Passive immunity

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In immunology, passive immunity is the transfer of active humoral immunity of ready-made antibodies. Passive immunity can occur naturally, when maternal antibodies are transferred to the fetus through the placenta, and it can also be induced artificially, when high levels of antibodies specific to a pathogen or toxin (obtained from humans, horses, or other animals) are transferred to non-immune persons through blood products that contain antibodies, such as in immunoglobulin therapy or antiserum 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 or immunosuppressive 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]

Contents

Naturally acquired

Maternal passive immunity

Maternal passive immunity is a type of naturally acquired passive immunity, and refers to antibody-mediated immunity conveyed to a fetus or infant by its mother. Naturally acquired passive immunity can be provided during pregnancy, and through breastfeeding. [4] In humans, maternal antibodies (MatAb) are passed through the placenta to the fetus by an FcRn 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 antibody isotype 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 as tuberculosis, hepatitis B, polio, and pertussis, 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 through colostrum and breast milk, which contain IgA 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 ]

Other

A preprint 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

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 animal blood plasma or serum, 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 as monoclonal antibodies (MAb). Passive transfer is used to prevent disease or used prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia. [12] [13] It is also used in the treatment of several types of acute infection, and to treat poisoning. [2] Immunity derived from passive immunization lasts for a few weeks to three to four months. [14] [15] There is also a potential risk for hypersensitivity reactions, and serum sickness, especially from gamma 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]

History and applications of artificial passive immunity

A vial of diphtheria antitoxin, dated 1895 Antitoxin diphtheria.jpg
A vial of diphtheria antitoxin, dated 1895

In 1888 Emile Roux and Alexandre Yersin showed that the clinical effects of diphtheria were caused by diphtheria toxin and, following the 1890 discovery of an antitoxin-based immunity to diphtheria and tetanus by Emil Adolf von Behring and Kitasato 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 and antibiotics, 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 severe respiratory diseases until the 1930s, even after sulfonamides were introduced. [13]

This image is from the Historical Medical Library of The College of Physicians of Philadelphia. This displays the administration of diphtheria antitoxin from horse serum to young child, dated 1895. Administration of Diphtheria Antitoxin from Horse Serum.jpg
This image is from the Historical Medical Library of The College of Physicians of Philadelphia. This displays the administration of diphtheria antitoxin from horse serum to young child, dated 1895.

In 1890 antibody therapy was used to treat tetanus, 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 horse antitoxin remains the only specific pharmacologic treatment available for botulism. [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 with toxic shock syndrome, during the 1970s tampon 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, human vaccinia immunoglobulin (VIG) was used to prevent the spread of smallpox during an outbreak in Madras, India, and continues to be used to treat complications arising from smallpox vaccination. Although the prevention of measles is typically induced through vaccination, it is often treated immuno-prophylactically upon exposure. Prevention of rabies infection still requires the use of both vaccine and immunoglobulin treatments. [13]

During a 1995 Ebola virus outbreak in the Democratic 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 the herpes simplex virus (HSV), varicella zoster virus, Epstein-Barr virus (EBV), and cytomegalovirus (CMV). [13]

FDA licensed immunoglobulins

The following immunoglobulins are the immunoglobulins currently approved for use for infectious disease prophylaxis and immunotherapy, in the United States. [23]

FDA approved products for passive immunization and immunotherapy
DiseaseProduct [lower-alpha 1] SourceUse
Botulism Specific equine IgG horse Treatment of wound and food borne forms of botulism.
Despeciated equine IgG [24]
Human specific IgG [24] humanTreatment of infant botulism types A and B; brand name "BabyBIG".
Cytomegalovirus (CMV) hyperimmune IVIG humanProphylaxis, used most often in kidney transplant patients.
Diphtheria Specific equine IgG horseTreatment of diphtheria infection.
Hepatitis B Hepatitis B Ig humanPost-exposure prophylaxis, prevention in high-risk infants
(administered with Hepatitis B vaccine).
Hepatitis A, measles Pooled human Ig human serumPrevention of Hepatitis A and measles infection,
treatment of congenital or acquired immunodeficiency.
ITP, Kawasaki disease,
IgG deficiency 		Pooled human IgG human serumTreatment of ITP and Kawasaki disease,
prevention/treatment of opportunistic infection with IgG deficiency.
Rabies Rabies Ig humanPost-exposure prophylaxis (administered with rabies vaccine).
Tetanus Tetanus Ig humanTreatment of tetanus infection.
Vaccinia Vaccinia Ig humanTreatment of progressive vaccinia infection
including eczema and ocular forms (usually resulting from
smallpox vaccination in immunocompromised individuals).
Varicella (chicken-pox) Varicella-zoster Ig humanPost-exposure prophylaxis in high risk individuals.
Rh disease Rho(D) immune globulin humanPrevention of RhD isoimmunization in Rh(D)-negative mothers [25]
  1. ↑ Specific or not noted: hyperimmune globulin or antitoxin. Pooled: mixed Ig from ordinary sources, also known as normal human immunoglobulin.

