Artificial induction of immunity
Encyclopedia
Artificial induction of immunity is the artificial induction of immunity to specific diseases - making people immune to disease by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering.
Immunity
against 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.
The earliest recorded artificial induction of immunity in humans was by variolation or inoculation
, which is the controlled infection of a subject with a less lethal natural form of smallpox (known as Variola Minor) 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.
Variolation had the disadvantage that the inoculating agent used 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.
and Edward Jenner
.
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. 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. Jenner described and generalised the process and then arranged to propagate cowpox for therapeutic use and he is credited with the discovery. Vaccination took over from variolation.
Jenner, like all members of the Royal Society
in those days, was an empiricist
. The theory to support further advances in vaccination came later.
and germ theory.
Louis 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.
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.
, 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 and time 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 the tetanus toxin is easily denature
d losing its ability to produce disease, but leaving it able to induce immunity to tetanus when injected into subjects. The denatured toxin is called a toxoid
.
See also Botulism
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.
A more contemporary approach for "boosting" the immune response to simpler immunogenic molecules (known as antigen
s) 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
.
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 proteins.
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.
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.
Immunity
Immunity (medical)
Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
against infections that can cause serious illness is generally beneficial. Since Pasteur
Pasteur
Pasteur could refer to* Louis Pasteur , French chemist and microbiologist who invented:**Pasteurization**The pasteur pipette, both named after him-Things and places named after Louis Pasteur:* Pasteur Institute* Pasteur point, level of oxygen...
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.
Variolation and smallpox
Inoculation
Inoculation is the placement of something that will grow or reproduce, and is most commonly used in respect of the introduction of a serum, vaccine, or antigenic substance into the body of a human or animal, especially to produce or boost immunity to a specific disease...
, which is the controlled infection of a subject with a less lethal natural form of smallpox (known as Variola Minor) 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
Lady Mary Wortley Montagu
The Lady Mary Wortley Montagu was an English aristocrat and writer. Montagu is today chiefly remembered for her letters, particularly her letters from Turkey, as wife to the British ambassador, which have been described by Billie Melman as “the very first example of a secular work by a woman about...
and perhaps others. From England, the technique spread rapidly to the Colonies, and was also spread by African slaves arriving into Boston.
Variolation had the disadvantage that the inoculating agent used 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 vaccinationVaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...
and Edward Jenner
Edward Jenner
Edward Anthony Jenner was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire...
.
In 1796, Edward Jenner
Edward Jenner
Edward Anthony Jenner was an English scientist who studied his natural surroundings in Berkeley, Gloucestershire...
, a doctor and scientist who had practiced variolation, performed an experiment based on the folk-knowledge that infection with cowpox
Cowpox
Cowpox is a skin disease caused by a virus known as the Cowpox virus. The pox is related to the vaccinia virus and got its name from the distribution of the disease when dairymaids touched the udders of infected cows. The ailment manifests itself in the form of red blisters and is transmitted by...
, a disease with minor symptoms which was never fatal, also conferred immunity to smallpox. 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
Benjamin Jesty
Benjamin Jesty was a farmer at Yetminster in Dorset, England, notable for his early experiment in inducing immunity against smallpox using cowpox....
, who had not publicized his discovery. Jenner described and generalised the process and then arranged to propagate cowpox for therapeutic use and he is credited with the discovery. Vaccination took over from variolation.
Jenner, like all members of the Royal Society
Royal Society
The Royal Society of London for Improving Natural Knowledge, known simply as the Royal Society, is a learned society for science, and is possibly the oldest such society in existence. Founded in November 1660, it was granted a Royal Charter by King Charles II as the "Royal Society of London"...
in those days, was an empiricist
Empiricism
Empiricism is a theory of knowledge that asserts that knowledge comes only or primarily via sensory experience. One of several views of epistemology, the study of human knowledge, along with rationalism, idealism and historicism, empiricism emphasizes the role of experience and evidence,...
. The theory to support further advances in vaccination came later.
Germ theory
See main articles Louis PasteurLouis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
and germ theory.
Louis Pasteur
Louis Pasteur
Louis Pasteur was a French chemist and microbiologist born in Dole. He is remembered for his remarkable breakthroughs in the causes and preventions of diseases. His discoveries reduced mortality from puerperal fever, and he created the first vaccine for rabies and anthrax. His experiments...
perfected experiments which disproved the then-popular theory of spontaneous generation
Spontaneous generation
Spontaneous generation or Equivocal generation is an obsolete principle regarding the origin of life from inanimate matter, which held that this process was a commonplace and everyday occurrence, as distinguished from univocal generation, or reproduction from parent...
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
Anthrax
Anthrax is an acute disease caused by the bacterium Bacillus anthracis. Most forms of the disease are lethal, and it affects both humans and other animals...
