Vaccine refusal, a global flu pandemic, and antimicrobial resistance are 3 of the top 10 threats to global health in 2019 listed by the World Health Organization. Widespread knowledge about evidence/myths related to these threats is critical. Members of TheSciCommunity (@thescicommunity on IG) teamed up to help raise awareness about immune system and virus mechanisms.
The immune system is very complex. Its main job is to protect you from invaders, like viruses, bacteria, and allergens. Evidence suggests that there are two subsystems that work on different levels. The image above shows key cells within each subsystem but is not a complete list (for example, dendritic cells are also an important cell type).
The innate subsystem acts as a general and first line of defense. It includes your skin, mucosal linings, immune cells, and their
production sites. There are several ways this subsystem protects you from invaders: 1) acts as barriers to prevent invaders from entering your body, 2) detects intruders, 3) removes/kills intruders, and 4) alerts the adaptive subsystem.
The adaptive subsystem provides specialized defenses that are molded over time. The cells in this system learn from invaders you come into contact with (like cold or flu viruses) to create specific antibodies that remain in your body. These antibodies provide quick protection from the same invader in the future. The main cells of this system are T and B Cells, but evidence suggests that natural killer cells also have adaptive functions.
When all goes well, symptoms signaling that your immune system is fighting the invader stop after a reasonable time span. Some people, however, have immune dysregulation via very weak/absent responses (i.e., immunodeficiency) or erroneous attacks on healthy cells (i.e., autoimmunity), which can be life-threatening and/or impact quality of life.
How do Viruses Work?
Viruses cause illnesses in humans, animals, plants, and even bacteria! Did you know that 8% of our genome is estimated to be of viral origin? One virus particle, or virion, consists of a genome and a protein protective layer (capsid). Some viruses have extra lipid and protein layers, which either provide more protection or help in getting inside cells. A virus’s purpose is to replicate: to produce new virus particles. Because most viruses are quite simple, and don’t encode many genes, they need a host cell’s ribosomes and replication machinery to assemble new viruses.
Viruses cause problems for the host cell they infect. Sometimes they will completely shut-down the operations of the host cell, and turn it into a virus factory. Eventually the cell will die or be killed.
Flu is caused by Influenza virus, and colds by rhinovirus, coronavirus, and several others. But what happens when an influenza virion gets inside you and meets one of your cells?
The virus enters the cell by endocytosis having bound to sialic acid (1). The low pH of the endosome triggers the virus membrane to fuse to the endosome, and
the genome is released into the cytoplasm. In the case of influenza virus, the genome consists of several single-stranded segments of negative stranded RNA, in complex with “ribonucleoproteins”. These proteins have signals on them which target them to the nucleus (2) where replication occurs. A viral RNA polymerase is also bound to the genome, which carries out transcription and replication of the viral RNA genome (3). Once new copies of the viral genome and viral proteins have been made, new viruses can assemble on the inside of the cell membrane, and begin to bud off the membrane (4), where they are then free to infect other cells.
During recent outbreaks of bird flu you may have heard of the drugs oseltamivir/Tamiflu or zanamivir/Relenza: these molecules mimic sialic acid, and so inhibit a viral neuraminidase enzyme responsible for cleaving virions from the membrane at this final step.
Have you ever found yourself competing with someone only to find out that no matter how hard you try they're always at the same level as you? Have you ever felt like you were constantly pushing yourself to improve just to keep up with those around you? If so you may have more in common with viruses and your immune system than you know.
This phenomenon of constantly improving just to keep up is known as the "Red Queen Effect" or the "Red Queen Hypothesis" named after a scene from the book Alice, Through the Looking Glass (a sequel to the popular children's story Alice's Adventures in Wonderland) where the Red Queen tells Alice that "it takes all the running you can do just to stay in the same place."In terms of evolutionary biology, we apply this concept to describe the arms race between two competing
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organisms. For instance, the competition between viruses to control your body and your immune system to keep you protected. Both, team virus and team immune system, are constantly "running-as-fast-as-they-can" in order to evolve new ways to beat each other. An example of this is how our cells evolved to kill themselves when they notice a virus has gotten in to them in order to protect other cells from getting infected. However viruses are also evolving to get around these defenses and have developed proteins that can block the cell from shutting itself down.
