leukocyte activation

Definition

Target type: biologicalprocess

A change in morphology and behavior of a leukocyte resulting from exposure to a specific antigen, mitogen, cytokine, cellular ligand, or soluble factor. [GOC:add]

Leukocyte activation is a complex process that involves multiple steps, leading to the mobilization of leukocytes from the bloodstream to the site of infection or injury. It is triggered by a variety of stimuli, including pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and inflammatory mediators.

1. **Recognition of Stimuli:** Leukocytes express pattern recognition receptors (PRRs) that recognize PAMPs and DAMPs. These include Toll-like receptors (TLRs), C-type lectin receptors (CLRs), and NOD-like receptors (NLRs). Recognition of these stimuli triggers intracellular signaling pathways, leading to the activation of transcription factors such as NF-κB and AP-1.

2. **Adhesion and Rolling:** Activated leukocytes express adhesion molecules such as selectins and integrins. Selectins mediate initial rolling of leukocytes along the endothelium, while integrins mediate firm adhesion. This process is facilitated by chemokines produced by the endothelium, which attract leukocytes towards the site of inflammation.

3. **Transmigration:** Once firmly adhered, leukocytes transmigrate through the endothelium by squeezing between endothelial cells. This process is mediated by matrix metalloproteinases (MMPs), which degrade the extracellular matrix, and by integrins, which interact with the basement membrane.

4. **Chemotaxis:** Leukocytes migrate towards the site of inflammation guided by chemoattractants such as chemokines and bacterial products. These chemoattractants bind to receptors on the leukocyte surface, activating signaling pathways that direct the cell's movement.

5. **Phagocytosis and Killing:** Once at the site of inflammation, leukocytes engage in phagocytosis and killing of pathogens. Phagocytosis involves the engulfment of pathogens into a phagosome, which fuses with lysosomes containing enzymes and reactive oxygen species that kill the pathogen.

6. **Cytokine Production:** Activated leukocytes release cytokines, which amplify the inflammatory response and attract other immune cells. These cytokines include TNF-α, IL-1β, IL-6, and IL-8.

7. **Resolution of Inflammation:** After the pathogen is eliminated, the inflammatory response must be resolved to prevent tissue damage. This involves the production of anti-inflammatory cytokines such as IL-10 and TGF-β, and the apoptosis of activated leukocytes.

Leukocyte activation is a crucial process in the immune response, allowing the body to defend against pathogens and repair damaged tissues. However, uncontrolled or prolonged activation can lead to chronic inflammation and autoimmune diseases.'
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Proteins (1)

Compounds (2)