neuroimmune-pruning

name	neuroimmune-pruning
description	Immune substrate of biological active inference — microglia + complement (C1q→C3b→CR3) tag and phagocytose synapses, acting as the body's TMS justifier / garbage collector. Immunosurveillance = nogood-repair; autoimmunity = the false nogood. Use when modeling immune editing of neural priors, neuroinflammation gating plasticity, or the immune-vascular latch coupling.
license	MIT
metadata	{"trit":0,"source":"https://doi.org/10.1126/science.1202529"}

neuroimmune-pruning

The immune substrate (0 / witness) of the three-substrate vasocomputation stack. The neuroimmune system is the body's garbage collector and TMS justifier: microglia, using the classical complement cascade (C1q → C3b opsonization → CR3-mediated phagocytosis), tag and eliminate synapses — literally editing the neural prior set. Perivascular mast cells couple the immune leg to the vascular leg; pro-inflammatory cytokines (IL-1β, TNF-α) gate whether a held pattern is allowed to consolidate.

Use When

• Modeling the immune system as the editor of neural priors (microglial synaptic pruning)
• Neuroinflammation as precision-weighting on the consolidation (−1) step
• The immune–vascular coupling that maintains or releases a latch (latched-hyperprior)
• Distinguishing healthy immunosurveillance (nogood-repair) from autoimmunity (false nogood)

Core Concepts

• Complement tagging = EnsureJustification: a synapse with no closing justification is opsonized by C1q/C3b and phagocytosed by microglia — a measured retraction (a nogood), not an assigned one. (Stevens 2007; Schafer 2012.)
• Immunosurveillance = the −1 / coplay nogood-repair leg: the body detects defected/latched/cancerous subagents and clears them. Levin: latched cells that bioelectrically disconnect are exactly what surveillance should catch.
• Autoimmunity = the false nogood: complement tags self — excess C3/C4 synaptic pruning is implicated in schizophrenia and Alzheimer's. This is the worm Goodharting its self/non-self boundary: forcing content-H¹ (real signal) to 0 by attacking valid synapses.
• Latch maintenance: latch → hypoxia (HIF-1α) → inflammatory recruitment → more VSMC tone. Trying to wall off a perturbation, the immune system can stabilize the latch — the latch spiral as a granuloma-like, immune-defended locus.
• Mast cells: perivascular sentinels; degranulation (a fast "grab") triggers the vascular event that becomes a latch.

GF(3) Balanced Triad

vasocomputation (+1) ⊗ neuroimmune-pruning (0) ⊗ neural-potentiation (−1) = 0 (mod 3)

Skill Trit: 0 (Witness — the justifier/GC that decides what is kept; cf. the PAM JustifierAgent maintaining the justification lattice).

Honesty markers

Grounded: microglial complement-mediated synaptic pruning; perivascular mast cells; cytokine modulation of LTP; HIF/hypoxia–inflammation; immunosurveillance of cancer. Speculative weld (marked, not asserted): framing the immune system as a free-energy / active-inference learner, and the GF(3) substrate→trit assignment as an organizing correspondence.

Concomitant Skills

Skill	Trit	Interface
vasocomputation	+1	vascular substrate it co-regulates
neural-potentiation	−1	gates / prunes the synaptic store
latched-hyperprior	−1	unlatch (resolve) vs. defend (granuloma)
cybernetic-immune	0	immune system as a cybernetic controller
sheaf-cohomology	0	pruning = trivializing a nogood cocycle
affective-taxis	−1	self/non-self boundary = valence boundary

Current literature (2024–2026)

• Stevens et al. (2007, Cell); Schafer et al. (2012, Neuron) — classical complement (C1q→C3) opsonizes weak synapses; microglial CR3/C3 engulfment is activity-dependent (weaker inputs preferentially pruned) — a measured valence gradient, not a stamp.
• Sekar et al. (2016, Nature) — schizophrenia MHC signal traced to C4 alleles; risk scales with C4A; C4 sits between C1q and C3 = the convertase gain knob (excess −1 retraction).
• Hong et al. (2016, Science) — complement drives early synapse loss in Alzheimer models before plaques; inhibition rescues LTP.
• Stellwagen & Malenka (2006, Nature); Yirmiya & Goshen (2011) — glial TNF-α is sufficient for synaptic scaling; cytokines gate LTP/consolidation in an inverted-U (low pg/mL enhances, inflammatory ng/mL impairs).
• Bhat, Parr, Ramstead & Friston (2021), immunoceptive inference; Dunn, Old & Schreiber (2004), immunoediting (Elimination / Equilibrium / Escape = surveillance / latent-nogood / false-negative).
• Exact cascade: C1q → C4/C2 → C3 convertase → C3b/iC3b opsonin → microglial CR3 → engulfment.
• Hook: synaptic C1q/C3b density predicts microglial engulfment volume; C4A expression ∝ elimination rate; cytokine dose sets consolidation gain.
• Grounded: complement pruning, C4-schizophrenia, TNF-α scaling, mast-cell vasoactivity, immunoediting. Speculative weld: "microglia = TMS justifier," "autoimmunity = false nogood" — framing licensed by Friston/Tauber, computes no cohomology.

References

• Stevens, B. et al. (2007). The classical complement cascade mediates CNS synapse elimination. Cell 131(6).
• Schafer, D.P. et al. (2012). Microglia sculpt postnatal neural circuits in an activity- and complement-dependent manner. Neuron 74(4). doi:10.1126/science.1202529 (program).
• Yirmiya, R. & Goshen, I. (2011). Immune modulation of learning, memory, neural plasticity and neurogenesis. Brain Behav. Immun. 25(2).
• Levin, M. (2022). TAME. Front. Syst. Neurosci. 16. (Defection / cancer / surveillance.)