Quick-reference definitions for key cPNI terms. See the full concept notes for detailed mechanisms and connections.
ACE2: Angiotensin-converting enzyme 2; a membrane-bound enzyme that converts angiotensin II to angiotensin 1-7, serving as the entry receptor for SARS-CoV-2.
ACEs: Adverse childhood experiences; traumatic events before age 18 that increase lifelong risk of chronic disease through epigenetic and neuroimmune mechanisms.
acute inflammation: A protective, time-limited biological response to tissue injury or infection, characterized by rubor, calor, tumor, dolor, and functio laesa. Essential for tissue repair and pathogen clearance.
acute phase proteins: Plasma proteins (CRP, fibrinogen, haptoglobin, serum amyloid A) whose concentrations change by >25% during inflammation, produced mainly by the liver in response to IL-6.
adaptive immunity: The antigen-specific immune response mediated by T and B lymphocytes, characterized by immunological memory and clonal expansion.
adiponectin: An anti-inflammatory adipokine secreted by adipose tissue that enhances insulin sensitivity and fatty acid oxidation; levels inversely correlate with visceral fat mass.
Adrenaline: Catecholamine hormone (epinephrine) released from the adrenal medulla during acute stress, mediating fight-or-flight responses including heart rate increase and bronchodilation.
Allostasis: The process of achieving stability through physiological change; the body's active adaptation to predictable and unpredictable stressors.
Allostatic load: The cumulative physiological wear and tear from chronic activation of allostatic systems (HPA axis, autonomic nervous system, immune and metabolic systems).
Amygdala: Almond-shaped cluster of nuclei in the medial temporal lobe that processes emotions, particularly fear, threat detection, and emotional learning.
angiogenesis: The formation of new blood vessels from pre-existing vasculature, essential during wound healing and pathological in tumour growth.
antibodies: Immunoglobulin proteins produced by B cells that bind specific antigens, enabling neutralization, opsonization, and complement activation.
antioxidants: Molecules that neutralize reactive oxygen species and prevent oxidative damage to cellular components including DNA, proteins, and lipids.
aromatase: Enzyme (CYP19A1) that converts androgens to estrogens; found in adipose tissue, brain, bone, and gonads.
atherosclerosis: Chronic inflammatory disease of arterial walls involving lipid accumulation, immune cell infiltration, and plaque formation driven by low-grade inflammation.
autoimmune disease: Conditions where the immune system attacks self-tissues due to loss of tolerance, molecular mimicry, or dysregulated immune regulation.
autophagy: Cellular self-digestion process removing damaged organelles and proteins, activated by intermittent stress including fasting, exercise, and cold exposure.
B cells: Lymphocytes of the adaptive immune system responsible for antibody production, antigen presentation, and immunological memory.
BDNF: Brain-derived neurotrophic factor; a neurotrophin critical for neuroplasticity, neurogenesis, synaptic strengthening, and cognitive function. Increased by exercise and reduced by chronic stress.
beta-endorphin: Endogenous opioid peptide produced from POMC cleavage, mediating pain relief, reward, and immune modulation; released during exercise and stress.
Bile acids: Cholesterol-derived amphipathic molecules produced by the liver that aid fat digestion and serve as signaling molecules via FXR and TGR5 receptors.
blood-brain barrier: A highly selective semipermeable border of endothelial cells with tight junctions that separates circulating blood from brain extracellular fluid.
Bradykinin: Vasoactive peptide produced during inflammation that causes vasodilation, increased vascular permeability, and pain through B1 and B2 receptor activation.
Butyrate: A short-chain fatty acid produced by bacterial fermentation of dietary fibre that serves as the primary energy source for colonocytes and modulates immune function.
