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Plastic waste degrades slowly in aquatic environments, transforming into microplastics (MPs) and nanoplastics (NPs), which are subsequently ingested by fish and other aquatic organisms, causing both physical blockages and chemical toxicity. The fish immune system serves as a crucial defense against viruses and pollutants present in water. It is imperative to comprehend the detrimental effects of MPs on the fish immune system and conduct further research on immunological assessments. In this paper, the immune response and immunotoxicity of MPs and its combination with environmental pollutants on fish were reviewed. MPs not only inflict physical harm on the natural defense barriers like fish gills and vital immune organs such as the liver and intestinal tract but also penetrate cells, disrupting intracellular signaling pathways, altering the levels of immune cytokines and gene expression, perturbing immune homeostasis, and ultimately compromising specific immunity. Initially, fish exposed to MPs recruit a significant number of macrophages and T cells while activating lysosomes. Over time, this exposure leads to apoptosis of immune cells, a decline in lysosomal degradation capacity, lysosomal activity, and complement levels. MPs possess a small specific surface area and can efficiently bind with heavy metals, organic pollutants, and viruses, enhancing immune responses. Hence, there is a need for comprehensive studies on the shape, size, additives released from MPs, along with their immunotoxic effects and mechanisms in conjunction with other pollutants and viruses. These studies aim to solidify existing knowledge and delineate future research directions concerning the immunotoxicity of MPs on fish, which has implications for human health. [Display omitted] [ABSTRACT FROM AUTHOR]

CD28 and CD80/86 are crucial co-stimulatory molecules for the T cell activation. Previous study illustrated that CD28 and CD80/86 present on T cells and antigen-presenting cells in flounder (Paralichthys olivaceus), respectively. The co-stimulatory molecules were closely associated with cell immunity. In this paper, recombinant protein of flounder CD80/86 (rCD80/86) and phytohemagglutinin (PHA) were added to peripheral blood leukocytes (PBLs) in vitro. Lymphocytes were significantly proliferated with CFSE staining, and the proportion of CD4+ and CD28+ lymphocytes significantly increased. In the meantime, genes related to the CD28-CD80/86 signaling pathway or T cell markers were significantly upregulated (p < 0.05). For further study, the interaction between CD80/86 and CD28 was confirmed. The plasmid of CD28 (pCD28-FLAG and pVN-CD28) or CD80/86 (pVC-CD80/86) was successfully constructed. In addition, pVN-ΔCD28 without the conserved motif "TFPPPF" was constructed. The results showed that bands of pCD28-FLAG bound to rCD80/86 were detected by both anti-FLAG and anti-CD80/86. pVN-CD28 complemented to pVC-CD80/86 showing positive fluorescent signals, and pVN-ΔCD28 failed to combine with pVC-CD80/86. The motif "TFPPPF" in CD28 played a crucial role in this linkage. These results indicate that CD28 and CD80/86 molecules interact with each other, and their binding may modulate T lymphocytes immune response in flounder. This study proved the existence of CD28-CD80/86 signaling pathway in flounder. • RCD80/86 and PHA induced lymphocyte proliferation and proportion of CD4+ cells in flounder. • RCD80/86 and PHA upregulated the expression of B7-CD28 signaling pathway genes, T cell markers, and cytokines. • PCD28-FLAG bound to rCD80/86, and pVN-CD28 complemented to pVC-CD80/86 in vitro. • Motif of "TFPPPF" in CD28 plays crucial role in the interaction between CD28 and CD80/86. [ABSTRACT FROM AUTHOR]