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78
CHAPTER 12
A. Eosinophils comprise 0%–4% of the leukocytes in the peripheral circulation.
B. Eosinophils have a bilobed nucleus.
C. Eosinophils have highly eosinophilic granules
that contain major basic protein (MBP; binds
to and disrupts membrane of parasites),
eosinophil cationic protein (works with MBP),
histaminase, and peroxidase.
D. Eosinophils have immunoglobulin E (IgE) an-
tibody receptors.
E.
Eosinophils play a role in parasitic infection
(e.g., schistosomiasis, ascariasis, trichinosis).
F.
Eosinophils play a role in reducing the sever-
ity of allergic reactions by secreting histami-
nase and PGE
1
and PGE
2
, which degrades his-
tamine (secreted by mast cells) and which
inhibits mast cell secretion, respectively. A
large number of eosinophils are found in
asthma patients.
G. Eosinophils have a lifespan of 1–10 hours; up
to 10 days in tissues.
● Figure 12-2 Eosinophil. EG
eosinophilic
granules; MBP
major basic protein; ECP
eosinophilic cationic protein.
PGE
1
PGE
2
MBP
ECP
Histaminase
Peroxidase
EG
IgE antibody
receptors
A. Basophils comprise 0%–2% of the leukocytes in the peripheral circulation (i.e., the least
abundant leukocyte).
B. Basophils have highly basophilic granules that
contain heparin, histamine, 5-hydroxytrypta-
mine, and sulfated proteoglycans.
C. Basophils have IgE antibody receptors.
D. Basophils play a role in Type I hypersensitiv-
ity anaphylactic reactions causing allergic
rhinitis (hay fever), some forms of asthma, ur-
ticaria, and anaphylaxis.
E.
Basophils have a lifespan of 1–10 hours; vari-
able in tissues.
A. Mast cells arise from stem cells in the bone
marrow.
B. Mast cells play a role in Type I hypersensitiv-
ity anaphylactic reactions, inflammation, and
allergic reactions.
● Figure 12-3 Basophil. BG
basophilic
granules.
Heparin
Histamine
5-hydroxytrytamine
Sulfated proteoglycans
BG
IgE antibody
receptors
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79
CELL BIOLOGY OF THE IMMUNE SYSTEM
C. Mast cells have IgE antibody receptors on
their cell membranes that bind IgE produced
by plasma cells upon first exposure to an al-
lergen (e.g., plant pollen, snake venom, for-
eign serum), which sensitizes the mast cells.
D. Mast cells secrete the following substances
upon second exposure to the same allergen,
causing the classic wheal-and-flare reaction in
the skin:
1.
Heparin,
which is an anticoagulant and
cofactor for lipoprotein lipase.
2.
Histamine
(produced by decarboxylation
of histidine), which increases vascular
permeability, causes vasodilation, causes
smooth muscle contraction of bronchi,
and stimulates HCl secretion from parietal
cells in the stomach.
3.
Leukotriene C
4
and D
4
(are eicosanoids
and components of slow-reacting substance
of anaphylaxis), which increase vascular
permeability, cause vasodilation, and cause
smooth muscle contraction of bronchi.
4.
Eosinophil chemotactic factor,
which at-
tracts eosinophils to the inflammation
site.
● Figure 12-4 Mast cell. MG
mast cell
granules; ECF-A
eosinophilic chemotactic
factor; LTC
4
leukotriene C
4
; LTD
4
leuko-
triene D
4
.
LTC
4
LTD
4
Heparin
Histamine
ECF-A
MG
IgE antibody
receptors
A. Monocytes comprise 2%–9% of the leukocytes in the peripheral circulation.
B. Monocytes migrate into peripheral tissues where they differentiate into tissue-specific
macrophages whose function is PHAGOCYTOSIS and ANTIGEN PRESENTATION.
