27 Jul 2020
Issue #17: The ‘I’ language of immunology
Setting it Straight - Issue #17
Written by Nobel Laureate Professor Peter Doherty
Some of the early essays in this series were about immunity, but not much has been said so far about how the immune system actually works. Immunity is immensely complex, and it’s challenging to write about in ways that are simple, engaging and informative. But it’s time to ‘stiffen the sinews, summon up the blood’ (Henry V Act 3, scene 1) and get on with the job. ‘Summon up the blood’ is good! Immunity is a lot about blood and, as mentioned earlier (The Red and the White), very much about the white blood cells (WBCs).
Part of the problem with writing simply about any area of medical complexity is the shorthand (for the practitioners) of specialist-speak. It helps to know a little Latin: the grammar and word usage passed down to us from ancient Rome has had an enormous influence on the contemporary languages of Europe and that’s also true for, at least, early medical terminology. It used to be the case that high school Latin (I took it for two years) was a required pre-requisite for a career in the medical arts and sciences.
All drug prescriptions were written in Latin, the muscles of the body have Latin names, bacteria are classified by Latin binomials, and so on. Starting from the Latin can help a lot when first reading a pathology textbook and, as discussed previously (Immuno essay), the word immunity comes to us straight from Imperial Rome. Before launching seriously into the dissection of immunity, let’s indulge in a ‘playday’ with some of the Latin-influenced terminology and abbreviations of immunology!
For both obvious and less obvious reasons, words and shorthand beginning with ‘I’ are prominent in ‘immune speak’. The Latin word for ‘I’ is, of course, ‘ego’, but the scientific term ‘ego’ belongs to neuroscience, not immunology. Appropriated by Austrian neurologist Sigmund Freud, ego refers to conscious thought while he also took the Latin Id (it) to summarise unconscious thought. While the brain does influence immunity via, for example, neurohormone secretion, we can’t modify an ongoing immune response by any known thought process that doesn’t involve some medical intervention!
Fully capitalise Id to ID and we leave neurology for immunology. While brain function is triggered by sights, sounds and smells in the external environment, nothing is registered by the immune system until the inducing agent is actually in the body. ID is the abbreviation for intradermal. ‘Intra’ is Latin for ‘within’, or ‘into’, and ‘dermis’ is the skin.
Given delicately with a small needle, an ID injection goes straight into the thick layer of the epidermis and dermis. Pinch-up the skin on your arm and you’ll know what I mean. Anything introduced into that thick fold immediately enters the extracellular fluid that drains via the lymphatics to the lymph nodes where all ‘naïve’ immune responses first develop. As an alternative to the ‘maximally invasive’ hypodermic needle, stick-on ‘patches’ with tiny microneedles can be used for vaccine delivery. A ‘hypodermic’ injection under the skin layer is described as ‘subcutaneous’ (SC), with both words again coming from the Latin. Most vaccines are injected IM, intramuscularly, which is another way of introducing material into the lymphatics: IM is when the nurse, aiming the needles straight as an arrow, sticks the needle into your upper arm.
If we wanted to focus an immune response to the airways, we might give a vaccine via the IN (intranasal) route, either as droplets or as an ‘inhaler’ spray (INH). Injecting COVID-19 convalescent serum for prophylaxis or therapy, the likely route would be intravenous IV, the same way we take a blood sample but putting stuff in rather than taking it out. Another ‘stuff in’ route used more commonly for experiments in lab animals is IP, where material is injected trough the body wall into the peritoneal cavity.
Continuing with the I abbreviation theme, the most important family of molecules when it comes to vaccines and the development of highly specific immune responses are the Igs or immunoglobulins. The Latin origin of ‘immuno’ was discussed earlier, while ‘globus’ is a circle or sphere. The Igs belong to the large family of globular proteins that I will start to discuss in the next essay. We’ve met them briefly before as we explored passive immunity (Horses for courses) where we were, in effect, talking about what the professionals refer to as IVIg.
And, as we go onto discuss the details of immunity we will, from time to time, encounter one or other of the interleukins, the ILs: ‘inter’ is Latin for ‘among’ and ‘leuko’, is the ancient Greek word for ‘white’. The ILs are all proteins that are secreted by the leukocytes, or WBCs. They play a variety of roles, from driving the division and differentiation of immune cells to promoting, or diminishing, inflammation where large numbers of WBCs invade into (for example) infected body tissues.
For the present discussion of language, the persistence of the classical tradition into modern biomedical terminology is exemplified by the fact that, while the IL-1 slot was used retrospectively to describe other WBC-derived ‘factors’ that had been found much earlier, the first molecule to be called an interleukin, IL-2, was discovered in 1976. Now, we recognise IL-1 to IL-38 all of which, from IL-2 on, emerged during the course of my career as an immunologist. Next week, we’ll drop the word games and begin with our series that addresses the basics of immunity.