Immune Cell Heterogeneity
Overview of Immune System
Depending on the rapidity and specificity of a reaction, immunity is split into two distinct categories. These are referred to as innate and adaptive responses, although there is substantial interaction between both.
Physical, chemical, and microbiological barriers are sometimes included in the term innate immunity. Nonetheless, it typically includes the elements of the immune system (neutrophils, monocytes, macrophages, complement, cytokines, and acute phase proteins) that offer immediate host defense. Moreover, the extremely conserved character of the response, which can be observed in even the simplest of species, demonstrates its significance for survival.
Higher animal immune systems are characterized by adaptive immunity. This response is comprised of T lymphocyte and B lymphocyte antigen-specific responses. Unlike the innate reaction, which is quick but can cause damage to normal tissues due to its lack of specificity, the adaptive response takes days or weeks to develop but is more effective and exact. In addition, the adaptive response has a memory, so subsequent exposure results in a more robust and quick reaction, although this is not instantaneous.
Fig.1 The origins of diversity in the human immune system. (Liston, 2018)
Heterogeneity in Immune Responses
Heterogeneity has long been recognized as a hallmark of the immune system. The bulk output of an immune response represents the combined behaviors of a highly diverse ensemble. Many unique subsets of cells work together to fight potential threats, maintain long-term memory, and establish tolerance. Moreover, the interaction between these cells establishes checks and balances, which are essential for protecting against autoimmunity or immunodeficiency.
Fig.2 The acute inflammatory response. (Delves, 2000)
Heterogeneity in Immune Cells
- Regulatory T-cell Heterogeneity
Regulatory T cells (Tregs) are crucial for reducing autoreactive T cells in surrounding cells and suppressing immunological responses once an infection has resolved. Tregs have traditionally been recognized as forkhead box P3 (FOXP3+) T cells in order to establish such connections. Recent research has revealed that regulatory populations are extremely varied, and that this heterogeneity is crucial for the function of Tregs. The heterogeneity of Treg may influence the prognostication of patients, and distinct Treg populations may have distinct effects on malignancies.
- Monocyte Heterogeneity
Monocytes are circulating leukocytes that are crucial for tissue homeostasis and immunology. They continuously enter the bloodstream from the bone marrow, constituting 4% of the total amount of white blood cells in mice and 10% in humans. Three functionally different monocyte subsets have been discovered in human peripheral blood based on the expression of their surface markers, CD14 and CD16. Monocytes constitute the connection between inflamed conditions and adaptive immune responses. Although monocyte subsets share some common features, classical monocytes, intermediate monocytes, and non-classical monocytes have distinct functions.
The role of monocyte heterogeneity in generating immune cells during inflammation has always been a hot spot in immunology research, and new insights have brought monocyte heterogeneity into the spotlight.
Fig.3 The origin and differentiation of peripheral blood monocytes. (Sprangers. 2016)
References
- Liston, A.; Goris, A. The origins of diversity in human immunity. Nature Immunology. 2018, 19(3): 209-210.
- Delves, P.J.; Roitt, I.M. The immune system. New England Journal of Medicine. 2000, 343(1): 37-49.
- Sprangers, S.; et al. Monocyte heterogeneity: consequences for monocyte-derived immune cells. Journal of Immunology Research. 2016: 1475435.
