Three key elements of GVHD pathophysiology: tissue damage, impaired repair, and alloreactvity. Typically, tissue damage is inflicted during conditioning chemotherapy and radiotherapy, at a time when tissue repair mechanisms are most impaired. However, tissue damage can occur at any time, for example, as a result of viral infection or viral reactivation. In the presence of alloreactive immune cells and in the absence of tissue repair mechanisms, this can lead to GVHD. B, B cells; T, T cells. Blue symbols: microbiome.