Maternal Passive Immunity
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Passive immunity is the transfer of active
humoral immunity 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 in ...
of ready-made
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
. Passive
immunity Immunity may refer to: Medicine * Immunity (medical), resistance of an organism to infection or disease * ''Immunity'' (journal), a scientific journal published by Cell Press Biology * Immune system Engineering * Radiofrequence immunity desc ...
can occur naturally, when maternal antibodies are transferred to the
fetus A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
through the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
, and it can also be induced artificially, when high levels of antibodies specific to a
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
or
toxin A toxin is a naturally occurring organic poison produced by metabolic activities of living cells or organisms. Toxins occur especially as a protein or conjugated protein. The term toxin was first used by organic chemist Ludwig Brieger (1849– ...
(obtained from
human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
s,
horse The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million y ...
s, or other animals) are transferred to non-
immune In biology, immunity is the capability of multicellular organisms to resist harmful microorganisms. Immunity involves both specific and nonspecific components. The nonspecific components act as barriers or eliminators of a wide range of pathogens ...
persons through blood products that contain antibodies, such as in
immunoglobulin therapy Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin or NHIG) to treat several health conditions. These conditions include primary immunodeficiency, immune thrombocytopenic purpura, chronic inflammatory de ...
or
antiserum Antiserum is a blood serum containing monoclonal or polyclonal 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 ...
therapy. 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.Microbiology and Immunology On-Line Textbook
: USC School of Medicine
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.


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 A fetus or foetus (; plural fetuses, feti, foetuses, or foeti) is the unborn offspring that develops from an animal embryo. Following embryonic development the fetal stage of development takes place. In human prenatal development, fetal deve ...
or infant by its mother. Naturally acquired passive immunity can be provided during pregnancy, and through breastfeeding. In humans, maternal antibodies (MatAb) are passed through the
placenta The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate mater ...
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 Immunoglobulin G (Ig G) is a type of antibody. Representing approximately 75% of serum antibodies in humans, IgG is the most common type of antibody found in blood circulation. IgG molecules are created and released by plasma B cells. Each IgG a ...
(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. Maternal antibodies protect against some diseases, such as measles, rubella, and tetanus, more effectively than against others, such as polio and pertussis. Maternal passive immunity offers immediate protection, though protection mediated by maternal IgG typically only lasts up to a year. Passive immunity is also provided through colostrum and breast milk, which contain
IgA Iga may refer to: Arts and entertainment * Ambush at Iga Pass, a 1958 Japanese film * Iga no Kagemaru, Japanese manga series * Iga, a set of characters from the Japanese novel '' The Kouga Ninja Scrolls'' Biology * ''Iga'' (beetle), a gen ...
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.. 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. Other species besides humans transfer maternal antibodies before birth, including primates and lagomorphs (which includes rabbits and hares). 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.


Other

A
preprint In academic publishing, a preprint is a version of a scholarly or scientific paper that precedes formal peer review and publication in a peer-reviewed scholarly or scientific journal. The preprint may be available, often as a non-typeset versio ...
suggested that (SARS-CoV-2) antibodies in or transmitted through the air are an unrecognized mechanism by which, transferred, passive immune protection occurs. Antibodies from vaccination can be present in saliva and thereby may have utility in preventing infection.


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 Serum may refer to: *Serum (blood), plasma from which the clotting proteins have been removed **Antiserum, blood serum with specific antibodies for passive immunity * Serous fluid, any clear bodily fluid * Truth serum, a drug that is likely to mak ...
, 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 A monoclonal antibody (mAb, more rarely called moAb) is an antibody produced from a cell Lineage made by cloning a unique white blood cell. All subsequent antibodies derived this way trace back to a unique parent cell. Monoclonal antibodies ca ...
(MAb). Passive transfer is used to prevent disease or used prophylactically in the case of
immunodeficiency Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
diseases, such as hypogammaglobulinemia.Keller, Margaret A. and E. Richard Stieh
''Passive Immunity in Prevention and Treatment of Infectious Diseases''
Clinical Microbiology Reviews, October 2000, p. 602-614, Vol. 13, No. 4
It is also used in the treatment of several types of acute infection, and to treat
poison Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
ing. Immunity derived from passive immunization lasts for a few weeks to three to four months. There is also a potential risk for hypersensitivity reactions, and serum sickness, especially from
gamma globulin 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 ga ...
of non-human origin. 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.


History and applications of artificial passive immunity

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.Silverstein, Arthur M. (1989) History of Immunology (Hardcover) Academic Press. Note: The first six pages of this text are available online at:
Amazon.com easy reader
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. By 1896, the introduction of diphtheria antitoxin was hailed as "the most important advance of the
9th 9 (nine) is the natural number following and preceding . Evolution of the Arabic digit In the beginning, various Indians wrote a digit 9 similar in shape to the modern closing question mark without the bottom dot. The Kshatrapa, Andhra and ...
Century in the medical treatment of acute infective disease". 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 In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this group is unreactive. ...
were introduced. 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. The administration of horse antitoxin remains the only specific pharmacologic treatment available for botulism. Antitoxin also known as heterologous hyperimmune serum is often also given prophylactically to individuals known to have ingested contaminated food. IVIG treatment was also used successfully to treat several patients with toxic shock syndrome, during the 1970s tampon scare. 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. 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 Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
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. During a 1995
Ebola Ebola, also known as Ebola virus disease (EVD) and Ebola hemorrhagic fever (EHF), is a viral hemorrhagic fever in humans and other primates, caused by ebolaviruses. Symptoms typically start anywhere between two days and three weeks after becom ...
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. Immune globulin or immunoglobulin has been used to both prevent and treat reactivation of the
herpes simplex virus Herpes simplex virus 1 and 2 (HSV-1 and HSV-2), also known by their taxonomical names ''Human alphaherpesvirus 1'' and '' Human alphaherpesvirus 2'', are two members of the human ''Herpesviridae'' family, a set of viruses that produce viral inf ...
(HSV), varicella zoster virus, Epstein-Barr virus (EBV), and
cytomegalovirus ''Cytomegalovirus'' (''CMV'') (from ''cyto-'' 'cell' via Greek - 'container' + 'big, megalo-' + -''virus'' via Latin 'poison') is a genus of viruses in the order ''Herpesvirales'', in the family ''Herpesviridae'', in the subfamily ''Betaherpe ...
(CMV).


FDA licensed immunoglobulins

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


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 Graft-versus-host disease (GvHD) is a syndrome, characterized by inflammation in different organs. GvHD is commonly associated with bone marrow transplants and stem cell transplants. White blood cells of the donor's immune system which remain wit ...
. This technique has been used in humans to treat certain diseases including some types of cancer and
immunodeficiency Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
. 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.


Advantages and disadvantages

An individual's immune response of passive immunity is "faster than a vaccine" and can instill immunity in an individual that does not "respond to immunization", often within hours or a few days. 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. 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. 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.


See also

*
Active immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and processes that eliminate pathogens or prevent their growth. The acquired immune system ...
* Immunity (medical) * Antitoxin * Immunoglobulin therapy * Hyperimmune globulin


References

{{Breastfeeding Immunology Antibodies