After studying this chapter, you should be able to:
Understand the significance of immunity for defending the body against microbial invaders.
Define the cell types that contribute to immune and inflammatory responses.
Describe how phagocytes kill internalized bacteria.
Identify the functions of hematopoietic growth factors, cytokines, and chemokines.
Delineate the roles and mechanisms of innate, acquired, humoral, and cellular immunity.
Understand the basis of inflammatory responses and wound healing.
As an open system, the body is continuously called upon to defend itself from potentially harmful invaders. This is accomplished by the immune system, subdivided into innate and adaptive branches. The immune system is composed of specialized cells that sense and respond to nonhost molecular patterns. Likewise, the immune system clears the body’s own cells that have become senescent or abnormal. Finally, normal host tissues occasionally become the subject of inappropriate immune attack. The student of physiology should have a working knowledge of immune functions because the immune system contributes to normal physiologic regulation as well as pathophysiology.
Many immune cells circulate in the blood as the white blood cells. In addition, the blood delivers precursors that develop into tissue immune cells. Circulating immunologic cells include granulocytes (polymorphonuclear leukocytes, PMNs), comprising neutrophils, eosinophils, and basophils; lymphocytes; and monocytes. Immune responses in the tissues are further amplified by these cells following their extravascular migration, as well as tissue macrophages (derived from monocytes) and mast cells (related to basophils). Acting together, these cells provide the body with powerful defenses.
All granulocytes have cytoplasmic granules that contain biologically active substances involved in inflammatory and allergic reactions.
The average half-life of a neutrophil in the circulation is only 6 h. Many neutrophils enter the tissues. They are attracted to the endothelial surface by cell adhesion molecules known as selectins, and they roll along it. They then bind firmly to integrins and insinuate themselves through the walls of the capillaries by diapedesis. Many of those that leave the circulation enter the gastrointestinal tract and are eventually lost from the body.
Invasion of the body by bacteria triggers the inflammatory response. Bacterial products trigger production of agents that attract neutrophils to the area (chemotaxis). Chemotactic agents include a component of the complement system (C5a); leukotrienes; and chemokine polypeptides from lymphocytes, mast cells, and basophils. Other plasma factors coat the bacteria to make them “tasty” to the phagocytes (opsonization). The principal opsonins are immunoglobulin G and complement proteins. The coated bacteria then bind to G-protein–coupled receptors on the neutrophil membrane. This triggers increased motor activity of the cell, exocytosis, and the respiratory burst. Increased motor activity leads to ingestion of the bacteria by endocytosis (phagocytosis). By exocytosis, neutrophil granules discharge their contents into phagocytic vacuoles containing bacteria and also into the interstitial space ...