Phenomenon of Immunity

Phenomenon of Immunity

The earliest written reference to the phenomenon of immunity can be traced back to Thucydides, the great historian of the Peloponnesian War. Describing a plague in Athens, in 430 BC, he wrote that only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time.

     The earliest known smallpox inoculation took place in China, perhaps as early as the fifth century AD. The Chinese method was reported to the Royal Society by an English mer-chant, John Lister, during early 1900s. A Jesuit priest, Father d’Entrecolles, provided details of the method, which he said was to collect scabs from the pustules and blow a powder made from them into an infant’s nose. The scabs or a thread coated with the pus could be stored, but the operation was usually done face-to-face with a sick patient. The same method was used in Japan beginning in 1747. In precolonial India, a tika or dot would be made on a child, usually on the sole of the foot, by traditional tikadars who were invited into home (this professional niche was later blacklisted by colonial-era medical practitioners).

     The method was significantly improved by the English phy-sician Edward Jenner in 1798. Jenner was intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to smallpox, a disfiguring and often fatal disease. He believed that introducing fluid from a cowpox pustule into people (i.e., inoculating them) might protect them from smallpox. To test this idea, he inoculated an 8-year-old boy with fluid from a cowpox pustule and later intentionally infected the child with smallpox. As predicted, the child did not develop smallpox. Pasteur followed this up with development of vaccines for chicken cholera, anthrax, and rabies. Although Pasteur proved that vaccination worked, but he did not under-stand how.

Mechanisms of Immunit

The experimental work of Emil von Behring and ShibasaburoKitasato in 1890 gave the first insight into the mechanism of immunity. They demonstrated that serum contained elements that protected against infections thus laying the foundation for the identification of humoral immunity. In recognition of this work, von Behring received the Nobel Prize in Medicine in 1901.

   In 1884, even before the discovery that a serum component could transfer immunity, Elie Metchnikoff demonstrated that cells also contribute to the immune state of an animal. He observed that certain white blood cells, which he termed phago-cytes, were able to ingest (phagocytose) microorganisms andother foreign material. Noting that these phagocytic cells were more active in animals that had been immunized, Metchnikoff hypothesized that cells, rather than serum components, were the major effector of immunity. The active phagocytic cells identified by Metchnikoff were most likely blood monocytes and neutrophils.

Specificity of the Antibody Molecule

One of the greatest enigmas facing early immunologists was the specificity of the antibody molecule for foreign material or antigen. Following theories were proposed to explain this mechanism of specificity:

The selective theory: The earliest conception of theselective theory dates to Paul Ehrlich in 1900. In the 1930s and 1940s, the selective theory was challenged by various instructional theories, in which antigen played a central role in determining the specificity of the antibody molecule.

The instructional theory: According to the instructionaltheories, a particular antigen would serve as a template around which the antibody would fold. This concept was first postulated by Friedrich Breinl and Felix Haurowitz in the 1930s and redefined in the 1940s in terms of protein folding by Linus Pauling.

The clonal selection theory: The instructional theorieswere formally disproved in the 1960s, during which information was beginning to appear regarding the struc-ture of DNA, RNA, and protein. These information offered new insights into the vexing problem of how an individ-ual could make antibodies against almost anything. In the 1950s, selective theories resurfaced as a result of new experimental data and through the pioneering contribu-tions of Niels Jerne, David Talmadge, and F Macfarlane Burnet, who refined into a theory that came to be known as the clonal selection theory.