About the group
To understand how adaptive immune systems of vertebrates evolved and function, we focus on experimental and bioinformatic analysis of "unusual" immune systems of fishes. The group is fully integrated with the group of Shuo-Wang Qiao in the Immunology Department at Institute of Clinical Medicine and collaborates closely with the group of Kjetill Jakobsen at the CEES at IBV, where project participant Naomi Croft Guslund has her primary affiliation.
Project Background
The “big bang of adaptive immunity” occurred about 550 million years ago, shortly after the split between jawless vertebrates (agnatha) and jawed vertebrates (gnathostomes). Thus, the cardinal features of our adaptive immune system evolved in a common ancestor of cartilaginous fish, ray-finned fish, amphibians, reptiles and mammals. This includes: i) major histocompatibility complex class I and class II genes important for recognition of pathogens and distinguishing self from non-self; ii) B cell and T cell receptors and the molecular machinery for generation of diversity in the adaptive immune system; iii) T cell co-receptors CD4 and CD8, important for immune regulation and cellular cytotoxicity, respectively.
Codfishes specifically lost MHC class II and its receptor CD4 about 100 million years ago, but are evolutionarily successful and not particularly prone to disease in the wild. Interestingly, lack of MHC class II in humans cause a severe immunodeficiency incompatible with life. Similarly, if the CD4 T cell level of an HIV infected individual falls below a critical threshold, full blown AIDS will develop.
Innate immune defence reacts quickly to pathogens, recognizing general motifs of viruses, bacteria, fungi and parasites with the use of a limited set of germline-encoded recognition receptors. The adaptive immune system uses somatic recombination to generate a plethora of antigen receptors for remarkable specificity: each B- or T cell clone express a single unique BCR or TCR, respectively. Upon first encounter with pathogen (or vaccine), cells that express receptors recognizing a particular antigen are stimulated to proliferate and differentiate into effector cells and memory cells providing long-lasting immunity. T cells recognize foreign antigens only after ingestion, digestion and presentation of antigen on MHC molecules. All nucleated cells express MHC class I molecules, which present antigen to CD8+ T cells, but only professional antigen-presenting cells (APCs) express MHC class II molecules needed to present antigen to CD4+ T cells. Priming of naïve CD8+ T cells by APCs generates cytotoxic T cells capable of directly killing pathogen-infected cells (cell-mediated immunity), while priming of naïve CD4+ T cells generates a diverse array of effector cells. CD4+ T cells are the principal conductors of orchestrated immune responses in vertebrates. However, MHC class II and CD4 have been selectively lost in Atlantic cod and other gadiformes. How the Atlantic cod is able to stay healthy without MHC class II and if there are compensatory immune mechanisms in codfishes are major research questions that we focus on.
Resources
Our experiments start with live cod, which we purchase from Havbruksstasjonen in Tromsø and keep at NIVA aquaculture research station at Solbergstrand about 45 minutes from campus. We use the common FYSCELL labs in Kristine Bonnevie's Hus and we have our own droplet generator at the Immunology Department, Rikshospitalet, that we use for single-cell transcriptomic analysis.