• Natalie Intven

How Vaccines Work

Exploring the vaccine response at a cellular level



THE IMMUNE SYSTEM: The body’s natural response to infection


To understand how vaccines work, it is important to first learn about our immune system. The human body has several layers of protection to ward against infection from harmful organisms. We have physical barriers such as skin, hair, and mucus that help to prevent foreign materials from entering the body. When those are bypassed, our immune system is ready to defend against the invaders. The body’s immune response involves many complex cellular defence mechanisms that work together to keep us healthy. When a body is infected with a new pathogen for the first time, the immune response sometimes requires more time than it takes for the infection to take hold, resulting in illness. Luckily, we can get better at fighting off some pathogens after initial exposure. Vaccines make use of this natural process to grant acquired immunity to specific infections, without ever getting sick.


THE INVADERS: Major villains on Team Infection



Pathogens are microorganisms, such as bacteria and viruses, that can cause disease in another organism.


Bacteria release toxins and damage cells, resulting in illness.


Viruses invade healthy host cells, then replicate themselves to infect more cells.


Antigens are a specific part of a pathogen that can be recognized as foreign and potentially dangerous, which triggers an immune response.



THE DEFENDERS: Major superheroes on Team Immunity


Antibodies are special Y-shaped proteins produced by our immune system that identify and neutralize specific antigens and signal other components of the immune system to respond.


B cells (or B lymphocytes) are a type of white blood cell that can detect pathogens, become activated, and then quickly clone themselves to produce specialized B cells and antibodies.


Plasma cells are a type of B cell that rapidly produce antibodies.


Memory B cells are a type of B cell that remember past infections and are able to trigger an accelerated immune response when encountering that particular antigen again.


T cells (or T lymphocytes) are another type of white blood cell that become activated when an antigen is presented to them. Special types of T cells include helper T cells and cytotoxic T cells.


Helper T cells recruit other parts of the immune system, including B cells, cytotoxic T cells, and macrophages by stimulating them with signalling molecules called cytokines.


Cytotoxic T cells (or killer T cells) attack body cells that have already been infected.


Dendritic cells are a type of antigen-presenting cell, or APC. They ingest pathogens, break them down, and then present antigen materials to T cells, enabling T cell activation.


Macrophages are a type of white blood cell that can surround and digest microorganisms and dead cells.


 

THE FIRST BATTLE: Invaders Vs. Defenders in the primary immune response



  1. INFECTION: A new pathogen, such as a virus, enters the body through the mouth, nose, eyes, or a cut in the skin.

  2. RECOGNITION: The pathogen is detected by B cells and T cells (with the help of dendritic cells), which begins the immune response.

  3. RESPONSE: Helper T cells help to activate B cells using cytokines as chemical messengers. Activated B cells rapidly multiply to produce an army of plasma cells that manufacture and release antibodies specific to the new pathogen.

  4. TAGGING: These antibodies bind to the antigens (parts of the pathogen), neutralizing the antigens and tagging the pathogens for destruction.

  5. DESTRUCTION: Infected body cells are destroyed by cytotoxic T cells, extinguishing reservoirs of infection, and preventing them from manufacturing more pathogens. Pathogens tagged by antibodies are now easily recognized and destroyed, either digested by macrophages or killed by other processes that rupture their membrane.

  6. MEMORY: Activated B cells also produce long-living memory B cells.

  7. ADAPTIVE IMMUNITY: During a second exposure to the same pathogen, memory B cells will be able to respond much more quickly compared to initial exposure, resulting in the rapid production of many specific antibodies, and swift destruction of the invading pathogen. This “immunologic memory” is part of adaptive immunity, which allows vaccines to be effective.

 

UNDERSTANDING VACCINES: Preparing our immune system warriors for a future battle


Vaccines prepare the immune system to effectively fight against specific pathogens, without direct exposure to the entire disease-causing particle. Vaccines make use of our body’s natural processes by introducing a specific particle to induce an immune response. As we learned above, this response includes creating a “memory” (via memory B cells), so that the next time our body encounters this same pathogen, we can fight it off quickly and effectively before the infection causes illness.


