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References: The Immune System as a Sense Organ

  1. 21.2 Barrier Defenses and the Innate Immune Response - OpenStax, Anatomy and Physiology 2e (CC BY 4.0) - Free open textbook section on barriers, pattern recognition receptors, cytokines, and the four signs of inflammation. A clear review of Sections 4.3 and 4.6.

  2. 23.5 The Small and Large Intestines - OpenStax, Anatomy and Physiology 2e (CC BY 4.0) - Describes the gut lining, Peyer's patches in the lower small intestine, and how dendritic cells sample microbes through tight junctions. Background for Sections 4.4 and 4.5.

  3. The total mass, number, and distribution of immune cells in the human body - Sender R, et al. Proceedings of the National Academy of Sciences, 2023 - The careful count behind this chapter's correction of the "70% of your immune system is in your gut" claim: about 3% of immune cells, but about 70% of plasma cells, live in the gut.

  4. From inflammation to sickness and depression: when the immune system subjugates the brain - Dantzer R, et al. Nature Reviews Neuroscience, 2008 - The classic review of sickness behavior, the cytokines that cause it, and how long-lasting immune signaling may lead to depression in vulnerable people. Free full text; the introduction is readable for motivated students.

  5. Brain-immune communication pathways - Quan N, Banks WA. Brain, Behavior, and Immunity, 2007 - Review that lists the four routes immune signals use to reach the brain: nerves, circumventricular organs, transport across the blood-brain barrier, and signals from barrier cells.

  6. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression - Raison CL, et al. JAMA Psychiatry, 2013 - The trial analyzed in this chapter's "How to read a gut-brain claim" box. Free full text, including the funding statement and the high-CRP subgroup results.

  7. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward - Eisenberger NI, et al. Biological Psychiatry, 2010 - A randomized experiment in 39 healthy adults showing that a short burst of inflammation lowered mood and the brain's reward response. Human evidence that sickness behavior is real and caused by inflammation.

  8. Prevalence and risk factors for fatigue in adults with inflammatory bowel disease - D'Silva A, et al. Clinical Gastroenterology and Hepatology, 2022 - Meta-analysis of 20 studies finding fatigue in about 47% of adults with IBD (72% with active disease, 47% in remission). Useful for anyone who wants to understand IBD fatigue.

  9. Inflammatory markers in depression: a meta-analysis - Osimo EF, et al. Brain, Behavior, and Immunity, 2020 - Combines 107 studies of more than 10,000 people and shows that depression comes with higher average inflammation markers, an association rather than proof of cause.

  10. Host microbiota constantly control maturation and function of microglia in the CNS - Erny D, et al. Nature Neuroscience, 2015 - The germ-free mouse study behind this chapter's Preliminary Hype Meter card on gut microbes and microglia. A good example of an exciting mouse finding that still needs human evidence.

  11. Treatment of Flu - Centers for Disease Control and Prevention (CDC) - The CDC's plain-language page on flu treatment, including why prescription antiviral medicines work best when started within two days of symptoms. Source for the At the Bedside case.

  12. A prospective population-based study of triggers of symptomatic flares in IBD - Bernstein CN, et al. American Journal of Gastroenterology, 2010 - Year-long study of 704 people with IBD in Manitoba in which high perceived stress was the only factor linked to later symptom flares in the final analysis. An association, not proof of cause; the source for the stress-to-gut arrow in this chapter's MicroSim.