. 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.
Pasteur also isolated a crude preparation of the infectious agent for rabies
Rabies
Rabies is a viral disease that causes acute encephalitis in warm-blooded animals. It is zoonotic , most commonly by a bite from an infected animal. For a human, rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms...
. 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
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
, and rabies is known to be caused by a virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
. 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.
Toxoids
Some diseases, such as tetanusTetanus
Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod-shaped, obligate anaerobic bacterium Clostridium tetani...
, cause disease not by bacterial growth but by bacterial production of a toxin
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
. Tetanus toxin is so lethal that humans cannot develop immunity to a natural infection, as the amount of toxin and time required to kill a person is much less than is required by the immune system to recognize the toxin and produce antibodies
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
against it. However the tetanus toxin is easily denature
Denaturation (biochemistry)
Denaturation is a process in which proteins or nucleic acids lose their tertiary structure and secondary structure by application of some external stress or compound, such as a strong acid or base, a concentrated inorganic salt, an organic solvent , or heat...
d losing its ability to produce disease, but leaving it able to induce immunity to tetanus when injected into subjects. The denatured toxin is called a toxoid
Toxoid
A toxoid is a bacterial toxin whose toxicity has been weakened or suppressed either by chemical or heat treatment, while other properties, typically immunogenicity, are maintained. In international medical literature the preparation also is known as Anatoxin or Anatoxine...
.
See also Botulism
Botulism
Botulism also known as botulinus intoxication is a rare but serious paralytic illness caused by botulinum toxin which is metabolic waste produced under anaerobic conditions by the bacterium Clostridium botulinum, and affecting a wide range of mammals, birds and fish...
Adjuvants
See also main article on adjuvants in immunology.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
Memory B cell
Memory B cells are a B cell sub-type that are formed following primary infection.-Primary response, paratopes, and epitopes:In wake of first infection involving a particular antigen, the responding naïve cells proliferate to produce a colony of cells, most of which differentiate into the plasma...
. However, adding certain substances to the mixture, for example adsorbing tetanus toxoid onto alum
Alum
Alum is both a specific chemical compound and a class of chemical compounds. The specific compound is the hydrated potassium aluminium sulfate with the formula KAl2.12H2O. The wider class of compounds known as alums have the related empirical formula, AB2.12H2O.-Chemical properties:Alums are...
, 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.
A more contemporary approach for "boosting" the immune response to simpler immunogenic molecules (known as antigen
Antigen
An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...
s) 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
Polysaccharide
Polysaccharides are long carbohydrate molecules, of repeated monomer units joined together by glycosidic bonds. They range in structure from linear to highly branched. Polysaccharides are often quite heterogeneous, containing slight modifications of the repeating unit. Depending on the structure,...
from the capsule of the bacteria responsible for most lobar pneumonia
Lobar pneumonia
Lobar pneumonia is a form of pneumonia that affects a large and continuous area of the lobe of a lung.It is one of the two anatomic classifications of pneumonia .- Symptoms :...
.
Temporarily-induced immunity
See also immunoglobulin.Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
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
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
), and injecting this serum into the person for whom immunity is desired. This is known as passive immunity
Passive immunity
Passive immunity is the transfer of active humoral immunity in the form of readymade antibodies, from one individual to another. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and can also be induced artificially, when high levels...
, and the serum that is isolated from one subject and injected into another is sometimes called antiserum
Antiserum
Antiserum is blood serum containing polyclonal antibodies. Antiserum is used to pass on passive immunity to many diseases. Passive antibody transfusion from a previous human survivor is the only known effective treatment for Ebola infection .The most common use of antiserum in humans is as...
. 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 proteins.
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
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
antibodies from its mother across the placenta
Placenta
The placenta is an organ that connects the developing fetus to the uterine wall to allow nutrient uptake, waste elimination, and gas exchange via the mother's blood supply. "True" placentas are a defining characteristic of eutherian or "placental" mammals, but are also found in some snakes and...
, 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.
Synthetic (recombinant
Recombinant DNA
Recombinant DNA molecules are DNA sequences that result from the use of laboratory methods to bring together genetic material from multiple sources, creating sequences that would not otherwise be found in biological organisms...
or cell-clone) human immunoglobulins can now be made, and for several reasons (including the risk of prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
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
Pathogen
A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...
, such as a bacterium, a virus, or a prion
Prion
A prion is an infectious agent composed of protein in a misfolded form. This is in contrast to all other known infectious agents which must contain nucleic acids . The word prion, coined in 1982 by Stanley B. Prusiner, is a portmanteau derived from the words protein and infection...
. At present, the science to understand this process is available but not the technology to perform it.