25.11 : Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.

Phagocytes

Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general classes of phagocytes – microphages and macrophages.

Microphages include the neutrophils and eosinophils that generally circulate in the blood. These phagocytes leave the bloodstream and enter peripheral tissues subjected to injury or infection. Neutrophils are abundant, mobile, and quick to phagocytize cellular debris or invading bacteria. The less abundant eosinophils target and destroy foreign substances or pathogens coated with antibodies or complement proteins.

Macrophages are large, active phagocytes primarily derived from circulating blood monocytes. They can be classified as wandering or fixed macrophages. The wandering macrophages move throughout the body, whereas the fixed macrophages reside permanently within specific tissues, such as the Kupffer cells in the liver, where they monitor and capture pathogens that bypass the initial defense lines. However, this distinction is not absolute. During certain infections, fixed macrophages may lose their attachments and start moving around the damaged tissue.

This extensive network of phagocytes is known as the monocyte-macrophage system, also referred to as the reticuloendothelial system.

Phagocytosis is a complex multi-step process that is initiated when phagocytes recognize and bind to foreign particles through surface receptors. This binding triggers the phagocyte to extend its membrane around the particle, encapsulating it within a compartment known as a phagosome. Subsequently, the phagosome merges with lysosomes to form a phagolysosome. Here, the foreign particle is broken down and destroyed by enzymes. The remnants are then expelled from the phagocyte, concluding the process of phagocytosis.

Natural Killer Cells

Natural killer (NK) cells are large granular lymphocytes comprising about 5–10% of lymphocytes in the blood and lymph. NK cells differ from phagocytes in their mode of action. Instead of engulfing pathogens, they directly recognize and eliminate the infected or cancerous cells. They do so by detecting changes in the surface proteins of these cells. Infected cells often display reduced levels of major histocompatibility complex (MHC) class I molecules, which are responsible for presenting antigens to T cells. NK cells can also recognize stress-induced molecules on infected cells through activating receptors. Upon recognition, NK cells release cytotoxic granules containing perforin and granzymes, which induce apoptosis in the target cells. This mechanism allows NK cells to rapidly respond to a variety of infections and prevent the spread of disease.