5 pincers, with IgA having two. IgM is the most common and first antibody to be made. It’s quite effective as it can clump multiple pathogens together with its ten crab claws, and helps activate the complement system.  IgG is a specialist, and has many similarish but different jobs. It’s not as good as activating the complement system as IgM. So it’s good near the end of an attack. IgA is not very good against most pathogen invasion, but is present in other spots. Like the no go areas talked about before. This is to find pathogens in those areas as quickly as possible. Also it can’t activate the complement system. This may seem bad for attacks in those areas, but an activated complement system means inflation. And inflation in those areas is very very bad. IgE is the reason you will have an allergic shock or reaction. Why would your body do this? Well they are meant to fight parasites and worms, but do cause allergic reactions. Now how do your B cells and plasma cells know what antibody to make. Way back in the process when the dendritic cell takes the snapshot of the battlefield, this gives context on what antibodies to make. This information is then passed on to the T cell, and then to the B or plasma cell.

 

 

After the enemy is defeated, all of your immune cells start to kill themselves to save resources. To help disable inflation and the complement system, a variant of T cell called respiratory T cells is here to help. They release cytokines to help calm down the immune system. They also are present in the no go areas like the gut to stop things such as chronic inflation. To make sure that the enemy is no longer a threat, a few of your T cells, and B cells turn into memory cells. The memory T cells will patrol your lymph vessel looking for that specific antigen or enemy. And if they find traces of that enemy, they will activate your heavy weaponry in hours instead of days. As for your B cells, they will produce a low amount of antibodies that will attack that enemy if it ever sees it again.

 

Allergies are when your IgE antibodies think that the proteins on food or other substances matches with the proteins of parasites and worms. An analogy on how it could work is your IgE antibody is Darth Vader from Star Wars, and a peanut is a storm trooper. Darth Vader mistakes the storm trooper for Luke Skywalker and attacks the harmless storm trooper. This is what your IgE antibodies do to something like a peanut. It’s just your body making a silly mistake. It’s a thing that can happen from birth or develop later in life. They trigger mast cells, which is another immune cell meant to kill worms and parasites. Sometimes the mast cells can trigger other immune cells like macrophages which can trigger a way worse reaction from the immune system.

 

Infected cells can fall under either viruses that infected your cells, or cells that mutate into cancer. Cancer cells and cells infected by viruses both do different things, but are both cells that try to be undetected by your immune system to survive. So it’s like a spy hiding in enemy territory. For infected cells overall there are a few main ways to detect them. Viruses are a very weird enemy to deal with. Viruses are very basic, even more basic than cells. Because of this, some scientists think they are alive and some don’t. Either way, viruses enter a cell through its membrane ortlining, and try to get to the nucleus of the cell. The nucleus of the cell contains the DNA and RNA of the cell. This is what tells the cell what to do and when to do it. Viruses take advantage of this by taking over the nucleus of the cell and programming it to make thousands of new viruses. When the cell is filled to the brim with viruses it breaks open and the cycle repeats itself. Because of this viruses spend the majority of its time in a cell. And if a virus does not find a cell to infect and is caught by a macrophage it’s dealt with easily. As outside a cell, viruses are defenseless. Now to help your body slow down production of viruses, when a cell gets infected, it releases a special cytokine called inferons. This helps slow the production of viruses, and tells all surrounding cells to do the same 

 

Infected cells have a few main things they try to hide from the outside world, mainly MHC I molecules. MHC II molecules are used to present antigens to specific cells, MHC I molecules are used to display antigens inside a cell. And if a virus is inside a cell, the MHC I molecules display virus antigens. The cells that detect these infected cells are a killer T cell, and natural killer cells. Killer T cells are activated the same way as helper T cells through dendritic cells. They check if a cell has MHC I molecules displaying a virus antigen and if it doesn’t, then it orders the cell to kill itself through apoptosis. Then macrophages come in and eat up all the viruses, cleaning up the mess. 

 

 Now some infected cells and evolved viruses get smart and stop the production of MHC I molecules, to hide what they are doing inside. If there are no MHC I molecules on a cell's surface, your killer T cells can’t check what antigen it’s displaying, making it useless. This is where your natural killer cells come in. Natural killer cells don’t need to be activated by any sort of cell. They patrol your lymph vessels, and come to battle through cytokines from immune cells. They arrive 2-3 days after the attack. All they check for is if a cell is displaying MHC I molecules, and if it isn’t, it orders the cell to kill itself through apoptosis.

 

The other part of the infected cells is cancer cells. These act like infected cells but are more like mutated cells. They are made by our body, but like how immune cells in the adaptive immune system can vary on what enemy they have the weapon for, every cell also has the chance to mutate. For your immune cells with mutations they are killed by the thymus, bone marrow, and lymph nodes. Regular cells don’t go through that level of screening. So they can go into your body easier. Because of this you will always have a couple of mutated/cancer cells in your body. Sometimes the mutated cells aren’t killed by your killer T cells or natural killer cells, and they have the chance to reproduce. Now you have a clump of mutated cells. Every time they reproduce different mutations happen. Some are downgrades and some are huge upgrades. And cancer like skin cancer, which you can increase the chance of it happening, works because of these mutations. The suns radiant rays can damage the DNA and RNA of cells, making them easier to mutate.

