# Local design fixture, not a curated module or a proposed disease entry. name: Example - Senescent skin fibroblast immune evasion category: Module description: >- An existing-schema illustration of cell identity, a senescent state, and an immune-effector mechanism. The setting is human skin fibroblasts and in-vitro immunosurveillance experiments, not a claim about every senescent cell or every age-related disease. This file is intentionally outside kb/. notes: >- The primary study is Pereira et al. (2019). The supplied Shakur et al. review discusses this mechanism on page 5, Mechanisms of immune evasion by senescent cells. Its HLE-A spelling is not copied into the curated description: the primary source identifies HLA-E. The assay example below is review-level methodological context, not a new measured result or a clinical test. pathophysiology: - name: Senescent skin fibroblast state biological_scale: CELLULAR description: >- Senescent human skin fibroblasts express HLA-E. Cell identity remains skin fibroblast; the display label and mechanism description express its state. The study includes experimentally induced senescence. No universal senescence marker or irreversible-fate guarantee is inferred. cell_types: - preferred_term: senescent skin fibroblast term: id: CL:0002620 label: skin fibroblast located_in: preferred_term: skin of body term: id: UBERON:0002097 label: skin of body description: >- The senescent target population in this example; this qualification does not apply to the natural killer cells on the downstream node. biological_processes: - preferred_term: cellular senescence term: id: GO:0090398 label: cellular senescence evidence: - reference: PMID:31160572 supports: SUPPORT directness: DIRECT quote_role: PRIMARY_RESULT evidence_source: IN_VITRO snippet: senescent dermal fibroblasts express the non-classical MHC molecule HLA-E explanation: >- The source identifies the senescent fibroblast population expressing HLA-E; experimental senescence induction and co-marker assessment are described in Results, Senescent cells express atypical MHC molecules, and Figure 1. This is not evidence that HLA-E alone identifies senescence. downstream: - target: HLA-E-associated reduction of NK cytotoxicity description: >- HLA-E on the senescent target engages inhibitory NKG2A on NK cells. The primary paper also studies highly differentiated CD8-positive T cells; this node deliberately illustrates only the NK effector branch. evidence: - reference: PMID:31160572 supports: SUPPORT directness: INDIRECT quote_role: PRIMARY_RESULT evidence_source: IN_VITRO snippet: blocking the interaction between HLA-E and NKG2A boosts immune responses explanation: >- The blockade result supports an inhibitory interaction through a perturbation inference. It does not establish clinical efficacy or the contribution of this mechanism to every tissue's senescent burden. - name: HLA-E-associated reduction of NK cytotoxicity biological_scale: CELLULAR description: >- NK effector activity against the senescent fibroblast target is inhibited by the HLA-E/NKG2A interaction. The NK cell is an effector whose function is inhibited in this interaction; the record does not call it senescent. cell_types: - preferred_term: natural killer cell term: id: CL:0000623 label: natural killer cell biological_processes: - preferred_term: natural killer cell mediated cytotoxicity modifier: DECREASED term: id: GO:0042267 label: natural killer cell mediated cytotoxicity biochemical: - name: SA-beta-gal activity as a supportive senescence assay context: >- Methodological illustration from Shakur et al., page 2, Senescent cells and their role in inflammaging, and Figure 1. No numerical observation, diagnostic cutoff, or tissue-specific sensitivity is supplied. biomarker_term: preferred_term: senescence-associated beta-galactosidase activity at pH 6.0 term: id: NCIT:C107438 label: Beta-Galactosidase assays: - preferred_term: senescence-associated beta-galactosidase assay at pH 6.0 notes: >- The NCIT term identifies the protein, not the assay or its pH-dependent activity. The assay and activity interpretation are stated explicitly. A positive result alone is insufficient to identify a senescent cell. readouts: - target: Senescent skin fibroblast state relationship: READOUT_OF direction: THRESHOLD_DEPENDENT interpretation: >- A supportive assay interpreted alongside arrest and other senescence features. This link illustrates assessment of the state, not causation of the state, and does not assert a validated clinical endpoint. evidence: - reference: PMID:42518598 supports: SUPPORT directness: INDIRECT quote_role: REVIEW_SYNTHESIS evidence_source: OTHER snippet: >- While no universal marker for senescent cells exists, they develop a signature marked by molecular and phenotypic changes including morphological changes, expression of cyclin-dependent kinase inhibitors (p16INK4a, and p21CIP1), loss of nuclear structure and release of chromatin fragments into the cytoplasm, DNA damage signaling, enzymatic changes including senescence-associated β-galactosidase (SA-β-Gal) activity at pH 6.0, and the adoption of a secretory phenotype explanation: >- The review identifies the assay as one component of a multi-feature signature and explicitly denies a universal marker. Applying that general assay to the example's fibroblast state is illustrative; this quote does not report an assay result in that experiment.