International Journal of Molecular Zoology 2024, Vol.14, No.4, 197-210 http://animalscipublisher.com/index.php/ijmz 198 2 Overview of the Immune System The immune system is a complex network of cells, tissues, and organs that work together to defend the body against harmful pathogens and maintain homeostasis. It is broadly categorized into two main components: innate and adaptive immunity. Innate immunity provides the first line of defense and is characterized by its rapid response and broad specificity. Adaptive immunity, on the other hand, is highly specific and involves the generation of immunological memory, allowing for a more efficient response upon subsequent exposures to the same pathogen. 2.1 Components of the immune system The immune system comprises various components that work in concert to protect the host. Innate immunity includes physical barriers like the skin and mucous membranes, chemical barriers such as antimicrobial peptides, and cellular components like macrophages, neutrophils, and natural killer cells. These elements recognize and respond to pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) (Romo et al., 2016). Adaptive immunity involves lymphocytes, including B cells and T cells. B cells are responsible for antibody production, which neutralizes and clears pathogens. T cells, particularly CD4+ T cells, play a crucial role in supporting B cell differentiation into memory and plasma cells, a process regulated by T follicular helper (TFH) cells (Tangye et al., 2013). The adaptive immune system's ability to remember past infections and respond more effectively upon re-exposure is a hallmark of its function. 2.2 Evolution of immune mechanisms in vertebrates The evolution of the immune system in vertebrates has been marked by the development of both innate and adaptive immunity. Innate immunity is ancient and conserved across all animals, providing a rapid and generalized response to pathogens. Adaptive immunity, however, is a vertebrate-specific innovation that relies on somatically derived lymphocytes and exhibits near-limitless genetic diversity and long-term memory (Dishaw et al., 2012). Studies on deuterostome invertebrates, such as amphioxus, have provided insights into the evolutionary origins of vertebrate immunity. Amphioxus possesses homologs of many innate immune receptors found in vertebrates, with significant expansions in gene families that enhance the innate immune repertoire. This suggests that the complexity of the vertebrate immune system arose from innovations in innate immune mechanisms, which later facilitated the development of adaptive immunity. 2.3 Key immune pathways and their roles in health and longevity Several key immune pathways are integral to both health and longevity. The insulin/TOR network, MAPK pathways (ERK, p38, JNK), JAK/STAT, TGF-β, and NF-κB pathways are evolutionarily conserved and play pleiotropic roles in regulating immunity and lifespan (Fabian et al., 2021). These pathways are involved in various cellular processes, including stress response, inflammation, and cellular repair, which are crucial for maintaining health and extending lifespan. For instance, the p38 MAPK pathway is essential for innate immune signaling and has been shown to enhance pathogen resistance and longevity in model organisms like Caenorhabditis elegans. Disruption of mitochondrial function can activate the mitochondrial unfolded protein response (mitoUPR) and p38 signaling, leading to increased innate immunity and extended lifespan (Campos et al., 2021). Similarly, the GABAergic transcription factor PITX/UNC-30 in C. elegans regulates a tradeoff between immunity and longevity, highlighting the interconnectedness of these pathways (Figure 1) (Otarigho and Aballay, 2021). The study of Otarigho and Aballay (2021) presented in the image suggest that the UNC-30 gene plays a significant role in regulating both immune responses and age determination pathways in C. elegans. The gene ontology and pathway analyses reveal that genes related to immune defense and aging are upregulated in UNC-30 mutants compared to wild-type (WT) animals. The qRT-PCR results further confirm the increased expression of specific
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