• Roopkatha Bhattacharya

The story of how we came to know about our immune system

April 29 is observed as the International Day of Immunology. This is the first in a series of articles in which Biobugs will explore the history of immunology and infectious diseases.


Humans live in a world full of microorganisms like bacteria, viruses many of whom cause infectious diseases. But, although we are exposed to these pathogens all the time, we rarely get infected or fall ill. This is because our body has an immune system consisting of defence mechanisms that protect us against infections. The branch of biology devoted to studying our body's defences against infection is called immunology.



Of cowpox and miracle cures


During the pandemic, scientific terms from the field of immunology for example “antibody”, “immunity” have made their way into household conversations. Immunology is a relatively new scientific discipline that arose during the latter half of the 18th century. The concept of immunity from disease, though, can be traced back to Greece in the 5th century BC. Thucydides, the famous Greek historian, wrote about individuals who had suffered and recovered from the plague and as a result, became immune to the disease. One of the earliest documented attempts at intentionally inducing immunity to a particular disease came from China. The process was called variolation. It involved exposing healthy people to substance collected from sores or lesions caused during diseases like smallpox, either by scratching it into the skin or blowing into the nostrils. Variolation went on to be practised in different countries until vaccines started being developed.

Edward Jenner, an English physician developed a vaccine for smallpox using the substance obtained from pustules caused by cowpox, a milder disease that affected dairymaids who milked cows. The year was1798 when he took the bold step of inoculating a young boy with cowpox. After six weeks, he observed that even after inoculation with smallpox, the boy did not develop the disease. Thus, inoculation with cowpox protected against smallpox which was a dreaded disease of that era. Gradually, this method became popular throughout Europe as it was both safe and effective.

Almost two centuries and widespread immunization later, in 1980, the World Health Organization declared the world free of smallpox.


Of germs and serendipity


Although the credit for introducing vaccines goes to Jenner, he did not know much about the infectious agents that caused diseases. It was the work of bitter scientific rivals Louis Pasteur, a French microbiologist and Robert Koch, a German physician in the late 19th century that helped shape the world's understanding of infectious diseases. Koch had inoculated rabbits with anthrax, a deadly disease and found that the bacteria living in the dead animal’s body could be used to infect other animals. His experiments had led to the conclusion that the various infectious diseases that human beings suffered from, were caused when some microscopic organisms invaded our bodies. These tiny yet harmful invaders were called germs or pathogens. The 'germ theory of disease' eventually became the accepted scientific theory for many diseases.

Meanwhile, Pasteur was studying the fatal disease of fowl cholera by injecting chickens with live cholera-causing bacillus bacteria. One of his assistants was tasked with injecting chickens with fresh bacterial culture but forgot and left for a holiday. After the holiday was over, the flask full of bacteria that had remained in the lab all this while was injected into chickens. These chickens became mildly ill but did not die from the disease. Pasteur then injected fresh bacteria into these birds but they remained healthy, with no signs of the disease. According to Pasteur, the infectious bacteria in the culture had lost their ability to cause infection and disease as a result of ageing or being exposed to oxygen for a long time. Pasteur had realized that the weakened bacteria could be a potential treatment that protected against cholera. He named the treatment, vaccine. The word “vacca” in Latin meant “cow” and this was Pasteur’s tribute to the successful experiments that Edward Jenner had performed using cowpox almost a century earlier. Thus, a serendipitous discovery in a laboratory led to the development of vaccines.



Of cells and molecules


The question remained that when the germs invaded, how did our bodies that acted as hosts to these microorganisms, defend themselves? The germ theory did not answer this question. Ilya Metchnikoff, a Russian zoologist did while studying starfish larvae. He found a type of cell in the host that could engulf and digest the germs or particles that he had injected into the larva. Metchnikoff called them “phagocytes” derived from Greek words for "devouring or eating cells". Since these cells are always present in the body and ready to act, he believed them to be the first line of defence against pathogens.

Towards the end of the nineteenth century, around the same time that Metchnikoff was identifying cellular components of our immune system, German biologist Emil Von Behring together with Shibasaburo Kitasato, a guest researcher from Japan, working in Berlin, uncovered the possible mechanism by which our immune systems worked. They had observed that the blood serum of animals that were already immune to diphtheria contained a soluble substance that could act against diphtheria toxin. Transferring serum from animals immune to diphtheria to animals that were susceptible to the disease ensured immunization of the susceptible individuals. The scientists concluded that it was the soluble molecules or “anti-toxins” present in the serum that were responsible for the animals becoming immune to diphtheria. Today, we call these molecules 'antibodies'. In 1900, Paul Ehrlich, another German scientist attempted to explain how and why the serum antibodies arose in the animal’s blood in response to an infection. Ehrlich believed that there were specific kinds of cells in the blood that expressed these antibody molecules which could interact, bind to and inactivate infectious disease-causing microorganisms that enter our body. There were specific serum antibody molecules that could bind to a specific infectious agent tightly, like a lock and its key. On entry of an infection-causing organism, the cells started to produce more antibody molecules to combat the infection. These discoveries and theories gave rise to the study of immunology as we know it now, a study of the immune system's component cells and molecules.


Of hope


Over the decades, vaccination has become a widely accepted method of immunization and effective public health measure in protecting us from many devastating infectious diseases. Widespread immunization programmes against infectious diseases have saved numerous lives, especially in countries like ours. An example is the well-known Polio vaccination programme in India which led to WHO declaring the country to be polio-free in 2014.One hopes for a similar success story in the case of vaccines against the COVID-19 virus.



References:

  1. A Concise History of Immunology by Steven Greenberg(http://www.columbia.edu/itc/hs/medical/pathophys/immunology/readings/ConciseHistory Immunology.pdf)

  2. Kuby Immunology by Thomas J. Kindt, Barbara A. Osborne, Richard Goldsby (Sixth Edition)

  3. Immunology’s coming of Age by Stefan H. E. Kaufmann

  4. (Front. Immunol., 03 April 2019 | https://doi.org/10.3389/fimmu.2019.00684)

  5. https://vaccine-safety-training.org/history-of-vaccine-development.html

  6. https://www.historyofvaccines.org/timeline/all

  7. Editorial: A living history of Immunology (Front. Immunol., 29 September 2015 | https://doi.org/10.3389/fimmu.2015.00502)

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