Immunity (medical)

Overview
Immunity is a medical 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 pathogens to stop infection by micro-organisms before they can cause disease. Other components of the immune system adapt themselves to each new disease encountered and are able to generate pathogen-specific immunity.

Specific, or adaptive immunity is often sub-divided into two major types depending on how the immunity was introduced. Natural immunity occurs through contact with a disease causing agent, when the contact was not deliberate, whereas artificial immunity develops only through deliberate actions. Both natural and artificial immunity can be further subdivided, depending on the amount of time the protection lasts. Passive immunity is short lived, and usually lasts only a few months, whereas protection via active immunity lasts much longer, and is sometimes life-long. The diagram below summarizes these divisions of immunity.

A further subdivision of adaptive immunity is characterized by the cells involved; humoral immunity is the aspect of immunity that is mediated by secreted antibodies, whereas the protection provided by cell mediated immunity involves T-lymphocytes alone. Humoral immunity is active when the organism generates it’s own antibodies, and passive when antibodies are transferred between individuals. Similarly, cell mediated immunity is active when the organisms’ own T-cells are stimulated and passive when T cells come from another organism. 

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 method 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). However, it was with 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 insults. The birth of passive immunotherapy may have begun with Mithridates VI of Pontus, who sought to harden himself against poison, and took daily sub-lethal doses of poison 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. 

Passive immunity
Passive immunity is the transfer of active 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 of human (or horse) antibodies specific for a pathogen or toxin are transferred to non-immune individuals. Passive immunization is used when there is a high risk of infection and insufficient time for the body to develop its own immune response, or to reduce the symptoms of ongoing or immunosuppressive diseases. Passive immunity provides immediate protection, but the body does not develop memory, therefore the patient is at risk of being infected by the same pathogen later.

Naturally acquired passive immunity
Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus by its mother during pregnancy. Maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn receptor on placental cells. This occurs around the third month of gestation. IgG is the only antibody isotype that can pass through the placenta. Passive immunity is also provided through the transfer of IgA antibodies found in breast milk that are transferred to the gut of the infant, protecting against bacterial infections, until the newborn can synthesize its own antibodies.

Artificially acquired passive immunity
see also: Temporarily-induced immunity

Artificially acquired passive immunity is a short-term immunization induced by the transfer of antibodies, which can be administered in several forms; as human or animal plasma or serum, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, and in the form of monoclonal antibodies (MAb). Passive transfer is used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia. It is also used in the treatment of several types of acute infection, and to treat poisoning. Immunity derived from passive immunization lasts for only a short period of time, and there is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma globulin of non-human origin.

The artificial induction of passive immunity has been used for over a century to treat infectious disease, and prior to the advent of antibiotics, was often the only specific treatment for certain infections. Immunoglobulin therapy continued to be a first line therapy in the treatment of severe respiratory diseases until the 1930’s, even after sulfonamide antibiotics were introduced.

Passive transfer of cell-mediated immunity
Passive or "adoptive transfer" of cell-mediated immunity, is conferred by the transfer of "sensitized" or activated T-cells from one individual into another. It is rarely used in humans because it requires histocompatible (matched) donors, which are often difficult to find. In unmatched donors this type of transfer carries severe risks of graft versus host disease. It has, however, been used to treat certain diseases including some types of cancer and immunodeficiency. This type of transfer differs from a bone marrow transplant, in which (undifferentiated) hematopoietic stem cells are transferred.

Active Immunity
When B cells and T cells are activated by a pathogen, memory B-cells and T- cells develop. Throughout the lifetime of an animal these memory cells will “remember” each specific pathogen encountered, and are able to mount a strong response if the pathogen is detected again. This type of immunity is both active and adaptive because the body's immune system prepares itself for future challenges. Active immunity often involves both the cell-mediated and humoral aspects of immunity as well as input from the innate immune system. The innate system is present from birth and protects an individual from pathogens regardless of experiences, whereas adaptive immunity arises only after an infection or immunization and hence is "acquired" during life.

Naturally acquired active immunity
Naturally acquired active immunity occurs when a person is exposed to a live pathogen, and develops a primary immune response, which leads to immunological memory. This type of immunity is “natural” because it is not induced by man. Many disorders of immune system function can affect the formation of active immunity such as immunodeficiency (both acquired and congenital forms) and immunosuppression.

Artificially acquired active immunity
Artificially acquired active immunity can be induced by a vaccine, a substance that contains antigen. A vaccine stimulates a primary response against the antigen without causing symptoms of the disease. The term vaccination was coined by Edward Jenner and adapted by Louis Pasteur for his pioneering work in vaccination. The method Pasteur used entailed treating the infectious agents for those diseases so they lost the ability to cause serious disease. Pasteur adopted the name vaccine as a generic term in honor of Jenner's discovery, which Pasteur's work built upon. In 1807, the Bavarians became the first group to require that their military recruits be vaccinated against smallpox, as the spread of smallpox was linked to combat. Subsequently the practice of vaccination would increase with the spread of war.

There are four types of traditional vaccines:
 * Inactivated vaccines are composed of micro-organisms that have been killed with chemicals and/or heat and are no longer infectious. Examples are vaccines against flu, cholera, bubonic plague, and hepatitis A. Most vaccines of this type are likely to require booster shots.
 * Live, attenuated vaccines are composed of micro-organisms that have been cultivated under conditions which disable their ability to induce disease. These responses are more durable and do not generally require booster shots. Examples include yellow fever, measles, rubella, and mumps.
 * Toxoids are inactivated toxic compounds from micro-organisms in cases where these (rather than the micro-organism itself) cause illness, used prior to an encounter with the toxiod. Examples of toxoid-based vaccines include tetanus and diphtheria.
 * Subunit -vaccines are composed of small fragments of disease causing organisms. A characteristic example is the subunit vaccine against Hepatitis B virus.

Most vaccines are given by hypodermic injection as they are not absorbed reliably through the gut. Live attenuated Polio and some Typhoid and Cholera vaccines are given orally in order to produce immunity based in the bowel.