Exploration of How Your Body Attacks Itself
When the immune system mistakes self for enemy
Your immune system loses its ability to distinguish "self" from "non-self." Central tolerance (thymus screening) and peripheral tolerance (regulatory T cells) both fail, allowing self-reactive immune cells to escape destruction.
T cells, B cells, neutrophils, and dendritic cells orchestrate coordinated attacks on your own tissues. Th1 and Th17 cells drive inflammation while regulatory mechanisms fail to suppress the response.
Autoantibodies, immune complexes, and cytokine storms cause progressive damage. Complement punches holes in cells, enzymes digest cartilage, and chronic inflammation leads to permanent fibrosis and scarring.
Epitope spreading exposes new targets, damaged tissue releases danger signals (DAMPs), and inflammatory feedback loops amplify the response—creating a vicious cycle that sustains itself.
Hover over each cell to learn its role
Rapid-response shock troops that flood tissues, release toxic enzymes, and form DNA "nets" (NETs) that trap microbes but also damage your own tissues and expose nuclear antigens that become autoimmune targets.
Orchestrate autoimmune destruction. Th1 cells produce inflammatory cytokines (IFN-γ, TNF), Th17 cells secrete IL-17 driving tissue inflammation, while regulatory T cells fail to suppress the response.
Produce autoantibodies that recognize self-tissues, present antigens to T cells, secrete inflammatory cytokines, and form ectopic germinal centers—factories that churn out more autoreactive B cells.
Critical orchestrators that capture self-antigens from damaged tissues and present them to T cells in an activated, inflammatory context—triggering full autoimmune responses instead of tolerance.
From silent autoimmunity to clinical disease
Autoantibodies and autoreactive T cells appear in your blood without noticeable symptoms. Your immune system has begun targeting self-tissues, but damage hasn't reached clinical thresholds.
Tissue damage accumulates and early symptoms emerge, though organ function remains largely intact. You feel something is wrong but don't yet meet diagnostic criteria.
Substantial tissue damage and impaired organ function meet diagnostic criteria. This stage triggers formal diagnosis and disease-modifying treatment.
From silent autoimmunity to active disease
Viral or bacterial infections provide inflammatory signals and molecular mimicry—microbial proteins resemble self-proteins, triggering cross-reactive immune responses. EBV infection linked to MS onset.
Strongly linked to ACPA-positive RA progression, especially with susceptible HLA alleles. Drives citrullination and post-translational modifications in lung tissues that become autoimmune targets.
Creates chronic low-grade inflammation, alters adipokines and cytokines, lowers threshold for clinical autoimmunity. Particularly impacts RA and metabolic autoimmune conditions.
HLA genes strongly influence susceptibility. Specific variants efficiently present self-antigens to T cells. Over 80 genes implicated in lupus alone. Explains familial clustering and sex differences.
Initial tissue damage releases new self-antigens not previously accessible. Immune system expands targets, recruiting fresh waves of autoreactive lymphocytes—amplifying the autoimmune response.
Cytokines (IL-6, TNF, IL-17) create positive feedback loops. Inflammatory environment overrides regulatory mechanisms, preventing Tregs from suppressing the autoimmune response.
Alterations disrupt immune tolerance through effects on T cell differentiation, dendritic cell function, and cytokine production. Dysbiosis linked to multiple autoimmune conditions.
Trichloroethene, silica, mercury, pesticides linked to higher autoimmune risk. Climate change, pollution, and chemicals may confuse immune system in susceptible individuals.
Click signals to trigger immune cascades • Compose your inflammatory symphony
DAMP
PAMP
Cytokine
Stress Signal
NET
Click danger signals to activate immune cascades • Watch the ripple effects
How destruction unfolds at the molecular level
Antibodies that recognize self-antigens cause damage through multiple pathways:
Pro-inflammatory signaling molecules flood affected tissues:
In severe cases, these signals amplify in catastrophic positive feedback loops—a true "cytokine storm" that can be life-threatening.
Damage-Associated Molecular Patterns released from stressed or dying cells perpetuate autoimmunity:
This creates a vicious cycle: autoimmune attack causes tissue damage → releases DAMPs → activates more immune cells → causes more damage.
A cascade of 30+ proteins that normally help clear pathogens but in autoimmunity attacks self:
Deficiencies in complement regulatory proteins (like Factor H) increase autoimmune risk by allowing uncontrolled complement activation.
Chronic inflammation causes progressive structural damage:
This is why early intervention is critical—to prevent irreversible structural damage before it accumulates.
Neutrophil Extracellular Traps (NETs) are a double-edged sword in autoimmunity: