700-660 million years ago

sponge cells

Sponges are the most primitive multicellular organisms alive today. Like modern sponges, the first animals must have possessed collagen and immunoglobulin proteins. Collagen is the major extracellular protein of all animals. Higher animals possess hundreds of immunoglobulin genes which perform a variety of functions ranging from fighting microbes to guiding embryonic development.

Collagen is the major extracellular protein of all animals and is even found in the simplest animals. A number of invertebrates have collagen fibrils very similar to the type of collagen found in vertebrates; collagen fibrils are even known from cnidarians and sponges. Sponge collagen is homologus to that of vertebrates. Since sponges can contain both fibrillar and non-fibrillar collagens, the amplification of this gene family had begun in the early animals (Exposito, 1990). Although collagen was once thought to exist only in animals, it has been found in fungi where it composed the fimbriae which function in cell to cell communication. Animal cells can interact with fungal collagen in a way similar to the manner in which they interact with animal collagens (Celerin, 1996). Collagen sequences may have functioned long before collagen was an extracellular protein. Collagenous sequences are known from vertebrate proteins such as acetylcholinesterase, C1q (a complement protein), pulmonary surfactant apoprotein, several lectins, and type I macrophage scavenger receptor. The bacteria Streptococcus pyogenes possesses a collagen-like sequence in enzyme hyaluronidase (Stern, 1992).

One of the first problems that animals had to solve was how to be multicellular. In a multicellular organism, cells must interact with each other. Once primitive animal cells began to express the immunoglobulin domain on their cell surfaces, other cells expressing the same (or slightly modified) domains could interact with them. As vertebrate animals began to live longer (and put off reproduction until later in life), the issue of distinguishing between one's own cells and foreign cells became ever more important and important families of immunoglobulins within the immunoglobulin superfamily evolved such as MHC proteins, antibodies, and T-Cell receptors.
A very early duplication of ancestral immunoglobulin/fibronectin molecules produced fibronectin and immunoglobulin families. The functional domains of each of these molecules became incorporated into a variety of multi-domain proteins which can have single or multiple fibronectin domains and single or multiple immunoglobulin domains.
The immunoglobulin branch of the immunoglobulin/fibronectin superfamily includes genes known in both vertebrates and invertebrates, including the simplest invertebrates. An immunoglobulin-like domain is present in the extracellular part of the receptor tyrosine kinase in some sponges (Schacke, 1994). Two Ig-like molecules are known from fruit flies, another from squid, and from sponges (the C2 set of Ig domains) (Schacke, 1994a).
Sponges can distinguish between self and non-self in that a sponge can reject a graft made from another sponge. Wandering phagocytes combat microbes in sponges and some flatworms, indicating that a primitive immune resistance predated the evolution of circulatory systems. Invertebrates do not have a lymphatic system or any aspects of acquired immunity, but certain parts of their immune systems do display characteristics observed in vertebrates. Although there is no complement system, there is a prophenoloxidase system which involves a cascade, including enzymes which kill microbes and clot blood. Although invertebrates do not possess antibodies, there are molecules called lectins (found in bacteria, plants, and all animals) which can cause foreign cells to clump by binding to sugar groups.
In tunicates, both macrophages and morula cells participate in the rejection of foreign cells. The numbers of morula cells can increase four times within the first 2 hours of the reaction. Morula cells are similar to vertebrate lymphocytes in this feature and in some morphological characterisitics (Rinkevich, 1998).
Lectins are a group of cell surface proteins which, like the immunoglobulin domain, have been utilized by many animals for immune reactions (Hofer, 2001). Sponges possess lectins homologous to those found in vertebrates (Gamulin, 1994; Schacke, 1994a). In invertebrates, lectins bind to foreign particles and facilitate phagocytosis (as do antibodies in vertebrates). The human protein collectin (related to the lectins) coats foreign particles before phagocytosis, just as antibodies do (OMIM). Mannose-binding lectin (MBL) is produced by liver hepatocytes and functions in the blood. Variable immunoglobulin domains are known in cell surface molecules of plants and fungi in addition to a diversity of animals, including the most primitive animals, the sponges (Muller, 2001; Muller, 2001a).