Passive immunity is the transfer of active
humoral immunity of ready-made
antibodies. 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 dev ...
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 mate ...
, 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, cultu ...
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 yea ...
s, or other
animal
Animals are multicellular, eukaryotic organisms in the Kingdom (biology), biological kingdom Animalia. With few exceptions, animals Heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, are Motilit ...
s) 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 product
A blood product is any therapeutic substance prepared from human blood. This includes whole blood; blood components; and plasma derivatives. Whole blood is not commonly used in transfusion medicine. Blood components include: red blood cell conc ...
s 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 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
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
diseases.
[Microbiology and Immunology On-Line Textbook](_blank)
: 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
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 ...
-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 dev ...
or infant by its mother. Naturally acquired passive immunity can be provided during pregnancy, and through
breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
. 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 mate ...
to the fetus by an
FcRn
The neonatal Fc receptor (also FcRn, IgG receptor FcRn large subunit p51, or Brambell receptor) is a protein that in humans is encoded by the ''FCGRT'' gene. It is an IgG Fc receptor which is similar in structure to the MHC class I molecule an ...
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
Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, i ...
,
hepatitis B
Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. ...
,
polio
Poliomyelitis, commonly shortened to polio, is an infectious disease caused by the poliovirus. Approximately 70% of cases are asymptomatic; mild symptoms which can occur include sore throat and fever; in a proportion of cases more severe s ...
, and
pertussis
Whooping cough, also known as pertussis or the 100-day cough, is a highly contagious bacterial disease. Initial symptoms are usually similar to those of the common cold with a runny nose, fever, and mild cough, but these are followed by two or t ...
, 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
Colostrum, also known as beestings or first milk, is the first form of milk produced by the mammary glands of mammals (including humans) immediately following delivery of the newborn. Colostrum powder is rich in high protein and low in sugar and ...
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.
[.] 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 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
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...
or
serum, as pooled human immunoglobulin for intravenous (
IVIG
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 ...
) 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
prophylactic
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
ally in the case of
immunodeficiency diseases, such as
hypogammaglobulinemia
Hypogammaglobulinemia is a problem with the immune system in which not enough gamma globulins are produced in the blood (thus '' hypo-'' + ''gamma'' + ''globulin'' + '' -emia''). This results in a lower antibody count, which impairs the immune sys ...
.
[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
poisoning.
[ Immunity derived from passive immunization lasts for a few weeks to three to four months. There is also a potential risk for ]hypersensitivity
Hypersensitivity (also called hypersensitivity reaction or intolerance) refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. They are usually referred to as an over-reaction of the immune ...
reactions, and serum sickness
Serum sickness in humans is a reaction to proteins in antiserum derived from a non-human animal source, occurring 5–10 days after exposure. Symptoms often include a rash, joint pain, fever, and lymphadenopathy. It is a type of hypersensitivity ...
, especially from gamma globulin 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
Emil or Emile may refer to:
Literature
*'' Emile, or On Education'' (1762), a treatise on education by Jean-Jacques Rousseau
* ''Émile'' (novel) (1827), an autobiographical novel based on Émile de Girardin's early life
*'' Emil and the Detecti ...
and Alexandre Yersin
Alexandre Emile Jean Yersin (22 September 1863 – 1 March 1943) was a Swiss- French physician and bacteriologist. He is remembered as the co-discoverer of the bacillus responsible for the bubonic plague or pest, which was later named in hi ...
showed that the clinical effects of diphtheria were caused by diphtheria toxin
Diphtheria toxin is an exotoxin secreted by '' Corynebacterium diphtheriae'', the pathogenic bacterium that causes diphtheria. The toxin gene is encoded by a prophageA prophage is a virus that has inserted itself into the genome of the host ...
and, following the 1890 discovery of an antitoxin
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 ...
-based immunity to diphtheria
Diphtheria is an infection caused by the bacterium '' Corynebacterium diphtheriae''. Most infections are asymptomatic or have a mild clinical course, but in some outbreaks more than 10% of those diagnosed with the disease may die. Signs and s ...
and tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
by Emil Adolf von Behring
Emil von Behring (; Emil Adolf von Behring), born Emil Adolf Behring (15 March 1854 – 31 March 1917), was a German physiologist who received the 1901 Nobel Prize in Physiology or Medicine, the first one awarded in that field, for his discovery ...
and Kitasato Shibasaburō
Baron was a Japanese physician and bacteriologist. He is remembered as the co-discoverer of the infectious agent of bubonic plague in Hong Kong during an outbreak in 1894, almost simultaneously with Alexandre Yersin.
Kitasato was nominate ...
, 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 9thCentury in the medical treatment of acute infective disease".
