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24.8: Inflammation

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24.8: Inflammation


In response to tissue injury and infection, mast cells initiate inflammation. Mast cells release chemicals that increase the permeability of adjacent blood capillaries and attract additional immune cells to the wound or site of infection. Neutrophils are phagocytic leukocytes that exit the bloodstream and engulf invading microbes. Blood clotting platelets seal the wound and fibers create a scaffold for wound healing. Macrophages engulf aging neutrophils to end the acute inflammatory response.

Acute Inflammation Protects the Body

Tissue injury and infection are the primary causes of acute inflammation. Inflammation protects the body by eliminating the cause of tissue injury and initiating the removal of cell debris resulting from the initial damage and related immune cell activity. Inflammation involves mediators of both the innate and adaptive immune system. Proper regulation of inflammation is crucial to clear the pathogen and remove cell debris without overly damaging healthy tissue in the process. If inflammatory processes are not properly regulated, chronic inflammation can arise that is often fatal.

Mast Cells Initiate and Regulate Inflammation

Mast cells are the first to respond to tissue injury, as they are primarily located in areas that have contact with the exterior: the skin, gut, and airways. Mast cells have an arsenal of receptors on their cell surface and can hence be activated by a wide variety of stimuli, such as microbial antigens, products of complement activation, animal venom and damage-associated molecular patterns, which signal cellular damage or stress.

Upon activation, mast cells engage in complex bidirectional interactions with macrophages, mesenchymal stem cells, dendritic cells, natural killer cells, and B and T cells. These interactions are mediated by a cocktail of chemical signals that mast cells release into the surrounding tissue. The effect of these chemicals is two-fold: they attract effector cells of the immune system that follow the chemical trail (chemotaxis) and affect surrounding blood vessels. For instance, one of the chemicals released by mast cells is histamine, which increases the permeability of capillaries in a process called vasodilation. This expansion of local blood vessels, in turn, facilitates blood flow to the injured tissue, resulting in redness and warmth.

Neutrophils Target Foreign Elements with Sophisticated Methods

Vasodilation also allows phagocytic neutrophils to leave the bloodstream, a process called leukocyte extravasation, or diapedesis. Neutrophils follow the chemical trail left by mast cells and enter the tissue by squeezing through the now widened junctions in the capillaries. At the site of infection, they capture pathogens via neutrophil extracellular traps (NETs) that are formed of DNA fibers and proteins. Neutrophils engulf invaders (in a process known as phagocytosis) or release antimicrobial components (degranulation). Neutrophils are short-lived (hours or days) and are replaced by macrophages and lymphocytes in later phases of the inflammatory response.

Platelets Promote Closure of Wounds and Healing

Platelets (also called thrombocytes) are cell fragments with no nuclei that are a constituent of blood and derived from bone marrow megakaryocytes. They also follow the chemical signal of mast cells to the affected tissue. Platelets release growth factors to induce wound healing, patch disrupted tissue by aggregating in response to blood vessel damage and can even engulf pathogens.

Chronic Inflammation Is the Most Common Cause of Death

Three of five people in the world die due to chronic inflammatory diseases, such as stroke, chronic respiratory diseases, heart disorders, some cancers, obesity, and diabetes. The proper regulation of inflammatory processes is therefore crucial for proper bodily function.

Atherosclerosis is the narrowing of arteries due to the formation of plaques along the lining of the blood vessels. Narrower vessels transport less blood, which hinders oxygen flow. The reduced oxygen flow is one problem caused by atherosclerosis. An additional issue is the potential rupture of the plaque, which triggers blood clotting, further reducing or totally blocking the blood flow. Depending on which arteries are affected, the function of the heart, brain, arms, legs, pelvis, and kidneys can be impaired, with potentially fatal consequences.

The formation of plaques starts with a small injury of the vessel, initiating an acute inflammatory response, including vasodilation. Neutrophils and monocytes can then move beneath the endothelium (the lining of the blood vessel) via diapedesis. Monocytes differentiate into macrophages and start to take up free low-density lipoprotein (LDL) via phagocytosis. The process continues until macrophages are laden with fat, at which point they are referred to as foam cells. An accumulation of foam cells is called a fatty streak, the first visual sign of atherosclerosis that might later turn into a hardened plaque.

In atherosclerosis, the initial inflammatory response does not stop, but becomes chronic, recruiting more and more immune cells. Anti-inflammatory signals do not replace pro-inflammatory signals, and dead effector cells are not adequately removed, creating a mass of dead cells (necrotic center) in the fatty streak. The onset and progression of atherosclerosis can be delayed by minimizing the amount of LDL cholesterol in the blood, maintaining a moderate physical exercise regimen, refraining from smoking, and taking certain medications.

Suggested Reading


Inflammation Acute Inflammation Immune Response Infection Injury Mast Cells Histamines Prostaglandins Vasodilation Blood Flow Redness Warmth Vascular Permeability Gaps Exudate Swelling Pain Neutrophils White Blood Cells Margination Diapedesis Chemotaxis Proteins Clotting Fibrin Mesh Healing Process

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