IMMUNOLOGY OF THE SKIN（皮膚の免疫学）
A. Innate immunity of the skin（皮膚の自然免疫）
Rapid defense mechanisms of the skin:
- b-defensin（HBD-1, HBD-2 and HBD-3）is secreted from keratinocytes.
- Toll-like receptors (TLR) on the Langerhans cells, monocytes/macrophages and neutrophils bind microbial components to induce NFk-B-mediated cytokine expression.
B. Cells involved in the skin immunity and inflammation
（皮膚の免疫と炎症に関わる細胞）
Skin is a highly developed immune organ composed of Langerhans cells（ランゲルハンス細胞）, keratinocytes（角化細胞）, endothels（血管内皮細胞）, fibroblasts（線維芽細胞）, T lymphocytes（Tリンパ球）, eosinophils（好酸球）, mast cells（肥満細胞） and macrophades（マクロファージ）. Among them, Langerhans cells play a central role due to their strong antigen uptake and presenting activity.
1. Langerhans cell（LC、ランゲルハンス細胞）
- LCs are bone marrow-derived dendric cells distributed in the prickled cell layer of epidermis and contain Birbeck granules（バーベック顆粒）in their cytoplasm.
- LC expresses MHC class II Ag, CD45, Fc-IgG receptor II, ICAM-1 and CD1a.
- LC uptakes antigens, presents their peptide on the cell surface with MHC
class II molecule, moves to a regional lymph node and activates both CD4+ and CD8+ naive T cells.
2. Keratinocyte（角化細胞）
- Keratinocyte participates inflammatory and immunologic processes by producing interleukins (IL-1a, IL-6, IL-10, IL-12, TNF-a), chemokines (IL-8, MCP-1, MIP-3 a, RANTES, TARC), colony stimulating factors (GM-CSF, M-CSF) and growth factors (TGF-a, TGF-b, PDGF, NGF, SCF, bFGF, VEGF).
3. Mast cell（肥満細胞）
- Mast cell is derived from bone marrow and contains basophilic granules (stained in purple-red by Toluidin blue).
- Mast cell contains and/or produces chemical mediators including histamine,
heparin, tryptase, kimase, prostaglandin D2, leukotrien (LTB4, LTC4) and
cytokines (IL-3, IL-5, IL-6, IL-13, GM-CSF, TNF-a, TGF-b).
- Chemical mediators are secreted by allergic (bind of IgE to FceR1[高親和性IgE受容体]) and non-allergic (complement, neuropeptides, drug, physical stimuli) mechanisms.
4. Eosinophil（好酸球）
- Eosinophils infiltrate the skin not only in allergic diseases (atopic dermatitis,
drug eruption, Urticaria, Churg-Strauss syndrome) but also in bullous dermatoses, parasite infection and malignancy.
-Eosinophils produce major basic protein (MBP), eosinophil cationic protein
(ECP), PAF and LTC4 and modify inflammation of the skin.
C. Neuropeptides（ニューロペプチド）
- Sensory neurons (C fibers) distribute to the upper dermis and epidermis.
- Stimulation to the skin mediates release of neuropeptides (substance P, neurokinin A, calcitonin gene-related peptide CGRP) from the ends of the sensory neurons.
- Neuropeptides mediate histamine release from mast cells and increase extravasation of inflammatory cells.
D. Classification of allergic skin disease（アレルギーの古典的分類と皮膚疾患）
Type I（I型アレルギー）: skin eruption within 30 min after exposure to the antigen, mediated by chemical mediators from mast cells; Atopic dermatitis（アトピー性皮膚炎）、Urticaria（蕁麻疹）.
Type II（II型アレルギー）: cytotoxic reaction induced by the specific antibody and activation of complements; Lupus erythematosus（エリテマトーデス）、Pemphigus vulgaris（尋常性天疱瘡）、Bullous pemphigoid（水疱性類天疱瘡）.
Type III（III型アレルギー）: deposit of immune complex and activation of complements; anaphylactoid purpura （アナフィラクトイド紫斑）、polyarteritis nodosa（結節性多発性動脈炎）、granulomatous vasculitis（肉芽腫性血管炎）.
Type IV（IV型アレルギー）: immune reaction mediated by the sensitized T cell; allergic contact dermatitis（アレルギー性接触性皮膚炎）、granulomatous reaction（肉芽腫反応）.