CHAPTER ONE
INTRODUCTION
1.1 Introduction
1.1.1 History of Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of immune system in all living organisms. It is the branch of medicine and biology concerned with immunity. Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. The concept of immunity has intrigued mankind for thousands of years (Silverstein, 1989). The prehistoric view of disease was that it was caused by supernatural forces, and that illness was a form of theurgic punishment for “bad deeds” or “evil thoughts” visited upon the soul by the gods or by one’s enemies (Lindquester, 2006). The ancient historic view was that disease was spontaneously generated instead of being created by microorganisms that grow by reproduction (Madigan and Martinko, 2005). Between the time of Hippocrates and the 19th century, when the foundations of the scientific methods were laid, diseases were attributed to an alteration or imbalance in one of the four humors (blood, phlegm, yellow bile or black bile), (Silverstein, 1989). Also popular during this time was the miasma theory, which held that diseases such as cholera or the Black Plague were caused by a miasma, a noxious form of “bad air” (Lindquester, 2006). If someone were exposed to the miasma, they could get the disease.
The word “immunity” derives from the Latin word: immunis, meaning exemption from military service, tax payments or other public services (Gherardi, 2006). The first written descriptions of the concept of immunity may have been made by the Athenian, Thucydides who, in 430 BC, described that when the plague hit Athens “the sick and the dying were tended by the pitying care of those who had recovered, because they knew the course of the disease and were themselves free from apprehensions. For no one was ever attacked a second time, or not with a fatal result” (Gherardi, 2006). The term “immunes”, is also found in the epic poem “Pharsalia” written around 60 B.C. by the poet Marcus Annaeus Lucanus to describe a North African tribe’s resistance to snake venom (Silverstein, 1989).
The first clinical description of immunity which arose from a specific disease causing organism is probably Kitab fi al-jadari wa-al-hasbah (A Treatise on Smallpox and Measles), translated in 1848 (Al-Razi, 2003) and written by the Islamic physician, Al-Razi in the 9th century. In the treatise, Al-Razi describes the clinical presentation of smallpox and measles and goes on to indicate that exposure to these specific agents confers lasting immunity (although he did not use this term) (Silverstein, 1989). However, it was with Louis Pasteur’s Germ theory of disease, which states that many diseases are caused by the presence and actions of specific micro-organisms within the body (Worboys, 2008), that the fledgling science of immunology began to explain how bacteria caused disease, and how, following infection, the human body gained the ability to resist further infections (Gherardi, 2006), though microorganisms were first directly observed by Anton Van Leeuwenhoek, who is considered the father of microbiology. Building on Leeuwenhoek’s work, Nicolas Andry argued in 1700 that microorganisms (which he called worms) were responsible for smallpox and other diseases (Andry, 1700).
- The role of smallpox in the development of vaccination
Immunology is the study of the immune system, which protects organisms against disease, while a vaccine is an agent that helps make the body immune to a specific disease or illness. The vaccine triggers the immune system’s infection-fighting ability and memory without exposure to the actual disease-producing germs. The immunity developed following vaccination is similar to the immunity acquired from natural infection. Immunization had existed in various forms for at least a thousand years, (Gherardi, 2006). The earliest use of immunization is unknown, but around 1000 AD, the Chinese began practicing a form of immunization by drying and inhaling powders derived from the crusts of smallpox lesions (Gherardi, 2006). However, the earliest recognized attempt to intentionally induce immunity to an infectious disease was in the 10th century in China, where smallpox was endemic. The process of “variolation” involved exposing healthy people to material from the lesions caused by the disease, either by putting it under the skin, or, more often, inserting powdered scabs from smallpox pustules into the nose. Variolation was known and practiced frequently in the Ottoman Empire, where it had been introduced by Circassian traders around 1670, (Gherardi, 2006). Unfortunately, because there was no standardization of the inoculum, the variolation occasionally resulted in death or disfigurement from smallpox, thus limiting its acceptance.
Variolation later became popular in England, mainly due to the efforts of Lady Mary Wortley Montague (Gherardi, 2006) who survived smallpox but lost a brother to it. Lady Montague was married to Lord Edward Wortley Montague, the ambassador to the Sublime Porte of the Ottomans in Istanbul. While in Istanbul, Lady Montague observed the practice of variolation. Determined not to have her family suffer as she had, she directed the surgeon of the Embassy to learn the technique and, in March 1718, to variolate her five year-old son. After her return to England, she promoted the technique, and had her surgeon variolate her four year-old daughter in the presence of the king’s physician (Greenberg, 1957). The surgeon, Charles Maitland, was given leave to perform what came to be known as the Royal Experiment, in which he variolated six condemned prisoners who later survived. By these and other experiments, the safety of the procedure was established. Subsequently, the practice of variolation spread rapidly throughout England in the 1740s and then to the American colonies.
1.1.1.2 Edward Jenner and the development of the first safe vaccine for smallpox
Although Jenner is celebrated for his development of cowpox as a safe vaccine for
smallpox, he was not the first to make use of a relatively non-pathogenic virus to induce
immunity. In 1774, Benjamin Jesty, a farmer, inoculated his wife with the vaccinia virus
obtained from “farmer Elford of Chittenhall, near Yetminster.” In 1796, Jenner inoculated James Phipps with material obtained from a cowpox lesion that appeared on the hand of a dairymaid. (Silverstein, 1989). Six weeks later, he inoculated the experimental subject with smallpox without producing disease. Although this experiment justifiably lacked an appropriate control, further studies by Jenner established the efficacy of his vaccination procedure (Jerner, 1955). For this feat, Jenner received a cash prize of 30,000 pounds and election to nearly all of the learned societies throughout Europe (Silverstein, 1989).
- Koch, Pasteur, and the germ theory of disease
In 1875, Robert Koch, a country physician with no formal scientific training, inoculated the ear of a rabbit with the blood of an animal that had died of anthrax. The rabbit died the next day. He isolated infected lymph nodes from the rabbit and was able to show that the bacteria contained within them could transfer disease to other animals. He developed and refined techniques necessary for the cultivation of bacteria, including the development of agar growth medium (Greenberg, 1957). He was appointed to the Institute of Hygiene in Berlin, where his ultimate goal was to identify the organism responsible for the “White Death”-tuberculosis.
Quite independently, Louis Pasteur began his studies of the “chicken cholera bacillus.” In a serendipitous discovery, Pasteur inadvertently left a flask of the bacillus on the bench over the summer and inoculated 8 chickens with this “old but viable” stock of chicken cholera bacillus (Greenberg, 1957). He found that not only did the chickens not die, but they did not even appear ill! Pasteur said that the virulent chicken cholera bacillus had become attenuated by sitting on the bench over the summer months. The similarity between these results and those of Jenner using vaccinia virus was immediately apparent to him. In honor of Jenner, Pasteur called his treatment vaccination. Pasteur later worked on anthrax and rabies and developed the first viable vaccine for anthrax and rabies.
