Inimmunology,passive immunity is the transfer of activehumoral immunity of ready-madeantibodies. Passiveimmunity can occur naturally, when maternal antibodies are transferred to thefetus through theplacenta, and it can also be induced artificially, when high levels of antibodies specific to apathogen ortoxin (obtained fromhumans,horses, or otheranimals) are transferred to non-immune persons throughblood products that contain antibodies, such as inimmunoglobulin therapy orantiserum therapy.[1]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 orimmunosuppressive diseases.[2] Passive immunization can be provided when people cannot synthesize antibodies, and when they have been exposed to a disease that they do not have immunity against.[3]
Maternal passive immunity is a type of naturally acquired passive immunity, and refers toantibody-mediated immunity conveyed to afetus or infant by its mother. Naturally acquired passive immunity can be provided during pregnancy, and throughbreastfeeding.[4] In humans, maternal antibodies (MatAb) are passed through theplacenta to the fetus by anFcRn receptor on placental cells. This occurs predominately during the third trimester of pregnancy, and thus is often reduced in babies born prematurely.Immunoglobulin G (IgG) is the only antibodyisotype that can pass through the human placenta, and is the most common antibody of the five types of antibodies found in the body. IgG antibodies protects against bacterial and viral infections in fetuses. Immunization is often required shortly following birth to prevent diseases in newborns such astuberculosis,hepatitis B,polio, andpertussis, however, maternal IgG can inhibit the induction of protective vaccine responses throughout the first year of life. This effect is usually overcome by secondary responses to booster immunization.[5] Maternal antibodies protect against some diseases, such as measles, rubella, and tetanus, more effectively than against others, such as polio and pertussis.[6] Maternal passive immunity offers immediate protection, though protection mediated by maternal IgG typically only lasts up to a year.[6]
Passive immunity is also provided throughcolostrum and breast milk, which containIgA antibodies that are transferred to the gut of the infant, providing local protection against disease causing bacteria and viruses until the newborn can synthesize its own antibodies.[7] Protection mediated by IgA is dependent on the length of time that an infant is breastfed, which is one of the reasons the World Health Organization recommends breastfeeding for at least the first two years of life.[8]
Other species besides humans transfer maternal antibodies before birth, including primates and lagomorphs (which includes rabbits and hares).[9] In some of these species IgM can be transferred across the placenta as well as IgG. All other mammalian species predominantly or solely transfer maternal antibodies after birth through milk. In these species, the neonatal gut is able to absorb IgG for hours to days after birth. However, after a period of time the neonate can no longer absorb maternal IgG through their gut, an event that is referred to as "gut closure". If a neonatal animal does not receive adequate amounts of colostrum prior to gut closure, it does not have a sufficient amount of maternal IgG in its blood to fight off common diseases. This condition is referred to as failure of passive transfer. It can be diagnosed by measuring the amount of IgG in a newborn's blood, and is treated with intravenous administration of immunoglobulins. If not treated, it can be fatal.[citation needed]
Apreprint suggested that (SARS-CoV-2) antibodies in or transmitted through the air are an unrecognized mechanism by which, transferred, passive immune protection occurs.[10][better source needed]
Antibodies from vaccination can be present in saliva and thereby may have utility in preventing infection.[11][better source needed]
Artificially acquired passive immunity is a short-term immunization achieved by the transfer of antibodies, which can be administered in several forms; as human or animalblood plasma orserum, as pooled human immunoglobulin for intravenous (IVIG) or intramuscular (IG) use, as high-titer human IVIG or IG from immunized donors or from donors recovering from the disease, and asmonoclonal antibodies (MAb). Passive transfer is used to prevent disease or usedprophylactically in the case ofimmunodeficiency diseases, such ashypogammaglobulinemia.[12][13] It is also used in the treatment of several types of acute infection, and to treatpoisoning.[2] Immunity derived from passive immunization lasts for a few weeks to three to four months.[14][15] There is also a potential risk forhypersensitivity reactions, andserum sickness, especially fromgamma globulin of non-human origin.[7] 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 unless they acquire active immunity or vaccination.[7]
In 1888Emile Roux andAlexandre Yersin showed that the clinical effects of diphtheria were caused bydiphtheria toxin and, following the 1890 discovery of anantitoxin-based immunity todiphtheria andtetanus byEmil Adolf von Behring andKitasato Shibasaburō, antitoxin became the first major success of modern therapeutic immunology.[16][17] Shibasaburo and von Behring immunized guinea pigs with the blood products from animals that had recovered from diphtheria and realized that the same process of heat treating blood products of other animals could treat humans with diphtheria.[18] By 1896, the introduction of diphtheria antitoxin was hailed as "the most important advance of the [19th] Century in the medical treatment of acute infective disease".[19]
Prior to the advent of vaccines andantibiotics, specific antitoxin was often the only treatment available for infections such as diphtheria and tetanus. Immunoglobulin therapy continued to be a first line therapy in the treatment of severerespiratory diseases until the 1930s, even aftersulfonamides were introduced.[13]
