Adaptive Immunity Models
1 T Cell Dynamics
T cell dysfunction in ME/CFS includes altered CD4⁺/CD8⁺ ratios, increased expression of exhaustion markers (PD-1, Tim-3), and reduced proliferative capacity. The T cell model distinguishes naïve (\(T_n\)), effector (\(T_e\)), memory (\(T_m\)), and exhausted (\(T_{\text{ex}}\)) populations:
\[ \begin{aligned} \frac{d T_n}{d t} &= s_T - k_{\text{prime}} \cdot A(t) \cdot T_n - d_n T_n \\ \frac{d T_e}{d t} &= k_{\text{prime}} \cdot A(t) \cdot T_n + \rho_T T_e (1 - \frac{T_e}{T_{\text{max}}}) - k_{\text{mem}} T_e - k_{\text{Tex}} T_e - d_e T_e \\ \frac{d T_m}{d t} &= k_{\text{mem}} T_e - k_{\text{reactivate}} \cdot A(t) \cdot T_m - d_m T_m \\ \frac{d T_{\text{ex}}}{d t} &= k_{\text{Tex}} T_e - d_{\text{ex}} T_{\text{ex}} \end{aligned} \tag{1}\]
where \(A(t)\) is the antigen signal (from infection or autoimmune stimulation), \(\rho_T\) is the proliferation rate with logistic growth, \(k_{\text{mem}}\) is the rate of memory cell formation, and \(k_{\text{Tex}}\) is the exhaustion rate. In ME/CFS, persistent antigenic stimulation (from chronic viral reactivation or autoimmune processes) drives continuous \(T_n -> T_e\) priming and accelerated \(T_e -> T_{\text{ex}}\) exhaustion. The model predicts an expanded \(T_{\text{ex}}\) compartment with reduced effector function—consistent with the immunological phenotype observed in ME/CFS patients (Che et al. 2025).
2 B Cell and Autoantibody Production
B cell-mediated autoimmunity has been implicated in ME/CFS by studies documenting autoantibodies against neurotransmitter receptors and autonomic nervous system components (Loebel et al. 2016) (Freitag et al. 2021) (Bynke et al. 2020). The B cell model tracks naïve B cells (\(B_n\)), activated B cells (\(B_a\)), and long-lived plasma cells (\(P\)) that produce autoantibodies (\(\text{Ab}\)):
\[ \begin{aligned} \frac{d B_a}{d t} &= k_{\text{Bact}} \cdot T_e \cdot B_n - k_{\text{plasma}} B_a - d_{B a} B_a \\ \frac{d P}{d t} &= k_{\text{plasma}} B_a - d_P P \\ \frac{d [\text{Ab}]}{d t} &= \sigma_{\text{Ab}} \cdot P - \delta_{\text{Ab}} [\text{Ab}] \end{aligned} \tag{2}\]
where \(k_{\text{Bact}}\) is the T cell-dependent B cell activation rate and \(\sigma_{\text{Ab}}\) is the antibody secretion rate per plasma cell. The long half-life of plasma cells (\(d_P^{-1} \approx\) months to years) means that autoantibody production persists long after the initial B cell activation—a mechanism potentially explaining why B cell depletion therapy (rituximab) showed delayed and variable responses in ME/CFS trials (Fluge et al. 2011) (Fluge et al. 2015) (Fluge et al. 2019). The model predicts that clinical response requires waiting for pre-existing plasma cells to die naturally, with response timing inversely proportional to \(d_P\).