C. Monocytes are members of the monocyte-
macrophage system, which includes Kupffer
cells in liver, alveolar macrophages,
macrophages (histiocytes) in connective tis-
sue, microglia in brain, Langerhans cells in
skin, osteoclasts in bone, and dendritic anti-
gen-presenting cells (APCs).
D. Monocytes have granules that are endolyso-
somes that contain acid hydrolases, aryl sul-
fatase, acid phosphatase, and peroxidase.
E.
Monocytes respond to dead cells, microor-
ganisms, and inflammation by leaving the pe-
ripheral circulation to enter tissues and are
then called macrophages.
● Figure 12-5 Monocyte.
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80
CHAPTER 12
F.
Monocytes have a lifespan of 1–3 days; circulate in blood for 12–100 hours, and then
enter connective tissue.
Macrophages (Histiocytes; Antigen-Presenting Cells) (Figure 12-6)
A. Macrophages arise from monocytes within the circulating blood and bone marrow.
B. Macrophages are activated by lipopolysaccha-
rides (a surface component of gram-negative
bacteria) and interferon-
(IFN-).
C. Macrophages secrete interleukin-1 (IL-1;
stimulates mitosis of T lymphocytes), inter-
leukin-6 (IL-6; stimulates differentiation of
B lymphocytes into plasma cells), pyrogens
(mediate fever), tumor necrosis factor-
(TNF-
), and granulocyte-macrophage colony-
stimulating factor (GM-CSF).
D. Macrophages have granules that are endolyso-
somes that contain acid hydrolases, aryl sul-
fatase, acid phosphatase, and peroxidase.
E.
Macrophages impart natural (innate) immunity
along with neutrophils and NK cells.
F.
MACROPHAGES HAVE A PHAGOCYTIC
FUNCTION
● Figure 12-6 Macrophage. LPS
lipo-
polysaccharide; TNF-
tumor necrosis
factor-
; GM-CSF granulocyte-macrophage
colony-stimulating factor.
X
X
IL-1
IL-6
Pyrogens
TNF-
α
GM-CSF
Complement
opsonized
pathogen
Antibody
opsonized
pathogen
Bacteria
LPS
Class II
MHC
F
receptors
antibody
C complement
receptors
1.
F
C
antibody
receptors on the macrophage cell membrane bind antibody-coated for-
eign material and subsequently phagocytose the material for lysosomal digestion.
2.
C3 (a component of complement) receptors
on the macrophage cell membrane
bind bacteria and subsequently phagocytose the bacteria (called opsonization) for
lysosomal digestion.
3.
Certain phagocytosed material (e.g., bacilli of tuberculosis and leprosy, Try-
panosoma cruzi, Toxoplasma, Leishmania, asbestos) cannot undergo lysosomal di-
gestion, so macrophages will fuse to form foreign body giant cells.
4.
In sites of chronic inflammation, macrophages may assemble into epithelial-like
sheets called epithelioid cells of granulomas.
G. MACROPHAGES HAVE AN ANTIGEN-PRESENTING FUNCTION
1.
Exogenous antigens
circulating in the bloodstream are phagocytosed by
macrophages and undergo degradation in phagolysosomes.
2.
Antigen proteins are degraded into antigen peptide fragments, which are presented
on the macrophage cell surface in conjunction with class II major histocompati-
bility complex (MHC).
3.
CD4
helper T cells
with antigen-specific T-cell receptor (TCR) on its cell surface
recognize the antigen peptide fragment.
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CELL BIOLOGY OF THE IMMUNE SYSTEM
A. The NK cell is a member of the null cell pop-
ulation (i.e., lymphocytes that do not express
the TCR or cell membrane immunoglobulins
that distinguish lymphocytes as either T cells
or B cells, respectively).
B. NK cells are CD16
and capable of cytotoxic-
ity without prior antigen sensitization.
C. NK cells attack damaged cells, virus-infected
cells, and tumor cells by release of perforins,
cytolysins, lymphotoxins, and serine es-
terases which cause membrane porosity and
● Figure 12-7 Natural killer cell.
