Conceptual framework for mechanisms of HLH. HLH represents a group of syndromes in which pathologic inflammation results from a combination of immune dysfunction and immune activation. The contributions of inherited and acquired immune defects relative to the role of antigen stimulation may vary with age. For example, an infant in the NICU with PRF1 mutations with first upper respiratory infection would fall on the left, whereas an adult with HLH arising from persistent activation of transformed T cells in subcutaneous panniculitis-like T-cell lymphoma would fall on the right.