In 1890 antibody therapy was used to treattetanus, when serum from immunized horses was injected into patients with severe tetanus in an attempt to neutralize the tetanus toxin, and prevent the dissemination of the disease. Since the 1960s, human tetanus immune globulin (TIG) has been used in the United States in unimmunized, vaccine-naive or incompletely immunized patients who have sustained wounds consistent with the development of tetanus.[13] The administration of horseantitoxin remains the only specific pharmacologic treatment available forbotulism.[20] Antitoxin also known as heterologous hyperimmune serum is often also given prophylactically to individuals known to have ingested contaminated food.[6] IVIG treatment was also used successfully to treat several patients withtoxic shock syndrome, during the 1970stampon scare.[citation needed]
Antibody therapy is also used to treat viral infections. In 1945,hepatitis A infections, epidemic in summer camps, were successfully prevented by immunoglobulin treatment. Similarly,hepatitis B immune globulin (HBIG) effectively prevents hepatitis B infection. Antibody prophylaxis of both hepatitis A and B has largely been supplanted by the introduction of vaccines; however, it is still indicated following exposure and prior to travel to areas of endemic infection.[21]
In 1953, humanvaccinia immunoglobulin (VIG) was used to prevent the spread ofsmallpox during an outbreak inMadras, India, and continues to be used to treat complications arising from smallpox vaccination. Although the prevention ofmeasles is typically induced through vaccination, it is often treated immuno-prophylactically upon exposure. Prevention ofrabies infection still requires the use of both vaccine and immunoglobulin treatments.[13]
During a 1995Ebola virus outbreak in theDemocratic Republic of Congo, whole blood from recovering patients, and containing anti-Ebola antibodies, was used to treat eight patients, as there was no effective means of prevention, though a treatment was discovered recently in the 2013 Ebola epidemic in Africa. Only one of the eight infected patients died, compared to a typical 80% Ebola mortality, which suggested that antibody treatment may contribute to survival.[22] Immune globulin or immunoglobulin has been used to both prevent and treat reactivation of theherpes simplex virus (HSV),varicella zoster virus,Epstein-Barr virus (EBV), andcytomegalovirus (CMV).[13]
The following immunoglobulins are the immunoglobulins currently approved for use forinfectious diseaseprophylaxis andimmunotherapy, in the United States.[23]
| Disease | Product[a] | Source | Use |
|---|---|---|---|
| Botulism | Specific equine IgG | horse | Treatment of wound and food borne forms of botulism. |
| Despeciated equine IgG[24] | |||
| Human specific IgG[24] | human | Treatment of infant botulism types A and B; brand name "BabyBIG". | |
| Cytomegalovirus (CMV) | hyperimmune IVIG | human | Prophylaxis, used most often inkidneytransplant patients. |
| Diphtheria | Specific equine IgG | horse | Treatment of diphtheria infection. |
| Hepatitis B | Hepatitis B Ig | human | Post-exposure prophylaxis, prevention in high-risk infants (administered with Hepatitis Bvaccine). |
| Hepatitis A,measles | Pooled human Ig | human serum | Prevention of Hepatitis A and measles infection, treatment ofcongenital or acquiredimmunodeficiency. |
| ITP,Kawasaki disease, IgG deficiency | Pooled human IgG | human serum | Treatment of ITP and Kawasaki disease, prevention/treatment ofopportunistic infection with IgG deficiency. |
| Rabies | Rabies Ig | human | Post-exposure prophylaxis (administered with rabies vaccine). |
| Tetanus | Tetanus Ig | human | Treatment of tetanus infection. |
| Vaccinia | Vaccinia Ig | human | Treatment of progressive vaccinia infection including eczema and ocular forms (usually resulting from smallpoxvaccination inimmunocompromised individuals). |
| Varicella (chicken-pox) | Varicella-zoster Ig | human | Post-exposure prophylaxis in high risk individuals. |
| Rh disease | Rho(D) immune globulin | human | Prevention ofRhD isoimmunization in Rh(D)-negative mothers[25] |
The one exception to passive humoral immunity is the passive transfer ofcell-mediated immunity, also calledadoptive immunization which involves the transfer of mature circulating lymphocytes. It is rarely used in humans, and requireshistocompatible (matched) donors, which are often difficult to find, and carries severe risks ofgraft-versus-host disease.[2] This technique has been used in humans to treat certain diseases including some types ofcancer andimmunodeficiency. However, this specialized form of passive immunity is most often used in a laboratory setting in the field ofimmunology, to transfer immunity between "congenic", ordeliberately inbred mouse strains which are histocompatible.[citation needed]
Passive immunity starts working faster than vaccines do, as the patient's immune system does not need to make its own antibodies:B cells take time to activate and multiply after a vaccine is given. Passive immunity works even if an individual has a immune system disorder that prevents them from making antibodies in response to a vaccine.[18] In addition to conferring passive immunities, breastfeeding has other lasting beneficial effects on the baby's health, such as decreased risk of allergies and obesity.[26]
A disadvantage to passive immunity is that producing antibodies in a laboratory is expensive and difficult to do. In order to produce antibodies for infectious diseases, there is a need for possibly thousands of human donors to donate blood or immune animals' blood would be obtained for the antibodies. Patients who are immunized with the antibodies from animals may develop serum sickness due to the proteins from the immune animal and develop serious allergic reactions.[6] Antibody treatments can be time-consuming and are given through an intravenous injection or IV, while a vaccine shot or jab is less time-consuming and has less risk of complication than an antibody treatment. Passive immunity is effective, but only lasts a short amount of time.[18]
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