Ganong's Review of Medical Physiology, 23rd Edition

74 SECTION I Cellular & Molecular Basis for Medical Physiology
TABLE 3–3 Human immunoglobulins. a
Immunoglobulin Function
Diversity is brought about in part by the fact that in immune
globulin molecules there are two kinds of light chains and eight
kinds of heavy chains. As noted previously, there are areas of
great variability (hypervariable regions) in each chain. The variable
portion of the heavy chains consists of the V, D, and J segments.
In the gene family responsible for this region, there are
several hundred different coding regions for the V segment,
about 20 for the D segment, and 4 for the J segment. During B cell
development, one V coding region, one D coding region, and one
J coding region are selected at random and recombined to form
the gene that produces that particular variable portion. A similar
variable recombination takes place in the coding regions responsible
for the two variable segments (V and J) in the light chain. In
addition, the J segments are variable because the gene segments
join in an imprecise and variable fashion (junctional site diversity)
and nucleotides are sometimes added (junctional insertion diversity).
It has been calculated that these mechanisms permit the
production of about 10 15 different immunoglobulin molecules.
Additional variability is added by somatic mutation.
Similar gene rearrangement and joining mechanisms operate
to produce the diversity in T cell receptors. In humans, the
α subunit has a V region encoded by 1 of about 50 different
genes and a J region encoded by 1 of another 50 different
genes. The β subunits have a V region encoded by 1 of about
50 genes, a D region encoded by 1 of 2 genes, and a J region
encoded by 1 of 13 genes. These variable regions permit the
generation of up to an estimated 10 15 different T cell receptors
(Clinical Box 3–2 and Clinical Box 3–3).
A variety of immunodeficiency states can arise from defects
in these various stages of B and T lymphocyte maturation.
These are summarized in Figure 3–12.
PLATELETS
Heavy
Chain
Platelets are circulating cells that are important mediators of
hemostasis. While not immune cells, per se, they often participate
in the response to tissue injury in cooperation with in-
Additional
Chain Structure
Plasma Concentration
(mg/dL)
IgG Complement activation γ 1 , γ 2 , γ 3 , γ 4 Monomer 1000
IgA Localized protection in external
secretions (tears, intestinal secretions,
etc)
α 1 , α 2 J, SC Monomer; dimer with J or SC
chain; trimer with J chain
IgM Complement activation μ J Pentamer with J chain 120
IgD Antigen recognition by B cells δ Monomer 3
IgE Reagin activity; releases histamine
from basophils and mast cells
a In all instances, the light chains are k or γ.
ε Monomer 0.05
flammatory cell types (see below). They have a ring of
microtubules around their periphery and an extensively invaginated
membrane with an intricate canalicular system in
contact with the ECF. Their membranes contain receptors for
collagen, ADP, vessel wall von Willebrand factor (see below),
and fibrinogen. Their cytoplasm contains actin, myosin, glycogen,
lysosomes, and two types of granules: (1) dense granules,
which contain the nonprotein substances that are
secreted in response to platelet activation, including serotonin,
ADP, and other adenine nucleotides; and (2) α-granules,
which contain secreted proteins other than the hydrolases in lysosomes.
These proteins include clotting factors and plateletderived
growth factor (PDGF). PDGF is also produced by
macrophages and endothelial cells. It is a dimer made up of A
and B subunit polypeptides. Homodimers (AA and BB), as
well as the heterodimer (AB), are produced. PDGF stimulates
wound healing and is a potent mitogen for vascular smooth
muscle. Blood vessel walls as well as platelets contain von
Willebrand factor, which, in addition to its role in adhesion,
regulates circulating levels of factor VIII (see below).
When a blood vessel wall is injured, platelets adhere to the
exposed collagen and von Willebrand factor in the wall via
receptors on the platelet membrane. Von Willebrand factor is
a very large circulating molecule that is produced by endothelial
cells. Binding produces platelet activations which release
the contents of their granules. The released ADP acts on the
ADP receptors in the platelet membranes to produce further
accumulation of more platelets (platelet aggregation).
Humans have at least three different types of platelet ADP
receptors: P2Y 1 , P2Y 2 , and P2X 1 . These are obviously attractive
targets for drug development, and several new inhibitors
have shown promise in the prevention of heart attacks and
strokes. Aggregation is also fostered by platelet-activating
factor (PAF), a cytokine secreted by neutrophils and monocytes
as well as platelets. This compound also has inflammatory
activity. It is an ether phospholipid, 1-alkyl-2acetylglyceryl-3-phosphorylcholine,
which is produced from
membrane lipids. It acts via a G protein-coupled receptor to
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