Cutaneous Immunology

Cutaneous Immunology - Skin's Guardian Squad

• Skin-Associated Lymphoid Tissue (SALT): Integrated system for cutaneous immune surveillance.
• Innate Immunity (Rapid Defense):
  • Keratinocytes: Barrier; cytokines (IL-1, TNF-α), antimicrobial peptides (AMPs).
  • Langerhans Cells (LCs): Epidermal dendritic cells; potent antigen-presenting cells (APCs).
  • Others: Dermal Dendritic Cells (DDCs), Macrophages, Mast cells, NK cells.
• Adaptive Immunity (Specific & Memory):
  • T-lymphocytes: CD4+ Helper (Th1, Th2, Th17, Treg), CD8+ Cytotoxic.
  • B-lymphocytes: Antibody production via plasma cells.
• Key Cytokines (Cellular Messengers):
  • Pro-inflammatory: TNF-α, IL-1, IL-6, IL-17, IFN-γ.
  • Anti-inflammatory: IL-10, TGF-β.

⭐ Langerhans cells, key epidermal APCs, uniquely contain Birbeck granules (tennis-racket shape on EM), crucial for initiating skin immune responses.

Cutaneous Immunology - Antigen Alert System

• Skin's surveillance: Detects pathogens via Pattern Recognition Receptors (PRRs) e.g., Toll-like Receptors (TLRs).
• Key Antigen Presenting Cells (APCs):
  • Langerhans Cells (LCs): Epidermal; migrate to lymph nodes.
  • Dermal Dendritic Cells (DDCs): In dermis.
  • Keratinocytes: Can express MHC-II; produce cytokines (TNF-α, IL-1).
• Process: APCs capture, process, and present antigens on MHC molecules to T-cells, initiating adaptive immunity.

⭐ Langerhans cells uniquely contain Birbeck granules (tennis-racket shaped organelles on EM) and express CD1a & Langerin (CD207). 📌 Birbeck = Tennis Racket shape on EM for LCs!

Cutaneous Immunology - Itch & Scratch Saga

• Hypersensitivity Reactions: Immune overreactions causing tissue damage & pruritus. 📌 Mnemonic: ACID
  • Type I (A - Allergic/Anaphylactic): IgE-mediated; mast cell degranulation (histamine).
    • Urticaria, angioedema. Intense itch.
  • Type II (C - Cytotoxic): IgG/IgM vs. cell-bound antigens.
    • Ex: Pemphigus.
  • Type III (I - Immune Complex): Ag-Ab complex deposition.
    • Ex: Cutaneous vasculitis.
  • Type IV (D - Delayed): T-cell mediated (Th1, CTLs).
    • Ex: Allergic contact dermatitis (ACD). ACD: severe itch.
• Pruritus Mediators: Histamine, serotonin, Prostaglandins (PGs), Leukotrienes (LTs), Substance P, IL-31.
• Itch-Scratch Cycle: Itch → Scratch → Skin barrier disruption → Inflammation → ↑Itch → Lichenification.

⭐ Type IV hypersensitivity is the mechanism behind allergic contact dermatitis, a common cause of severe, T-cell driven itch and eczematous skin changes.

Cutaneous Immunology - Self-Sabotage Stories

• Autoimmunity: Immune system attacks skin's self-antigens due to failed self-tolerance.
• Key Mediators:
  • Autoantibodies: Target skin structures (e.g., desmogleins in Pemphigus).
  • Autoreactive T-cells: Drive inflammation/damage (e.g., Lichen Planus).
  • Cytokines (TNF-α, IL-17): Amplify response.
• Damage Mechanisms:
  • Type II Hypersensitivity: Antibody-driven (Pemphigus, Bullous Pemphigoid).
  • Type IV Hypersensitivity: Cell-mediated (Lichen Planus).
• Common Autoimmune Skin Diseases:
  • Pemphigus Vulgaris (PV): Anti-desmoglein 3, 1. Intraepidermal.
  • Bullous Pemphigoid (BP): Anti-BPAG1 (BP230), BPAG2 (BP180). Subepidermal.
  • Lupus Erythematosus (LE): ANA, anti-dsDNA.
  • Dermatomyositis (DM): Anti-Mi-2, anti-Jo-1.

⭐ Pemphigus vulgaris often presents with oral mucosal erosions before skin lesions develop.

High‑Yield Points - ⚡ Biggest Takeaways

• Langerhans cells: Epidermal APCs; crucial for initiating Type IV hypersensitivity.
• Keratinocytes: Active source of cytokines (IL-1, TNF-α); contribute to innate and adaptive skin immunity.
• Th1 cells: Mediate Delayed-Type Hypersensitivity (DTH) (e.g., contact dermatitis) via IFN-γ.
• Th2 cells: Key in atopic dermatitis and urticaria, producing IL-4, IL-5, IL-13.
• Mast cells: Release histamine and mediators in urticaria and anaphylaxis.
• Autoantibodies: Anti-desmoglein (Pemphigus Vulgaris), anti-BPAG1/2 (Bullous Pemphigoid) are key markers.
• CLA (Cutaneous Lymphocyte Antigen): Marker for skin-homing T lymphocytes.