In 1908, Ehrlich and Mechnikov shared the Nobel Prize in Medicine for their independent studies that set the scene for the modern understanding of innate and adaptive immunity. However, 20th century immunology thinking was dominated by aberrant adaptive immunity but this never adequately explained the full spectrum of inflammatory disease. This article draws on medical observations, from where immunology originated, and uses the example of the eye to illustrate how the integration of medicine and immunology leads to an improved understanding of inflammation against self. The spectrum of ocular inflammation can be viewed as either predominantly adaptive immune mediated (mostly the realm of immunology), or predominantly due to ocular tissues factors that lead to regional innate immune activation (the realm of medicine), or a variable interaction between the two. Just as the thorns that Mechnikov inserted into molluscs lead to localized innate immune activation; ocular inflammation can likewise be driven by non-immune factors that include tissue degeneration or microdamage. The present article emphasizes the importance of such factors in the initiation or phenotypic expression of ocular immunopathology allowing different immunological dogmas including self-non-self discrimination, immunological tolerance and immunoprivilege to be viewed in a different light. This scheme also leads to an appreciation of how the innate immune system may be the sole perpetuator of some ocular immunopathologies. We propose that this integrated view of medicine and immunology is crucial for understanding immunology from a translational angle and has implications far beyond ocular disease.