11.2 Applications and skills
11.2.1 Histamines, vaccines and monoclonal antibodies
- Histamines facilitate specific and non-specific immune responses.
- Vaccines contain antigens that trigger a specific immune response, but do not cause disease.
- Monoclonal antibodies are produced commercially, and are used in diagnostic tests.
Histamines cause allergic symptoms
Figure 11.2.1a shows how histamines normally facilitate the immune response:
- White blood cells called mast cells reside in tissues. When a tissue is infected, mast cells are triggered to release histamines.
- Histamines are small molecules that cause increased blood flow and capillary swelling in the infected area. Phagocytes and lymphocytes then move from the bloodstream into the surrounding tissue.
- Phagocytes begin the non-specific immune response (inflammatory response). Lymphocytes begin the specific immune response.
- Localised swelling and inflammation of the skin are symptoms of allergic reactions caused by the histamine response.
- Anti-histamine drugs may be taken to relieve allergy symptoms.
- In an anaphylactic reaction, skin rash and swelling occur rapidly and may be deadly. Intramuscular injection of epinephrine should be administered for anaphylaxis.
The principle of vaccination
- Vaccines are injected into the body and trigger the production of antibodies, but do not cause disease.
- Vaccines are made either of attenuated (inactivated) virus or sub-units of virus antigens, and chemical adjuvants that aid in the immune response.
Figure 11.2.1b – Vaccines are made of attenuated virus or viral sub-units.
Application: The eradication of smallpox
- Smallpox is a devastating skin disease caused by the virus Viriola.
- A related pox virus called Vaccinia is the principle component of the modern smallpox vaccine. Due to their similarity in antigen structure, inoculation with Vaccinia results in immunity to smallpox.
- The WHO established the smallpox eradication unit in 1967 and the last wild case of smallpox was reported in 1977.
- The programme was successful because of international cooperation but also for a number of reasons related to the pathology of the disease:
- Smallpox has a short incubation period. Symptoms emerge quickly, allowing for vaccination teams to inoculate the people around the person infected before they are exposed to the virus.
- Viriola is not zoonotic. The virus is unable to live in any host other than humans. Once eradicated from human populations, the virus has nowhere to hide.
- Immunity to smallpox lasts a very long time, compared to other viral infections, such as flu, due to low mutation rates in the DNA genome.
Production of monoclonal antibodies
- Antibodies can be harvested from the blood serum of laboratory mammals (especially mice) after an immune response is induced by the introduction of a foreign antigen.
- This simple method produces a range of antibodies that are derived from many different B-lymphocytes. These are polyclonal antibodies.
- Monoclonal antibodies are derived from a single B-cell lineage. As a result, they are much more uniform in shape and antigen specificity.
- The production of monoclonal antibodies requires a special type of cell, called a hybridoma, which is produced by fusing a tumour cell with an antibody-producing plasma cell from the spleen of the mouse. The process is summarised in Figure 11.2.1c.
Figure 11.2.1c – Production of monoclonal antibodies
Application: Monoclonal antibodies in pregnancy test kits
- Monoclonal antibodies are used in medical diagnostic tests, as well as therapies for some autoimmune disorders and cancers.
- A home pregnancy test consists of a dip strip that is loaded at one end with monoclonal antibodies for the hormone HCG, human chorionic gonadotropin.
- HCG is secreted by a developing embryo and appears in the urine during the very early stages of pregnancy.
Figure 11.2.1d – HCG reacts with monoclonal antibodies in a positive test.
- The test strip is submerged to point S in urine. As the liquid moves across the test strip, two areas in the results window are activated. At point A, a line appears if HCG associates to the antibody. The antibody alone activates point B – a line will appear in every valid test.
Figure 11.2.1f – Pregnancy test
Monoclonal antibodies are used in home pregnancy tests.
- A virus is attenuated (inactivated) by laboratory processes – for example, in culture with cells from a foreign host (not the normal human host).
- Myeloma is a cancer that affects plasma cells. Recall from 1.1.6 that cancer results divide very quickly and lack mechanisms for apoptosis. When a hybridoma cell is bathed in an appropriate medium, it will divide quickly and indefinitely to produce large amounts of monoclonal antibody.
- Specificity is the key to an effective immune response.
Figure 11.2.1h – Vaccination
Vaccines contain attenuated virus and adjuvants that boost the immune response.
The WHO initiated the campaign for the global eradication of smallpox in 1967. The campaign was deemed a success in 1977, only 10 years later.
Nature of Science
Ethical implications of research: Edward Jenner is known as ‘the father of immunology’ because his smallpox vaccine was the first vaccine ever invented. One of Jenner’s most famous test subjects was an 8-year-old boy named James Phipps. By today’s standards of medical ethics, Jenner would not have been justified in testing his vaccine in this way.
Read more about how biological warfare shaped history in:
Diamond, Jared (1997) Guns, Germs and Steel: The Fates of Human Societies. New York: W.W Norton.