Neutrophils - Structure, Functions, and Their Clinical Significance

Introduction

Blood contains several defending cells called leukocytes that fight the body against diseases and infections. Among them, neutrophils are considered the first line of defense cells; they help fight and attack infectious agents, thereby protecting the body. They have an integral role in all the major disorders. They account for a major percentage of the white blood cells in the body (around 60 to 70 percent).

What Is Its Structure?

They are generally seen as multi-lobulated structures with around 3 to 5 joined segmentations. Therefore, they are also called polymorphonuclear leukocytes. They are about 12 to 15 micrometers in diameter. The neutrophils contain a lot of granules in their cytoplasm. They are:

1. Primary (Azurophilic Granules): They are the largest and most present. They contain many enzymes like myeloperoxidase, defensins, and lysozyme.

2. Secondary Granules (Specific Granules): These are smaller and contain more proteins. Key components include lactoferrin and collagenase.

3. Tertiary Granules (Gelatnase): These contain gelatinase, which makes an important contribution to the migration and infiltration of neutrophils.

What Are the Functions of Neutrophils?

1. Defense :

   1. Phagocytosis: Neutrophils are the first to arrive at the site of infection. They can perform various defensive operations to protect the body, including phagocytosis. They engulf the pathogenic substances like bacteria, fungi, and protozoa. The neutrophil receptors go towards the site and attach to the surface molecule on the pathogen's surface. They internalize it and form phagosomes, undergoing different complex mechanisms and destroying the ingested pathogen. Reactive oxygen species may be released, which can lead to oxidative stress.

   2. Chemotaxis: Recognize foreign agents and enemies. Neutrophils are known for their role in moving toward the site of infection and damage. During injury or infection, the cells release chemicals that possess these molecules to attract the defending cells. This movement of neutrophils towards the site is known as chemotaxis. This is an integral step of antimicrobial function.

   3. Chemomediators: Neutrophils produce several chemo mediators like cytokines and chemokinesis. These molecules act as signaling agents to help generate inflammatory responses and coordinate defense mechanisms. The pro-inflammatory cytokines neutrophils may release include interleukin 1, 6,8—tumor necrosis factor-alpha.

   4. Helps in Adaptive Immunity: Neutrophils have a role in influencing other immune cells like macrophages and dendritic cells either by contacting directly or through messengers and chemical mediators. When they interact, they help in modulating the adaptive immunity to a great extent.

   5. Extracellular Trap Formation: There has been tremendous research signifying the role of neutrophils releasing extracellular traps as a response to stimulation by pathogens. The function of these traps is that they contain antimicrobial protein and chromatin fibers. They also have potent enzymes in them. When activated, they ensure that the pathogen is killed outside the cell. Therefore, this helps in stopping the infection and its spread.

How Is It Regulated?

The regulation is a complex interplay of various body cells, molecules, mediators, and mechanisms. They act during the various stages of neutrophils, like migration, activation, or resolution. The mediators like pro-inflammatory and anti-inflammatory cytokines like interleukin 10 try to balance the inflammatory response and activation. Several adhesion molecules, receptors, and feedback mechanisms all regulate the potential action of neutrophils. Molecules such as lipoxins and resolvins are considered protective, and they decrease the inflammatory content and relate to neutrophil activation. They help in clearing the site of infection. In addition to all this, additional defense cells like T regulatory cells affect the action of cytokines, thereby affecting the eutrophic. Hormones such as cortisol and catecholamines may also affect neutrophils and aid in their regulation. They can exert an anti-inflammatory effect by decreasing the proinflammatory expression. They also help modulate the adhesion of neutrophils by affecting the signaling components.

What Is the Clinical Significance of Neutrophils?

They are a key component of the leukocytes in the body, which form a significant part of the immune and defense system of the body. They are implicated in several diseases.

1. Neutrophilia and Neutropenia: An increased count of neutrophils much higher than the absolute levels is called neutrophilia. This can occur in infections, tissue injury in surgery or burns, trauma, or side effects of certain medicines. It requires strict monitoring and appropriate antibiotic therapy when combined with an increase in other inflammatory markers. When there is a decreased count, it is called neutropenia. They might be due to any bone marrow disorders, owing to reduced production, congenital disorders like cyclic neutropenia, and Fanconi anemia., as a response to chemotherapy or radiation therapy. Certain viral infections like HIV and hepatitis can decrease the neutrophils and cause neutropenia. Because of reduced neutrophils, the body gets more prone to further infections and higher chances of developing sepsis and shock.

2. Prognostic Marker: There is a calculator of neutrophils and lymphocytes, which is used as a marker to indicate immune status in various medical conditions like sepsis, cancer, cardiovascular disease, etc. An increase in this ratio means a bad prognosis and outcome.

3. Immunomodulation: Since neutrophils have a role in inflation as well as define. They can be utilized to make targeted therapeutic interventions to inhibit the activated neutrophils selectively. They have been tried in particular cases of inflammatory bowel disease.

4. Neutrophils have a potential role in being diagnostic biomarkers and developing newer drug formulations.

Conclusion

Neutrophils have a crucial role in the innate immune system of the body. They are involved in body defense as the first line of defense. Their remarkable ability to protect, defend, eliminate, and modulate the immune response shows their importance in both health and diseased conditions. Ongoing research aims to formulate newer novel diagnostic and therapeutic strategies involving targeted neutrophil therapy. This can open doors to cure several infectious diseases and inflammatory conditions in a more conservative approach. Further deeper understanding of neutrophils and their complex mechanisms will make it easier for clinicians and researchers to understand the disease and help the patient with better cures and care.