Circulating proteins. Several plasma proteins recognize microbes and function to destroy blood-borne microbes and to stimulate inflammation at tissue sites of infection. The complement system reacts against microbes and produces mediators of inflammation (discussed later). A circulating protein called mannose-binding lectin recognizes microbial sugars and promotes ingestion of microbes and activation of the complement system. Other proteins called collectins also bind to microbes and promote their phagocytosis.
Inflammation is a beneficial host response to foreign invaders and necrotic tissue, but also may cause tissue damage.
The main components of inflammation are a vascular reaction and a cellular response; both are activated by mediators that are derived from plasma proteins and various cells.
The steps of the inflammatory response can be remembered as the five Rs:(1) recognition of the injurious agent,(2) recruitment of leukocytes, (3) removal of the agent, (4) regulation (control) of the response, and (5) resolution (repair).
The causes of inflammation include infections, tissue necrosis, foreign bodies, trauma, and immune responses.
Epithelial cells, tissue macrophages and dendritic cells, leukocytes, and other cell types express receptors that sense the presence of microbes and necrotic cells. Circulating proteins recognize microbes that have entered the blood.
The outcome of acute inflammation is either elimination of the noxious stimulus followed by decline of the reaction and repair of the damaged tissue, or persistent injury resulting in chronic inflammation.
Acute inflammation has three major components: (1) dilation of small vessels, leading to an increase in blood flow, (2) increased permeability of the microvasculature, enabling plasma proteins and leukocytes to leave the circulation, and (3) emigration of the leukocytes from the microcirculation, their accumulation in the focus of injury, and their activation to eliminate the offending agent (
Fig. 3.1 ). When an injurious agent, such as an infectious microbe or dead cells, is encountered, phagocytes that reside in all tissues try to eliminate these agents. At the same time, phagocytes and other sentinel cells in the tissues recognize the presence of the foreign or abnormal substance and react by liberating soluble molecules that mediate inflammation. Some of these mediators act on small blood vessels in the vicinity and promote the efflux of plasma and the recruitment of circulating leukocytes to the site where the offending agent is located.
Reactions of Blood Vessels in Acute Inflammation
The vascular reactions of acute inflammation consist of changes in the flow of blood and the permeability of vessels, both designed to maximize the movement of plasma proteins and leukocytes out of the circulation and into the site of infection or injury. The escape of fluid, proteins, and blood cells from the vascular system into interstitial tissues or body cavities is known as exudation (
Fig. 3.2 ). An exudate is an extravascular fluid that has a high protein concentration and contains cellular debris. Its presence implies that there is an increase in the permeability of small blood vessels, typically during an inflammatory reaction. In contrast, a transudate is a fluid with low protein content, little or no cellular material, and low specific gravity. It is essentially an ultrafiltrate of blood plasma that is produced as a result of osmotic or hydrostatic imbalance across vessels with normal vascular permeability (Chapter 4). Edema denotes an excess of fluid in the interstitial tissue or serous cavities; it can be either an exudate or a transudate. Pus, a purulent exudate, is an inflammatory exudate rich in leukocytes (mostly neutrophils), the debris of dead cells, and, in many cases, microbes.
Changes in vascular flow and caliber begin early after injury and consist of the following: