The macrophages reside in the subepithelial tissues of the skin and intestine and line the alveoli of the lungs. Microbes that penetrate an epithelial surface will encounter local tissue macrophages called histocytes. If organism enters via blood or lymph, then defense is provided by fixed macrophages called Kupffer cells, which line the sinusoids of the liver. Similar fixed macrophages called Langerhans cells are also present in the epidermis of the skin. Once engaged with the organism, these macrophages release a number of macrophage-derived cytokines, which nonspecifically amplify the immunological and inflammatory reactions to the invading microbe.