For most of history and the long origin story of vaccines, we have known very little about the mechanics of how bodies defend against disease. The practice of variolation—purposefully exposing individuals to dried infected material to stimulate immunity—was borne out of the simple observation that people who survive sickness don’t tend to get sick again. The science of immunity didn’t really fall under much scientific scrutiny until the 19th century after Edward Jenner made his pivotal cowpox/smallpox vaccine discovery. Cowpox and smallpox were clearly different diseases with differences in severity, animal host, and mode of transmission. But, despite these differences, the body appeared to treat them as if they were the same illness. This simple observation provided a valuable basis for both the germ theory of disease—the idea that diseases are caused and transmitted by microorganisms—and the field of immunology. The immune system has turned out to be one of the most complex physiological systems we have—one we still don’t fully understand today. It’s an adaptive and coordinated band of cellular soldiers engaged in an invisible war that has waged since life began.
The immune system has two main strategies for defending you against foreign invaders: innate immunity and adaptive immunity. Innate immunity, the type of immunity you are born with, is a primarily defensive strategy. Much like the walls and defenses of a castle fortress, the purpose of the innate immune system is to keep foreign invaders from breaching the walls at any cost. The first lines of defense are the physical barriers—the walls and moats that make entry more difficult combined with lookouts and guards that cut down individual invaders. In the body, the skin acts as a physical barrier for most pathogens, and those pathogens that do get through the mouth or nose get trapped in sticky mucus, digested by the enzymes in saliva, or torn up by caustic stomach acid. These physical defenses can be highly effective, keeping out the majority of bacteria and viruses you come in contact with daily. But even the best defenses can fail—the barrier of skin can be breached by a cut or scrape or a particular virus can evolve to slip past the guards in the nose and mouth. This is when the more active defenses start to kick in.
In a siege, many different lines of offensive defense are deployed—archers rain arrows from above, vats of tar are poured over combatants and lit on fire, soldiers are spread over the ramparts and inner courtyards to fight off anyone who makes it past the first defenses. In the body under siege, the coordinated system of defensive attack involves a complex network of immune cells, signal molecules, and localized inflammation. Say for instance you slice your hand open trying to cut a cardboard box (something that has happened to me). The moment the wound opens, thousands of bacteria and viruses rush into it, and the first line of defense your body has is an inflammatory response.
The surviving skin cells around the wound start the defense by raising a chemical alarm—like bells used in a fortress to warn of an attack. This chemical alarm comes in the form of chemokines released into the fluid beneath the skin. These chemokines act as messengers that warn many different systems of the ongoing attack. One such system is the network of mast cells sitting just below the skin, which can be triggered by cytokines and other stimuli into releasing another chemical messenger—histamine. Histamine is an important player in the inflammatory response. It stimulates vasodilation—the swelling of capillaries beneath a wound that causes blood to pool and allows various proteins and cells to move into the cut from the bloodstream (and vice versa). This localized swelling of the capillaries helps the chemokines to move into the bloodstream, where they recruit the host of soldiers and archers of the immune system to mount a defense.
There are multiple different types of phagocytic cells in the immune system whose main job is to eat and kill foreign pathogens indiscriminately (a pretty brutal warfare tactic if you ask me). These soldier cells slip through the new gaps in the capillaries into the battlefield surrounding the wound. Macrophages, neutrophils, and dendritic cells are some of the main immune system soldiers, each with their own skills and modes of attack. Another type of cell called the natural killer cell traverses the battlefield looking for human cells that have already been infected and triggering them to commit suicide. Imagine a fortress physician whose job is to pass out poison to wounded soldiers so they won’t be taken prisoner by the foreign enemy (another brutal strategy).
In most cases, this initial defense is enough to stave off invasion long enough for the wound to clot and scab over, preventing further invasion (I suddenly feel terrible for picking at scabs—how many noble soldier cells have given their lives for my recklessness?) The remaining pathogens are picked off by phagocytes, and the localized heat caused by the histamine-triggered swelling helps the skin cells repair faster and form a more permanent barrier. But, in some cases, the defenses of the innate immune system are not enough, the phagocytes are overrun, and the pathogens move in to sack the fortress. In this case, the overwhelmed soldier cells send out new chemical alarms called pyrogens that travel to the body’s thermostat—the hypothalamus—and relay the order to burn everything. The hypothalamus raises the body’s temperature, resulting in a fever that speeds up healing and kills off some of the pathogens. Fever can also buy the body more time to mount a more specialized and deadly offense against the pathogens through adaptive immunity. The fortress is overrun by foreign invaders and engulfed by flame—it’s time to call in the cavalry.
We’ll discuss the complex system of adaptive immunity in more detail next week before we dive into how these new vaccines operate. 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!
