Immune System

The word "immunity" (L: immunis - free of) was used in the context of being free of the burden of taxes or military conscription. The history of immunology is really slightly more than 100 years if you consider Louis Pasteur as the "Father of immunology" as most do. If one thinks about cellular immunology, the "real" history begins in the late 1950's.

From early writings, it is clear that primitive man knew about disease and its ravages . One finds in the Babylonian Epic of Gilgamesh (2000 B.C. - Mesopotamian hero) records of the presence of pestilence and disease. In other, more recent writings from old dynasties of ancient Egypt, one finds even more descriptions of disease. Further, one can even identify the disease of which they spoke. Recall that, in those days, disease and pestilence was punishment rendering as a result of "bad deeds" or "evil thoughts". Even the old testament is filled with pestilence that God wrought upon those who "crossed" him. From these writings, it is equally apparent that man knew that once he had been afflicted with disease, if he survived, he was normally not able to contract it again.

The science of immunology grew from the common knowledge that those who survived many of the then common infectious diseases, rarely contracted that disease again. This was an observation that was made long before the establishment of the germ theory of disease. Louis Pasteur and Robert Koch were instrumental in defining microorganisms as the etiological agents of a large number of diseases.

In 430 B.C., Thucydides recorded that while the plaque was raging in Athens, the sick and dying would have received no attention had it not been for those individuals who had already contracted the disease and recovered and recognized their "immune" status. Beginning around 1000 A.D., the ancient Chinese practiced a form of immunization by inhaling dried powders derived from the crusts of smallpox lesions. Around the fifteenth century, a practice of applying powdered smallpox "crusts" and inserting them with a pin or "poking" device into the skin became commonplace. The process was referred to as variolation and became quite common in the Middle East. However, the primary intent of variolation was that of "preserving" the beauty of their daughters and no mention was made of saving lives.

From Turkey, the process of variolation can be traced to the inhabitants of a country called Arcassia. The people that populated this land were poor but were blessed with large number of beautiful women, which unfortunately was the chief trade and very important to the Arcassian economy. Most sales were to the Sultan of Turkey.

Eventually, the process was popularized in Great Britain, largely through the efforts of Mary Wortley Montagu. It was vehemently opposed by the Church and was highly discouraged, particularly if one were Christian. The clergy stated that it could only work of an "UnChristian" who was an infidel in the eyes of the Lord.

To complicate matters more, because there was no standardization of the inoculum engrafted, the practice occasionally resulted in death/disfigurement from smallpox. This coupled with the widespread acceptance of herbal medicine resulted in it not being widely accepted. In 1721, Mary Wortley Montagu's daughter was the first person to be engrafted in Great Britain

The first step to a safer procedure was to substitute material derived from the lesion of a cowpox (vaccinia) for the inoculation. Cowpox is a benign disease due to infection with a virus closely related to the smallpox (variola) virus.

Some notable events in "early" Immunology

1774- Benjamin Jesty, a farmer who inoculated his wife with the vaccinia virus obtained from "farmer Elford of Chittenhall, near Yetminster". First record of anyone using vaccinia virus to "protect" against smallpox.

In 1798, Jenner inoculated a young by named James Phipps with material obtained from a cowpox lesion. The results were conclusive but were met with great resistance by the Church. Ignorance can be hard to combat!! For this feat, Jenner received a cash prize of 30,000 pounds . The acceptance of Jenner's thesis was strengthened when 70 of the principal physicians and surgeons of London threw their weight behind him. He was elected to membership to all of the learned societies throughout Europe with the exception of the College of Physicians. They required that he pass an examination in Classics which Jenner refused.

To further advance the fledgling science of immunology required the development of the Germ theory of disease. It is here that Louis Pasteur played a pivotal role in the evolution of the science. While Pasteur's work at the Pasteur Institute in Paris was concerned with bacterial infectious disease, he was most concerned with the prevention of diseases that bacteria caused and how the human body was changed subsequent to infection so as to resist further insults. Louis Pasteur became the first experimental immunologist.

Pasteur proceeded to develop valid methods for immunization.

His first quest was with the disease chicken cholera. It was known that chicken cholera was due to infection with the "chicken cholera bacillus". Pasteur had a flask of the organism which he inadvertently left on the bench over the summer (I guess he took "summer breaks"). When Pasteur again turned his attention to the organism, he found that the culture had lost its ability to cause disease in the chicken. Briefly, this is what Pasteur did. Desiring to infect several chickens, he took his "old but viable" culture of chicken cholera bacillus and injected 8 chickens with it. Surprising, the chickens did NOT die in the usual period of time. In fact, they did not even get sick! Somewhat vexed by the loss of time, he prepared a new stock of bacteria and re-injected the original 8 AND 10 new fresh chickens (he had to make up for lost time). After 48 hours, the 10 newly injected chickens were "sick and dying" while the original 8 were the "picture of health". Pasteur envisioned that somehow the original 8 chickens had been "changed" by the old culture and were no longer susceptible (he tried three more times to kill those stupid 8 chickens but they never got sick).

