• Jacqueline Siu

Immunological Memory as Our Line of Defence

Updated: May 19

Researchers are relying on the knowledge about immunological memory to fight against diseases such as COVID-19.

(Image: Pixabay).

In the human body, how do we tell the difference between friend or foe? John Locke had suggested that “the only defence against the world is a thorough knowledge of it”; similarly, our immune system draws from its past experiences to fight diseases and keep us alive. Immunological memory is a vital part of this defence system. Without it, the production of effective antibodies—specialised proteins that find hazardous particles (antigens) and mark them for destruction—would be diminished. More precisely, immunological memory refers to the immune system’s ability to specifically recognise an antigen the body has previously encountered and initiate a response against it faster than before. An advantage of this second response is the rapid production of antibodies to prevent the further spread of the virus or bacteria.

This faster second response can prevent disease. For example, children who have previously suffered from chickenpox and recovered are unlikely to get sick again from the same virus. Because during the first infection, the immune system would develop cells that specifically patrol the body and target the chickenpox virus—forming an immunological memory of the virus. These chickenpox-specific memory cells will initiate a prompt immune response if the chickenpox virus enters the body again.

Aspects of this defence artillery are also shared between a mother and her child. A new-born baby is extremely vulnerable as its immune system develops. At first, the mother’s antibodies, and thus a part of her immune defence, can be temporarily passed on to the child after birth and from her breast milk; however, these antibodies eventually degrade, and the new-born loses this temporary protection. The new-born cannot produce more antibodies because it lacks the immunological memory to do so. The best way to gain immunological memory without the risk of disease is through vaccination. Despite the advancement of different technologies, all vaccines fundamentally do the same thing: they safely introduce our immune system to antigens of dangerous organisms without the harmful infection, establish immunological memory towards specific parts of a disease-causing organism, and increase the immune defences against the disease for the future. This biomedical breakthrough has helped eradicate deadly diseases such as smallpox and polio. Today, we are hoping that vaccines can once again help end the COVID-19 pandemic.

While the COVID-19 pandemic has taken a toll globally, hundreds of potential treatments and preventative measures for COVID-19 are being explored clinically. These largely fall into two categories: antivirals that prevent the virus from multiplying, and measures that boost the immune system’s virus fighting ability. Many of these immune modulators aim to augment the effects of immunological memory towards the virus.

By building on the typically unrecognised but important fundamental scientific discoveries such as the immune system of llamas, crucial clinical treatments can be developed.

For extremely ill COVID-19 patients, some treatments aim to introduce antibodies from recovered patients or lab manufactured ones that already recognise coronavirus to help fight against it—similar to the passive immunity shared between a mother and her new-born child. Besides breast milk, antibodies can also be found in plasma, the largest component of blood. Transferring plasma from recovered individuals to critically ill patients, whose bodies are not producing enough antibodies, has shown to improve clinical outcome. However, given the limited supply of appropriate plasma donations, there has also been a concerted effort to produce a lab-based product instead. For instance, one antibody cocktail treatment can reduce the amount of virus and alleviates symptoms in hospitalised patients.

Some scientists have further looked at llamas and their smaller antibody structure to develop “nanobodies”, tiny antibodies to block coronaviruses. These nanobodies are cheaper to produce, more stable for transport, and easier to modify. Most importantly, unlike normal human antibodies, nanobodies can be aerosolized and inhaled to coat the lungs. All these treatments are now undergoing clinical trials to determine if they are successful in modulating the patient’s ability to harness immunological memory.

Alternatively, we can also train our bodies to produce these antibodies using vaccines. As the best protection against coronavirus, COVID-19 vaccines aim to mimic parts of the real virus to train the immune system to respond more rapidly and efficiently. By injecting the vaccine into the upper arm muscle, the “training session” provided by the vaccine is longer and initiates a better immune response with less inflammation than if the vaccine was introduced directly into a vein.

From nanobodies from llamas to designing an anti-virus training boot camp, researchers are racing to develop more efficient and preventative measures to fight against diseases such as COVID-19; and they are relying on the knowledge about immunological memory to do so. By building on the typically unrecognised but important fundamental scientific discoveries such as the immune system of llamas, crucial clinical treatments can be developed. The COVID-19 pandemic has highlighted how findings from basic, fundamental research have enabled the rapid development of clinical applications today.

*This article was written in early 2021, and additional developments may have been made since then.

During her PhD, Jacqueline Siu [2016, Churchill College] investigated how the immune system changes between different organs. She is now a Postdoctoral Research Associate at King’s College London.