C-reactive protein: Acute phase protein produced by the liver in response to IL-6; a clinical marker of systemic inflammation, with levels >3 mg/L indicating cardiovascular risk.
central sensitisation: Maladaptive neuroplastic change in the CNS characterized by increased excitability of nociceptive neurons, amplifying pain responses beyond tissue damage.
cholinergic anti-inflammatory pathway: A neurally-mediated reflex where vagus nerve activation releases acetylcholine to suppress macrophage pro-inflammatory cytokine production.
chronic inflammation: Persistent, unresolved inflammation characterized by continuous immune cell activation, tissue damage and repair occurring simultaneously, and failure to switch to resolution mediators.
circadian rhythm: Endogenous approximately 24-hour biological oscillations that regulate sleep-wake cycles, hormone secretion, immune function, and metabolism.
Clinical PNI: Clinical Psychoneuroimmunology; an integrative clinical discipline applying evolutionary medicine, immunology, neuroscience, and psychology to understand and treat chronic disease.
COX-2: Cyclooxygenase-2; an inducible enzyme that converts arachidonic acid to prostaglandins during inflammation, and is also the substrate for aspirin-triggered resolvin production.
Cortisol: The primary glucocorticoid hormone in humans, produced by the adrenal cortex under HPA axis control, with effects on metabolism, immune function, and stress responses.
cortisol awakening response: The 50-75% rise in cortisol within 30 minutes of waking; a biomarker of HPA axis function and stress adaptation.
CRH: Corticotropin-releasing hormone; hypothalamic peptide that initiates the HPA axis cascade, stimulating ACTH release from the anterior pituitary.
CRP: C-reactive protein; see C-reactive protein.
CTRA: Conserved Transcriptional Response to Adversity; a genomic pattern linking social stress to upregulated inflammatory gene expression and downregulated antiviral genes.
Cytokine storm: A life-threatening systemic inflammatory response involving massive, uncontrolled release of pro-inflammatory cytokines, seen in severe infections and autoimmune crises.
Cytokines: Small signaling proteins that mediate immune responses, inflammation, and cellular communication through paracrine, autocrine, and endocrine mechanisms.
DAMPs: Damage-Associated Molecular Patterns; endogenous danger signals released from damaged cells that activate innate immune responses through pattern recognition receptors.
dendritic cells: Professional antigen-presenting cells that bridge innate and adaptive immunity by capturing, processing, and presenting antigens to T cells.
Depression: A neuroimmune disorder characterized by persistent low mood, anhedonia, and neurovegetative symptoms, strongly linked to chronic low-grade inflammation and HPA axis dysregulation.
diseases of civilization: Chronic conditions (diabetes, cardiovascular disease, autoimmunity, cancer) arising from evolutionary mismatch between ancestral biology and modern environments.
dysbiosis: Imbalance in the composition, diversity, or function of the microbiome, driving chronic low-grade inflammation and contributing to numerous disease states.
Efferocytosis: The clearance of apoptotic cells by phagocytes, a critical step in inflammation resolution that triggers anti-inflammatory signaling and SPM production.
Endocannabinoid System: A lipid signaling network of endocannabinoid ligands (anandamide, 2-AG), cannabinoid receptors (CB1, CB2), and metabolizing enzymes that regulates neurotransmission, inflammation, and energy balance.
Endotoxaemia: The presence of bacterial lipopolysaccharide (LPS) in the bloodstream, typically from intestinal barrier dysfunction, driving systemic low-grade inflammation.
epigenetics: Heritable changes in gene expression without alterations to the DNA sequence, mediated by DNA methylation, histone modification, and non-coding RNA.
Evolutionary medicine: A framework applying evolutionary biology to understand why humans are vulnerable to disease, emphasizing mismatch, trade-offs, and adaptive function of symptoms.
Evolutionary mismatch: The discordance between human biology adapted to Paleolithic environments and the novel conditions of modern industrialized societies, creating chronic disease vulnerability.
Exosomes: Small extracellular vesicles (30-150 nm) released by cells carrying proteins, lipids, and nucleic acids for intercellular communication and immune modulation.
Ferritin: Iron storage protein; elevated levels indicate inflammation (acute phase reactant) or iron overload, while low levels indicate iron deficiency.
