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Although the humoral and cellular arms of immune responses have been considered as separate and distinct components, it is important to understand that the response to any particular antigen, be it a pathogen or other foreign molecular structure, may involve a complex interaction between them, as well as the components of innate immunity. All this with the purpose of ensuring a maximal survival advantage for the host by eliminating the antigen and, as we shall see, by protecting the host from mounting an immune response against self. As was pointed out at the beginning of this introductory chapter, the normally tuned immune system continuously aims to maintain homeostasis in the context of host defenses. A complex set of factors influences how our immune system achieves homeostasis or immune balance. These include an individual’s genotype, diet, and environmental conditions, as well as neurological influences related to how we respond to stress and even potential consequences of mental health disorders on immune homeostasis.

The significance of the microbiome on gut–brain–immune system homeostasis has become a major area of study. The community of microbes that reside in our gut significantly impacts the integrity of our mucosal (gut) immune system. For example, when gut barrier integrity is the norm, we live symbiotically with our gut microbiome. In contrast, under abnormal conditions of gut barrier permeability, we can experience gut–brain–immune system dysregulation or microbiome dysbiosis. The latter can occur during periods of high stress, changes in diet, or other lifestyle changes. These conditions lead to immune imbalance that can manifest as chronic inflammation, autoimmunity, and allergic disease. Specific examples of disease associated with increased gut permeability include type 2 diabetes, inflammatory bowl disease, and mood disorders, just to name a few.

It is important to note that in addition to the impact of the gut microbiome on immune homeostasis, we are becoming increasingly aware of the importance of the early gut microbiome for neonatal immune system development and disease pathogenesis. The increase in allergies and other immune‐mediated diseases in industrialized countries has been hypothesized to be a result of deficiencies in early life exposure to microbial organisms and their products, resulting in impaired immune system development. This concept was first introduced as the hygiene hypothesis. The first six months after birth are considered the window of opportunity during which contact with specific microbe‐associated molecular patterns triggers a cascade of reactions crucial for infant gut maturation, including the developing mucosal immune system.