CD16
Membrane porosity
Endonuclease-mediated apoptosis
Perforin
Cytolysin
Lymphotoxin
Serine Esterase
endonuclease-mediated apoptosis of the damaged cell, virus-infected cell, or tumor cell.
D. They impart natural (innate) immunity along with neutrophils and macrophages.
In the early fetal development, B-cell lymphopoiesis
(B-cell formation) occurs in the fetal liver. In later fetal development and throughout the
rest of adult life, B-cell lymphopoiesis occurs in the bone marrow. In humans, the bone
marrow is considered the primary site of B-cell lymphopoiesis.
A. HEMOPOIETIC STEM CELLS originating in the bone marrow differentiate into lym-
phoid progenitor cells which later form B stem cells.
B. B stem cells form Pro-B cells which begin heavy chain gene rearrangement.
C. PRE-B CELLS continue heavy chain gene rearrangement.
D. IMMATURE B CELLS (IgM
) begin light chain gene rearrangement and express anti-
gen-specific IgM (i.e., will recognize only one antigen) on its cell surface.
E.
MATURE (OR VIRGIN) B CELLS (IgM
IgD
) express antigen-specific IgM and IgD
on their cell surface. Mature B cells migrate to the outer cortex of lymph nodes, lym-
phatic follicles in the spleen, and gut-associated lymphoid tissue (GALT) to await
antigen exposure.
F.
EARLY IMMUNE RESPONSE
1.
Early in the immune response, mature B cells bind antigen using IgM and IgD.
2.
As a consequence of antigen binding, two transmembrane proteins (CD79a and
CD79b) that function as signal transducers cause proliferation and differentiation
of B cells into plasma cells that secrete either IgM or IgD.
G. LATER IMMUNE RESPONSE
1.
Later in the immune response, APCs (macrophages) phagocytose the antigen
where it undergoes lysosomal degradation in endolysosomes to form antigen pep-
tide fragments.
2.
The antigen peptide fragments become associated with the class II MHC and are
transported and exposed on the cell surface of the APC.
3.
The antigen peptide fragment
class II MHC on the surface of the APC is recog-
nized by CD4
helper T cells which secrete IL-2 (stimulates proliferation of B and
T cells), IL-4 and IL-5 (activate antibody production by causing B-cell differentia-
tion into plasma cells and promote isotype switching and hypermutation), TNF-
(activates macrophages), and IFN-
(activates macrophages and NK cells).
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CHAPTER 12
4.
Under the influence of IL-4 and IL-5, mature B cells undergo isotype switching
and hypermutation.
a.
Isotype switching is a gene rearrangement process whereby the
(mu; M)
and
(delta; D) constant segments of the heavy chain (C
H
) are spliced out
and replaced with
(gamma; G),
ε
(epsilon; E), or
(alpha; A) C
H
segments.
This allows mature B cells to differentiate into plasma cells that secrete IgG,
IgE, or IgA.
b.
Hypermutation is a mutation process whereby a high rate of mutations occurs
in the variable segments of the heavy chain (V
H
) and light chain (V
or V
).
This allows mature B cells to differentiate into plasma cells that secrete IgG,
IgE, or IgA that will bind antigen with greater and greater affinity.
● Figure 12-8 B-cell lymphopoiesis.
Hemopoietic stem cell
Lymphoid progenitor cell
B stem cell
Pro-B cell
• heavy chain
gene rearrangement
Pre-B cell
• heavy chain
gene rearrangement
Immature B cell
• light chain
gene rearrangement
Mature (virgin)
B cell
Antigen
exposure
Isotype switching
Hypermutation
Bone
marrow
Migrate to:
• Outer cortex of lymph nodes
• Lymphatic follicles of spleen
• Gut-associated lymphoid tissue
and await antigen exposure
Plasma cell
CD79a
CD79b
I
g
M
I
g
M
I
g
D
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