Fibrosis: Excessive deposition of extracellular matrix (especially collagen) resulting from chronic inflammation and failure of resolution, leading to tissue scarring and organ dysfunction.
FKBP5: FK506 binding protein 5; a co-chaperone that regulates glucocorticoid receptor sensitivity, with polymorphisms linked to stress vulnerability and PTSD risk.
GABA: Gamma-aminobutyric acid; the primary inhibitory neurotransmitter in the CNS, essential for neuronal excitability balance, anxiety regulation, and sleep.
Ghrelin: Hunger hormone produced mainly by the stomach that stimulates appetite, growth hormone release, and has anti-inflammatory and neuroprotective properties.
GLP-1: Glucagon-like peptide-1; an incretin hormone released by intestinal L-cells that enhances insulin secretion, suppresses glucagon, and promotes satiety.
Glucocorticoid Receptor: Nuclear receptor for cortisol that, upon activation, translocates to the nucleus to regulate transcription of anti-inflammatory and metabolic genes.
Gluconeogenesis: The metabolic pathway producing glucose from non-carbohydrate substrates (amino acids, glycerol, lactate), primarily in the liver during fasting or stress.
Glutathione: The body's master antioxidant (GSH); a tripeptide of glutamate, cysteine, and glycine critical for detoxification, immune function, and oxidative stress defence.
Gluten: Storage proteins (gliadins and glutenins) in wheat that can trigger immune responses ranging from coeliac disease to non-coeliac gluten sensitivity through zonulin-mediated barrier disruption.
gut-brain axis: Bidirectional communication network between the gastrointestinal tract and the brain, mediated by the vagus nerve, immune signaling, microbial metabolites, and hormones.
Hashimoto's thyroiditis: Autoimmune thyroid disease where immune cells attack thyroid tissue, causing progressive thyroid destruction and hypothyroidism.
Hepcidin: Master regulator of iron homeostasis; a liver-produced peptide that inhibits ferroportin-mediated iron export, increased during inflammation causing functional iron deficiency.
Hippocampus: Medial temporal lobe structure critical for memory consolidation, spatial navigation, and stress regulation; one of few brain regions with ongoing adult neurogenesis.
HLA: Human leukocyte antigen; the human major histocompatibility complex that presents antigens to T cells and determines immune recognition of self vs non-self.
Homeostasis: The maintenance of a stable internal environment through regulatory feedback mechanisms across physiological systems.
Hormesis: Adaptive biological phenomenon where low-to-moderate doses of stress produce beneficial effects through a biphasic dose-response relationship.
HPA axis: The hypothalamic-pituitary-adrenal axis; the neuroendocrine stress response system involving CRH, ACTH, and cortisol release.
HRV: Heart rate variability; the beat-to-beat variation in heart rate reflecting autonomic balance; higher HRV indicates better parasympathetic tone and stress resilience.
hygiene hypothesis: The theory that reduced microbial exposure in modern environments leads to immune dysregulation and increased allergic and autoimmune disease.
Hypothalamus: Brain region serving as master regulator of homeostasis, integrating nervous, endocrine, and immune systems to control temperature, appetite, stress responses, and reproduction.
IFN-γ: Interferon-gamma; a cytokine primarily produced by Th1 cells and NK cells that activates macrophages, promotes cell-mediated immunity, and inhibits Th2 responses.
IgA: Immunoglobulin A; the predominant antibody at mucosal surfaces, secreted as sIgA to protect gut, respiratory, and urogenital barriers.
IL-1β: Interleukin-1 beta; a potent pro-inflammatory cytokine released by activated macrophages via inflammasome activation, driving fever, acute phase response, and sickness behaviour.
IL-6: Interleukin-6; a pleiotropic cytokine with both pro- and anti-inflammatory functions; elevated in chronic disease but also released by muscle during exercise as a myokine.
IL-10: Interleukin-10; a key anti-inflammatory cytokine that suppresses macrophage activation and Th1 responses, essential for immune regulation and tolerance.
