Immunity (medical) - History of Theories of Immunity

History of Theories of Immunity

The concept of immunity has intrigued mankind for thousands of years. 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. 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). 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". If someone were exposed to the miasma, they could get the disease.

The modern word “immunity” derives from the Latin immunis, meaning exemption from military service, tax payments or other public services. 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”. 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.

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 1848) 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 that exposure to these specific agents confers lasting immunity (although he does not use this term). The first scientist who developed full theory of immunity was Ilya Mechnikov after he revealed phagocytosis in 1882. Louis Pasteur’s Germ theory of disease 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.

The birth of active immunotherapy may have begun with Mithridates VI of Pontus. To induce active immunity for snake venom, he recommended using a method similar to modern toxoid serum therapy, by drinking the blood of animals which fed on venomous snakes. According to Jean de Maleissye, Mithridates assumed that animals feeding on venomous snakes acquired some detoxifying property in their bodies, and their blood must contain attenuated or transformed components of the snake venom. The action of those components might be strengthening the body to resist against the venom instead of exerting toxic effect. Mithridates reasoned that, by drinking the blood of these animals, he could acquire the similar resistance to the snake venom as the animals feeding on the snakes. Similarly, he sought to harden himself against poison, and took daily sub-lethal to build tolerance. Mithridates is also said to have fashioned a 'universal antidote' to protect him from all earthly poisons. For nearly 2000 years, poisons were thought to be the proximate cause of disease, and a complicated mixture of ingredients, called Mithridate, was used to cure poisoning during the Renaissance. An updated version of this cure, Theriacum Andromachi, was used well into the 19th century. In 1888 Emile Roux and Alexandre Yersin isolated diphtheria toxin, and following the 1890 discovery by Behring and Kitasato of antitoxin based immunity to diphtheria and tetanus, the antitoxin became the first major success of modern therapeutic Immunology.

In Europe, the induction of active immunity emerged in an attempt to contain smallpox. Immunization, however, had existed in various forms for at least a thousand years. The earliest use of immunization is unknown, however, around 1000 A.D. the Chinese began practicing a form of immunization by drying and inhaling powders derived from the crusts of smallpox lesions. Around the fifteenth century in India, the Ottoman Empire, and east Africa, the practice of variolation (poking the skin with powdered material derived from smallpox crusts) became quite common. Variolation was introduced to the west in the early 18th century by Lady Mary Wortley Montagu. In 1796, Edward Jenner introduced the far safer method of inoculation with the cowpox virus, a non-fatal virus that also induced immunity to smallpox. The success and general acceptance of Jenner's procedure would later drive the general nature of vaccination developed by Pasteur and others towards the end of the 19th century.