Publisher Summary This chapter focuses on the activation and regulation of the first complement component. . The chapter outlines the history of the classical pathway of the complement system. Clq and C1 are bound and activated by immune complexes or aggregates containing IgG or IgM but not by those containing IgA, IgD, or IgE . Among IgG subclasses, IgG3 is most reactive followed by IgG1, and IgG2; intact IgG4 is minimally reactive, although its Fc region binds C1. C1-In does not efficiently regulate C1 activation induced by immune complexes. It, thus, appears that immune complex dependent activation is not under positive host regulation. This is apparently largely true. However, C1 activation by small immune complexes or complexes formed with nonavid antibody or with ratios of antigen to antibody far from equivalence, all of which are poor C1 activators, may well be regulated by C1-In.

The classical complement pathway: activation and regulation of the first complement component.

Natural‘antibodies’are substances found in the blood of animals that have not been immunised against infective agents. However, exposure to these agents or to cross-reacting antigens may well have taken place. Fish contain naturally-occurring, relatively nonspecific, lectin-like proteins or glycoproteins, which are distinct from immunoglobulins, and which react with a wide variety of antigens and may confer some degree of immunity against natural infection. In most cases the cause of the antigenic stimulus is not obvious although the formation of these‘antibodies’may have been brought about by exposure to various micro-organisms. Many of these antibody-like molecules behave in a similar manner to immune antibodies or immunoglobulins and cross-react with specific carbohydrate moieties on the cell walls of bacteria, erythrocytes and certain other cellular antigens, due to the presence of similar antigenic determinants.

It is difficult to ascribe an appropriate definition to the term‘natural antibody’. In fish, these‘antibodies’have been so designated on the basis of functional rather than structural criteria. Such naturally-occurring, low grade, antibody-like‘immune’substances include‘acute phase’proteins, lysozyme and chitinase, interferon, agglutinins, lysins, complement and properdin, precipitins, and non-immunoglobulin, lectin-like molecules. In addition to the above non-immunoglobulin materials, natural immunoglobulins identifiable as IgM have also been reported in fish. Furthermore, mucus contains many biochemical agents capable of reaction against infective organisms and thus providing the host with an immediate or a first line of defence mechanism.

This review compiles some of the relevant information in the literature concerned with natural‘immune’substances, present in the serum and mucus of fish, involved in protection against pathogens. Wherever possible the basic physicochemical properties of these substances are indicated and their potential immunobiological functions discussed.

Substances involved in the natural resistance of fish to infection - a review.

Acquired Abnormalities Alterations in the complement system associated with human disease have been appreciated since early in this century,152 but only within recent years have measurements of ser...

The complement system of man. I.

The recent accumulation of genomic information of many representative animals has made it possible to trace the evolution of the complement system based on the presence or absence of each complement gene in the analyzed genomes. Genome information from a few mammals, chicken, clawed frog, a few bony fish, sea squirt, fruit fly, nematoda and sea anemone indicate that bony fish and higher vertebrates share practically the same set of complement genes. This suggests that most of the gene duplications that played an essential role in establishing the mammalian complement system had occurred by the time of the teleost/mammalian divergence around 500 million years ago (MYA). Members of most complement gene families are also present in ascidians, although they do not show a one-to-one correspondence to their counterparts in higher vertebrates, indicating that the gene duplications of each gene family occurred independently in vertebrates and ascidians. The C3 and factor B genes, but probably not the other complement genes, are present in the genome of the cnidaria and some protostomes, indicating that the origin of the central part of the complement system was established more than 1,000 MYA.

https://link.springer.com/content/pdf/10.1007%2Fs00251-006-0142-1.pdf

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Phylogeny and Function of the Complement System