Table 1.

Features and function of main tissues representing the three pillars of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). HPA: hypothalamic–pituitary–adrenal.

System	Tissue/Cell	Feature	Ref.
Central Neurological System	Neuron	The symptomatology is related to a variety of sources of chronic neurological disturbance and associated distortions and chronicity in noxious sensory signaling and neuroimmune activation	[9]
	Glial cells	There is a significant blood–brain barrier permeability, microglia activation through toll-like receptors (TLR) signaling, secretion of IL-1B, upregulation of 5-HTT in astrocytes, reduced extracellular 5-HT levels, and hence a reduced activation of 5-HT receptors	[10]
Immune System	Lymphocytes Th1/Th2	Significant bias toward Th2 immune responses in CFS patients leading to an effector memory cell bias toward type 2 responsiveness	[11]
	NK cells	Reduction of cytotoxic activity in CFS, leading to a higher susceptibility of infection	[12]
	B cells	Persistence of autoreactive cells that can generate autoantibodies during common infections	[13]
Endocrine System	Hypothalamus–pituitary–adrenal (HPA) axis	Enhanced corticosteroid-induced negative feedback, basal hypocortisolism, attenuated diurnal variation, and a reduced responsivity to challenge	[14]