Across evolved biological immunity and engineered cybersecurity, we find meaningful parallels in how the defensive contexts are framed, strategies chosen, and performance evaluated. Especially as technological advances allow these two defensive systems to resemble one another more closely, we believe that carefully drawn analogies between these systems can reveal general principles of defensive design to protect against unpredictable attacks. Lists of proposed principles already exist in some fields , but their generality across systems has not been examined in depth, either theoretically or practically. We hope the open questions articulated above will spark collaborative study, whether by sharing data and analytical techniques or constructing theoretical models. Finally, as general defensive design principles emerge, we hope to see them vetted and successfully deployed in other realms, such as national defense against domestic and international terrorism, and public health defense against zooneses and epidemics.