As a result of his work, Pasteur said that the virulent chicken cholera bacillus had become attenuated by sitting on the bench over the summer months. The similarity between this situation and Jenner's variolation with the vaccinia virus was immediately apparent to him and in honor of Jenner, Pasteur called his treatment vaccination.

In 1886, Theobold Smith (an American microbiologist) demonstrated that heat killed cultures of chicken cholera bacillus were also effective in protection from cholera. This demonstrated that the microorganisms did not have to be viable to induce the protection.

Pasteur proceeded to do the same with anthrax. Robert Koch had shown that the disease was due to a bacterium called Bacillus anthracis. He maintained the culture under adverse laboratory conditions (incubation at 42-43C) and in this manner, he produced the vaccine that was used for the famous demonstration at Pouilly-le-Fort.

On May 5, 1881 Pasteur vaccinated 24 sheep, 1 goat, and 6 cows with five drops of the living attenuated anthrax bacillus. On May 17, he inoculated all of the animals with a less attenuated strain. On May 31, all of the animals received viable virulentanthrax bacilli. Additionally, 24 more sheet, 1 goat and 3 cows received the virulent microorganism without the protection of the vaccination. On June 2, 1881 all of the non vaccinated animals had died while only two sheep of the protected group had succumbed. One of the sheep had died due to pregnancy complications.

A third means of virulence attenuation was soon found to involve the passage of the microorganism in an unnatural host.

The most dramatic demonstration of a vaccine's effectiveness was with rabies. Isolating the virus from a fox, Pasteur passed the virus in an "unnatural host" the rabbit. By infecting one rabbit, allowing it to become ill, and then re-isolating the virus and injecting a new rabbit, Pasteur "selected" for variants of the virus that were less pathogenic for the fox. Pasteur dried the spinal cord taken from an infected rabbit and prepared a vaccine from it. To test it however, he needed a human subject who was undoubtedly going to come down with rabies.

The first human trial was on July 6, 1885. A nine-year old lad named Joseph Meister had been severely bitten by a rabid dog two days earlier. His parents knew that he "was a goner" and were desperate for any ray of hope. They heard of Pasteur's work and traveled to Paris, France in hopes that Pasteur would "work a miracle". Pasteur injected the attenuated virus into young Joey and they waited. Well, you can guess the rest of the story. Joseph Meister, after receiving the immunization, survived rabies. This was the first known case of an individual being bit and surviving rabies. Joseph Meister was later to become the gate porter of the Pasteur Institute in Paris and served as guard to Pasteur's crypt. Within a year, over 350 people bitten by rabid animals had been treated with no fatalities.

Other events soon served to catapult immunology from the microbiology labs.

In 1888, Roux and Yersin discovered the diphtheria toxin. Two years later, in 1890, Von Behring and Kitasato demonstrated the presence of anti-toxin in the blood of individuals recovering from diphtheria. Von Behring was the first to use this antiserum in treating active disease. Forerunner to what we call "serotherapy" today.

The ideas of circulating neutralizing anti-toxins predominated early immunological thought and the French and German schools dominated immunological research. At the turn of the century, immunology developed into two schools of thought.

1. Humoralists - immunity was due to humoral substances, i.e. antibodies. A Pioneer in this area was Paul Ehrlich. He proposed what was the most plausible humoral theory of antibody formation the "side chain theory". Emil Von Behring (worked at the Koch Institute in Germany) used serum to treat diseases. Germans were big proponents of humoral immunity.

2. Cellularists - immunity due to the existence of "phagocytic" cells within our bodies. The pioneer here was Eli Metchnikoff and he became the strongest proponent of cellular immunity after observing water Daphnia phagocytose smaller materials and examining blood cells devour foreign bacteria in blood samples. Metchnikoff was allied with Louis Pasteur (he worked at the Pasteur Institute) and he had many a vitriolic fights with the Germans who were proponents of humoral immunity.

Today, we know that immunity is due to both of these facets. We will address humoral antibody in the form of immunoglobulins and we will talk about Cellularists when we deal with T cell biology and cytotoxicity with regulation.

· 1903, Maurice Arthus, described the localizing allergic reaction called the Arthus response. In 1905, a Frenchman by the name of Von Pirquet shocked the world when he provided evidence that immune responses can be deleterious. He was studying serum sickness, a form of hypersensitivity or allergy.

· 1930, American scientists Landsteiner and Kabat described detailed experiments of the specificity of the immune response by chemically altering antigens. In 1944-45, another American named Peter Medawar provided the immunological basis of transplantation immunology.

· 1958 - clonal selection theory as proposed by Sir McFarland Burnet and Neils Jerne

· 1960's - Porter and Edelman enzymatically digested antibodies and we learned about their chemical structure.

· 1960 - The first real demonstration of a cellular basis for humoral and cellular immunity. The terms T and B cells became vernacular.

There is, of course, a lot more immunology. The late 60's to early 70's have been referred to as the beginning of modern immunology. The molecular/genetic techniques of the 70's have revolutionized our understanding of how the immune system works.

Source : the internet