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Evolution of the Response to Injury

The human organism responds to injury with complex predetermined patterns that, at a tissue level, have their analogues in lower animals. In animal phyla, the first responses to injury to evolve were phagocytosis and regeneration (present in amebas, hydras, sponges, etc). Phagocytosis, which at the level of these organisms is the engulfment of a solid particle by a cell, involves only simple recognition of damage or of status as foreign versus self. A more advanced level of response occurs in larger multicellular animals (invertebrates such as worms, mollusks, insects), in which the existence of a vascular system permits mobilization and transport of specialized inflammatory cells (phagocytes) to the site of injury. This nonspecific acute inflammatory response goes beyond simple recognition and phagocytosis to include chemotaxis (movement of cells in response to a chemical concentration gradient) and microcirculatory changes. In vertebrates, a highly specific immune response exists that enhances the efficiency of phagocytosis and the acute inflammatory response to injury. This enhancement is possible because of the presence of cells (lymphocytes) that remember an encounter with an injurious agent and produce a greater, more specific, and faster response when they meet that particular agent again. Specificity, memory, and amplification are the trio of features that distinguish the immune response from the acute inflammatory reaction.

Sequence of Host Responses

In humans, the first visible tissue change begins immediately after an injury. It is the microcirculatory response accompanied by mobilization of phagocytic cells—the acute inflammatory response (Chapter 3: The Acute Inflammatory Response).

The immune response (Chapter 4: The Immune Response) is triggered at the time of the injury but takes several days to manifest microscopically visible changes at the site of injury. The term chronic inflammation (Chapter 5: Chronic Inflammation) is applied to the complex of changes in tissues that represents a combined inflammatory and immune response against an agent that persists in the tissues long enough so that the microscopic changes of the immune response can appear. Chronic inflammation also shows changes associated with tissue damage and repair.

Many texts present acute and chronic inflammation together, with separate discussions of immunity. We chose the sequence of acute inflammatory response → immune response → chronic inflammation, because we think it provides a more logical explanation of the sequence of events in injury.

Types of Noxious Agents

Noxious agents causing tissue injury may be classified into 2 broad categories:

  1. Physical or chemical agents and other mechanisms that are not recognized by the immune system. These induce primarily a basic microcirculatory and phagocytic response (inflammation).

  2. Agents that are recognized by the immune system (eg, ...

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