It is fitting that an introduction to the nature and mechanisms of immune responses begins with innate immunity, as the cells, tissues, and molecules of this system play a crucial role in providing early protection against infection. The first line of defense is formed by the epithelial layers, which prevent the majority of environmental pathogens from entering the body. The tightly connected epithelial cells of the skin and the mucosal and glandular tissues lining the body’s openings act as a physical barrier to pathogen entry. These surfaces are also coated with various chemical substances, including acidic pH levels and antimicrobial peptides and proteins, such as enzymes, that regulate pathogen populations. Due to its extensive size and critical function as a barrier, the skin is often regarded as the body’s most important immunological organ.Despite this typically effective first line of defense, infections can still establish themselves within the body through means such as skin wounds, respiratory epithelial infections with influenza virus, or intestinal infections. In such cases, the second line of defense—comprising the innate immune system’s cells, particularly myeloid leukocytes like macrophages, monocytes, neutrophils, and dendritic cells—takes over. These cells detect infections through their pattern recognition receptors (PRRs) and initiate an appropriate response tailored to the specific pathogen. Given the vast diversity of pathogens, including viruses, bacteria, fungi, and parasites, and their ability to evolve by mutating or acquiring host genes to evade innate defenses, it is unsurprising that PRRs, their signaling pathways, and the resulting responses are highly varied and complex. Over millions of years of animal evolution, humans have inherited genes encoding a limited yet effective array of PRRs, such as those for Toll-like receptors (TLRs), which date back to the earliest stages of animal evolution. These receptors are strategically located to provide optimal immune defense.

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