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, gamma delta 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 gamma delta 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.