Have you ever wondered why we get fevers when we’re down with the flu? The immune system is a highly complex and efficient system of cells that carry out specific processes at a molecular level. Each one of these processes relies on another, working 24/7 to keep you feeling fine. This also means that when something goes wrong, the fragility of the entire system can be exposed. We explore the workings of our immune systems by zooming 1000x into our micro security detail – you’d need an electron microscope to count your bodyguards!
The Immune System
The role of the immune system is to protect us from ‘bad stuff’ or pathogens: viruses, bacteria, and even our own cells gone rogue. These pathogens are also known as antigens if our immune cells are able to ‘recognize’ them and trigger a response – such as the production of chemicals to destroy them. Antigens are recognized by antibodies, basically molecular puzzle pieces that immune cells poke around with until it finds something that fits its shape – then destroys it1.
There are two kinds of immunity: innate and adaptive. As the name implies, we are already born with innate immunity. It consists of a range of defenses: physical barriers like our skin, chemicals in our blood and also certain cells in the immune system. These processes are quick to activate but lack specificity; inflammation is one such process, where chemicals released by injured cells trigger a string of responses that causes redness, pain, and even fever.
Adaptive immunity is built up over time and ‘learns’ how to defend the body against antigens by working with the innate immune system. By uniquely identifying antigens when they are first discovered, they are able to produces specific antibodies that serve as ‘memory’ so that in the future it is quickly be recognized and destroyed. This is the reason why many illnesses (like measles) only occur once in a person’s life2.
Zooming into our Micro-Casino
Let’s put our security detail to good use by deploying them at a casino; like our immune system consists of many cells that have specific tasks to fulfill, so too does a casino’s security department. Yeah, they should do well here.
When a person is suspected of cheating or illegal entry, bouncers are the first on the scene, quickly apprehending the suspect. In the body our ‘bouncers’ are cells from the innate immune system that are quick to jump on anything suspicious and destroy them. Sometimes however, these suspects are just innocent patrons who got lucky a few times, and similarly the innate immune system might incorrectly trigger responses to harmless foreign particles (think allergies and asthma).
Because the bouncers might be unsure if a suspect is actually cheating, some of them might choose to call the higher-ups in security who can better decide on how to deal with them. In the body the cellular equivalent of these bouncers are dendritic cells, serving as a link between the innate and adaptive immune system. They can engulf and transport the suspected antigen to specialized cells known as lymphocytes – B cells or T cells – that can then differentiate to deal with the threat appropriately.
They do this by expressing the antigen (or part of it) on their membranes, allowing them to specifically target and inactivate the antigen. In general the difference between B and T cells is that B cells attack and inactivate an antigen directly, whereas T cells target host cells that have already been infected.
In reality there are a range of subgroups that work together to form the adaptive immune system; an important subgroup are the T helper cells, that are responsible for immunological ‘memory’. They are kept in the body for an extended period of time so that a returning antigen can be identified and destroyed much more quickly – cheaters are marked with a life-long house ban3,4.
But Does The House Always Win?
While we have many layers of security, due to the complexity of the system a small slip-up can have a massive impact on our body; pathogens constantly develop ingenious ways to ‘trick’ our immune systems so that they can slip past undetected or delay our immune responses long enough to wreak havoc.
Herpesviridae are one such class of viruses that tend to infect a host for life by hiding out in the cells of the nervous system. By doing this, the immune system is unable to rid the body of the virus and proliferation can be re-activated in the future by stress or hormonal fluctuations5. These are known as latent infections and viruses from this family include the Epstein-Barr virus and the herpes simplex virus.
One family of viruses that has gained notoriety for its ability to upset the balance of the immune system is the human immunodeficiency virus – HIV. An estimated 36.9 million people around the world are infected, with the resulting acquired immune deficiency syndrome (AIDS) claiming around one million lives per year6.
Viruses require host cells to carry out replication as they lack the machinery required for protein synthesis. However instead of hijacking the protein machinery of regular cells and risk getting caught, HIV attacks and enters specific cells that are key parts of the immune system itself – such as T helper cells and dendritic cells. The virus inserts its own genome into the cell protein machinery by reverse-transcription and releases the copies, killing the host cell in the process7.
