Melanocytes Flag Themselves for Immune Attack
Stressed melanocytes upregulate MHC-I, marking themselves as targets.
- MHC-I: Antigen (Surface presentation)
- Oxidative stress: Trigger (Melanocyte damage)
- MelanA/gp100: Key antigen (Melanocyte proteins)
- Early: Onset (Pre-clinical phase)
Why melanocytes become targets
Cellular stress exposes melanocyte antigens to surveillance.
Role of innate signaling
Danger signals recruit dendritic cells to the skin.
Autoreactive CD8+ T-Cells Get Switched On
Dendritic cells prime CD8+ T-cells against melanocyte antigens.
- CD8+ CTL: Cell type (Cytotoxic T-lymphocyte)
- Lymph node: Priming site (Antigen presentation)
- IFN-γ: Cytokine (Drives activation)
- CXCR3+: Homing (Skin-directed migration)
Priming and clonal expansion
Activated clones expand and migrate toward the skin.
Skin-homing chemokines
CXCL9/10 gradients pull T-cells into the epidermis.
Granzyme and Perforin Destroy Melanocytes
T-cells deliver lytic granules that trigger melanocyte apoptosis.
- Perforin pores: Mechanism (Granzyme delivery)
- Apoptosis: Outcome (Melanocyte death)
- IFN-γ, TNF-α: Key cytokine (Amplify killing)
- Immune synapse: Contact type (Direct cell contact)
The cytotoxic synapse
Close contact focuses lytic granules on the target.
Feedback amplification
Dying cells release more antigen, worsening the attack.
Melanin Output Declines as Cells Die
Fewer surviving melanocytes means steadily less melanin made.
- Melanin: Pigment (Produced by melanocytes)
- Progressive: Trend (Worsens over months)
- Lightening skin: Visible sign (Early clinical clue)
- Partial: Reversibility (With early treatment)
Gradual color fade
Skin lightens unevenly as melanocyte density drops.
Clinical detection
Wood lamp exam highlights early depigmented areas.
Depigmented Zones Merge Into Visible Patches
Adjacent dead zones coalesce into classic white vitiligo patches.
- Vitiligo patch: Result (Well-demarcated white skin)
- Symmetric: Distribution (Common presentation)
- Chronic: Course (Relapsing and remitting)
- Immunomodulation: Management (JAK inhibitors, light therapy)
Patch coalescence
Small depigmented spots expand and fuse together.
Long-term course
Disease activity fluctuates between flares and stability.