Immunogram: A diagnostic framework visualizing the balance between immune activation and regulation across multiple parameters.
Immunometabolism: The study of how metabolic pathways control immune cell function and how immune activation reprograms cellular metabolism.
immunosenescence: Age-related deterioration of immune function characterized by thymic involution, reduced naive T cells, and increased inflammaging.
inflammaging: Chronic low-grade inflammation associated with aging, resulting from immunosenescence, accumulated cellular damage, and persistent antigenic stimulation.
Inflammasome: A multiprotein complex (especially NLRP3) that activates caspase-1 to process IL-1beta and IL-18, triggering inflammatory responses and pyroptosis.
innate immunity: The evolutionarily conserved immune system present from birth providing rapid, non-specific defense through pattern recognition, phagocytosis, and antimicrobial peptides.
insulin resistance: Reduced cellular responsiveness to insulin signaling; adaptive during acute stress but pathological when chronic, driving metabolic syndrome and type 2 diabetes.
Intermittent Living: Pruimboom's therapeutic philosophy combining multiple simultaneous hormetic stressors (heat, cold, fasting, exercise, hypoxia) to create antifragility and adaptive capacity.
Intestinal permeability: The regulated passage of molecules across the intestinal epithelium; increased permeability (leaky gut) allows bacterial products to enter systemic circulation.
interoception: The sense of the internal state of the body, processed through vagal afferents, spinal afferents, and humoral signals converging on the insular cortex.
Kynurenic acid: Tryptophan metabolite via the kynurenine pathway with neuroprotective and anti-inflammatory properties; acts as an NMDA receptor antagonist.
Lactoferrin: Iron-binding glycoprotein in milk and mucosal secretions with antimicrobial, anti-inflammatory, and immunomodulatory properties.
leaky gut: Colloquial term for increased intestinal permeability, where disrupted tight junctions allow bacterial products and food antigens to cross the gut barrier.
Leptin: Adipokine produced by fat cells that signals energy status to the hypothalamus; leptin resistance in obesity drives continued hunger despite excess adiposity.
Lipoxins: Anti-inflammatory lipid mediators derived from arachidonic acid via 15-LOX/5-LOX interaction; the first identified specialized pro-resolving mediators.
Low-Grade Inflammation: Chronic subclinical immune activation characterized by 2-4 fold elevation in inflammatory markers without acute illness; the universal mechanism underlying chronic diseases.
LPS: Lipopolysaccharide; a component of gram-negative bacterial cell walls that potently activates innate immunity through TLR4 signaling.
Macrophage Polarization: The spectrum of functional states macrophages adopt, from pro-inflammatory M1 to anti-inflammatory/pro-resolution M2, regulated by metabolic and environmental signals.
Maresins: Specialized pro-resolving mediators derived from DHA via 12-LOX in macrophages that promote inflammation resolution and tissue regeneration.
Mast cells: Tissue-resident immune cells containing granules of histamine, proteases, and cytokines; key mediators of allergic responses and innate immunity at barriers.
Melatonin: Pineal gland hormone regulating circadian rhythms, sleep, and immune function; a potent antioxidant with anti-inflammatory properties.
Metabolic flexibility: The ability to efficiently switch between glucose and fatty acid oxidation depending on fuel availability and metabolic demand.
Metaflammation: Metabolically-triggered chronic low-grade inflammation driven by nutrient excess, visceral adiposity, and metabolic stress.
Metamodels: The five core diagnostic frameworks in cPNI used to integrate knowledge across molecular, physiological, and clinical domains.
Microglia: Resident immune cells of the CNS derived from yolk sac progenitors; serve as the brain's primary innate immune system and perform synaptic pruning.
microbiome: The collective genome of all microorganisms inhabiting the body, particularly the gut, encoding metabolic functions essential for host health.
mitochondria: Double-membraned organelles that produce ATP through oxidative phosphorylation and serve critical functions in calcium regulation, apoptosis, and metabolic signaling.
