The Fish Immune System: Mucus Barrier, Innate and Adaptive Immunity

How fish defend themselves: the skin and mucus barrier, innate and adaptive immunity, immune organs without bone marrow, temperature effects, cortisol and stress, and vaccination basics.

Living in a microbe-rich medium

Water carries more nutrients for microbes than land habitats do, so fish are surrounded by bacteria and other microorganisms from the embryonic stage onward. Most pathogens enter through the mucosal surfaces: the gills, the gut and wounds in the skin. Bony fish defend themselves with both innate and adaptive immunity, each with cellular and humoral (dissolved, non-cellular) components.

Skin and mucus: the first line of defence

The skin, the gills, the gut lining and the mucus layer that covers them form the first barrier against infection. Mucus is a physical shield, but it is also chemically active: it carries antimicrobial peptides, immunoglobulins (antibodies), lysozymes, complement proteins, lectins, proteases and antiproteases. Goblet cells and lymphocytes sit in these tissues, and the skin contains its own skin-associated lymphoid tissue (SALT) that can mount local immune responses. The mucosal surfaces also host commensal microbes (the gills and the microbiome have their own guides).

Innate immunity

Innate immunity is the main, immediate and non-specific defence of fish. It aims to stop or contain an infection until the slower, more targeted adaptive response develops.

Physical and chemical barriers: skin, scales, mucosal surfaces and the molecules in mucus.
Humoral factors in plasma and body fluids: complement proteins, cytokines and lysozymes. Activated complement attracts immune cells and promotes inflammation.
Cells: macrophages and neutrophils recognise and engulf invaders and release reactive oxygen and nitrogen species; lymphocytes join if pathogens get past the barriers.

Adaptive immunity and immune organs

Adaptive immunity is inducible and pathogen-specific and generally creates immunological memory through B cells, T cells and antibodies. Fish lack bone marrow and lymph nodes. In bony fish the anterior (head) kidney is the main blood-forming and lymphoid organ and is essential for B cell development, the thymus matures T cells, and the spleen is the main secondary lymphoid organ; scattered immune tissue also lies in the skin, gills, gut and gonads. A lymphatic system resembling that of mammals was described in zebrafish in 2006.

Three antibody classes have been identified in teleosts: IgM, IgD and IgT (also called IgZ).
IgM dominates systemic responses in blood and organs such as the spleen and head kidney.
IgT is the most ancient antibody class specialised for mucosal surfaces, comparable in role to mammalian IgA; it helps clear mucosal pathogens and keep the commensal microbiota in balance.
Mucosa-associated lymphoid tissues have been described in the gut, skin, gills, nose, mouth and pharynx.
In zebrafish, circulating antibodies become detectable at about 28 days after fertilisation.

Temperature dependence

Fish are poikilothermic: a change in water temperature is a change in body temperature, and the immune system follows. Temperatures above a species' range trigger a stress response that can impair immunity, and a review of cold effects (Abram, Dixon and Katzenback 2017) concludes that acute or chronic exposure to suboptimal low temperatures is generally suppressive, especially for adaptive immunity. Effects differ between species.

Rainbow trout kept at 5 °C for more than two months showed weaker complement activity and lower phagocytosis by blood leukocytes than fish at 10 °C or above.
In common carp (Cyprinus carpio), T lymphocyte proliferation rose from 12 °C to 20 °C to 28 °C, and antibody levels at 12 °C were significantly lower than at 20 °C or 28 °C.
In channel catfish, circulating B cells fell after exposure to 11 °C and recovered only after about five weeks, which suggests gradual acclimation.
Macrophage and neutrophil activity generally showed no change or even an increase at suboptimal temperatures, so innate cells appear less affected than lymphocytes.

Stress and cortisol

Stress hormones link the environment to immune function (the stress response itself is covered in the separate guide on stress in fish). In fish, as in mammals, chronic stress and its main hormone, cortisol, have a clearly immunosuppressive effect; this is thought to have evolved to save energy for survival when homeostasis is under strain. In experiments comparing hormones, cortisol suppressed immune gene expression more than adrenaline or noradrenaline did and reduced the expression of the cytokines examined. In mammals, acute short-term stress can enhance some immune functions; in fish its effects appear to differ from those of chronic stress, but they are still poorly understood.

Vaccination basics

Vaccines train adaptive immunity and are used in aquaculture rather than in home aquaria (fish vaccination in aquaculture is covered in a separate guide). The route of exposure shapes the response: in rainbow trout, immersion exposure to Yersinia ruckeri raised IgT in the gut mucosa, whereas injection produced mainly IgM in systemic tissues. Intraperitoneal injection is the predominant method, but it is costly and complex for large-scale farming, which is why immersion and oral mucosal vaccines are being developed to protect the gills, skin and gut where pathogens enter. Cold water can also weaken antibody responses to vaccines.

Diet supplements are sometimes linked to immunity, but the evidence is species-specific: in the Midas cichlid (Amphilophus citrinellus), carotenoid supplementation did not enhance innate immunity.