The eye imposes limitations on the efficacy and safety of the immune system, which are particularly demanding and contradictory. In contact with the environment, it forms, with its appendages, a small organ which is particularly exposed but apparently not very vulnerable thanks to its various means of defence: a microbial flora similar to that of the skin; blinking of the eyes; the constant flow of lachrymal fluid, whose composition is complex and variable, making it aggressive against microorganisms but protective and nutritive for the cornea, and optically more favourable; and finally, mucosa-associated lymphoid tissue which is characterized by an abundant production of IgA1, IgD and natural antibodies. Both vitreous and a final barrier, the cornea has all the elements necessary for an effective response but as a result of its positioning and its resting state, the eye employs this barrier only as a last resort. The eye is also an optical instrument extending the central nervous system; its vessels must therefore not be connected to the optical axis as any inflammation risks being harmful to the nervous system. This “privileged immunity” is a result of local control of lymphoid cells and immune reactions by molecular exclusion due to hemato-ocular barriers, an inhibitory molecular environment and various cellular interactions that are capable of generating apoptosis and regulatory lymphocytes. In addition, this control can be combined with a systemic response characterized by diminished delayed hypersensitivity, facilitating the production of noncomplement fixing antibodies and the generation of antigen-specific regulatory T cells, a phenomenon called “immune deviation associated with the anterior chamber of the eye”. However, the relative inaccessibility of the immune system to the healthy eye can make the mechanisms of peripheral immune tolerance less effective and lead to a particular vulnerability to autoimmunity and antiretinal autoantibodies in paraneoplastic syndromes. The eye is thus armed to react but its response is closely controlled and oriented; the link between eye diseases and the HLA and the complement systems are also keys to a better understanding of the molecular mechanisms at work there.