ABD - American Board of Dermatology Basic Science and Immunology Questions and Answers 1 — Questions and Answers
Question 1: Which cytokine is considered central to the pathogenesis of psoriasis by acting on T cells to promote their differentiation into and maintenance of the Th17 phenotype?
- Interleukin-4 (IL-4)
- Interleukin-10 (IL-10)
- Interleukin-23 (IL-23) (Correct answer)
- Transforming growth factor-β (TGF-β)
Correct answer: Interleukin-23 (IL-23)
Interleukin-23 (IL-23), produced primarily by dendritic cells, is a key regulatory cytokine that drives the pathogenesis of psoriasis. It is crucial for the survival, expansion, and pathogenic function of Th17 cells, which in turn produce effector cytokines like IL-17 and IL-22 that cause keratinocyte hyperproliferation and inflammation.
Question 2: A newborn presents with widespread blistering and erosions following minor trauma. A skin biopsy with immunofluorescence mapping shows a split below the lamina densa of the basement membrane zone. A mutation in the gene encoding which of the following structural proteins is the most likely cause?
- Keratin 14
- Plectin
- Laminin 332
- Type VII collagen (Correct answer)
Correct answer: Type VII collagen
A tissue split below the lamina densa is characteristic of dystrophic epidermolysis bullosa (DEB). This condition is caused by mutations in the COL7A1 gene, which encodes type VII collagen. Type VII collagen is the primary component of anchoring fibrils, which secure the lamina densa of the basement membrane to the underlying papillary dermis.
Question 3: A patient with a history of recurrent severe herpes simplex virus (HSV) infections is suspected of having a defect in innate immune recognition. Which of the following Toll-like receptors, located within the endosome, is most critical for recognizing viral genomic DNA and initiating an interferon response?
- TLR2
- TLR9 (Correct answer)
- TLR4
- TLR5
Correct answer: TLR9
Toll-like receptor 9 (TLR9) is an intracellular pattern recognition receptor located in the endosomal compartment. It specializes in recognizing unmethylated CpG motifs present in bacterial and viral DNA, such as that from HSV. This recognition is a key step in triggering a type I interferon response critical for antiviral immunity.
Question 4: Allergic contact dermatitis, such as the classic reaction to urushiol in poison ivy, is an example of which type of Gell and Coombs hypersensitivity reaction?
- Type I (IgE-mediated)
- Type II (Antibody-dependent cytotoxicity)
- Type III (Immune complex-mediated)
- Type IV (Delayed-type, cell-mediated) (Correct answer)
Correct answer: Type IV (Delayed-type, cell-mediated)
Allergic contact dermatitis is a classic example of a Type IV, or delayed-type, hypersensitivity reaction. It is not mediated by antibodies but by hapten-specific T-lymphocytes. Following sensitization, re-exposure to the allergen leads to activation of memory T-cells, which recruit and activate other inflammatory cells, causing a dermatitic reaction that typically peaks 48-72 hours after contact.
Question 5: A 60-year-old fair-skinned individual with a history of extensive sun exposure develops multiple actinic keratoses. The primary type of DNA damage directly induced by the ultraviolet B (UVB) component of sunlight, which is responsible for the mutations leading to these lesions, is the formation of:
- Pyrimidine dimers (Correct answer)
- Reactive oxygen species
- Single-strand breaks
- DNA-protein crosslinks
Correct answer: Pyrimidine dimers
UVB radiation is directly absorbed by DNA, causing photochemical reactions that form covalent bonds between adjacent pyrimidine bases (thymine or cytosine). These lesions, primarily cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts, distort the DNA helix, leading to mutations during replication if not repaired by the nucleotide excision repair pathway.
Question 6: The cornified cell envelope is a critical component of the epidermal barrier, formed by the cross-linking of proteins like loricrin and involucrin during terminal keratinocyte differentiation. Which enzyme is primarily responsible for catalyzing the formation of these covalent isopeptide bonds?
- Caspase-14
- Transglutaminase 1 (Correct answer)
- Kallikrein-5
- Bleomycin hydrolase
Correct answer: Transglutaminase 1
Transglutaminase 1 (TGM1) is the key calcium-dependent enzyme that cross-links structural proteins (e.g., loricrin, involucrin, small proline-rich proteins) to form the highly insoluble and mechanically resilient cornified cell envelope. Defective TGM1 function, due to genetic mutations, is the cause of lamellar ichthyosis.
ABD - American Board of Dermatology Basic Science and Immunology Questions and Answers 1
Which cytokine is considered central to the pathogenesis of psoriasis by acting on T cells to promote their differentiation into and maintenance of the Th17 phenotype?