The innate immune system is represented by a complex of cellular and h
umoral factors and processes that protect the organism against pathoge
nic attack. Certain of these elements arose early in the evolution of
multicellular animals and have been preserved throughout the evolution
ary divergence of the different animal phyla. Two mediators that have
interested us are alpha(2)-macroglobulin and the pentraxins. Both func
tion as elements in the plasma defense systems of arthropods and verte
brates. The ability to purify significant quantities of both proteins
from the plasma of the American horseshoe crab Limulus polyphemus has
enabled us to investigate their functions at the molecular and organis
mal levels. In Limulus alpha(2)-macroglobulin functions as a broad-spe
ctrum protease-binding molecule that mediates the clearance of proteas
es from the plasma. Limulus has at least two pentraxins in the plasma,
an abundant form designated Limulus C-reactive protein, which is of u
nknown function, and limulin, a low-abundance form with sialic acid re
cognition capabilities, which mediates a cytolytic reactivity for the
destruction of foreign cells that have contacted the plasma.