Immunity to bacteria in fish

Abstract

Fish have many non-specific and specific, humoral and cellular mechanisms to resist bacterial diseases. Non-specific humoral factors include growth inhibiting substances, e.g. transferrin and antiproteases; lysins, e.g. lysozyme, C-reactive protein (CRP), bactericidal peptides and most importantly, complement which has lytic, proinflammatory, chemotactic and opsonic activities thus making a link with non-specific phagocyte responses. These are primarily executed by neutrophils and macrophages. The phagocytes contain many hydrolytic enzymes and when stimulated by bacteria produce reactive oxygen species (ROS), especially the hydroxyl radical, via generation of superoxide anions and nitric oxide. ROS are highly bactericidal. In addition, the neutrophils possess large quantities of myeloperoxidase (MPO) which generates bactericidal hypohalite ions from halide ions and H2O2. Macrophages can receive MPO from neutrophils and this may enhance their bactericidal activity. Antibody constitutes a specific humoral defence by inhibiting bacterial adherence or invasion of non-phagocytic host cells and neutralising bacterial toxins. Antibody can act as an opsonin and by activating complement by the classical pathway may lyse the bacterial cell, activate inflammation, phagocyte influx and further enhance phagocytosis. Macrophage bactericidal activity can be markedly increased by cytokines released by T lymphocytes on contact with their specific antigen. Pathogenic bacteria have evolved many ways of subverting these defence mechanisms of fish. These include the in vivo production of high affinity iron uptake systems (e.g. siderophores and their surface receptors, in Aeromonas salmonicida, Vibrio anguillarum). Some bacteria e.g. V. anguillarum strains of serotype 01, while being resistant to the alternative pathway of complement activation in normal serum, are killed in immune serum. In other bacteria, surface layers, capsules and elongated lipopolysaccharide (LPS) 0-antigens protect against classical complement-mediated killing (e.g. A. salmonicida, Photobacterium piscicida, V. anguillarum serotype 02 respectively). While some important pathogens (e.g. P. piscicida) are readily killed by macrophages, others (A. salmonicida) possess specialised superoxide dismutase and catalase to resist ROS and are toxic themselves to macrophages. Renibacterium salmoninarum uses antibody, complement and other serum components to activate the respiratory burst of macrophages on immediate contact thus exhausting this macrophage bactericidal mechanism before the bacterium is phagocytosed. Subsequently, R, salmoninarum is taken up by the macrophage where it multiplies as an intracellular pathogen. However, these two highly adapted pathogens, A. salmonicida and R. salmoninarum are both killed by activated macrophages indicating that the whole concerted efforts of specific and non-specific, humoral and cell-mediated immune responses are required for immunity against these two important pathogens.