TYPES OF VACCINES


There are several different types of vaccines. The key particle that the vaccine introduces can be (1) a weakened version of the whole pathogen, (2) a small inactive part of the pathogen like a membrane spike protein, or (3) a blueprint that uses the body’s cells to produce an antigen which the immune system can then identify and attack. These vaccine components do not cause the disease that the live pathogen would. However, they can still trigger the immune system to recognize, destroy, and remember the pathogen in case of future infection.



  1. Whole microbe → Example: Live Attenuated Vaccine This approach uses a weakened form of the virus that can not produce the illness, but will induce a similar immune response. Common examples include the MMR and chickenpox vaccines.

  2. Subunit → Example: Protein subunit vaccines This type of vaccine uses small components of the pathogen (such as a protein from the membrane) to cause an immune response. An example of this type is the Hepatitis B vaccine.

  3. Genetic material → Example: mRNA vaccines This method uses a piece of genetic material that serves as a blueprint for one small part of the pathogen. Messenger RNA (mRNA) carries the instructions that our cells use to build specific proteins. mRNA vaccines deliver this genetic information into the muscle tissue at the injection site. Body cells accept the mRNA into their cytoplasm, and can then manufacture the specific protein required to generate an immune response. The mRNA from the vaccine never enters the nucleus of the cell, and does not change the cell’s own DNA. Shortly after the mRNA is translated to build proteins, it is broken down and destroyed. All of this occurs without ever encountering the whole disease-causing virus. The COVID-19 mRNA vaccines fall into this category.

 

TRAINING THE IMMUNE SYSTEM: Vaccine response


Vaccines prepare the immune system for the real battle, without the same threat of infection and illness. Let’s take a look at an example of how the body responds to the COVID-19 mRNA vaccine.



  1. VACCINATION: The COVID-19 mRNA vaccine is administered into the recipient’s muscle. In the cytoplasm of the body cells, the genetic instructions from the mRNA are translated to build the SARS-CoV-2 spike protein. These spike proteins are then expressed on the surface of the body cells, where they can be detected by the cells of the immune system. The mRNA from the vaccine is subsequently destroyed and is no longer functional.

  2. RECOGNITION: The spike protein (antigen) is recognized by B cells and T cells as new and potentially dangerous.

  3. RESPONSE: The immune cells works together to quickly produce a large number of antibodies specific to that antigen.

  4. TAGGING: Antibodies attach to the spike proteins on the surface of body cells.

  5. DESTRUCTION: The cells with spike proteins are destroyed by cytotoxic T cells and macrophages.

  6. MEMORY: Memory B cells remember how to quickly produce specific antibodies the next time this same antigen (the spike protein) appears. This vaccine response takes about 2 weeks to be effective.

  7. ADAPTIVE IMMUNITY: If this antigen is encountered again in the future (as part of the SARS-CoV-2 virus), the immune system will be ready to mount a fast and effective immune response, preventing the virus from infecting more cells and causing serious illness.

 

THE POST-VACCINE IMMUNITY CHALLENGE: Secondary immune response


When a specific pathogen is re-introduced to the body after a vaccine has been administered and given enough time to work, the immune system response is much faster and stronger than it would have been the first time this pathogen was encountered. The body already has some residual antibodies available to neutralize and tag the invading pathogen for destruction. Memory B cells spring into action, making more plasma cells that manufacture even more antibodies. The invading pathogen is quickly recognized and destroyed, without having the chance to multiply enough to cause severe illness. After a secondary immune response, antibody concentrations can remain elevated for an extended period of time.



Because the immune response is time-sensitive, we sometimes require more than one dose of a vaccine in order to keep our immune systems equipped with sufficient antibodies and memory cells for long-term immunity. Booster shots ensure that the immune system is ready for a call to action at any time.


Vaccines provide protection for the person who is vaccinated, as well as those around them since vaccinated people are less likely to become ill and pass it on. Vaccines are not always 100% effective, but they do provide our bodies with the best chance possible for quickly defending against common dangerous infections.


 

Learn more


Vaccines explained: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines/explainers


Immune response to vaccination: https://www.labxchange.org/library/items/lb:LabXchange:6f1b3ece:lx_simulation:1


How vaccines work against SARS-CoV-2: https://ici.radio-canada.ca/info/2021/03/vaccination-variants-covid-19-arn-pfizer-moderna-spicule-infection-immunite/en


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