The Immune Response to Pathogen Invasion

The immune response is composed of innate and adaptive components. The initial responder to pathogens is the innate component, comprised mainly of phagocytic cells (e.g., neutrophils, monocytes, macrophages, and dendritic cells) able to engulf and kill pathogens. After phagocytosing and digesting pathogens and then processing pathogen‐derived antigens, innate immune cells release inflammatory mediators and cytokines, and present the processed antigen to T helper cells and B lymphocytes, leading to the development of the more specific adaptive immune response. The T cells and B cells are responsible for the antigen‐specific recognition and destruction of pathogens. Traditionally, the classical adaptive response was attributed to T and B cells able to express different receptors for maximal specificity based on the antigen being presented, while the innate response was understood to rely on receptors only able to recognize highly conserved microbial structures. More recently, it is evident that innate cells have the ability to modify responses by pattern recognition, leading to the concept of innate immune memory or innate immune training.

The main challenge for the innate immune system is to differentiate self or benign from pathogenic antigens. Evolution's ingenious solution has been to identify microbe‐ or pathogen‐associated molecular patterns (MAMPs or PAMPs), which are different motifs present in invading microorganisms that are lacking in higher eukaryotes. During the early phase of the immune response, MAMPs are recognized by pattern recognition receptors (PRRs) and complement binding (e.g., dectin‐1 and complement receptor 3 for β‐glucan signaling), which prompt a rapid detection and control of pathogen invasion via initiation of an innate immune response. PRRs are expressed on dendritic cells, the classical antigen presenting cells (APCs), and play an essential role in recognizing endogenous (host‐derived) and exogenous (environmental) ligands prior to phagocytosis. APCs are specialized phagocyte like dendritic cells and macrophages distributed across the host. Following pathogen internalization and phagosome formation, a key aspect of the antimicrobial component of the innate immune response is the production of reactive oxygen species (ROS) against pathogens, a phenomenon known as oxidative burst. This response has been reported against β‐glucans from fungal and yeast cell walls, and results in the phosphorylation of the NADPH oxidase complex and ultimately production of ROS (e.g., superoxide anion).