The four cardinal signs of inflammation of tissues are swelling, redness, pain, and heat. Inflammation is caused by a complex network of mediators, receptors, and white blood cells that interact with the vasculature and nerve fibers. In recognizing inflammation histologically, the swelling and redness come from localized edema secondary to enhanced vascular permeability in the postcapillary venules and tissue infiltration by leukocytes. When the leukocytes are predominantly polymorphonuclear neutrophils, the process is usually acute. In chronic inflammation, in contrast, the infiltrating cells are lymphocytes and mononuclear phagocytes. The answer as to why inflammatory response exists lies in the nature of innate and acquired immunity, and the complex response of multicellular organisms to threats from the environment.