Prior to the advent of vaccines and antibiotics
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention o ...
, 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 disease
Respiratory diseases, or lung diseases, are pathological conditions affecting the organs and tissues that make gas exchange difficult in air-breathing animals. They include conditions of the respiratory tract including the trachea, bronchi, bro ...
s until the 1930s, even after sulfonamides were introduced.[
]
In 1890 antibody therapy was used to treat tetanus
Tetanus, also known as lockjaw, is a bacterial infection caused by ''Clostridium tetani'', and is characterized by muscle spasms. In the most common type, the spasms begin in the jaw and then progress to the rest of the body. Each spasm usually ...
, 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
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 ...
remains the only specific pharmacologic treatment available for botulism
Botulism is a rare and potentially fatal illness caused by a toxin produced by the bacterium ''Clostridium botulinum''. The disease begins with weakness, blurred vision, feeling tired, and trouble speaking. This may then be followed by weakne ...
. 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
Toxic shock syndrome (TSS) is a condition caused by bacterial toxins. Symptoms may include fever, rash, skin peeling, and low blood pressure. There may also be symptoms related to the specific underlying infection such as mastitis, osteomyeli ...
, during the 1970s tampon scare.
Antibody therapy is also used to treat viral infections. In 1945, hepatitis A
Hepatitis A is an infectious disease of the liver caused by ''Hepatovirus A'' (HAV); it is a type of viral hepatitis. Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them ...
infections, epidemic in summer camps, were successfully prevented by immunoglobulin treatment. Similarly, hepatitis B
Hepatitis B is an infectious disease caused by the '' Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection.
Many people have no symptoms during an initial infection. ...
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
''Vaccinia virus'' (VACV or VV) is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, which encodes approximately 250 genes. The dimensions of the ...
immunoglobulin (VIG) was used to prevent the spread of smallpox
Smallpox was an infectious disease caused by variola virus (often called smallpox virus) which belongs to the genus Orthopoxvirus. The last naturally occurring case was diagnosed in October 1977, and the World Health Organization (WHO) c ...
during an outbreak in Madras, India
Chennai (, ), formerly known as Madras ( the official name until 1996), is the capital city of Tamil Nadu, the southernmost Indian state. The largest city of the state in area and population, Chennai is located on the Coromandel Coast of th ...
, 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
Rabies is a viral disease that causes encephalitis in humans and other mammals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: nausea, vomiting, ...
infection still requires the use of both vaccine and immunoglobulin treatments.[
During a 1995 Ebola virus outbreak in the ]Democratic Republic of Congo
The Democratic Republic of the Congo (french: République démocratique du Congo (RDC), colloquially "La RDC" ), informally Congo-Kinshasa, DR Congo, the DRC, the DROC, or the Congo, and formerly and also colloquially Zaire, is a country in ...
, 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 (HSV), varicella zoster virus
Varicella-zoster virus (VZV), also known as human herpesvirus 3 (HHV-3, HHV3) or ''Human alphaherpesvirus 3'' (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting chil ...
, Epstein-Barr virus (EBV), and cytomegalovirus (CMV).[
]
FDA licensed immunoglobulins
The following immunoglobulins are the immunoglobulins currently approved for use for infectious disease
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable di ...
prophylaxis
Preventive healthcare, or prophylaxis, consists of measures taken for the purposes of disease prevention.Hugh R. Leavell and E. Gurney Clark as "the science and art of preventing disease, prolonging life, and promoting physical and mental hea ...
and immunotherapy
Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
, 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
Cell-mediated immunity or cellular immunity is an immune response that does not involve antibodies. Rather, cell-mediated immunity is the activation of phagocytes, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in ...
, also called adoptive immunization which involves the transfer of mature circulating lymphocytes. It is rarely used in humans, and requires histocompatible
Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many un ...
(matched) donors, which are often difficult to find, and carries severe risks of graft-versus-host disease.[ This technique has been used in humans to treat certain diseases including some types of ]cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
and immunodeficiency. However, this specialized form of passive immunity is most often used in a laboratory setting in the field of immunology
Immunology is a branch of medicineImmunology for Medical Students, Roderick Nairn, Matthew Helbert, Mosby, 2007 and biology that covers the medical study of immune systems in humans, animals, plants and sapient species. In such we can see the ...
, to transfer immunity between "congenic
In genetics, two organisms that differ in only one Locus (genetics), locus and a linked segment of chromosome are defined as congenic. Similarly, organisms that are Coisogenic strain, coisogenic differ in one locus only and not in the surrounding ...
", 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
* Immunity (medical)
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 pathogen ...
* Antitoxin
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 ...
* 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 ...
* Hyperimmune globulin
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 ...
References
{{Breastfeeding
Immunology
Antibodies