Immunity against some infections that can cause serious illness is generally beneficial. Since Pasteur provided support for a germ theory of infectious disease, we have increasingly induced immunity against a widening range of diseases to prevent the associated risks from the wild infections. It is hoped that further understanding of the molecular basis of immunity will translate to improved clinical practice in the future. In a medical sense, immunity is a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. ... Louis Pasteur (December 27, 1822 – September 28, 1895) was a French microbiologist and chemist who demonstrated the germ theory of disease and developed techniques of inoculation, most notably the first vaccine against rabies. ... The germ theory of disease states that many diseases are caused by microorganisms, and that microorganisms grow by reproduction, rather than being spontaneously generated. ...

This article places the development of techniques in historical and logical sequence and points to detailed articles on each of the main topics.

Variolation and smallpox

See main articles variolation and smallpox. Obsolete: inoculation against smallpox using material from a vesicle or lesion of a person with smallpox. ... Smallpox (also known by the Latin names Variola or Variola vera) was a highly contagious viral disease unique to humans. ...

Typical site of inoculation in Europe and the British colonies

The earliest recorded artificial induction of immunity in humans was by variolation or inoculation, which is the controlled infection of a less lethal natural form of smallpox (known as Variola Minor) into a subject to make him or her immune to re-infection with the more lethal natural form, Variola Major. This was practiced in ancient times in China and India, and imported into Europe, via Turkey, around 1720 by Lady Montagu and perhaps others. From England, the technique spread rapidly to the Colonies, and was also spread by African slaves arriving into Boston.^{[1] [2]} Image File history File linksMetadata Inoculation. ... Image File history File linksMetadata Inoculation. ... Obsolete: inoculation against smallpox using material from a vesicle or lesion of a person with smallpox. ... Inoculation, originally Variolation, is a method of purposefully infecting a person with smallpox (Variola) in a controlled manner so as to minimise the severity of the infection and also to induce immunity against further infection. ... // Events January 6 - The Committee of Inquiry on the South Sea Bubble publishes its findings February 11 - Sweden and Prussia sign the (2nd Treaty of Stockholm) declaring peace. ... The Lady Mary Wortley Montagu (May 26, 1689 - August 21, 1762), was an English woman of letters. ...

Variolation had the disadvantage that the inoculating agent used, Variola Minor, was still an active form of smallpox and, although less potent, could still kill the inoculee or spread in its full form to others nearby. However, as the risk of death from inoculation with Variola Minor was just 1% to 2%, as compared to the 20% risk of death from the natural form of smallpox, the risks of inoculation were generally considered acceptable.

Vaccination

See main articles vaccination and Edward Jenner. Vaccination is the process of administering live, albeit weakened, microbes to patients, with the intent of conferring immunity against a targeted form of a related disease agent. ... Portrait of Edward Jenner Edward Jenner FRS (May 17, 1749 – January 26, 1823) was an English country doctor who studied nature and his natural surroundings from childhood and practiced medicine in Berkeley, Gloucestershire, England. ...

In 1796, Edward Jenner, a doctor and scientist who had practiced variolation, performed an experiment based on the folk-knowledge that infection with cowpox, a disease with minor symptoms which was never fatal, also conferred immunity to smallpox. ^[3] Jenner induced cowpox infection by transferring material from a lesion on one patient to another, thus infecting the second patient with cowpox. He then demonstrated that the latter was immune by exposing him to smallpox. The principle had been demonstrated some years earlier by Benjamin Jesty, who had not publicized his discovery. As it was Jenner who described and generalised the process and then arranged to propagate cowpox for therapeutic use, he is credited with the discovery.^[4] Vaccination took over from variolation. 1796 was a leap year starting on Friday. ... Portrait of Edward Jenner Edward Jenner FRS (May 17, 1749 – January 26, 1823) was an English country doctor who studied nature and his natural surroundings from childhood and practiced medicine in Berkeley, Gloucestershire, England. ... Cowpox is a disease of the skin caused by a virus (Cowpox virus) that is related to the Vaccinia virus. ... Benjamin Jesty was a farmer at Yetminster in Dorset, England. ...

Jenner, like all members of the Royal Society in those days, was an empiricist. The theory to support further advances in vaccination came later. The premises of the Royal Society in London (first four properties only). ... In philosophy, the term empiricism is used to describe a set of philosophical positions that emphasize the role of experience. ...

