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134 PA R T II / Physiologic and Pathologic Responses

thus stimulating the immune response. They are important in Because blood cells have a limited lifespan, they need to be re-
killing bacteria, protozoa, cells infected with viruses, and tumor placed constantly. Usually, the number of cells produced is fairly
cells. In addition to their phagocytic activity, macrophages se- constant, but depending on environmental stimuli such as bleed-
crete biologically active products, including cytokines that mod- ing, infection, or inflammation various cells may be needed in larger
ulate the immune response. than normal quantities at times. Thus, each of these cell lines is reg-
Lymphocytes are essential components of the immune sys- ulated by cytokines that influence the rate of growth and differenti-
tem. They recognize and are instrumental in the elimination of ation of the stem cells in the marrow. Cytokines are proteins that are
foreign proteins, pathogens, and tumor cells. Lymphocytes con- made by cells of the immune system and regulate the immune re-
trol the intensity and specificity of the immune response. There sponse. Some examples of cytokines are granulocyte–macrophage
are two general types of lymphocytes, T lymphocytes (or colony-stimulating factor, which stimulates the growth of granulo-
T cells), which provide cell-mediated and B lymphocytes (B cells), cytes and macrophages, and interleukin-3 (IL-3), which stimulates
which produce the antibodies of humoral immunity. Stem cell the stem cell. Cytokines also stimulate the function of mature im-
differentiation for the production of lymphocytes occurs in the mune cells.
bone marrow. It is in the thymus that T cells learn to differen-
tiate self from nonself. There are four separate subsets of T cells: Platelets
helper T cells, suppressor T cells, cytotoxic T cells, and memory
T cells. Cell-mediated activities are of great importance in de- Platelets are small cell fragments that are produced by the disin-
layed hypersensitivity reactions; graft rejection; graft-versus- tegration of megakaryocytes in the bone marrow, producing sev-
host disease; and in defense against fungal, protozoal, and most eral thousand platelets that are released into the circulation.
viral infections. Another important function of T cells is to reg- They are tiny, disc-shaped fragments that are capable of chang-
ulate immune activities through the secretion of lymphokines. ing shape and have a high metabolic rate. It takes approximately
B lymphocytes mature into cells that respond to stimulation 5 days for a stem cell to differentiate along the megakaryocyte
from foreign proteins by differentiating into memory cellsand line and produce platelets. Under normal circumstances,
plasma cells. The plasma cells produce specific antibodies that in- platelets circulate in the bloodstream for approximately 10 days.
activate or destroy foreign proteins and pathogens. These anti- The production of platelets is regulated by thrombopoietin,
bodies are particularly effective against bacterial infections, espe- which is a humoral hormone-like substance. Platelets are also
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cially encapsulated bacteria, such as pneumococci, streptococci, called thrombocytes, which means clot cell. They play a major
meningococci, and hemophilus influenzae, as well as certain role in hemostasis by adhering to a damaged blood vessel wall
viruses. The helper cells of the T cells stimulate B cells to produce and aggregating together to form a mechanical barrier to the
antibodies. Natural killer cells, another subset of lymphocytes, kill flow of blood thereby preventing blood loss. Platelets will then
tumor cells and cells infected by viruses. They play an important release various mediators to attract other cells and components
role in tumor surveillance. The activities of phagocytes and im- to the site so that fibrin formation can start. There are three stor-
mune cells overlap in numerous mutually beneficial ways. For ex- age granules in the platelets: alpha granules, dense bodies, and
ample, immune cells often participate in chronic inflammatory lysomes. Alpha granules contain and release fibrinogen. Dense
reactions. Conversely, engulfment of foreign protein by bodies release adenine nucleotides, serotonin, and platelet factor
1
macrophages is a preparatory step leading to antibody production. 4 (PF4). Lysomes contain degradative acid hydrolases. Platelets
Table 6-1 summarizes the WBC and their function. are sequestered in the spleen and are released as needed to com-
bat bleeding. Their function is vital to the coagulation process,
so much so that many cardiac interventions are now aimed at
disabling platelet function.
Table 6-1 ■ WHITE BLOOD CELLS
Coagulation Factors
Name Function
The major component of blood, plasma, contains many particles
WBC or leukocyte Combat pathogens and other foreign including proteins (clotting factors) that are involved in coagula-
substances that enter the body
tion. To standardize the identification of these proteins, an interna-
Granular Leukocytes
Neutrophils Phagocytosis or the destruction of bacteria tional committee assigned a nomenclature for these proteins using
with lysozyme, defensins, and strong Roman numerals listed in order of their discovery. However, the or-
oxidants der does not refer to the sequence of reactions in the coagulation
Eosinophils Combat the effects of histamine in allergic cascade. A lowercase “a” is also used to indicate the activated form
reactions, phagocytize antigen–antibody of a clotting factor. Table 6-2 lists these clotting factors. The liver
complexes
Basophils Liberate heparin, histamine, and serotonin plays a significant role in maintaining adequate amounts of these
in allergic reactions that intensify the clotting factors, because it is the primary site of protein synthesis.
overall inflammatory response Tissue thromboplastin, or tissue factor (III), is an exception that can
Agranular Leukocytes be found in most body tissues, especially around vessels and organs.
Lymphocytes (T cells, B cells, Mediate immune responses including Antihemophilic factor (VIII) is a factor that is synthesized in the
natural killer cells) antigen–antibody reactions endothelial cells. It is also important to recognize that there are
Monocytes Phagocytosis after transforming into
macrophages multiple enzymes and mediators that play key roles in the activa-
tion of these clotting factors. Synthesis of factors II, VII, IX, and
X requires vitamin K to be present, and these are known as vita-
Adapted from Tortora, G., & Grabowski, S. (2003). Principles of anatomy and
physiology. New York: John Wiley & Sons, Inc. min K-dependent factors. Calcium is also a coagulation factor