Allergy & Autoimmunity - Allergic Contact Dermatitis

Allergic Contact Dermatitis

Acute ACD
- Edema
- Erythema
- Vesiculation
- Desquamation
- Infiltration

Patch testing » detection of contact allergens

ACD phases
 Sensitization
1. Allergen-skin interaction
2. APC migration and maturation
3. T cell priming (in draining lymph node)
 Elicitation
4. Inflammation (inflammatory cytokines)


1. Allergen-skin interaction
 Skin penetration through the stratum corneum
Filaggrin in the skin barrier » defective skin barrier has NO filaggrin granules.
Filaggrin mutation frequent in Europeans and Asians.
 Filaggrin mutation and increased skin irritability are risk factors for
polysensitization to fragrances.

Dendritic cells (DC)
 Part of the innate immune system
 Antigen presenting cells
 Essential key-players for initiating adaptive immunity
Epidermal Langerhans cells
 Binding to (cell-surface) proteins
 Bonding: covalent to thiols, amines; coordinative
 Metabolisation of pro-haptens: PPD » Bandrowski’s base
(para-phenyleendiamine (PPD) kan contact allergy reaction
veroorzaken)
Activation Langerhans cells:
 Thiol group – NFkB & ERK1/2
 Amino group – MAPK-p38
» result: modified cell surface receptor expression

TLR on dendritic cells (TLR-2 & 4)
 PAMPS (pathogen associated molecular patterns), like LPS, viruses,..
 Contributing to irritancy of allergens
 “danger signal” » when allergen activate TLR-2 or 4

Nickel doesn’t activate the murine TLR4
Murine TLR4 has differences compared to human, missing histidines not
allowing nickel to bind to and stimulate TLR4 directly.
Hence, mice get hardly sensitized to nickel. Adjuvants (irritants) are needed!