Basic Sciences Relevant to Skin
Scope
This domain tests how structure and molecular machinery explain skin disease: epidermal differentiation, basement-membrane adhesion, dermal matrix, immune circuits, and the genetics of inherited disorders. Questions typically link a protein to a blister level, a cytokine to a biologic, or a mutation to a phenotype.
Core rules
- Keratins: K5/K14 in basal cells; K1/K10 suprabasal; K6/K16 in hyperproliferative epidermis. K5/K14 mutations cause epidermolysis bullosa simplex.
- Basement membrane: BPAG1 (230 kDa) and BPAG2 (180 kDa, collagen XVII) sit in hemidesmosomes; laminin-332 and integrin α6β4 in the lamina lucida; collagen VII anchors lamina densa to dermis.
- Melanocytes are neural-crest derived; MITF and c-KIT drive survival; tyrosinase is rate-limiting; melanosomes are transferred to keratinocytes.
- Adaptive immunity: IL-23/Th17 dominates psoriasis; Th2/IL-4/IL-13 in atopic dermatitis; Treg failure permits autoimmunity.
- Genetics: FLG null alleles cause ichthyosis vulgaris and raise atopic risk; PTCH1 causes BCC; NF1 and TSC1/2 cause neurocutaneous syndromes.
Worked example
A newborn has generalized blisters; immunofluorescence mapping shows cleavage in the lamina lucida with reduced BPAG2. Reasoning: hemidesmosome components (BPAG1/2, integrin) sit above the lamina densa, so their loss gives junctional EB. Cleavage below the lamina densa with absent collagen VII indicates dystrophic EB. The level predicts scarring and extracutaneous risk.
Traps
Do not confuse K6/K16 (hyperproliferation) with K1/K10 (differentiation). Desmoglein 3 loss gives mucosal-predominant pemphigus vulgaris; desmoglein 1 loss gives superficial foliaceus. Collagen XVII is both a hemidesmosome protein and the BP180 autoantigen.