As an open system, the body is continuously called upon to defend itself from potentially harmful invaders such as bacteria, viruses, and other microbes. This is accomplished by the immune system, which is subdivided into innate and adaptive (or acquired) branches. The immune system is composed of specialized effector cells that sense and respond to foreign antigens and other molecular patterns not found in human tissues. Likewise, the immune system clears the body’s own cells that have become senescent or abnormal, such as cancer cells.
Immune effector cells
Many immune effector cells circulate in the blood as the white blood cells. In addition, the blood is the conduit for the precursor cells that eventually develop into the immune cells of the tissues. The circulating immunologic cells include granulocytes (polymorph nuclear leukocytes, PMNs), comprising neutrophils, eosinophils, and basophils; lymphocytes; and mine diseases or in settings where normal cells are harmed as innocent bystanders when the immune system mounts an inflammatory response to an invader. It is beyond the scope of this volume to provide a full treatment of all aspects of modern immunology.
The average half-life of neutrophils in circulation is 6 hours. To maintain the normal circulating blood level, it is, therefore, necessary to produce over 100 billion neutrophils per day. Many neutrophils enter the tissues, particularly if triggered to do so by an infection or by inflammatory cytokines. They are attracted to the endothelial surface by cell adhesion molecules known as selections, and they roll along with it.
They then bind firmly to neutrophil adhesion molecules of the integrin family. They next insinuate themselves through the walls of the capillaries between endothelial cells by a process called diapedesis. Many of those that leave the circulation enter the gastrointestinal tract and are eventually lost from the body.
Mast cells are heavily granulated cells of the connective tissue that are abundant in tissues that come into contact with the external environment, such as beneath epithelial surfaces. Their granules contain proteoglycans, histamine, and many proteases. Like basophils, they degranulation when allergens bind to IgE molecules directed against them that previously coat the mast cell surface. They are involved in inflammatory responses initiated by immunoglobulin IgE and IgG (see below).
The inflammation combats invading parasites. In addition to this involvement in acquired immunity, they release TNF-α in response to bacterial products by an antibody-independent mechanism, thus participating in the nonspecific innate immunity that combats infections prior to the development of an adaptive immune response (see following text). Marked mast cell degranulation produces clinical manifestations of allergy up to and including anaphylaxis.
Granulocyte & macrophage colony-stimulating factors
The production of white blood cells is regulated with great precision in healthy individuals, and the production of granulocytes is rapidly and dramatically increased in infections. The proliferation and self-renewal of hematopoietic stem cells (HSCs) depend on stem cell factors (SCF). Other factors specify particular lineages. The proliferation and maturation of the cells that enter the blood from the marrow are regulated by glycoprotein growth factors or hormones that cause cells in one or more of the committed cell lines to proliferate and mature.
Development of the immune system
During fetal development, and to a much lesser extent during adult life, lymphocyte precursors come from the bone marrow. Those that populate the thymus become transformed by the environment in this organ into T lymphocytes. In birds, the precursors that populate the bursa of Fabrics, a lymphoid structure near the cloaca, become transformed into B lymphocytes. There is no bursa in mammals, and the transformation to B lymphocytes occurs in burial equivalents, that is, the fetal liver and, after birth, the bone marrow. After a residence in the thymus or liver, many of the T and B lymphocytes migrate to the lymph nodes.
Immune and inflammatory responses are mediated by several different cell types—granulocytes, lymphocytes, monocytes, mast cells, tissue macrophages, and antigen-presenting cells— that arise predominantly from the bone marrow and may circulate or reside in connective tissues.