Passive transfer of cell-mediated immunity

The one exception to passive humoral immunity is the passive transfer of cell-mediated immunity, also called adoptive immunization which involves the transfer of mature circulating lymphocytes. It is rarely used in humans, and requires histocompatible (matched) donors, which are often difficult to find, and carries severe risks of graft-versus-host disease. [2] This technique has been used in humans to treat certain diseases including some types of cancer and immunodeficiency. However, this specialized form of passive immunity is most often used in a laboratory setting in the field of immunology, to transfer immunity between "congenic", or deliberately inbred mouse strains which are histocompatible.[ citation needed ]

Advantages and disadvantages

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]

See also

Related Research Articles

<span class="mw-page-title-main">Emil von Behring</span> German physiologist (1854–1917)

Emil von Behring, was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery of a diphtheria antitoxin. He was widely known as a "saviour of children", as diphtheria used to be a major cause of child death. His work with the disease, as well as tetanus, has come to bring him most of his fame and acknowledgment. He was honoured with Prussian nobility in 1901, henceforth being known by the surname "von Behring".

<span class="mw-page-title-main">Diphtheria</span> Bacterial disease

Diphtheria is an infection caused by the bacterium Corynebacterium diphtheriae. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks, the mortality rate approaches 10%. Signs and symptoms may vary from mild to severe, and usually start two to five days after exposure. Symptoms often develop gradually, beginning with a sore throat and fever. In severe cases, a grey or white patch develops in the throat, which can block the airway, and create a barking cough similar to what is observed in croup. The neck may also swell, in part due to the enlargement of the facial lymph nodes. Diphtheria can also involve the skin, eyes, or genitals, and can cause complications, including myocarditis, inflammation of nerves, kidney problems, and bleeding problems due to low levels of platelets.

<span class="mw-page-title-main">Gamma globulin</span> Class of blood proteins

Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some gamma globulins are not immunoglobulins.

In biology, immunity is the state of being insusceptible or resistant to a noxious agent or process, especially a pathogen or infectious disease. Immunity may occur naturally or be produced by prior exposure or immunization.

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Antitoxin</span> Antibody with the ability to neutralize a specific toxin

An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, they can also kill bacteria and other microorganisms. Antitoxins are made within organisms, and can be injected into other organisms, including humans, to treat an infectious disease. This procedure involves injecting an animal with a safe amount of a particular toxin. The animal's body then makes the antitoxin needed to neutralize the toxin. Later, blood is withdrawn from the animal. When the antitoxin is obtained from the blood, it is purified and injected into a human or other animal, inducing temporary passive immunity. To prevent serum sickness, it is often best to use an antitoxin obtained from the same species.

In immunology, antiserum is a blood serum containing antibodies that is used to spread passive immunity to many diseases via blood donation (plasmapheresis). For example, convalescent serum, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for ebola infection with a high success rate of 7 out of 8 patients surviving.

This is a list of AIDS-related topics, many of which were originally taken from the public domain U.S. Department of Health Glossary of HIV/AIDS-Related Terms, 4th Edition.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

<span class="mw-page-title-main">Toxoid</span> Weakened form of a toxin, often used for vaccines

A toxoid is an inactivated toxin whose toxicity has been suppressed either by chemical (formalin) or heat treatment, while other properties, typically immunogenicity, are maintained. Toxins are secreted by bacteria, whereas toxoids are altered form of toxins; toxoids are not secreted by bacteria. Thus, when used during vaccination, an immune response is mounted and immunological memory is formed against the molecular markers of the toxoid without resulting in toxin-induced illness. Such a preparation is also known as an anatoxin. There are toxoids for prevention of diphtheria, tetanus and botulism.

