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Immune Surveillance by NK Cells and Phagocytes

JoVE Core
Anatomy and Physiology
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JoVE Core Anatomy and Physiology
Immune Surveillance by NK Cells and Phagocytes

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01:25 min

September 12, 2024

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.

Natural Killer Cells: The Fast Responders

NK cells are large granular lymphocytes found in the blood and lymphatic system. These lymphocytes respond quickly and are uniquely capable of recognizing and eliminating infected or cancerous cells. Unlike other immune cells, NK cells do not rely on phagocytosis — the process of engulfing and digesting foreign substances. Instead, they induce apoptosis (programmed cell death) in target cells, making them particularly effective against invading pathogens.

NK cells use pattern recognition receptors (PRRs) to identify stress-induced molecules on the surface of infected or malignant cells. These PRRs detect general patterns associated with pathogens and cellular distress, such as viral proteins or changes in the expression of major histocompatibility complex (MHC) class I molecules. Upon recognizing a target cell, NK cells become activated.

This activation triggers the realignment of the Golgi apparatus within the NK cell, directing it toward the target cell. The Golgi apparatus then releases secretory vesicles containing cytotoxic molecules such as perforin and granzymes. Perforin is a potent protein that forms pores in the membrane of the target cell, creating channels through which granzymes can enter. Once inside, granzymes activate apoptotic pathways, leading to the programmed cell death of the target. This method of inducing apoptosis is highly effective in eliminating virus-infected cells and cancerous cells without causing excessive inflammation or damage to surrounding tissues.

Role of Phagocytes: Neutrophils and Macrophages

Complementing the actions of NK cells, phagocytes also play a crucial role in immune surveillance. The two primary types of phagocytes are neutrophils and macrophages. These cells are responsible for ingesting microbes and clearing debris from the body, each with unique contributions.

Neutrophils are the most abundant type of white blood cells and often serve as the first responders to infections. These cells are highly mobile and can quickly reach sites of infection, where they engulf and destroy invading microbes. On the other hand, macrophages are larger phagocytes derived from monocytes. They are found in virtually all tissues and can be classified as fixed or wandering macrophages based on their location and mobility. Macrophages not only ingest and destroy microbes but also play a vital role in antigen presentation. This is essential to activate adaptive immune responses, which enables the immune system to recognize and remember specific pathogens and provide long-term immunity against repeated infections.

Neutrophils and macrophages also utilize PRRs to detect and bind to pathogens. Once a pathogen is identified, the phagocyte extends pseudopods to engulf the invader, enclosing it within a membrane-bound phagocytic vesicle called a phagosome. The phagosome then fuses with a lysosome, forming a phagolysosome. Within the phagolysosome, various digestive enzymes and reactive oxygen species degrade and destroy the pathogen. This process not only clears the infection but also provides antigens that can be presented to other immune cells, further enhancing the immune response.