Human immune system variation

Key Points

  • Human immune system composition and function are highly variable between healthy individuals, but they are relatively stable over time within a given individual.

  • Human immune systems vary as a consequence of heritable and non-heritable influences, but non-heritable influences explain most of the variation.

  • Understanding the specific factors that shape an individual's immune system is key for understanding immune competence and risk of immune-mediated and infectious diseases.

Abstract

The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual's immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases.

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Figure 1: The blood as a window for global immune system analysis in humans.
Figure 2: Variation in immune cells and proteins.
Figure 3: Distribution of immune system variation in human populations.

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Acknowledgements

P.B. is supported by a starting grant from the European Research Council, the Swedish Research Council, the Swedish Society for Medical Research, and Karolinska Institutet. M.M.D. is supported by NIH grants U19 AI090019, U19 AI057229 and the Howard Hughes Medical Institute.

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Correspondence to Petter Brodin.

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Glossary

Rheumatoid arthritis

An immunological disorder that is characterized by symmetrical polyarthritis, often progressing to crippling deformation after years of synovitis. It is associated with systemic immune activation, with acute-phase reactants being present in the peripheral blood, as well as rheumatoid factor (immunoglobulins specific for IgG), which forms immune complexes that are deposited in many tissues.

Cortisol

A steroid hormone produced by the adrenal glands and released in response to stress and has a generally suppressive function on the immune system.

Systemic lupus erythematosus

(SLE). An autoimmune disease in which autoantibodies that are specific for DNA, RNA or proteins associated with nucleic acids form immune complexes that damage small blood vessels, especially in the kidney. Patients with SLE generally have abnormal B cell and T cell functions.

Sjogren syndrome

A long-term autoimmune disease affecting mucous membranes and moisture-secreting glands of the eyes and mouth, resulting in decreased production of tears and saliva, but there are also systemic manifestations such as muscle and joint pain and fatigue.

Ankylosing spondylitis

A long-term inflammatory disease, more common in men than women, affecting the joints of the spine causing vertebrae to fuse together.

Hygiene hypothesis

A hypothesis stating that the lack of early childhood exposure to infectious and symbiotic microorganisms increases the susceptibility to allergic diseases later in life, by altering the normal development of the immune system.

Graft–versus–host disease

(GVHD). An immune response mediated by donor T cells contained in a transplanted allograft and directed against the recipient. GVHD is not associated with solid-organ transplantation but can occur with bone marrow or haematopoietic stem cell transplants.

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Brodin, P., Davis, M. Human immune system variation. Nat Rev Immunol 17, 21–29 (2017). https://doi.org/10.1038/nri.2016.125

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