Molecular Mimicry: Phenomenon where microbial antigens share structural similarity with self-antigens, leading to cross-reactive immune responses and autoimmune disease.
Myokines: Cytokines and peptides produced and released by contracting skeletal muscle during exercise, mediating anti-inflammatory and metabolic effects.
NF-κB: Nuclear factor kappa-B; a master transcription factor orchestrating inflammatory responses by regulating expression of over 200 genes including cytokines and chemokines.
NK cells: Natural killer cells; innate lymphocytes that kill virus-infected and tumour cells without prior sensitization, regulated by activating and inhibitory receptor balance.
NLRP3 inflammasome: A multiprotein complex that senses cellular stress and danger signals, activating caspase-1 to process IL-1beta, central to sterile inflammation in metabolic disease.
nocebo effect: A harmful health outcome resulting from negative expectations, anxiety, or negative treatment context; the counterpart to the placebo effect.
Noradrenaline: Norepinephrine; a catecholamine neurotransmitter and hormone involved in arousal, attention, stress responses, and immune cell trafficking.
neuroinflammation: Inflammatory processes within the central nervous system involving microglial activation, astrocyte reactivity, and cytokine production.
neuroplasticity: The brain's ability to reorganize its structure, function, and connections in response to experience, learning, injury, or environmental changes.
Omega-3 fatty acids: Essential polyunsaturated fatty acids (EPA, DHA, ALA) that serve as precursors for specialized pro-resolving mediators and have anti-inflammatory properties.
Osteocalcin: Bone-derived hormone produced by osteoblasts that regulates glucose metabolism, testosterone production, and brain function; undercarboxylated form is biologically active.
Oxidative Stress: An imbalance between reactive oxygen species production and antioxidant defences, causing damage to DNA, proteins, and lipids.
oxytocin: Neuropeptide produced in the hypothalamus promoting social bonding, trust, pain modulation, and anti-inflammatory effects; released during skin-to-skin contact and breastfeeding.
PAMPs: Pathogen-Associated Molecular Patterns; conserved molecular structures on microorganisms recognized by innate immune pattern recognition receptors.
pattern recognition receptors: Receptors (TLRs, NLRs, CLRs) on innate immune cells that detect conserved molecular patterns from pathogens and damaged tissues.
PGE2: Prostaglandin E2; a lipid mediator derived from arachidonic acid via COX-2 that promotes inflammation, fever, and pain, but also initiates the lipid mediator class switch toward resolution.
placebo effect: A beneficial health outcome resulting from the psychobiological treatment context rather than specific active intervention properties, producing real physiological changes.
POMC: Pro-opiomelanocortin; a precursor polypeptide cleaved into ACTH, beta-endorphin, and MSH, linking stress response, pain modulation, and appetite regulation.
Polyphenols: Plant-derived bioactive compounds with antioxidant, anti-inflammatory, and prebiotic properties; found in fruits, vegetables, tea, and spices.
Prostaglandins: Lipid mediators derived from arachidonic acid via cyclooxygenase enzymes that regulate inflammation, pain, fever, and vascular function.
Psychoneuroimmunology: The study of interactions between psychological processes, the nervous system, and the immune system; the scientific foundation of cPNI.
PTSD: Post-traumatic stress disorder; a trauma-related condition characterized by amygdala hyperactivity, hippocampal atrophy, HPA axis dysregulation, and chronic inflammation.
Quercetin: A flavonol found in onions, apples, and berries with anti-inflammatory, antioxidant, and mast cell-stabilizing properties.
Resoleomics: The study of specialized pro-resolving mediators (SPMs) derived from omega-3 and omega-6 fatty acids that actively resolve inflammation and promote tissue healing.
Resolvins: Specialized pro-resolving mediators derived from EPA (E-series) and DHA (D-series) that actively terminate inflammation and promote tissue repair.
rheumatoid arthritis: A chronic autoimmune disease causing joint inflammation and destruction through citrullination, molecular mimicry, and sustained immune activation.
sarcopenia: Age-related loss of skeletal muscle mass, strength, and function, driven by inflammation, hormonal changes, and physical inactivity.
