Neutrophils and its Important Role in the Immune System

Nuetrophils

Introduction

Neutrophils, also known as neutrocytes, heterophils, or polymorphonuclear leukocytes, represent a category of white blood cells, constituting the predominant type of granulocytes. They account for 40% to 70% of all white blood cells in the human body and play a crucial role in the innate immune system. Neutrophils undertake the vital task of eliminating bacteria and fungi, contributing to the body's defense against infections and facilitating the healing of wounds.

These cells originate from stem cells within the bone marrow, undergoing differentiation into distinct subpopulations known as neutrophil-killers and neutrophil-cagers. Characterized by their short lifespan, ranging from 5 to 135 hours, and exceptional mobility, neutrophils possess the ability to access tissue regions inaccessible to other cells or molecules. Segmented neutrophils and banded neutrophils (or bands) are two subtypes of neutrophils, collectively belonging to the polymorphonuclear cells family (PMNs), alongside basophils and eosinophils.

Functioning as phagocytes, neutrophils primarily circulate in the bloodstream. During the initial (acute) phase of inflammation triggered by bacterial infections, environmental exposures, or certain cancers, neutrophils act as first responders, migrating towards the inflamed site. This migration occurs through blood vessels and interstitial spaces, guided by chemical signals such as interleukin-8 (IL-8), C5a, fMLP, leukotriene B4, and hydrogen peroxide (H2O2) in a process known as chemotaxis. Neutrophils dominate the cellular composition of pus, contributing to its whitish/yellowish appearance.

The nomenclature "neutrophil" is derived from distinctive staining patterns observed in hematoxylin and eosin (H and E) histological or cytological preparations. In contrast to the dark blue staining of basophilic white blood cells and the bright red staining of eosinophilic white blood cells, neutrophils exhibit a neutral pink hue. Typically, neutrophils feature a nucleus divided into 2–5 lobes and are swiftly recruited to the injury site within minutes.

Leukocyte extravasation (Diapedesis)

Leukocyte extravasation, often referred to as the leukocyte adhesion cascade or diapedesis (the migration of cells through the intact vessel wall), encompasses the mobilization of leukocytes from the circulatory system toward areas of tissue damage or infection. This phenomenon is a crucial component of the innate immune response, facilitating the recruitment of nonspecific leukocytes to the affected site. Additionally, monocytes employ this mechanism not only in response to infection or tissue damage but also during their maturation into macrophages.

Phagocytosis

Neutrophils function as phagocytes, exhibiting the ability to engulf microorganisms or particles. Recognition of targets requires their coating with opsonins, a process termed antibody opsonization. Through this mechanism, neutrophils can internalize and eliminate numerous microbes, leading to the formation of phagosomes. Within these phagosomes, reactive oxygen species and hydrolytic enzymes are secreted during each phagocytic event. The utilization of oxygen in generating reactive oxygen species is known as the "respiratory burst," despite its lack of connection to respiration or energy production.

The respiratory burst entails the activation of the enzyme NADPH oxidase, producing significant amounts of superoxide, a reactive oxygen species. Superoxide undergoes spontaneous decay or is broken down by enzymes like superoxide dismutases (Cu/ZnSOD and MnSOD) into hydrogen peroxide. This hydrogen peroxide is then converted to hypochlorous acid (HClO) by the myeloperoxidase enzyme. While HClO is believed to possess bactericidal properties sufficient for neutralizing bacteria within neutrophil phagosomes, it may also serve as a crucial step for activating proteases.

Despite the effective microbial elimination by neutrophils, their interaction with microbes and microbial byproducts often influences neutrophil turnover. Microbial influence on neutrophil fate is diverse, microbe-specific, and ranges from extending neutrophil lifespan to inducing rapid neutrophil lysis post-phagocytosis. Some bacteria, notably intracellular pathogens like Chlamydia pneumoniae and Neisseria gonorrhoeae, have been reported to delay neutrophil apoptosis. Consequently, certain bacteria can prolong neutrophil lifespan by disrupting the normal processes of spontaneous apoptosis and/or phagocytosis-induced cell death (PICD). Conversely, pathogens such as Streptococcus pyogenes can alter neutrophil fate post-phagocytosis by promoting swift cell lysis and/or accelerating apoptosis to the extent of secondary necrosis.