Page 39 - Clinical Immunology_ Principles and Practice ( PDFDrive )

CHaPter 2 Organization of the Immune System 25

microbes extracellularly and then use autophagy to digest them Basophils and mast cells share a number of phenotypic and
intracellularly. 19 functional features that suggest derivation from a common
Neutrophils mature from CFU-GM progenitor cells and precursor. Both basophils and mast cells contain basophilic-
differentiate within a 10- to 14-day period. These progeni- staining cytoplasmic granules; both express the high-affinity IgE
tors give rise to myeloblasts, promyelocytes, myelocytes, and receptor (FcεRI); and both release a number of similar chemical
finally mature neutrophils. SCF, IL-3, IL-6, IL-11, and GM-CSF mediators that participate in immune and inflammatory responses,
promote the growth and development of neutrophil precursors. particularly anaphylaxis. They both have been implicated in
Other cytokines are important for differentiation of CFU-GM allergic inflammation and in fibrosis. However, basophils and
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progenitors into mature neutrophils. G-CSF induces matura- mast cells also have some distinct morphological and functional
tion of neutrophil precursors into mature neutrophils. IL-4 characteristics that suggest that they may be distinct lineages of
enhances neutrophil differentiation induced by G-CSF, while cells, rather than cells at different stages within the same lineage.
inhibiting the development of macrophages induced by IL-3 and In human, transcription factor analysis places basophils closer
M-CSF. to eosinophils than mast cells. 22
Basophils mature from a progenitor (CFU-BM) into basophilic
Eosinophils myeloblasts and then into basophilic promyelocytes, myelocytes,
Eosinophils typically comprise 2–5% of the white cells in blood. and finally mature basophils. Less is known about the stages of
They exhibit a unique form of diurnal variation. Peak production mast cell development, although they are probably derived from
occurs at night, perhaps because glucocorticoid levels are lower. the same CFU-BM progenitor as basophils.
Eosinophils are capable of phagocytosis followed by killing, In humans, SCF induces the most consistent effects on the
although this is not their main function. The granules in eosino- growth and differentiation of both basophils and mast cells.
phils are much larger than in neutrophils and are actually Both IL-3 and SCF are important for intestinal mast cell dif-
membrane-bound organelles. The crystalloid core of the granules ferentiation. Il-6 can also increase mast cell numbers. This
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contains a large amount of the major basic protein (MBP), which probably explains why T cells are needed for their development.
can neutralize heparin and is toxic. During degranulation, the Both IL-4 and IL-9 stimulate mast cell development in mice.
granules fuse to the plasma membrane, and their contents are However, in humans, only IL-9 acts in synergy with SCF to
released into the extracellular space. Organisms that are too large enhance mast cell growth. Additional cytokines that affect basophil
to be phagocytosed, such as parasites, can be exposed to cell growth include nerve growth factor and GM-CSF or TGF-β,
toxins by this mechanism. The MBP can damage schistosomes and IL-5 for basophil differentiation.
in vivo, although damage is minimized because the MBP is
confined to a small extracellular space. Eosinophils also release Platelets and Erythrocytes
products that counteract the effects of mast cell mediators. Hematopoietic stem cells give rise to platelets and erythrocytes.
Whether eosinophils are absolutely required for helminth control Platelets are necessary for blood clot formation and mediate a
is controversial. number of immune functions. Mature red blood cells are necessary
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Eosinophils mature from a progenitor (CFU-Eo) into an for oxygen delivery to tissues. Platelets derive from CFU-GEMM
eosinophilic myeloblast, then an eosinophilic promyelocyte, a progenitors, which differentiate into burst-forming units for
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myelocyte, and finally a mature eosinophil. Three cytokines megakaryocytes (BFU-MEG). BFU-MEG then differentiate into
are important in the development of eosinophils: GM-CSF, IL-3, CFU-MEG, promegakaryoblasts, megakaryoblasts, megakaryo-
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and IL-5. GM-CSF and IL-3 promote eosinophil growth and cytes, and finally platelets. Several cytokines, particularly
differentiation. SCF also has an effect on eosinophil function. thrombospondin, IL-1, IL-3, GM-CSF, IL-6, IL-11, and LIF, affect
Eotaxin (CCL11) promotes eosinophilia. IL-5 has more lineage- the growth and differentiation of platelets.
specific effects on eosinophil differentiation. Although it also Erythrocytes also derive from CFU-GEMM progenitors,
affects some subsets of T and B cells, it is important for eosinophil but their progenitors are burst-forming units for erythrocytes
survival and maturation. Eosinophils are involved in the patho- (BFU-E), which, in turn, differentiate into CFU-E, pronormo-
physiology of asthma, with contribution to airways dysfunction blasts, basophilic normoblasts, polychromatophilic normo-
and tissue remodeling, and IL-5 is being targeted to correct blasts, orthochromic normoblasts, reticulocytes, and finally
eosinophilia. erythrocytes. Again, several cytokines, notably GM-CSF, SCF,
IL-9, thrombospondin, and erythropoietin, regulate erythrocyte
Basophils and Mast Cells development.
Basophils represent less than 1% of the cells in the peripheral
circulation. They are characterized by large, deep-purple granules. Lymphocytes
Mast cells are found in proximity to blood vessels and are much Lymphocytes, the central cell type of the specific immune system,
larger than peripheral blood basophils. Their granules are less represent about 25% of the white blood cells in blood (see Table
abundant, and the nucleus is more prominent. There are two 2.4). Small lymphocytes range from 7–10 µm in diameter and
different types of mast cells—designated mucosal and connective contain a nucleus that stains dark purple with Wright staining,
tissue—depending on their location. Mucosal mast cells require and a small cytoplasm. Large granular lymphocytes range from
T cells for their proliferation, whereas connective tissue mast 10–12 µm in diameter and contain more cytoplasm and scattered
cells do not. Both types have granules that contain effector granules. The three types of lymphocytes that circulate in the
molecules. After degranulation, which is effected by cross-linkage peripheral blood—T cells, B cells, and ILCs, including NK
of cell surface IgE bound to cells via the high-affinity receptor cells—constitute approximately 80%, 10%, and 10% of the total
for IgE, basophils and mast cells release heparin, histamine, and blood lymphocyte population, respectively (Chapters 7, 8, and
other effector substances to mediate an immediate allergic attack 17). In the thymus, most of the lymphocytes (90%) are T cells;
(Chapters 23 and 42). however, in the spleen and lymph nodes, only about 30–40%