The virus and cells are in a constant race to beat each other because the second one of them slows down that can mean death and total annihilation by the other! Currently, our bodies have come up with a pretty great defense in this war against against viruses called our immune system. Our immune system produces proteins called antibodies which can recognize and block viruses even before they can get into our cells!
But true to that good ol' Red Queen Hypothesis, the viruses are right behind coming up with new tactics to evade our defenses. Viruses like the flu virus (influenza A) have the ability to rapidly create viruses with a bunch of different outside proteins (called glycoproteins) which can make it hard for our antibodies to recognize and eliminate them. This is why it is so important to get the new flu vaccine each year.
In order to understand the importance of vaccines, we first needed to understand what the immune system is and how it works at
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defending us against harmful pathogens.
What is a vaccine? A vaccine is primarily composed of an agent that resembles a disease-causing microorganism, known as an antigen. This often comes in the form of the killed or weakened form of the particular pathogen. Here is where some misconceptions start: although YES- you are being injected with components of a pathogen, NO- you will not get infected by this pathogen upon vaccination.
How does a vaccine work? When the body comes into contact with a particular pathogen, it begin making antibodies in response to the “foreign” invaders, and tags them for destruction. The best part is – these antibodies remain in our body
forever and provide quick recognition and destruction of certain pathogens when you come into contact with them later in life.
This immune memory (provided by vaccinations) not only allows an individual to quickly fight off an infection later in life, but it also lessens the likelihood that a pathogen will be passed on to other individuals. This is exactly where the idea of “safety in numbers” comes in. For example, polio - a paralyzing disease - has been completely eliminated from North America thanks to the polio vaccine.
However, more people are recently choosing not to vaccinate their children due to widespread myths (like the fallacy that vaccines cause autism – for a review, check out this link). If this trend continues, there is a higher the likelihood that vaccine-preventable diseases will persist in communities and viruses will continue to evolve and adapt. Even more unfortunate, the individuals who are most likely to be negatively affected are those with weaker immune systems, like the elderly, or people with immune deficiency like HIV, or children/youth.
Bacteria are neat little “boxes”- on the outside there is a cell wall and on the inside are all the cogs that keep it working: its genetic material and proteins. Antibiotics are designed to work on specific parts of the bacteria- either by attacking the cell wall (for example, penicillins and many other similar types of antibiotic), or the different proteins/protein machinery within the bacterial cell.
The thing is, viruses have different structures- in particular, they don’t have the cell walls that most of our effective antibiotics work on. So trying to treat your cold with antibiotics does nothing to the virus causing it. As with any drug, the effort to make antibiotics is a battle between targeting the right thing (ie, bacteria) without damaging any potentially similar proteins that your body makes (that’s why the cell wall is such a popular target- it’s only in bacteria, not humans nor viruses). But antibiotics are safe, right?
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Mostly yes, and if needed they can be life saving. However, it’s important to remember two things: 1, all drugs have side effects (if you don’t need the drug, why take even the smallest risk of potential damage?); and 2, unnecessary use of antibiotics increases the risk of any partially killed bacteria fighting back and becoming resistant to antibiotics, and 3, many of the bacteria in your body are your “friends on the inside.” Studies on the human microbiome (the community of bacteria and other organisms that live and work happily with your body) have shown that negatively changing the precious balance of good bacteria in and on your body can put people at risk of not just infection, but other diseases like diabetes, asthma, even auto-immune diseases.
So, next time you get a cold, spare a thought for all your good bacteria and don’t be surprised if your doctor wants to save them- unless your doctor thinks you have signs of an additional bacterial infection, you don’t need, and shouldn’t want, antibiotics.
 Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. The innate and adaptive immune systems. 2010 Dec 7 [Updated 2016 Aug 4]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279396/
 Tosi MF. Innate immune responses to infection. The Journal of Allergy and Clinical Immunology. 2005;116(2):241-249.
 Vivier, E., Raulet, D. H., Moretta, A., Caligiuri, M. A., Zitvogel, L., Lanier, L. L., Yokoyama, W. M., … Ugolini, S. (2011). Innate or adaptive immunity? The example of natural killer cells. Science (New York, N.Y.), 331(6013), 44-9.
 US NIH: Immune System and Disorders