The normal immune system is essential for protection against infection. Immune system is like a double-edged sword. Though it is protective in most of the situations, sometimes a hyperactive immune system may cause fatal diseases. Immunity is resistance (defense mechanism) exhibited by host against invasion by any foreign antigen, including microorganisms. Immune response is usually a protective process but sometimes it may be injurious. Hypersensitivity means that the body responds to particular antigens in an exaggerated fashion, which does not happen in normal circumstances. Injurious immune reactions are called hypersensitivity. Immediate (type I) hypersensitivity, antibody-mediated (type II) hypersensitivity, immune complex–mediated (type III) hypersensitivity, and T cell-mediated (type IV) hypersensitivity are related to hypersensitivity—immunologically mediated tissue injury, which are given in this chapter. A detailed discussion on the autoimmune diseases, systemic lupus erythematosus, acquired immunodeficiency syndrome, and amyloidosis has been provided in this chapter.