In this blog post, we will look at how the scientific principles of immunity were discovered, focusing on historical experiments and discoveries.
The concept of immunity, or the human body’s resistance to certain diseases, has been known for many years through empirical observation. In particular, during times when infectious diseases were prevalent, it was noticed early on that people who directly nursed patients with those diseases or handled their bodies did not become infected with the same disease again, or if they did, they only showed relatively mild symptoms. This phenomenon was an important clue suggesting that these people had acquired a certain level of “immunity” to the pathogen.
However, these intuitive and empirical observations alone were not sufficient to scientifically explain the nature and mechanism of the immune response. Until the mid-19th century, there was little experimental basis for a scientific understanding of the characteristics and mechanisms of immunity, and little was known about the specific biological factors and response pathways involved in immunity. Above all, at that time, the pathogenic microorganisms that cause disease had not yet been clearly identified, and there was no way to artificially induce an immune response, so immunology remained stagnant for a long time without a scientific framework.
The person who brought about a turning point in this situation was Louis Pasteur. In the late 19th century, he discovered the existence of pathogenic microorganisms and experimentally proved the concept that they could be manipulated to prevent disease. Pasteur developed the concept of “vaccination,” which induces an immune response without causing disease by weakening the pathogenicity of pathogens and injecting them into individuals.
One of his most famous experiments was his research on avian cholera bacteria. Pasteur injected chickens with cholera bacteria that had been left in a culture medium for a long time, thereby weakening their pathogenicity. As a result, the chickens temporarily showed symptoms of cholera, but most of them did not die, and even when they were injected with highly pathogenic cholera bacteria again, they did not contract the disease.
Through this experiment, Pasteur clearly demonstrated that pathogens can induce an immune response within an individual, which led to the establishment of artificial immune induction methods, or vaccines. However, Pasteur’s experiments only revealed that pathogens induce immunity, leaving questions about the physiological or molecular mechanisms behind immune responses.
In other words, a precise understanding of how immunity works and the components involved remained a challenge for the future.
These questions began to be answered one by one through subsequent research. Scientists later discovered that the production of antibodies against specific components of pathogens, called antigens, is the key to immunity. Antibodies recognize and bind to toxins produced by pathogens or the pathogens themselves, rendering them harmless or eliminating them, and thus act as the central mediators of the immune response.
The person who clearly established the concept of antibodies was the German bacteriologist Emil von Behring. Through experiments, he proved that the immune response to deadly diseases such as diphtheria and tetanus is not caused by the pathogens themselves, but by substances that neutralize the toxins produced by the pathogens, i.e., antibodies. He named these antibodies “antitoxins” and called the related immune response “antitoxin immunity.”
In particular, he confirmed that antitoxins do not only work within the body, but also have the same immune effect when extracted into serum and injected into other animals. Based on this discovery, at the end of the 19th century, people began to extract serum rich in anti-diphtheria antibodies from horse blood and inject it into humans to treat diphtheria. This was recorded as the first serum therapy in human history and was a groundbreaking achievement that proved that immunology was not just a theoretical discipline but could be applied to actual treatment. However, this does not mean that the role of antibodies is limited to neutralizing toxins. It has also been discovered that antibodies are involved in destroying pathogens themselves, in addition to neutralizing their toxins.
German bacteriologist Richard Pfeiffer conducted experiments related to this. He observed that when mice that had been immunized by injecting them with weakened cholera bacteria were injected with highly pathogenic cholera bacteria into their abdominal cavity, the bacteria were completely killed in the abdominal cavity. Conversely, when the same pathogen was injected into mice that had not been immunized, the mice became infected and died.
Interestingly, even when cholera bacteria were injected into immunized mice, the bacteria were killed when immune serum obtained from the blood of immunized mice was also injected. This shows that antibodies not only act against the toxins of pathogens, but also have the ability to directly destroy or kill the bacteria themselves.
Pfeiffer named these antibodies “bacteriolytic antibodies” and defined the immune response as “bacteriolytic immunity.” However, this experiment revealed another important limitation. This bacteriolytic immune response was not observed in a test tube, i.e., in an in vitro environment. In other words, although the immune response was strong inside the body, its effect seemed to disappear outside the body. This was a decisive clue suggesting that another component besides antibodies was involved in the expression of the immune response. The person who resolved this question was Belgian biologist Jules Bordet.
Through in vitro experiments based on Pfeiffer’s experiments, he discovered that fresh immune serum against cholera bacteria could exhibit sufficient bacteriolytic activity even in a test tube. However, this effect only appeared under certain conditions. When the immune serum was stored for a long time or exposed to a temperature of 56°C for a relatively short period of time, it no longer had the ability to kill cholera bacteria.
However, when a small amount of fresh serum from normal animals with no immunity was added to the inactivated serum, a strong immune response was surprisingly observed again. This proved that antibodies alone do not cause the immune response to function completely and that there is another factor that assists the action of antibodies.
Through this experiment, Borde concluded that two main components are necessary for an immune response. The first is antibodies, which are produced in animals that have acquired immunity, are resistant to heat, and are stably present in serum. The second is a component that assists the action of antibodies, which is already present in the serum of normal animals regardless of their immunity and is easily destroyed by heat or long-term storage. This second substance acts as a key helper, working with antibodies to destroy pathogens directly.
Today, this substance is called “complement” and plays a very important role in the immune system together with antibodies. Complement is activated when antibodies bind to pathogens and performs various physiological functions throughout the immune response, such as destroying the cell membranes of pathogens and providing signals necessary for phagocytes to recognize and eliminate pathogens.
In this way, our understanding of immunity has evolved from simple empirical facts to a sophisticated mechanism through systematic experimentation and scientific reasoning. These studies, which laid the foundation for immunology, have had a profound impact on many areas of modern medicine, particularly vaccine development, the understanding of autoimmune diseases, and immunotherapy. Even today, immunology is considered one of the most dynamic fields in the search for new medical breakthroughs.