Germ theory

See main articles Pasteur and germ theory. Louis Pasteur (December 27, 1822 – September 28, 1895) was a French microbiologist and chemist who demonstrated the germ theory of disease and developed techniques of inoculation, most notably the first vaccine against rabies. ... The germ theory of disease states that many diseases are caused by microorganisms, and that microorganisms grow by reproduction, rather than being spontaneously generated. ...

Pasteur perfected experiments which disproved the then-popular theory of spontaneous generation and from which he derived the modern germ theory of (infectious) disease. Using experiments based on this theory, which posited that specific microorganisms cause specific diseases, Pasteur isolated the infectious agent from anthrax. He then derived a vaccine by altering the infectious agent so as to make it harmless and then introducing this inactivated form of the infectious agents into farm animals, which then proved to be immune to the disease. Louis Pasteur (December 27, 1822 – September 28, 1895) was a French microbiologist and chemist who demonstrated the germ theory of disease and developed techniques of inoculation, most notably the first vaccine against rabies. ... Abiogenesis, in its most general sense, is the hypothetical generation of life from non-living matter. ... The germ theory of disease states that many diseases are caused by microorganisms, and that microorganisms grow by reproduction, rather than being spontaneously generated. ...

Pasteur also isolated a crude preparation of the infectious agent for rabies. In a brave piece of rapid medicine development, he probably saved the life of a person who had been bitten by a clearly rabid dog by performing the same inactivating process upon his rabies preparation and then inoculating the patient with it. The patient, who was expected to die, lived, and thus was the first person successfully vaccinated against rabies.

Anthrax is now known to be caused by a bacterium, and rabies is known to be caused by a virus. The microscopes of the time could reasonably be expected to show bacteria, but imaging of viruses had to wait until the development of electron microscopes with their greater resolving power in the 20th century. Subgroups Actinobacteria Aquificae Bacteroidetes/Chlorobi Chlamydiae/Verrucomicrobia Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Bacteria (singular: bacterium) are a major group of living organisms. ... Orders A virus is a submicroscopic particle that can infect the cells of a biological organism. ... A microscope (Greek: micron = small and scopos = aim) is an instrument for viewing objects that are too small to be seen by the naked or unaided eye. ... The electron microscope is a microscope that can magnify very small details with high resolving power due to the use of electrons rather than light to scatter off material, magnifying at levels up to 500,000 times. ...

Toxoids

Some diseases, such as tetanus, cause disease not by bacterial growth but by bacterial production of a toxin. Tetanus toxin is so lethal that humans cannot develop immunity to a natural infection, as the amount of toxin required to kill a person is much less than is required by the immune system to recognize the toxin and produce antibodies against it. However, heating the tetanus toxin enough to denature it causes it to lose its ability to produce disease, but still leaves it able to induce immunity to tetanus when injected into subjects. The heated, denatured toxin is called a toxoid. Tetanus is a serious and often fatal disease caused by the neurotoxin tetanospasmin which is produced by the Gram-positive, obligate anaerobic bacterium Clostridium tetani. ... The venom of the black widow spider is a potent latrotoxin. ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Denaturation is a structural change in biomolecules such as nucleic acids and proteins, usually caused by heat, acids, bases, detergents, or certain chemicals such as urea. ... A toxoid is a bacterial toxin whose toxicity as been weakened or supressed while other properties, typically immunogenicity, are maintained. ...

See also Botulism Botulism (from Latin botulus, sausage) is a rare but serious paralytic illness caused by a nerve toxin, botulin, that is produced by the bacterium Clostridium botulinum. ...

Adjuvants

The use of simple molecules such as toxoids for immunization tends to produce a low response by the immune system, and thus poor immune memory. However, adding certain substances to the mixture, for example adsorbing tetanus toxoid onto alum, greatly enhances the immune response. These substances are known as adjuvants. Several different adjuvants have been used in vaccine preparation. Adjuvants are also used in other ways in researching the immune system. Memory B cells are a B cell sub-type that are formed following primary infection. ... A crystal of Alum Alum, in chemistry, is a term given to the crystallized double sulfates of the typical formula M+2SO4·M3+2(SO4)3·24H2O, where M+ is the sign of an alkali metal (lithium, sodium, potassium, rubidium, or caesium), and M3+ denotes one of the trivalent metal... In medicine, adjuvants are agents which modify the effect of other agents while having few if any direct effects when given by themselves. ...

