"Article Summery" Name: "Immunity and the Invertebrates" Periodical: Scientific American Nov, 1996 Author: Gregory Beck and Gail S. Habicht Pages: 60 - 71 Total Pages Read: 9 The complex immune systems of humans and other mammals evolved over quite a long time - in some rather surprising ways. In 1982 a Russian zoologist named Elie Metchnikoff noticed a unique property of starfish larva. When he inserted a foreign object through it's membrane, tiny cells would try to ingest the invader through the process of phagocytosis. It was already known that phagocytosis occurred in specialized mammal cells but never in something less complex like a starfish. This discovery led him to understand that phagocytosis played a much broader role, it was a fundamental mechanism of protection in the animal kingdom. Metchnikoff's further studies showed that the host defense system of all animals today were present millions of years before when hey were just beginning to evolve. His studies opened up the new field of comparative immunology. Comparative immunologists studied the immune defenses of past and current creatures. They gained further insight into how immunity works. The most basic requirement of an immune system is to distinguish between one's own cells and "non-self" cells. The second job is to eliminate the non-self cells. When a foreign object enters the body, several things happen. Blood stops flowing, the immunity system begins to eliminate unwanted microbes with phagocytic white blood cells. This defensive mechanism is possessed by all animals with an innate system of immunity. Innate cellular immunity is believed to be the earliest form of immunity. Another form of innate immunity is complement, composed of 30 different proteins of the blood. If these mechanisms do not work to defeat an invader, vertebrates rely on another response: acquired immunity. Acquired immunity is mainly dealt by specialized white blood cells called lymphocytes. Lymphocytes travel throughout the blood and lymph glands waiting to attack molecules called antigens. Lymphocytes are made of two classes: B and T. B lymphocytes release antibodies while T help produce antibodies and serve to recognize antigens. Acquired Immunity is highly effective but takes days to activate and succeed because of it's complex nature. Despite this, acquired immunity offers one great feature: immunological memory. Immunological Memory allows the lymphocytes to recognize previously encountered antigens making reaction time faster. For this reason, we give immunizations or booster shots to children. So it has been established that current vertebrates have two defense mechanisms: innate and acquired, but what of older organisms ? Both mechanisms surprisingly enough can be found in almost all organisms (specifically phagocytosis). The relative similarities in invertebrate and vertebrate immune systems seem to suggest they had common precursors. The oldest form of life, Protozoan produce these two immune functions in just one cell. Protozoan phagocytosis is not uncommon to that of human phagocytic cells. Another basic function of immunity, distinguishing self from non-self, is found in protozoan who live in large colonies and must
be able to recognize each other. In the case of metazoan, Sponges, the oldest and simplest, are able to do this as well refusing grafts from other sponges. This process of refusing is not the same in vertebrates and invertebrates though. Because vertebrates have acquired immunologic memory they are able to reject things faster than invertebrates who must constantly "re-learn" what is and is not self. Complement and lymphocytes are also missing from invertebrates, but which offer an alternative yet similar response. In certain invertebrate phyla a response called the prophenoloxidase (proPO) system occurs. Like the complement system it is activated by enzymes. The proPO system has also been linked to blood coagulation and the killing of invading microbes. Invertebrates also have no lymphocytes, but have a system which suggests itself to be a precursor of the lymph system. For instance, invertebrates have molecules which behaving similarly to antibodies found in vertebrates. These lectin molecules bind to sugar molecules causing them to clump to invading objects. Lectins have been found in plants, bacteria, and vertebrates as well as invertebrates which seems to suggest they entered the evolutionary process early on. This same process occurs in human innate immune systems with collections of proteins called collectins which cover microbes n a thin membrane to make them easier to distinguish by phagocytes. And although antibodies are not found in invertebrates a similar and related molecule is. Antibodies are members of a super family called immunoglobulin which is characterized by a structure called the Ig fold. It is believed that the Ig fold developed during the evolution of metazoan animals when it became important to distinguish different types of cells wi thin one animal. Immunoglobulins such as Hemolin have been found in moths, grasshoppers, and flies, as well as lower vertebrates. This suggests that antibody-based defense systems, although only active in vertebrates, found their roots in the invertebrate immune system. Evolution seems to have also conserved many of the control signals for these defense mechanisms. Work is currently being done to isolate invertebrate molecules similar to the cytokines of vertebrates. Cytokines are proteins that either stimulate or block out other cells of the immune system as well as affecting other organs. These proteins are critical for the regulation of vertebrate immunity. It is suspected that invertebrates will share common cytokines with vertebrates or at least a close replication. Proteins removed from starfish have been found to have the same physical, chemical, and biological properties of interleukins (IL-1, IL-6), a common cytokine of vertebrates. This research has gone far enough to conclude that invertebrates possess similar molecules to the three major vertebrate cytokines. In the starfish, cells called coelomocytes were found to produce IL-1. The IL-1 stimulated these cells to engulf and destroy invaders. It is thus believed that invertebrate cytokines regulate much of their host's defense response, much like the cytokines of vertebrate animals in innate immunity. Comparative Immunology has also found defense mechanisms first in invertebrates only later to be discovered in vertebrates. Invertebrates use key defensive molecules such as antibacterial peptides and proteins, namely lysozyme, to expose bacterial cell walls. Thus targeting the invader. This offers great potential for medicinal purposes, because lysozyme is also found in the innate immunity of humans in it's defense
of the oral cavity against bacteria. Peptides of the silk moth are currently being developed as antibacterial molecules for use in humans. Two peptides found in the skin of the African clawed frog actively fight bacteria, fungi, and protozoa. Antibodies which bind to these two peptides also bind to the skin and intestinal lining of humans. The potential of these peptide antibiotics only now being discovered is a rather considerable thing to ponder. For that reason it is surprising that such little attention has been paid to invertebrate immune responses. In the end, the complexity of vertebrate immune systems can only be understood by studying the less complex systems of invertebrates. Further studies look to explain immunity evolution as well as aid in the solving of problems of human health.