Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages - PubMed
- ️Fri Jan 01 2021
Review
Evolution of Cellular Immunity Effector Cells; Perspective on Cytotoxic and Phagocytic Cellular Lineages
Edna Ayerim Mandujano-Tinoco et al. Cells. 2021.
Abstract
The immune system has evolved to protect organisms from infections caused by bacteria, viruses, and parasitic pathogens. In addition, it provides regenerative capacities, tissue maintenance, and self/non-self recognition of foreign tissues. Phagocytosis and cytotoxicity are two prominent cellular immune activities positioned at the base of immune effector function in mammals. Although these immune mechanisms have diversified into a wide heterogeneous repertoire of effector cells, it appears that they share some common cellular and molecular features in all animals, but also some interesting convergent mechanisms. In this review, we will explore the current knowledge about the evolution of phagocytic and cytotoxic immune lineages against pathogens, in the clearance of damaged cells, for regeneration, for histocompatibility recognition, and in killing virally infected cells. To this end, we give different immune examples of multicellular organism models, ranging from the roots of bilateral organisms to chordate invertebrates, comparing to vertebrates' lineages. In this review, we compare cellular lineage homologies at the cellular and molecular levels. We aim to highlight and discuss the diverse function plasticity within the evolved immune effector cells, and even suggest the costs and benefits that it may imply for organisms with the meaning of greater defense against pathogens but less ability to regenerate damaged tissues and organs.
Keywords: adaptive immunity; comparative immunology; cytotoxicity; innate immunity; phagocytosis.
Conflict of interest statement
The authors declare no conflict of interest.
Figures

Molecular mechanisms guiding phagocytosis in different organisms. Although the phagocytic lineages and their molecular mechanisms guiding the process of phagocytosis could be different, they share several basic mechanisms with their ancestral form. Shown here: (left) the Toll pathway in Drosophila is activated by spaetzle, leading to an intracellular signaling that results in the degradation of cactus and the concomitant release of DIF/DORSAL which translocate to the nucleus and activate the transcription of immune genes including AMPs and drosomycin, which secreted as a response to infection [46]. (center) BsTLR1, Ras, MAPK, NFκB and cytokine homologs have been associated with the modulation of phagocytosis in B. Schlosseri. (?)—Represents missing functional or molecular validation. Similarly (right), mammalian TLRs are activated by microbial- and self-derived products leading to the activation of intracellular signaling cascade that results in the translocation of NFκB to the nucleus to activate the transcription of different cytokines and chemokines which enhance the phagocytic activity of the cells [47]. Created with BioRender.com.

Evolution of phagocytic and cytotoxic cell lineages in the immune system. Among phagocytic lineages, amoebocytes and granulocytes are present in invertebrates, while myeloid lineage seems to evolve in the ancestor of tunicates and vertebrates. Cells representing the Level I cytotoxicity exist in Protostomes but might appear in cnidarian. Among specific cytotoxic cell lineages, morula cells have been found in tunicates although partial evidence suggests that they may evolve in earlier ancestors. Lymphoid cells are found in agnathans and have diversified in vertebrates, there are suggestions of their form in Tunicates but not validated yet. In the third column, we show examples of diversification of specialized receptors acting in both phagocytosis and cytotoxicity. TLR = Toll-like receptors, TCR = T-cell receptor, MHC = Major histocompatibility complex, KIR = Killer Inhibitory Receptors, BCR = B cell receptor, VLR = Variable lymphocyte receptor, BHF = Botryllus histocompatibility factor, TRF = Transformer proteins, NLR = NOD like receptors, DSCAM = Down syndrome cell adhesion molecule, FREP = Fibrinogen-related proteins, NK-L = Natural killer-like receptor. ?—Represents missing functional or molecular validation. Created with BioRender.com. Data sources are summarized in Table 1.
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