Origins of Immunology
The field of immunology came out of advances in bacteriology during the last part of the 19th century; consequently it is highly appropriate to introduce Immunology in introductory micro courses as we are. Today’s famous microbiologist is Emil Adolf von Behring, a German physician who was a Professor of Hygienics at the University of Marburg. He studied the body’s response to toxins in an effort to develop treatments for diphtheria, and was awarded the first Nobel Prize for Physiology or Medicine, in 1901.
Diphtheria is a highly contagious disease of the upper airway, which is passed from individual to individual via aerosolized droplet transmission. Historically, diphtheria has a high mortality rate (over 10%,) and in the 1920’s there were between 100,000 and 200,000 cases per year here in the US. Colonization of the upper airway by Corynebacterium diphtheriae leads to the production of a toxin, fortuitously named “Diphtheria toxin.” It is the action of the toxin that is responsible for the signs and symptoms of the disease, which include the formation of a pseudomembrane in the throat, sore throat, and low grade fever. Inflammation in the throat and enlargement of the draining lymph nodes can significantly impair swallowing and breathing. Diphtheria toxin actually has a very elegant mechanism of cellular destruction; it acts as an inhibitor of the process of protein translation (the conversion of mRNA into protein on ribosomes) by disrupting the host protein synthesis machinery. This is very reminiscent of the mode of action of antibiotics such as tetracycline, however in this case it is our ribosomes and RNA that is being affected, not the bacterial ribosomes and RNA!
Diphtheria can be treated with antibiotics, though generally they are not terribly effective for the following reason: the signs and symptoms are not caused by the growth of the bacterium, but instead by the damage caused by the toxin. Elimination of the bacterium would then be ineffective at eliminating the already present toxin. Typically, patients with diphtheria are put onto supportive therapy until their bodies heal from the damage, but in severe cases anti-diphtheria toxin may be administered to eliminate the toxin from their bodies.
Berhring’s great contribution was to understand the nature of anti-diphtheria toxin, and to develop this tool for the treatment of the disease. He noticed that blood products (serum) from an animal that had previously been exposed to the bacterium could offer protection in a naive (or unchallenged) animal to exposure of that disease. This treatment was referred to as serum therapy, and was also successfully applied to the disease tetanus too at the same time. Behring also extensively studied the disease tuberculosis as well, and developed a similar approach to preventing TB in cows, however this therapy has not effectively been translated to providing protection in humans.
Serum therapy is a process that we’ll see is very similar in concept to the process of vaccination, that we are all probably familiar with. Serum therapy is a form of passive immunity, however and only confers short term immunity to the patient that is lost within a few weeks or so. It is invaluable for treating an active medical condition, but is not effective at conferring long term protection against a pathogen. This has been accomplished for diphtheria in the form of the D-T-P (Diphtheria-Tetanus-Pertussis) vaccination, which is commonly administered here in the US. The process of vaccination, in contrast to the serum therapy of von Berhring, is a form of active immunity and confers long term protection against a pathogen that persists for many years.