Figure 1.

“Immune Gate” of psychopathology – mechanisms of gut derived immune activation leading to psychiatric manifestations. Image generated using Servier Medical Art. 1: Various detrimental factors compromising intestinal barrier lead to increased intestinal permeability. 2: Increased intestinal permeability is as a source of food derived and microbial, bacterial, parasitic antigens, and subsequent activation of inflammatory response with production of immunoglobulins against those antigens. Other markers of increased intestinal permeability. 3: Detrimental for the brain immune consequences of gut derived antigens modulate neuro-psychiatric symptomatology. 4: Peripheral autoimmunity (via molecular mimicry, covalent binding) due to various gut derived antigens and further activation of inflammatory response detrimental to CNS via e.g., pro-inflammatory cytokines, activation, and changes in kynurenic pathway metabolism. 5: Factors compromising blood-brain-barrier contribute to the periphery-derived activation of inflammatory response and its psychiatric and neurological manifestations. CRH, corticoliberin; SIBO, small intestine bacterial overgrowth; NF-κB, nuclear factor kappa B; NSAIDs, non-steroidal anti-inflammatory drugs; IgA, IgE, IgG, IgM, immunoglobulin A, E, G, M; LPS, bacterial lipopolysaccharide; LBP, lipopolysaccharide binding protein; sCD14, soluble CD14; NMDAR, N-methyl-D-aspartate glutamate receptor; MBP, myelin basic protein; MAG, myelin-associated glycoprotein; GM1, ganglioside; SULF, sufatide; CONSO4, chondroitin sulfate; MOG, myelin oligodendrocyte glycoprotein; α,β-CRYS, α,β-crystallin; NAFP, neurofilament proteins; CPP, Chlamydia pneumoniae; STM6P, streptococcal M protein; BTN, milk butyrophilin; DPP IV, dipeptidyl peptidase IV (synonym of CD26); ₅₁Cr-EDTA, chromium ethylenediaminetetraacetic acid; ASCA, IgG to Saccharomyces cerevisiae; TLR4, Toll-like receptor 4.