Protectant fungicides rely for their selectivity on physical barriers (e.g. the leaf cuticle) between their deposits and the protoplasts of the host plant. Systemic fungicides, by contrast, come into direct contact with host cells and need to be more selective. Nevertheless, important side-effects can occur, involving higher plants, animals and other microorganisms; examples of these are cited. Sometimes mycelium and spores of the target fungus show differing susceptibility; also, activity of a fungicide in vitro does not always reflect its effectiveness in vivo. An extreme form of selectivity is the undesirable emergence of insensitive strains from an otherwise sensitive fungal species.