Over the past several years there has been remarkable development in the area of fish immunology. There are several reasons for this sudden interest in piscine immunity:

1.  A general interest in comparative immunology among the various animal phyla.

2.  The complicated system in higher vertebrates has stimulated interest in the development and evolution of immune mechanisms.

3.  The worldwide increase in fish culture has increased the need for more effective treatments of fish diseases.

As a result of these interests, research on diseases and immunity has produced commercially available bath and spray vaccines for vibriosis, furunculosis, and ERM. Vaccines for Ichthyophthirius and Aeromonas salmonicida are in various stages of preparation. In developing these immunotherapeutic approaches to disease treatment, much information has been amassed on immunity in fish. This paper will briefly review the immune response in fish.

Temperature Dependence

Since fish are poikilothermic, their metabolism is directly dependent on the surrounding water temperature. Specific immunity, composed of a cell renewal system with a high proliferation rate, is especially vulnerable to alterations in metabolic rates induced by fluctuating temperatures. The dependence of the immune response on temperature has been substantially documented. This dependence is most frequently observed as the seasonal variation of the incidence of infectious diseases.

The first phase of the immune response, antigen recognition and processing, appears to be temperature independent. Subsequent cellular interactions are the first events to demonstrate temperature sensitivity. The following proliferation and differentiation of B-cells are temperature independent, while synthesis and release of antibody are the second temperature dependent processes. These events are evidenced by a delay in the appearance of circulating antibody, although the magnitude and duration of the humoral response are not affected. Experimental lowering of the temperature after immunization does not appear to inhibit an ongoing primary response. However, the ability to mount a clear anamnestic response is gradually lost at lower temperatures. Fish will develop a high antibody titer at low temperatures providing that a specific memory has previously been acquired at a higher temperature. Temperature effect is not absolute, the range over which the immune response can take place is related to the normal environmental temperature range of the species. In addition to species dependence, the affects of temperature are dependent on antigen dose, route of administration, and acclimation time.

Nonspecific Immunity

The problem most often experienced by fish farmers is the increased incidence of disease when water temperatures begin to rise. In spring, increasing temperatures are more favorable for infectious disease agents. At the same time, the capacity of fish to mount an adequate immune response has to be built up. Production of proteases and hyaluronidase by bacteria, fungi and protozoans may disrupt the primary barriers to invasion, epithelial surfaces with mucus secretions. The most vulnerable of epithelia, the gill surface, may provide easy access to pathogens. During this period, disease defense consists of nonspecific mechanisms. An increase of granulocytes in the spleen and kidney at lower temperatures, suggest that non-lymphoid defense becomes more important when circumstances are less favorable for antibody production.

The exact role of phagocytic leukocytes has not been clearly established and cell involvement may vary among species. For example, it has been demonstrated that granulocytes in carp are phagocytic, whereas neutrophil-like cells in plaice may not be phagocytic. In holosteans, mononuclear cells assume phagocytosis rather than granulocytes. There have even been reports suggesting phagocytic activity by thrombocytes, and macrophage activity from salmonid pronephros.

Nonspecific immunity also consists of noncellular factors which enhance phagocytosis and directly react with pathogens. A complement system analogous to that found in mammals has not been fully demonstrated, and as of yet C3 receptors have not been detected on fish leukocytes. However, evidence does indicate that a complement-like system is at work in fish. In salmonids and alternate pathway can be activated with a resulting increase in lytic activity.

C-Reactive Protein (CRP), one of the acute phase indicators of tissue damage, is present in fish and can trigger the complement cascade. CRP might afford additional protection while specific immuno globulins are synthesized. Tissue damage stimulates fish CRP levels to rise as dramatically as those observed in birds and mammals.

Other nonspecific agglutinins and lectins interact with carbohydrate in a recognition system separate from immunoglobulin recognition. No function has yet been assigned to these substances and their role in fish is unknown. Bacterial growth appears to be inhibited and speculation suggests lectins may be involved in recognition of sugar residues on the glycoproteins of bacterial cell surfaces. Protection from bacterial infection in the eggs of chinook salmon and reactions with fungal cells have been observed with lectins.

