Natural Immunity and Neuroimmune Host Defense

: Innate resistance is mediated by non‐immune defense and by natural immunity. Non‐immune defense includes diverse mechanisms (e.g., physico‐chemical defense by bile acids). Natural killer (NK) cells, γδ T lymphocytes and CD5+ B lymphocytes are key mediators of natural immunity. These cells utilize germ‐line coded receptors that recognize highly conserved, homologous epitopes (homotopes). Typically, it is not the antigen, but cytokines and hormones that regulate the level of NK‐mediated cytotoxicity. These include interleukin‐2, interferons, prolactin and growth hormone. Less is known about γδ T lymphocytes. CD5+ B lymphocytes produce germ‐line coded antibodies (predominantly IgM) that are polyspecific, and able to recognize a great variety of microorganisms, cancer cells and self‐components. Antigen is not an effective stimulus for natural antibody (NAb), but bacterial lipopolysaccharide (LPS) is. During the acute phase response (febrile illness) the T‐cell‐regulated adaptive immune response is switched off and natural immune mechanisms are amplified several hundred to a thousand times within 24‐48 hours (immunoconversion). This immunoconversion is initiated by immune‐derived cytokines, and involves profound neuroendocrine and metabolic changes, all in the interest of host defense. Immune recognition is assured by natural antibodies and by some liver‐derived acute phase proteins, such as C‐reactive protein or endotoxin‐binding protein, the level of which is elevated in the serum. Thus, natural immunity is essential for a first and last line of defense and the neuroendocrine system is an important promoter of this activity.