Passive immunity

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Passive immunity is the transfer of active humoral immunity in the form of ready-made 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.[1]

Naturally acquired passive immunity[edit]

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.[2] Immunoglobulin G is the only antibody isotype that can pass through the placenta.[2] Immunization is often required shortly following birth to prevent diseases such as tuberculosis, hepatitis B, polio, and pertussis, however, maternal antibodies 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.[3]

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.[4]

Artificially acquired passive immunity[edit]

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 prophylactically in the case of immunodeficiency diseases, such as hypogammaglobulinemia.[5] It is also used in the treatment of several types of acute infection, and to treat poisoning.[1] 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.[4] 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.[4]

History and applications of artificial passive immunity[edit]

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.[6][7] 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".[8]

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.[5]

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 un-immunized or incompletely immunized patients who have sustained wounds consistent with the development of tetanus.[5] The administration of horse antitoxin remains the only specific pharmacologic treatment available for botulism.[9] Antitoxin is often also given prophylactically to individuals known to have ingested contaminated food. IVIG treatment was also used successfully to treat several victims of 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.[10]

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.[5]

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 no effective means of prevention or treatment currently exists. Only one of the eight infected patients died, compared to a typical 80% Ebola mortality, which suggested that antibody treatment may contribute to survival.[11] 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).[5]

FDA licensed immunoglobulins[edit]

The following immunoglobulins are the immunoglubulins currently approved for use for infectious disease prophylaxis and immunotherapy, in the United States.[12]

FDA approved products for passive immunization and immunotherapy
Disease Product Source Use
Botulism Specific equine IgG horse Treatment of wound and food borne forms of botulism, infant
botulism is treated with human botulism immune globulin (BabyBIG).
Cytomegalovirus (CMV) hyper-immune IVIG human Prophylaxis, used most often in kidney transplant patients.
Diphtheria Specific equine IgG horse Treatment of diphtheria infection.
Hepatitis A, measles Pooled human Ig human serum Prevention of Hepatitis A and measles infection,
treatment of congenital or acquired immunodeficiency.
Hepatitis B Hepatitis B Ig human Post-exposure prophylaxis, prevention in high-risk infants
(administered with Hepatitis B vaccine).
ITP, Kawasaki disease,
IgG deficiency
Pooled human IgG human serum Treatment of ITP and Kawasaki disease,
prevention/treatment of opportunistic 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 occular forms (usually resulting from
smallpox vaccination in immunocompromised individuals).
Varicella (chicken-pox) Varicella-zoster Ig human Post-exposure prophylaxis in high risk individuals.

Passive transfer of cell-mediated immunity[edit]

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.[1] 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.

See also[edit]

References[edit]

  1. ^ a b c Microbiology and Immunology On-Line Textbook: USC School of Medicine
  2. ^ a b Coico, R., Sunshine, G., and Benjamin, E. (2003). "Immunology: A Short Course." Pg. 48.
  3. ^ Lambert, Paul-Henri, Margaret Liu and Claire-Anne Siegrist Can successful vaccines teach us how to induce efficient protective immune responses? (Full text-html) Nature Medicine 11, S54 - S62 (2005).
  4. ^ a b c Janeway, Charles; Paul Travers, Mark Walport, and Mark Shlomchik (2001). Immunobiology; Fifth Edition. New York and London: Garland Science. ISBN 0-8153-4101-6.  .
  5. ^ a b c d e Keller, Margaret A. and E. Richard Stiehm Passive Immunity in Prevention and Treatment of Infectious Diseases Clinical Microbiology Reviews, October 2000, p. 602-614, Vol. 13, No. 4
  6. ^ Dolman, C.E. (1973). "Landmarks and pioneers in the control of diphtheria.". Can. J. Public Health 64: 317–36. 
  7. ^ 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)
  8. ^ (Report) (1896). "Report of the Lancet Special Commission on the relative strengths of diphtheria antitoxic serums". Lancet 148 (3803): 182–95. 
  9. ^ Shapiro, Roger L. MD; Charles Hatheway, PhD; and David L. Swerdlow, MD Botulism in the United States: A Clinical and Epidemiologic Review Annals of Internal Medicine. 1 August 1998 Volume 129 Issue 3 Pages 221-228
  10. ^ Casadevall, A., and M. D. Scharff. 1995. Return to the past: the case for antibody-based therapies in infectious diseases. Clin. Infect. Dis. 21:150-161
  11. ^ Mupapa, K., M. Massamba, K. Kibadi, K. Kivula, A. Bwaka, M. Kipasa, R. Colebunders, and J. J. Muyembe-Tamfum on behalf of the International Scientific and Technical Committee. 1999. Treatment of Ebola hemorrhagic fever with blood transfusions from convalescent patients. J. Infect. Dis. 179(Suppl.):S18-S23
  12. ^ Samuel Baron MD (1996) Table 8-2. U.S. Licensed Immunoglobulin For Passive Immunization Medical Microbiology Fourth Edition The University of Texas Medical Branch at Galveston