A more contemporary approach for "boosting" the immune response of simpler immunogenic molecules (known as antigens) is to conjugate the antigens. Conjugation is the attachment to the antigen of another substance which also generates an immune response, thus amplifying the overall response and causing a more robust immune memory to the antigen. For example, a toxoid might be attached to a polysaccharide from the capsule of the bacteria responsible for most lobar pneumonia. An antigen is a substance that stimulates an immune response, especially the production of antibodies. ... Polysaccharides (sometimes called glycans) are relatively complex carbohydrates. ... The word capsule (from the Latin capsula, a small box), has many similar meanings in English: In botany, a capsule is a type of dry fruit as in the poppy, iris, foxglove, etc. ...

Temporarily-induced immunity

See also immunoglobulin. Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ...

Platypus: monotremes lack placental transfer of immunity

Temporary immunity to a specific infection can be induced in a subject by providing the subject with externally produced immune molecules, known as antibodies or immunoglobulins. This was first performed (and is still sometimes performed) by taking blood from a subject who is already immune, isolating the fraction of the blood which contains antibodies (known as the serum), and injecting this serum into the person for whom immunity is desired. This is known as passive immunity, and the serum that is isolated from one subject and injected into another is sometimes called antiserum. Antiserum from other mammals, notably horses, has been used in humans with generally good and often life-saving results, but there is some risk of anaphylactic shock and even death from this procedure because the human body sometimes recognizes antibodies from other animals as foreign. Wikipedia does not have an article with this exact name. ... Wikipedia does not have an article with this exact name. ... Families Kollikodontidae (extinct) Ornithorhynchidae - Platypus Tachyglossidae - Echidnas Steropodontidae (extinct) Monotremes are mammals that are best known for laying eggs, instead of giving birth to live young like marsupials and placental mammals (Eutheria). ... Schematic of antibody binding to an antigen An antibody is a protein used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Schematic of antibody binding to an antigen An antibody is a protein complex used by the immune system to identify and neutralize foreign objects like bacteria and viruses. ... Blood plasma is a component of blood. ... Antiserum is blood serum containing antibodies. ... Anaphylaxis is a severe and rapid systemic allergic reaction to a trigger substance, called an allergen. ...

Passive immunity is temporary, because the antibodies which are transferred have a lifespan of only about 3-6 months. Every placental mammal (including humans) has experienced temporarily-induced immunity by transfer of homologous antibodies from its mother across the placenta, giving it passive immunity to whatever its mother was immune to. This allows some protection for the young while its own immune system is developing. In biology, two or more structures are said to be homologous if they are alike because of shared ancestry. ... The placenta is an ephemeral (temporary) organ present only in female placental mammals during gestation (pregnancy). ...

Synthetic (recombinant or cell-clone) human immunoglobulins can now be made, and for several reasons (including the risk of prion contamination of biological materials) are likely to be used more and more often. However, they are expensive to produce and are not in large-scale production as of 2006. In the future it might be possible to artificially design antibodies to fit specific antigens, then produce them in large quantities to induce temporary immunity in people in advance of exposure to a specific pathogen, such as a bacterium, a virus, or a prion. At present, the science to understand this process is available but not the technology to perform it. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... A prion (pronounced pree-on) — short for proteinaceous infectious particle — is a unique type of infectious agent, as it is made only of protein. ... A pathogen or infectious agent is a biological agent that causes disease or illness to its host. ...

References

Further references given in the main articles indicated above.

1. ^ National Institutes of Health "Smallpox - A Great and Terrible Scourge" Variolation
2. ^ Andrew Dickson White "A History of the Warfare of Science with Theology - Chapter 10: Theological Opposition to Inoculation, Vaccination and the use of Anaesthetics" New York D. Appleton and Company 1898 Full text
3. ^ Harris F "Edward Jenner and Vaccination" World Wide School Full text
4. ^ François Marie Arouet de Voltaire (1694–1778). Lettres Philosophiques "Letter XI—On Inoculation" The Harvard Classics. 1909–14. English translation

• Essential Immunology. Roitt, I Blackwell Scientific Publications 3rt edition, subsequent revisions. ISBN 063200276X
• Pier GB, Lyczak JB, and Wetzler LM. (2004). Immunology, Infection, and Immunity. ASM Press. ISBN 1555812465
• Therapeutic antibodies Ganfyd on-line collaborative medical textbook.