Rarely will a mutated cell reproduce in to a super mutant. They are easier to hide from your immune system than others. After a couple of days of you having this clump of mutated cells, there are a couple thousand. The group of mutated cells is becoming a tumor. A small one but still a tumor. If you have one super mutant then it will likely reproduce into another super mutated, with and amount of super mutants in you body growing. At this point there are hundreds of thousands of mutated cells in the tumor, and you immune system knows it’s there. So out of the shadows the tumor is know just trying survive. It will order blood vessels to open up to feed the tumor. What your Immune system hopes to do is get rid of the supplies that are keeping the tumor alive. But this tactic takes time and time your body doesn't have if it close to your brain or vital organs. Here’s were chemotherapy has saved many lives. The drug targets the mutated cells ability to reproduce, killer off the tumor much faster than your bodies method. Then why are people still dying to cancer every day. If you catch the tumor when it’s only a couple thousand mutated cells, it’s much easier to kill than a tumor that has lots of super mutants and hundreds of thousands of mutated cells.

 

Question for expert: 

 

#1

Why are some people's immune systems weaker than others?

 

#2

What are things that people can do to strengthen their immune system?

 

#3

Why are there 4 different types of antibodies, instead of 1 that does it all?

 

1. Why are some people's immune systems weaker than others?

There are different reasons that a person's immune system can be weakened, and we divide these typically into two categories: Primary immunodeficiencies and Secondary Immunodeficiencies. Primary means that it is caused by a problem the patient is born with. This can include a lot of different genetic disorders where a person's body does not produce enough antibodies or immune cells. Some common examples would be XLA (X-linked agammaglobulinemia) or SCID (severe combined immune deficiency - this one is very severe and most children die very young because they don't have any functional immune system). Secondary immunodeficiencies are due to things that externally weaken a person's immune system, not due to genetic problems. Common examples are things like infections (AIDS is a disease caused by a virus that specifically kills people immune cells and they can't fight infections), medications (chemotherapy medicines make people's immune system's very weak. That's why people undergoing cancer treatment have to be very careful not to be around anyone that is sick) or things like severe eczema, where someone's skin doesn't block infections very well, and they can get infections through their skin. Things like lack of sleep and poor diet can also make someone's immune system weak, but not typically to the same degree as the above reasons. 

 

2. What are things that people can do to strengthen their immune system?

If a person has a primary immunodeficiency, we can do things like given them a medicine called IVIG, which is basically injecting them with antibodies if their body doesn't make it's own antibodies. We can also do stem cell transplants, where we replace a person's entire immune system (we do this for those children that have SCID and it makes them be able to live much longer). Things like eating well and sleeping well can also help people boost their immune systems. 

 

3. Why are there 4 different types of antibodies, instead of 1 that does it all?

Each antibody has a slightly different role, and there are actually 5 different types of antibodies, not 4, though IgD has very little role in the immune system and is not one we usually check in patients.

 

IgE is the one associated with allergies, and it's the one I mostly check in patients because if they have too much IgE, they're prone to eczema, asthma and allergies. 

 

Hope that helps! Good luck with the project!!

 

Alex

 

 

The immune system isn’t really a group of organs or micro organs that do the fighting, it's trillions of special immune cells. They are split into two different main groups. The innate and adaptive immune system. The innate side does all the fighting, though mainly the macrophages, and neutrophils. It also has other ways of fighting such as inflation and the complement system. Then if it gets too bad, a dendritic cell will come in and collect samples, and find the specific helper T cell that has the exact weapon for the pathogen. Then it goes to find the already partially activated B cells, and turns them into plasma cells. They produce antibodies, which can help clump together pathogens to be disposed of. If there are viruses or infected cells, then natural killer cells, and your killer T cells are here to help. The killer T cells check what antigens the MHC I molecules, and the natural killer cells check if they are displaying MHC I molecules at all. If they find anything bad, they order the cell to kill itself. Cancer cells are cells made by your body but they mutate. Some mutations don’t happen too much but some are super mutations. They can make tumors full of hundreds of thousands of mutated cells that often need cancer treatment like chemotherapy. Finally after the enemy is defeated, a respiratory T cell helps calm down things such as inflation and the complement system. A few of the cells won’t kill themselves, but will turn into memory cells. They will remember the enemy forever, keeping you immune.

 

The original question was: How does the immune system function, and how does it deal with unwanted guests? It turns out that it’s not like functioning organs that do most of it, it is quadrillions of cells, antibodies, and complement proteins. They work together to help slow down the enemy pathogens, to make more time for the cells that will dispose of them. It deals with the unwanted quest by eating them, throwing up acid, and little complement proteins rip holes in them till they die. Our hypothesis was way off, as we mainly thought the bone marrow controls all the immune system and it was white blood cells which then attack the enemy. This is true to some point, as the white blood cells do attack things in your bloodstream, but not in the other parts of the body. And organs like your lymph nodes and thymus make the immune cells.

Immune: A Journey Into The Mysterious System That Keeps You Alive: By Philipp Dettmer

 

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Fliedner, T. M., Graessle, D., Paulsen, C., & Reimers, K. (2002). Structure and function of bone marrow hematopoiesis: mechanisms of response to ionizing radiation exposure. Cancer Biotherapy & Radiopharmaceuticals, 17(4), 405–426. https://doi.org/10.1089/108497802760363204

Kono, H., & Rock, K. L. (2008). How dying cells alert the immune system to danger. Nature Reviews Immunology, 8(4), 279–289. https://doi.org/10.1038/nri2215

Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Innate Immunity. Nih.gov; Garland Science. https://www.ncbi.nlm.nih.gov/books/NBK26846/

Saldana, J. I. (2016). Macrophages | British Society for Immunology. Immunology.org. https://www.immunology.org/public-information/bitesized-immunology/cells/macrophages

Alex Lyttle, M.D., FRCPC who is a Pediatric Allergist and Immunologist

We would like to thank Dr. Alex Lyttle, M.D., FRCPC who is a Pediatric Allergist and Immunologist. He took the time to go over our list of questions on the immune system and he graciously answered them.