Vertebrate Adaptive Immunity-Comparative Insights from a Teleost Model

Abstract

The channel catfish (Ictalurus punctatus) and the ciliated protozoan parasite Ichthyophthirius multifiliis are used to study pathogen-specific protective immunity. In this review, we briefly describe this host-parasite system and discuss the comparative insights it provides on the adaptive immune response of vertebrates. We include studies related to cutaneous mucosal immunity, B cell memory responses, and analyses of αβ T cell receptor (TCR) repertoires. This host-parasite model has played an important role in elucidating host protective responses to parasite invasion and for comparative studies of vertebrate immunity. Recent findings from bioinformatics analyses of TCR β repertoires suggest that channel catfish preferentially expand specific clonotypes that are stably integrated in the genome. This finding could have broad implications related to diversity in lymphocyte receptors of early vertebrates.

Keywords: Ichthyophthirius multifiliis; T cell repertoire; adaptive immunity; channel catfish; immune memory; teleost.

Figure 1

A general model of adaptive immunity against Ichthyophthirius multifiliis (Ich). The natural physiological state of the skin has immune components that monitor and respond to infections, including resident macrophages, putative dendritic cell subsets, and resident T and B lymphocytes. Elements of mucosal and systemic immunity against Ich (some of which are hypothetical and others based on experimental data) are presented in panels (A) and (B) of this figure. This model is based on studies of Ich infection in channel catfish and various other fish species, and the figure is derived from a previous review of Ich immunity (50). (A) Infection of naive fish. Parasite invasion in the skin (upper section) elicits local and systemic inflammatory responses that include the recruitment of neutrophils, basophils, and eosinophils, and the production of cytokines and chemokines. The uptake of Ich Ags by macrophages and dendritic cells (APC) initiates the adaptive immune response. Ags are processed and presented by APC at inductive sites in the skin (hypothetical) and/or the anterior kidney and spleen (lower section), where plasmablasts, plasma cells, and memory B and T cells are generated. Components of the adaptive immune response exist as early as 7–10 days after initial infection, and last up to three years after the infection is resolved. (B) Infection of immune fish. Parasite entry into the epithelium of the skin elicits a cellular response that includes basophils, neutrophils, and eosinophilic granulocytic cells (EGCs), which are analogous to mammalian mast cells. Ab in the skin bind to invading theronts and elicit their pre-mature exit. Ich-specific Ab in the blood and skin are secreted by plasma cells in the central lymphoid organs and the skin, respectively. We hypothesize that plasmablasts generated in central lymphoid organs and the skin traffic between both sites through the blood. Blood vessels are depicted between the upper and lower sections of each panel.

Figure 2

The CDR3 DNA and amino acid sequence of clonotype CAAIMGGTQPAYF. (A) The genomic sequences of the Vβ2, Dβ, and Jβ24 genes that contribute to the CDR3 sequence are shown. Those nucleotides that were presumably deleted from the Vβ2, Dβ, and Jβ24 genes are underlined and the seven non-templated nucleotides added are italicized. (B) The CDR3 nucleotide and aa sequence of the transcribed TCRβ gene for CAAIMGGTQPAYF. This same nucleotide sequence was found in cDNAs generated from four fish.