The Immune System: Chickens, Dogs, Starfish and Magic Bullets

  This is a peacekeeping force that is always vigilant and ubiquitous during the Carnival of Life.
  It may be said that immunology research originated in a chicken.
  The story takes place at the University of Padua in northern Italy at the end of the 16th century. There was a young researcher named Fabricius who loved dissection—he dissected eyes, ears, animal embryos, and occasionally humans, but he was remembered for dissecting a chicken.
  One day, while dissecting a domestic chicken, Fabricius noticed a strange area under the chicken’s tail. He discovered a sac-like organ and named it bursa, which is Italian for purse. Since then, this organ has been called the bursa.
  This may seem pointless, but why do we bring it up? Why would God (this time in the 16th century) leave a sac-like “purse” to a chicken without giving it a corresponding use?
  I wonder if Fabricius believes that this tiny organ is the key to understanding why we humans have survived. Would he know that this simple discovery could save millions of lives in the future?
  In fact, many other discoveries beyond this, while seemingly unrelated, form the cornerstone of our understanding of the immune system.
  On July 23, 1622, an Italian scientist named Gaspare Acelli performed a groundbreaking operation in which he dissected a “dog that was well fed and alive.” In the dog’s stomach, he observed a “milky vein”. This observation is at odds with our understanding of the circulatory system that transports red blood. Even more bizarrely, these milky veins also appear to contain white blood. Aseli’s dissection kicked off a period of exploration known historically as “lymphatic mania,” in which hundreds of animals were dissected to study this little-understood body fluid called lymph.
  The role of this milky vein has remained unclear for many years. As the British journal Nature wrote centuries later, Aceri’s discovery “was forgotten in a corner for decades.” So what exactly is this particular circulatory system?
  In the summer of 1882, in northeastern Sicily, Italy, Eli Mechnikov looks at a sample through a microscope. Mechnikov, a zoologist from Odessa, Ukraine (then under the Russian Empire), went to Italy with his sister and her family when the unrest in Russia was on the rise. Mechnikov took his microscope to Sicily, and it was there that he had an epiphany: “The most important event of my scientific career happened.”
  One day, while his family was in the circus watching the orangutans During the performance, Mechnikov pointed the microscope at the transparent starfish larvae. He noticed some cells, which he described as “wandering cells,” moving around the tiny organism. It was at this moment that revelation came down from heaven.
  ”A new idea suddenly flashed through my mind. It occurred to me that similar cells might act as a defense in an organism against invasion,” Mechnikov wrote.
  He thought of a way to verify it – what would happen if a small foreign body was inserted into the starfish? In this case, would these cells somehow swarm, as if they were coming to the rescue?
  We have a small garden in our house, and a few days ago we had an orange tree dressed up as a Christmas tree; I snapped some thorns from it and stuck them into the skin of the beautiful, water-transparent starfish larvae. I was so excited that night that I couldn’t sleep, and I spent the night waiting for the results of my experiment. The next morning I couldn’t wait to see the results and confirm that the experiment was a great success. Indeed, there is a population of wandering cells clustered around the foreign body, seemingly engulfing the tissue that is invading and causing trouble. This experiment laid the foundations of phagocytic theory, a field I have dedicated my next 25 years to.
  Mechnikov’s sister wrote a biography of him and outlined the gist of his theory—a theory that took scientists years to fully embrace. “This very simple experiment shocked Metchnikov because of its resemblance to the phenomenon of pustule formation, and it is the wandering cells that cause inflammation in humans and other higher animals,” she wrote. In the biography , she defines inflammation as “a treatment response of the body, and the disease is mainly manifested in the struggle between mesodermal cells and microorganisms”.
  In other words: At the moment of being invaded, the body has an initial response, including the accumulation of phagocytes, which is not always pleasant, and this is what we call inflammation.
  Nine years later, in 1891, Paul Ehrlich, a contemporary of Mechnikov, the father of immunology from Berlin, Germany, started the search for “magic bullets” (targeting agents). Ehrlich hopes to shed light on one of the most elusive of all immunological questions: how exactly does our immune system recognize and attack foreign pathogens like viruses, bacteria and parasites? And how do cells like starfish know to rise up and devour foreign bodies?
  Ehrlich has a theory that, while flawed, is brilliant. He believes that perhaps the human defense system is based on a lock-and-key mechanism. When a disease occurs, a special cell in the body comes into contact with and attaches to the virus or bacteria. Ehrlich named these attachments “antibodies.”
  His idea was that antibodies would attach to disease-causing agents called antigens. Antibodies are the keys and antigens are the locks. Subsequently, the antibodies will destroy the cells. Although Ehrlich’s theory is advanced, there are some problems. First, he believes that immune cells carry a series of keys called “side chains” that, if shaped correctly, can be inserted into the lock. This, though later proven wrong, was still an amazing guess, and his idea did lead to one of the most important words in the language of the immune system—antibody.
  Ehrlich also discovered many other types of cells with different edges, shapes and seemingly different functions, which he named basophils and neutrophils, among others. So the question is, are these cells part of our defense system, or are they used for something else?
  Questions and observations also piled up over time. This is not surprising, after all, the immune system is one of the most complex organic systems in the world. Its origins far predate the evolution of human beings, and perhaps only the complexity of the human brain can match it.
  The origins of the immune system go back 3.5 billion years, around the time when bacteria, the first cellular organisms, emerged. Using advanced chemical and molecular tools, scientists have discovered that some bacteria appear to have sophisticated immune systems that recognize specific foreign threats and encode them in memory to eliminate them when invaded.
  The fact that our immune system has been around for so long speaks volumes about its power, as evolution does not allow useless functions to persist for that long.
  This is a peacekeeping force that is always vigilant and ubiquitous during the Carnival of Life.