The ancestry and cumulative evolution of immune reactions.

Abstract

The last two decades of study enriched greatly our knowledge of how the immune system originated and the sophisticated immune mechanisms of today's vertebrates and invertebrates developed. Even unicellular organisms possess mechanisms for pathogen destruction and self recognition. The ability to distinguish self from non-self is a prerequisite for recognition of sexual compatibility and ensuring survival. Molecules involved in these processes resemble those found in the phagocytic cells of higher organisms. Recognition of bacteria by scavenger receptors induces phagocytosis or endocytosis. The phagocytic mechanisms characterizing the amoeboid protozoans developed further during the evolution towards innate immunity. The scavenger receptor cysteine-rich domain SRCR is encoded in the genomes from the most primitive sponges to mammals. The immune system of sponges comprises signal transduction molecules which occur in higher metazoans as well. Sponges already possess recognition systems for pathogenic bacteria and fungi, based on membrane receptors (a lipopolysaccharide-interacting protein, a cell surface receptor recognizing β(1 → 3)-d-glucans of fungi). Perforin-like molecules and lysozymes are involved, among others, in defense in sponges. Reactive oxygen and nitrogen species function in the immunity of early metazoan. Genes encoding the family of reactive oxygen-generating NADPH oxidases (Noxes) are found in a variety of protists and plants. The NO synthases of cnidarians, mollusks, and chordates are conserved with respect to the mammalian NOS. The antimicrobial peptides of protozoans, amoebapores, are structural and functional analogs of the natural killer cell peptide, NK-lysin, of vertebrates. An ancestral S-type lectin has been found in sponges. Opsonizing properties of lectins and the ability to agglutinate cells justify their classification as primitive recognition molecules. Invertebrate cytokines are not homologous to those of vertebrate, and their functional convergence was presumably enabled by the general similarity of the lectin-like recognition domain three-dimensional structure. Sponges contain molecules with SCR/CCP domains that show high homology to the mammalian regulators of complement activation (RCA family). A multi-component complement system comprising at least the central molecule of the complement system, C3, Factor B, and MASP developed in the cnidarians and evolved into the multilevel cascade engaged in innate and acquired immunity of vertebrates. The adaptive immune system of mammals is also deeply rooted in the metazoan evolution. Some its precursors have been traced as deep as in sponges, namely, two classes of receptors that comprise Ig-like domains, the receptor tyrosine kinases (RTK), and the non-enzymic sponge adhesion molecules (SAM). The antibody-based immune system defined by the presence of the major histocompatibility complex (MHC), T-cell receptor (TCR), B-cell receptor (BCR) or recombination activating genes (RAGs) is known beginning from jawed fishes. However, genes closely resembling RAG1 and RAG2 have been uncovered in the genome of a see urchin. The ancestry of MHC gene remains unknown. Similarly, no homologue of the protein binding domain (PBD) in MHC molecules has been found in invertebrates. The pathway by which endogenous peptides are degraded for presentation with class I MHC molecules utilizes mechanisms similar to those involved in the normal turnover of intracellular proteins, apparently recruited to work also for the immune system. Several cDNAs coding for lysosomal enzymes, e.g., cathepsin, have been isolated from sponges. All chromosomal duplication events in the MHC region occurred after the origin of the agnathans but before the gnathostomes split from them. The V-domains of the subtype found in the receptors of T and B-cells are known from both agnathans and cephalochordates, although they do not rearrange. The rearrangement mechanism of the lymphocyte V-domains suggests its origin from a common ancestral domain existing before the divergence of the extant gnathostome classes. Activation-induced deaminase (AID) - homologous proteins have been found only in the gnathostomes. It appears thus that the adaptive immunity of vertebrates is a result of stepwise accumulation of small changes in molecules, cells and organs over almost half a billion years.

Molecular Cloning, Characterization, and Expression Analysis of a Prolyl 4-Hydroxylase from the Marine Sponge Chondrosia reniformis

“…For what concerns TGF-beta, although this cytokine is considered one of the master signals of fibrosis and of myofibroblast differentiation (Gharaee-Kermani et al 2009), to date no data are available on its direct involvement in P4H gene expression. Furthermore, in sponges and in invertebrates (molluscs, nematodes, insects, and echinoderms), no TGF-beta genes have been described so far but only BMP family-related proteins (Dzik 2010). Hence, these proteins and their receptors may not be involved in immune responses in invertebrates.…”

Myeloid Colony-Stimulating Factors as Regulators of Macrophage Polarization

“…It is evident, however, that polarized macrophage function existed prior to the development of adaptive immunity in evolution (22, 23). Moreover, mice with T- and B-cell deficiency still possess the potential for polarized function demonstrating that the M1 and M2 concept can exist in the absence of adaptive immunity and its products (4).…”

Sequential Immune Responses: The Weapons of Immunity

“…Around 475 mya, vertebrates developed with a central pumping organ and a separate circulatory system to distribute oxygen and other nutrients [5, 12]. As will be seen in SIR4: Macrophage Antigen Presentation, this system necessitated the appearance of the newest layer of protection: adaptive immunity.…”

“…In parallel, lymphoid cells with recombination-activating genes (RAG) appeared, allowing enhanced receptor diversity and which circulate more readily in the vasculature than in tissue-resident macrophages [18]. Finally, T and B lymphocytes appeared in fish, with the capacity to produce different and superior types of adaptive responses which were further refined into T cell-mediated cellular (cytotoxic) or antibody-type responses in birds about 300 mya [5]. Highlighting the central role of macrophages in immunity, T cells (in general) do not directly recognize pathogens [19].…”