Specific Immunity

Fish are the most ancient group in which an immune system characterized by the presence of immunoglobulin has been demonstrated. A high molecular weight immunoglobulin resembling a tetrameric IgM has been described in all classes of fish. Elasmobranchs are the most primitive group in which plasma cell differentiation and memory (although somewhat questionable) occur. In bony fish the existence of the carrier effect indicate the presence of a long term memory function maintained by T-Helper cells and sensitized precursor cells for antibody production. As in higher vertebrates carrier specific T-cells and hapten specific B-cells are present.

Recently a mucus immunoglobulin similar to the secretory antibody has been evidenced. This antibody is not derived from serum but in part appears to be synthesized locally by Ig producing cells in subepidermal and mucus layers of skin. The role of this mucus Ig as an antigen specific receptor for T-cells has also been postulated.

An organized thymus first appears in the lampreys. Ill higher fish the thymus develops near to hatching with subsequent appearance of small lymphocytes about seven days after hatching. The cell mediated response then develops over the first few months of life. Both helper function and T-cell memory are temperature dependent, although memory seems to be long lived. As in mammals, xenograft rejection occurs faster than allograft rejection. Second set grafts are rejected more rapidly with an infiltration of lymphocytes and mononuclear phagocytes. It has been suggested that in body fish at optimum temperature, rejection occurs faster than in mammals.

In recently developed cytotoxic assays utilizing target cells, lymphoid populations from peripheral blood, thymus, anterior kidney, but not spleen, demonstrated cytolytic activity. Results from these tests suggest a cytolytic effector cell population similar to natural killer cells in higher vertebrates.

This review has only briefly highlighted immunity in fish. It is obvious from the literature that our knowledge of fish immune responses has greatly increased. Because fish are the largest group of vertebrates, it is reasonable that the immune responses vary greatly across species lines. This phenomenon in addition to the role of temperature in the immune response should be considered in the study of fish immunology particularly in the development of immunotherapeutics for disease treatment.

References

1.  Avthalion, R. R., Wishkousky, A., and Katz, D. Regulatory effects of temperature on specific suppression and enhancement of the humoral response in fish. In: Phylogeny of Immunological Memory. (Manning, M. J. Ed.) Elsevier/North Holland Biomedical Press, Amsterdam, 113, 1980.

2.  Cone, R. E. and Marchalonis, J. J. Cellular and humoral aspects of the influence of environmental temperature on the immune response of poikilothermic vertebrates. J. Immunol., 108, 1972.

3.  Cooper, E. L. General immunology. Pergamon Press, N.Y., 1983.

4.  Cooper, F. L. (Editor-in-chief). Dev. Comp. Immunol. 7 (#4 special issue), 1983. Cuchens, M. A. and Clem, L. W. Phylogeny of lymphocyte heterogeneity II. differential effects of temperature on fish T-like and B-like cells. Cell. Immunol., 34, 1977.

5.  Evans D. L. et al. Nonspecific cytotoxic cells in fish (Ictalurus punctatus). III. Biophysical and biochemical properties affecting cytolysis. Dev. Comp. Immunol., 10, 1984.

6.  Hayden, B. J. and Laux, D. C. Cell-mediated lysis of murine target cells by nonimmune salmonid lymphoid preparations. Dev. Comp. Immunol., 9, 1985.

7.  Moody, C. E., Serreze, D. V. and P. W. Reno. Non-specific cytotoxic activity of teleost leukocytes. Dev. Comp. Immunol., 9, 1985.

8.  St. Louis-Cormier, E. A., Osterland, C. K., and Anderson, P. D. Evidence for a cutaneous secretory immune system in rainbow trout (Salmo gairdneri). Dev. Comp. Immunol., 8, 1984.

9.  Stolen, J. S. et al. The effect of environmental temperature on the immune response of a marine teleost (Paralichthys dentatus). Dev. Comp. Immunol., 8, 1984.

10. Van Muiswinkel, W. B. and Woper, E. L. (ed.) - Immunology and immunization of fish. Dev. C~m . Immunol. Supplement 2, 1982.