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15.4.16: Passive Immunity

Active humoral immunity is the development of antibodies in response to stimulation by an antigen. However, passive immunity involves that once formed, those antibodies can be removed from the host and transferred into another recipient where they provide immediate passive immunity.

Antisera Raised in Nonhuman Animals

Tetanus antitoxin

Tetanus antitoxin is an antiserum that has been produced by actively immunizing an animal (e.g., a horse) with tetanus toxoid. When a human may have been exposed to spores of the tetanus bacillus (e.g. in a dirty puncture wound) and has never or not for a long time (10 years) been actively immunized with tetanus toxoid, the physician, fearing that disease symptoms may occur before the patient is able to mount an active immune response, will inject tetanus antitoxin in order to provide immediate protection. The protection is short-lived, lasting only until the last of the injected antibodies have been catabolized.

Antivenoms

These antisera (raised in horses or sheep) provide immediate protection to people bitten by a venomous animal (e.g., a rattlesnake).

Figure 15.4.16.1: Milking a snake for the production of antivenom. Image used with permission from Wikipedia (CC-BY-2.0; Barry Rogge).

Immune Globulin (IG)

Horse and sheep proteins are foreign to the human patient and will, in due course, elicit an active immune response. This may lead to an allergic reaction such as systemic anaphylaxis or serum sickness. To avoid such problems, humans are often used as the source of passive antibodies.

  • IG is also used to provide protection to boys with X-linked agammaglobulinemia, who are unable to manufacture antibodies because of a mutation in their single (because on their X chromosome) gene for Bruton's tyrosine kinase.
  • hepatitis A ("infectious" hepatitis), measles, and rubella. Some immune globulin (IG) is prepared from the gamma globulin fraction of pooled plasma from the outdated blood of several thousand blood donors on the assumption that this large pool will contain good levels of antibodies against many common diseases such as
  • Some preparations of immune globulin are harvested from selected individual donors who have either recently recovered from the disease or who have been deliberately and intensively immunized against it. These are used to provide immediate protection against such diseases as rabies, tetanus, varicella (chicken pox), and complications arising from giving the smallpox vaccine (vaccinia immune globulin or VIG).
  • The recent need for an effective treatment for people with inhalational anthrax has led to the use of plasma donated by military personnel previously actively immunized with anthrax vaccine. Soon it should be possible to prepare a purified immune globulin from this plasma. Further down the road will be the use of antianthrax monoclonal antibodies.
  • Rh immune globulin (RhIg) or Rhogam is used to prevent Rh-negative mothers from becoming sensitized to the Rh antigen of their newborn child.

Advantages of human immune globulin

The preparation contains fewer irrelevant serum proteins and of those that remain, being human proteins, they are far less immunogenic and are catabolized more slowly than horse proteins. However, care must be (and is) taken to ensure that the preparations are not contaminated with human pathogens such as the AIDS virus (HIV) or hepatitis viruses.

Non-antigen-specific effects of human immune globulin

Intravenous injections of IG have helped patients with such autoimmune disorders as

  • immune hemolytic anemia
  • immune thrombocytopenic purpura
  • myasthenia gravis

The therapeutic effect seems to have nothing to do with the antigen specificities (e.g., antitetanus) of the antibodies in the preparation. Instead it is the C-region portion of the antibody molecules that provides the protection. Animal studies suggest that it does so by binding to a class of receptors on macrophages, which inhibits them from phagocytosing antibody-coated cells, e.g.,

  • antibody-coated red cells in immune hemolytic anemia
  • antibody-coated platelets in idiopathic thrombocytopenic purpura

The spleen is packed with macrophages and is where most of red blood cell and platelet destruction occurs in these diseases (and explains why removal of the spleen so often helps the patient).

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