Naturally, the number of immune system cells starts to drastically decrease, leading to compromised immunity. If left untreated, it typically results in full blown AIDS after 8-10 years. The immune system therefore doesn’t work the way it should and cannot protect the body against antigens; even the common cold can be a deadly threat 8.
An extremely quick replication cycle and a high chance of genome recombination combined with the enzyme in charge – reverse transcriptase – being rather error prone, means there is constant mutation of HIV’s protein structure. This makes it nearly impossible for our body to develop an effective immune response against it.
Our immune cells sometimes get too eager to take down threats and falsely recognize its fellow tissue cells as antigens. This results in autoimmune diseases, with symptoms and consequences that vary broadly. The root cause for this system failure has not been identified yet, but it’s thought to be connected to both genetic and external factors; certain interactions with antigens can also trigger an autoimmune response 9, 10.
What Doesn’t Kill You Makes You Stronger
The best way to strengthen our immune system is to present it with as many antigens as possible – after all, our bodies are designed as such. Exposure to bacteria, viruses and foreign particles allows the adaptive immune system to build up its ‘memory’, granting life-long immunity against these antigens. Studies have found that early age exposure to antigens lowers the chances of an individual developing allergies later in life11.
When an antigen is encountered, the process of developing adaptive immunity might take days or even weeks! Tuberculosis is one such example of a disease with a delayed immune response of up to 6 weeks12. This period of time allows for nasty symptoms to leave irreversible damage to the body or even overwhelm our immune system to the point of failure.
Vaccination works by priming the body for high-risk antigens so that if and when we are infected, we are granted ‘immunity’ by having our immune system’s response time reduced. They may contain antibodies (passive immunity) – usually produced by B cells – that target the pathogen directly, destroying it. Vaccines can also take the form of a small amount of a dead or inactivated antigen presented to our lymphocytes, so that they induce ‘memory’ the same way an actual antigen might (active immunity).
Vaccines have always been a hot topic in society, as well as the cause for controversy in the news and on social media. There is overwhelming evidence that vaccines have helped to drive certain diseases to the point of extinction – diseases that no doubt would have affect the lives of millions of people. One outstanding case study on the efficacy of vaccines is that of smallpox, that went from 50 million new infections every year to 0 in the span of 50 years (1948-1996), effectively eradicating the disease12,13.
So make sure you’re vaccinated! It’s the least you could do to help out your immune system that’s already fighting millions of pathogens on a daily basis.
- IQWiG (Institute for Quality and Efficiency in Health Care) (2016). How does the immune system work?
- Janeway CA Jr, Travers P, Walport M, et al. Immunobiology (2001). The Immune System in Health and Disease. 5th edition. New York: Garland Science. The course of the adaptive response to infection.
- Janeway CA Jr, Travers P, Walport M, et al. Immunobiology (2001). The Immune System in Health and Disease. 5th edition. New York: Garland Science. The components of the immune system.
- Janeway CA Jr, Travers P, Walport M, et al. Immunobiology (2001). The Immune System in Health and Disease. 5th edition. New York: Garland Science. Immunological memory.
- Arvin A, Campadelli-Fiume G, Mocarski E, et al., editors (2007). Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Cambridge: Cambridge University Press. Chapter 26.
- UNAIDS (2018): Global HIV & AIDS statistics — 2018 fact sheet.
- Cummins, N. W., & Badley, A. D. (2014). Making sense of how HIV kills infected CD4 T cells: implications for HIV cure. Molecular and Cellular Therapies, 2, 20.
- IARC Working Group on the Evaluation of Carcinogenic Risk to Humans (1996). Human Immunodeficiency Viruses and Human T-Cell Lymphotropic Viruses. Lyon (FR). International Agency for Research on Cancer. (IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, No. 67.) 1, Exposure Data.
- Arango MT, Shoenfeld Y, Cervera R, et al. Infection and autoimmune diseases. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors (2013). Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press. Chapter 19.
- National Institute of Environmental Health Sciences (2018). Autoimmune Diseases.
- Graham A W Rook, Laura Rosa Brunet (2014). Give us this day our Daily Germs. Royal Free and University College Medical School, London, UK.
- Urdahl, K. (2015) Understanding the Immune Response to M. tuberculosis. Nature Education 8(3):6
- Unicef (1996). Vaccines bring 7 diseases under control.
- World Health Organization: Bugs, drugs and smoke (2011). stories from public health. Chapter 1