<span class="mw-page-title-main">X-linked agammaglobulinemia</span> Medical condition

X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the white blood cell formation process does not generate mature B cells, which manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream. B cells are part of the immune system and normally manufacture antibodies, which defend the body from infections by sustaining a humoral immunity response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development and a reduced immunoglobulin production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.

Hypogammaglobulinemia is an immune system disorder in which not enough gamma globulins are produced in the blood. This results in a lower antibody count, which impairs the immune system, increasing risk of infection. Hypogammaglobulinemia may result from a variety of primary genetic immune system defects, such as common variable immunodeficiency, or it may be caused by secondary effects such as medication, blood cancer, or poor nutrition, or loss of gamma globulins in urine, as in nonselective glomerular proteinuria. Patients with hypogammaglobulinemia have reduced immune function; important considerations include avoiding use of live vaccines, and take precautionary measures when traveling to regions with endemic disease or poor sanitation such as receiving immunizations, taking antibiotics abroad, drinking only safe or boiled water, arranging appropriate medical cover in advance of travel, and ensuring continuation of any immunoglobulin infusions needed.

Rho(D) immune globulin (RhIG) is a medication used to prevent RhD isoimmunization in mothers who are RhD negative and to treat idiopathic thrombocytopenic purpura (ITP) in people who are Rh positive. It is often given both during and following pregnancy. It may also be used when RhD-negative people are given RhD-positive blood. It is given by injection into muscle or a vein. A single dose lasts 12 weeks. It is made from human blood plasma.

Artificial induction of immunity is immunization achieved by human efforts in preventive healthcare, as opposed to natural immunity as produced by organisms' immune systems. It makes people immune to specific diseases by means other than waiting for them to catch the disease. The purpose is to reduce the risk of death and suffering, that is, the disease burden, even when eradication of the disease is not possible. Vaccination is the chief type of such immunization, greatly reducing the burden of vaccine-preventable diseases.

<span class="mw-page-title-main">Hepatitis B vaccine</span> Vaccine against hepatitis B

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people, routine immunization results in more than 95% of people being protected.

A neutralizing antibody (NAb) is an antibody that defends a cell from a pathogen or infectious particle by neutralizing any effect it has biologically. Neutralization renders the particle no longer infectious or pathogenic. Neutralizing antibodies are part of the humoral response of the adaptive immune system against viruses, bacteria and microbial toxin. By binding specifically to surface structures (antigen) on an infectious particle, neutralizing antibodies prevent the particle from interacting with its host cells it might infect and destroy.

Vaccinia immune globulin (VIG) is made from the pooled blood of individuals who have been inoculated with the smallpox vaccine. The antibodies these individuals developed in response to the smallpox vaccine are removed and purified. This results in VIG. It can be administered intravenously. It is used to treat individuals who have developed progressive vaccinia after smallpox vaccination.

Immunoglobulin therapy is the use of a mixture of antibodies to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory demyelinating polyneuropathy, Kawasaki disease, certain cases of HIV/AIDS and measles, Guillain–Barré syndrome, and certain other infections when a more specific immunoglobulin is not available. Depending on the formulation it can be given by injection into muscle, a vein, or under the skin. The effects last a few weeks.

<span class="mw-page-title-main">Anti-tetanus immunoglobulin</span> Medication made up of antibodies against the tetanus toxin

Anti-tetanus immunoglobulin, also known as tetanus immune globulin (TIG) and tetanus antitoxin, is a medication made up of antibodies against the tetanus toxin. It is used to prevent tetanus in those who have a wound that is at high risk, have not been fully vaccinated with tetanus toxoid, or have HIV/AIDS. It is used to treat tetanus along with antibiotics and muscle relaxants. It is given by injection into a muscle. Part of the dose is injected at the site of the wound.

Passive antibody therapy, also called serum therapy, is a subtype of passive immunotherapy that administers antibodies to target and kill pathogens or cancer cells. It is designed to draw support from foreign antibodies that are donated from a person, extracted from animals, or made in the laboratory to elicit an immune response instead of relying on the innate immune system to fight disease. It has a long history from the 18th century for treating infectious diseases and is now a common cancer treatment. The mechanism of actions include: antagonistic and agonistic reaction, complement-dependent cytotoxicity (CDC), and antibody-dependent cellular cytotoxicity (ADCC).

References

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