Artificial induction of immunity

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Immunity against infectious disease is usually a good thing. Since Louis Pasteur provided support for a germ theory of infectious disease the theory of inducing immunity to disease without suffering the disease has been evolving. With recent understanding of the molecular basis of immunity the practice should advance further in the near future.

This is a historical overview and introductory article to a collection of detailed articles on the main topics.

Contents

Variolation and smallpox

See main articles Wikipedia:variolation and smallpox

The earliest recorded artificial induction of immunity in humans was with variolation or inoculation as practiced from ancient times in China and India, and imported into Europe via Turkey around 1720 by Lady Montagu and perhaps others. From England, and also by other accounts from an African involuntary immigrant to Boston the technique spread rapidly to the Colonies.

Variolation had the disadvantage that the agent used was in fact smallpox, albeit the selected less lethal form (Variola Minor) and that the disease could either kill the inoculee or spread in its full form to others nearby. Nevertheless it was a convincing improvement over waiting to catch smallpox when 20% of the population had been dying of it.

Vaccination

See main articles vaccination and Edward Jenner

In 1796 Jenner, a doctor and scientist (or natural philosopher as it was then) who had observed cowpox and conducted variolation over a considerable period acted on the folk-knowledge that cowpox infection conferred immunity to smallpox, and the observation that cowpox was never a fatal ailment.

He induced cowpox infection using material from a lesion on one patient, in another person, and then demonstrated that the latter was immune to Variola by variolating him. This had been demonstrated some years earlier by Benjamin Jesty, who had not however followed up by describing and generalising the process or by making arrangements to propagate cowpox.

Jenner was an empiricist, as were most members of the Royal Society at that time. The theory to support further advances arrived a while later.

Germ theory

See main articles Louis Pasteur and germ theory

Pasteur perfected the experiments demonstrating that spontaneous generation was not true, and derived a germ theory of (infectious) disease from them. This provided a theoretical basis to proceed, and Pasteur isolated infectious agents from first anthrax and then rabies (the latter a crude preparation) and altered them so as to make them harmless. He derived vaccines from them which immunised farm animals against anthrax and in a brave piece of rapid medicine development very probably saved the life of the first person immunised against rabies - who had been bitten by a clearly rabid dog and was expected to die.

Anthrax is bacterial and rabies viral and the microscopes around the time could reasonably be expected to show bacteria, but imaging of viruses had to wait for electron microscopes with their greater resolving power in the 20th century.

Toxoids

Some diseases such as tetanus, kill not by bacterial growth but by the production of a toxin. Heat treating the tetanus toxin denatured it enough to allow immunity to be developed without its toxic effect. Tetanus toxin is so lethal that humans are incapable of developing immunity to a natural infection, since the lethal dose is passed long before antibody production can rise to neutralise it. Tetanus toxoid injection however produced very good immunity.

See also Botulism

Adjuvants

Simple molecules such as toxoids tended to produce a low response, and poor immune memory. Adding certain substances - e.g. adsorbing tetanus toxoid onto alum greatly enhanced the immune response. Various adjuvants have been used, and are also used for other purposes to do with studying the immune system.

A much later - contemporary - approach, is to conjugate the antigen eg a polysacharide from the capsule of the bacteria responsible for most lobar pneumonia with another molecule such as a toxoid, The combination triggers immune memory rather than just a humoral antibody response.

Temporarily induced immunity

See also immunoglobulin

Once the fraction of the blood which contained the immune molecules - the antibodies - was known, it could be isolated and given to people. The portion of immunity which is humoural - carried in the humours or body fluids, rather than cell-mediated, could be transferred thus. Within reason it need not be from a human, and horse tetanus anti-serum has saved many lives, although since anaphylactic shock is a possibility with a cross-species transfer of such proteins, it has also cost a few.

Synthetic (recombinant or cell-clone) human immunoglobulins are now possible to produce and for several reasons including the risk of prion contamination of biological products are likely to become more used. They are not in industrial scale production in 2009. In the future it may be possible to design antibodies to fit an antigen, then produce them, and thus induce temporary immunity in people in advance of human exposure to a pathogen. At present the science to understand that is available, but not the technology to do so. Among other possible applications would be the the neutralisation of prions.

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