SCFA: Short-chain fatty acids (butyrate, propionate, acetate); bacterial fermentation products of dietary fibre that regulate immune function, gut barrier integrity, and energy metabolism.
selfish immune system: The concept that activated leukocytes prioritize their own metabolic needs over other tissues, competing for glucose and amino acids during inflammation.
Selfish brain theory: Peters' theory that the brain allocates energy resources selfishly, maintaining its supply at the expense of peripheral organs via the stress axes.
sepsis: Life-threatening organ dysfunction caused by a dysregulated host response to infection, involving overwhelming systemic inflammation and immune paralysis.
sickness behaviour: A coordinated set of adaptive behaviours (fatigue, social withdrawal, anorexia, fever) triggered by pro-inflammatory cytokines during infection to conserve energy for immune function.
SPMs: Specialized Pro-resolving Mediators; bioactive lipid molecules (resolvins, protectins, maresins, lipoxins) derived from omega-3 and omega-6 fatty acids that actively terminate inflammation.
Substance P: A neuropeptide involved in pain transmission, neurogenic inflammation, and immune cell activation; released from sensory nerve endings.
systemic inflammation: Widespread inflammatory state affecting multiple organ systems, driven by circulating cytokines, acute phase proteins, and activated immune cells.
Th1: T helper type 1 cells; CD4+ T cells that produce IFN-gamma and drive cell-mediated immunity against intracellular pathogens and tumour cells.
Th2: T helper type 2 cells; CD4+ T cells that produce IL-4, IL-5, and IL-13, driving humoral immunity, anti-parasitic responses, and allergic inflammation.
Tight junctions: Multiprotein complexes (claudins, occludins, ZO proteins) that seal the intercellular space between epithelial cells, regulating paracellular permeability.
TLR4: Toll-like receptor 4; the primary receptor for bacterial LPS that triggers NF-kB activation and pro-inflammatory cytokine production.
TNF-α: Tumour necrosis factor alpha; a potent pro-inflammatory cytokine produced mainly by macrophages that drives acute inflammation, fever, and cachexia.
Toll-like receptors: A family of pattern recognition receptors detecting conserved molecular patterns from pathogens and damage signals, initiating innate immune responses.
trained immunity: Epigenetically-mediated functional reprogramming of innate leukocytes enabling enhanced responsiveness to subsequent immune challenges.
Treg cells: Regulatory T cells (CD4+CD25+FoxP3+); a subset of T cells that suppress immune responses, maintain tolerance, and prevent autoimmunity.
Tryptophan: Essential amino acid and precursor for serotonin and melatonin synthesis; diverted to the kynurenine pathway during inflammation, linking immune activation to depression.
Type 2 Diabetes: A metabolic disease characterized by insulin resistance and progressive beta-cell dysfunction, driven by chronic low-grade inflammation, visceral adiposity, and metabolic mismatch.
Uric acid: The end product of purine metabolism in humans (due to uricase mutation); acts as an antioxidant in blood but pro-inflammatory when crystallized in tissues (gout).
Vagus nerve: The tenth cranial nerve providing bidirectional communication between brain and visceral organs; carries 80% afferent and 20% efferent signals for interoception and immune regulation.
VEGF: Vascular endothelial growth factor; a signaling protein stimulating angiogenesis, increased during wound healing, exercise, and tumour growth.
Vitamin D: A secosteroid hormone (not truly a vitamin) that modulates immune function, calcium metabolism, and gene expression through the VDR nuclear receptor.
Warburg Effect: Preferential use of glycolysis over oxidative phosphorylation for ATP production even with adequate oxygen; characteristic of cancer cells and activated immune cells.
Zonulin: The only known physiological modulator of intestinal tight junctions; functions as a biomarker and mediator of intestinal permeability. Released in response to gliadin and bacteria.
This glossary covers approximately 200 key cPNI terms. See A-Z Concept Index for a complete listing of all concept notes in the vault.