A new framework
For understanding your immune system, beyond infection
Traditional frameworks for understanding immunity often focus on concepts of ‘boosting’ our defence
These models view the immune system as a specialized system that protects the body from external threats, such as infectious pathogens or cancerous cells, through a series of defensive responses that aim to eliminate or neutralize these threats.
How infections shaped the image of the immune system
Immunology is a fairly new medical discipline. Following the germ theory of disease proposed by Louis Pasteur and Robert Koch in the 19th century, the defence function of the immune system was discovered through observations white blood cells and antibodies could protect from germs. And so immunology branched off from the older science of microbiology.
This is why it is conceptualised as a defence system and often described metaphorically as a military defence and war metaphor with various cells and molecules playing different roles in protecting the body from invading pathogens. This analogy is useful in that it highlights the complexity and organization of immune responses.
The immune system has different branches that specialize in different types of threats. For example, the innate immune system acts as a first line of defence, using cells such as neutrophils and macrophages to recognize and engulf foreign particles. The adaptive immune system, on the other hand, uses specialized cells such as T cells and B cells to produce highly specific responses to particular pathogens and develop immunological memory to provide long-term protection against reinfection. Like military defence, the immune system relies on communication and coordination among different cells and organs. This is accomplished through a variety of signalling molecules, such as cytokines and chemokines, which act like messengers to transmit information and coordinate responses across different parts of the body.
There is also an evolutionary story behind this view of our immune system framed as an arms race between germs and us. Like a tug-of-war where we develop increasingly complex immune defence mechanisms, and the germs, in turn, increasingly sophisticated ways to evade these immune defences. One example of how evolution has shaped our understanding of the immune system is through the study of natural selection. Natural selection favours organisms that have developed the ability to recognize and respond to pathogens efficiently. This has led to the development of complex immune systems in vertebrates, including humans, that are capable of recognizing and responding to a wide range of pathogens.
Another example of how evolution has shaped our understanding of the immune system is through the study of immune system genes. Studies have shown that immune system genes have evolved rapidly across species, suggesting that the immune system is under strong selective pressure to adapt to changing pathogens. Understanding these evolutionary changes in immune system genes can help us predict how the immune system will respond to new or emerging pathogens. Evolution has provided valuable insights into how the immune system works but has always narrowly focussed on infectious diseases.
The immune system is not a perfect military defence. Like any defence system, it can be prone to errors, such as mistaking self-tissue for foreign invaders or failing to recognize emerging pathogens. Like the military defence, the immune system must have peacekeepers who call the defence to stand down when no longer needed, avoiding unwanted collateral damage, such as inflammation and tissue damage, in its effort to eliminate threats.
A limited view
While this perspective can be useful for understanding certain aspects of immunity, it is also limiting and has several drawbacks. Primarily, many people think defence is the immune system’s only function - that we have an immune system for one reason and one reason only - to prevent microbes from overrunning us. The immune system is involved in many other activities than just defence against germs including tissue repair, the clearance of damaged or dead cells and debris, communication with the microbiome, developmental processes, pregnancy, growth and much more. This outdated view is limited in its ability to capture the complexity and diversity of immune responses across different contexts and individuals.
There are other issues with this limited view of the immune system as solely a defence system. For example, some of these immune defence functions are, in fact, carried out by non-immune cells, including microbes that form the microbiota, leading to “co-immunity”. Moreover, it can reinforce a reductionist and hierarchical view of the immune system that places it in opposition to the rest of the body and the environment. It invites talk of ‘boosting’ and strong/weak defence (guilty here as my second title uses this phrasing). The evolutionary advantages of a strong defence system are obvious in protecting against pathogens but neglect immune activities that are unrelated to germ defence and that do not fit the strong/weak narrative. This results in a very narrow view of what the immune system is and how it works, and of course why it sometimes fails.
An alternative framework, one that emphasizes the adaptability and interconnectedness of immune responses, and provides a more nuanced and comprehensive understanding of the immune system in health and disease is now needed more than ever. Infectious diseases are not going anywhere, but non-infectious (noncommunicable) diseases are now the leading cause of poor health and death worldwide.
Immunity is not just defence
The alternative framework for understanding immunity is one that emphasises the interconnectedness and adaptability of immune responses in different contexts. One that is not only involved in defence. This model views the immune system as a complex network of interactions that involve multiple cell types, tissues, and organs, as well as communication with other physiological systems in the body and external factors in the environment.
Rather than focusing solely on defence and strength, this framework recognizes that immune responses can take many forms, including tolerance, regulation, and repair, depending on the nature of the threat and the needs of the organism. It also acknowledges that immune responses can have both beneficial and detrimental effects on health, depending on their timing, duration, and intensity. We can then start to understand the nature of the immune system in terms of 3 key concepts: contextuality, regulation, and trade-offs.
Contextuality: The outcome of an immune response is essentially dependent on the context which in turn is determined by a multitude of factors. Rather than it being turned on when we become infected, it is always ‘on’ and constantly active in maintaining various functions and interacting with its (internal and external) environment.
Regulation: any immune function must be finely tuned and tightly regulated by both internal and external signals. For example, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has reminded us of the critical role of an effective host immune response and the devastating effect of immune dysregulation
Trade-offs: having a particular feature very often confers some benefit to the host with respect to some particular condition, while at the same time that very same feature also puts us at a disadvantage with respect to another condition. For example, there is a trade-off between resisting an infection, i.e., the clearance of pathogens, and the tissue damage arising from the immune response, i.e., the immunopathology. A ‘strong’ response, in this sense, may be associated with the vigorous clearance of pathogens while giving rise to a cytokine storm, an immune-mediated life-threatening condition. Similarly in a non-infectious setting, e.g., following liver damage, the transient induction and accumulation of senescent cells help to resolve fibrosis. However, senescent cells need to be cleared by the immune system since their prolonged existence is considered detrimental.
Conclusion
Metaphors play a significant—and unavoidable—role in shaping the narrative and perspective on the immune system as a boosted defence system. While they serve as tools for understanding, navigating, and organizing what would otherwise constitute a complex mess of individual facts, they may also shape a narrow perspective, overlooking other important aspects. We now need an alternative framework for understanding the immune system. One that considers the ways in which our immune system is shaped by factors such as genetics, nutrition, stress, social relationships, and exposure to different microbes and environmental toxins. It also invites us to explore the potential for enhancing immune resilience and adaptability through lifestyle choices, such as diet, exercise, sleep, and mindfulness practices.
Overall, this alternative framework for understanding immunity offers a more holistic and dynamic view of the immune system that can help us better appreciate its complexity and potential, and develop more effective strategies for promoting health and well-being.
For more easy-to-understand and clear information on all things immunity, check out my books.