The Inflammatory Response

The inflammatory response, also just called inflammation, is the immune system’s non-specific, immediate response to tissue injury. Its effects are aimed at neutralizing the cause of tissue injury, removing debris, and creating an environment for healing and repair.

Now, inflammation is a response to injury of vascularized tissue, which is any tissue that has a blood supply. Tissue injury can be related to pathogens such as bacteria, viruses, or fungi; physical injuries, like cuts, burns, and sprains; and environmental exposures, such as contact with allergens or toxins, or exposure to extremes of temperatures. Other factors can include tissue ischemia, like from a myocardial infarction or stroke.

Inflammation begins when immune cells, like monocytes, macrophages, and dendritic cells, respond to tissue injury. The macrophages begin to phagocytize, or eat up, any invading pathogens, cellular debris, or foreign substances that are present.

Meanwhile, molecules expressed by infectious agents, called pathogen-associated molecular patterns, or PAMPs, and molecules released by damaged and dying cells, called damage-associated molecular patterns, or DAMPs, are detected by special receptors on the immune cells, called pattern recognition receptors, or PRRs. When the PRRs bind to PAMPs or DAMPs, immune cells respond rapidly by releasing inflammatory mediators like histamine, prostaglandins, and leukotrienes. These chemical mediators initiate the inflammatory response that involves both a vascular response and a cellular response.

The vascular response begins when nerve endings at the site of injury cause transient vasoconstriction, followed by the effects of inflammatory mediators as they act on the endothelial cells of the nearby capillaries, arterioles, and venules. These effects include local vasodilation and increased vascular permeability, which is where the endothelial cells separate from each other. Vasodilation brings additional blood flow to the area of injury while slowing the velocity of blood flow. Increased vascular permeability allows plasma proteins to move out into the interstitial space, pulling fluid with them, resulting in an accumulation of fluid. The endothelial cells also help move this process along by releasing nitric oxide, which also causes vasodilation.

As far as the cellular response goes, neutrophils are attracted to the site of injury by a process called chemotaxis. Chemotactic molecules involved in this process include microbial products and chemokines, which are substances produced by injured tissues and cells like macrophages. Next, with the help of adhesion proteins expressed by the endothelial cells, the neutrophils attach and roll along the vessel wall, through a process called diapedesis. Once they reach the site of injury, the neutrophils squeeze through the gaps between the endothelial cells, a process called extravasation. Then, they immediately start phagocytizing damaged cells, cellular debris, and any microbes that are present.

Now while this is all happening, proteins in the complement system get activated and play a major role in opsonization, meaning that certain complement proteins bind to microbes so immune cells can more easily phagocytize them. Other complement proteins kill pathogens directly by forming a channel in their membrane. Dendritic cells continue to phagocytize pathogens and present bits of them to T lymphocytes. This activates the adaptive immune system, which kicks in after a few days.