So far, we’ve discussed the historical legacy of vaccines as man-made enhancements for our existing immune weaponry. And we’ve taken a look at some of the extensive defenses of the innate immune system that guard us day and night from the billions of natural viruses and bacteria roaming the earth. But like any fortress, there are vulnerabilities to be exploited. One way or another, pathogens can occasionally slip through and start using the body’s resources to replicate and cause major damage. In these cases, the immune system has to switch tactics from defensive to offensive. The first step is raising the alarm, often causing fever, inflammation, and congestion. These symptoms may seem awful at the time (and they can be deadly if they are too severe or long-lasting), but they also increase the speed and efficacy of your immune fighters and destroy some of the heat-sensitive pathogens. When the bells are rung, and the fortress is in flames, it’s time to call in the cavalry.
When the numerous, varied defenses of innate immunity fail to keep out the encroaching viral horde, the immune system switches to a more targeted offensive strategy. The adaptive immune system is composed of comparatively fewer types of cells and molecules. Where innate immunity is a brute tactic, adaptive immunity is precise and deadly. The system is mainly composed of B cells and T cells that use a specialized set of weapons called antibodies to destroy pathogens and infected cells. Because this system relies on the development and deployment of these specialized antibodies, it can take days or weeks before the immune system has the forces necessary to destroy all of the pathogens in the body. In the meantime, the innate immune defenses continue to utilize brute tactics like fever and inflammation to buy the immune system time and minimize the damage caused by infection. But if the adaptive immune system doesn’t rein in the infection quickly, these brute strategies can actually cause significant damage to the body—potentially leading to death.
B cells are born and bred in the bone marrow, possessing all the tools to fight pathogens without the appropriate specialized training. These untrained immune fighters are referred to as naïve B cells. Naïve B cells are covered in an array of antibodies that can bind to and recognize different antigens—the molecules of a pathogen that the immune system recognizes as foreign, like the wrong coat of arms on the chest plate of an invading soldier. Once an invading pathogen is identified, the naïve B cell matures and divides creating a specialized army to take that pathogen down. A subsection of this army becomes plasma cells—specialized B cells that release up to two thousand pathogen-specific antibodies per second into the bloodstream. These antibodies travel throughout the body, searching for more antigens to bind to and recognize. Antibodies latch onto free-floating pathogens—blocking them from infecting cells, clumping them together, and acting as a flare for nearby phagocytic cells. These antibodies restrain the pathogens long enough for the phagocytic cells to come in and execute them.
The antibodies churned out by the immune system are fairly effective at finding and marking pathogens, toxins, and other harmful molecules floating in the fluids of the body. But, once a pathogen enters a cell and begins infecting it, the antibodies can no longer stop it. As the cell becomes infected and its machinery gets hijacked, it starts signaling its surrender by presenting a chemical white flag that activates T cells. T cells are created in the bone marrow, but they mature in the thymus where they differentiate into different types of immune soldiers. These T cells are still considered naïve T cells until they encounter foreign antigens. Naïve T cells, like naïve B cells, are covered with different types of receptors, but they cannot recognize free-floating antigens. Instead, they only bind to antigens that are attached to Major Histocompatibility Complex (MHC) molecules presented on the outside of cells. MHC molecules are bits of protein that stick out of a cell and identify the cell as part of your body (this is also why transplants can be so difficult—your immune system can be fairly xenophobic).
Any body cell that is sick or infected can attach antigenic proteins to their MHC molecules, signaling to nearby T cells that they need to be killed. But to stimulate a full-fledged immune response, a naïve T cell needs to bind to an MHC-antigen complex on the outside of one of the innate immunity soldiers. When the phagocytic cells of the innate immune system consume and destroy a pathogen, they also take some of the protein from that pathogen and present it on the end of their special MHC molecules. This signals to the naïve T cells that the body is at war. They quickly mature and differentiate into a host of different fighters. Cytotoxic T cells are the main killers, identifying those infected cells with MHC-antigen complexes and triggering cell death before the infection can spread. Meanwhile, the helper T cells coordinate the entire immune attack, the commanders and generals of the adaptive immune response. They release cytokines that activate immune cells across the body, stimulate antibody production, and promote inflammation and fever. There are also some regulatory T cells to stop the activated T cells from running rampant and attacking your own cells (the basis of auto-immune disorders). All together, T cells and B cells work together to mount a coordinated attack against the invading pathogens and eliminate them from your body.
Like I said earlier in the post, the active immune response can require days or even weeks to identify and eliminate a novel invader. In that time, the innate immune system can wreak some serious havoc on your body as it tries to keep the pathogen at bay. This is essentially why you get sick when you encounter a disease for the first time—you’re lacking the antibodies needed to combat the pathogen and manufacturing them from scratch takes time. As a baby, for a very brief period of time, you have free-floating antibodies acquired from your mother that protect you from disease. But, by themselves, antibodies degrade, leaving your immune system vulnerable and unprepared. As you get exposed to new diseases though, you gain a new type of long-lasting immunity facilitated by your adaptive immune system.
In the process of mounting an immune attack, a subset of both B and T cells form specialized memory cells. Memory B cells cover themselves in the specific antibodies that recognize the pathogen. If they ever encounter the same pathogen again, they can quickly convert to mature plasma cells that release antibodies to stop an infection in its tracks. Similarly, memory T cells are primed to recognize and react to a second infection by the same pathogen, producing helper T cells, cytotoxic T cells, and regulatory T cells to eliminate infected cells and coordinate an immune response. Depending on the pathogen, this immunity can last your entire life following a single infection. Other pathogens may require multiple infections before long-lasting immunity is achieved. Of course, immunity is only really helpful if you survive the infection, which is where inoculation comes in. Exposing your body to a weakened, dead, or incomplete pathogen gives it the chance to essentially train and practice for specific opponents. It’s the difference between training specialized knights to defend your fortress versus leaving the defense to a bunch of 14-year-old boys in ill-fitting armor. The untrained immune system may still be equipped to fight off mild diseases, like the flu, but it could be easily overtaken by more aggressive or resilient pathogens. Vaccines can provide a safe and effective training ground to prepare the immune system for a future battle.
Next week, in the final post of this series, we are going to discuss some of the complicated science behind the new Covid-19 vaccines and how they help train the immune system for our new common foe. In the meantime, check out my blog post on vaccines from last spring and last month’s series on influential women in science! Comment on this post or email me at contact@anyonecanscience.com to let me know what you think about this week’s blog post and tell me what sorts of topics you want me to cover in the future. And subscribe below for weekly science posts sent straight to your email!
