Page 527 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
516
NK cells detect the presence of cancer cells by recogniz-
Affinity maturation is described in Chapter 60. In addition,
FDCs produce chemokines that attract B cells to the folli-
many cancer cells but not normal cells. Interaction of
cles in the spleen and lymph nodes.
MICA with a receptor on NK cells triggers the production
of cytotoxins by the NK cell and death of the tumor cell.
NATURAL KILLER CELLS
NK cells play two important roles in our innate host
defenses: (1) they kill virus-infected cells, and (2) they pro-
Neutrophils are a very important component of our innate
duce gamma interferon that activates macrophages to kill NEUTROPHILS
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bacteria ingested by the macrophage (Table 58–7).
host defenses, and severe bacterial infections occur if they
NK cells specialize in killing virus-infected cells and
are too few in number (neutropenia) or are deficient in
function, as in chronic granulomatous disease. They have
tumor cells by secreting cytotoxins (perforins and gran-
zymes) similar to those of cytotoxic T lymphocytes and by
with blood stains such as Wright stain, in contrast to
participating in Fas-Fas ligand-mediated apoptosis. They
eosinophils and basophils, whose granules stain red and
are called “natural” killer cells because they are active with-
blue, respectively. These granules are lysosomes, which
out prior exposure to the virus, are not enhanced by expo-
contain a variety of degradative enzymes that are important
sure, and are not specific for any virus. They can kill
in the bactericidal action of these cells. The process of
without antibody, but antibody (IgG) enhances their effec-
tiveness, a process called antibody-dependent cellular cyto-
described in detail in Chapter 8.
toxicity (ADCC) (see the section on effector functions of T
Neutrophils have receptors for IgG on their surface so
cells [earlier]). IL-12 produced by macrophages and inter-
IgG is the only immunoglobulin that opsonizes (i.e., makes
ferons alpha and beta produced by virus-infected cells are phagocytosis and the bactericidal action of neutrophils are
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bacteria more easily phagocytosed). Note that neutrophils
potent activators of NK cells. Approximately 5% to 10% of
do not display class II MHC proteins on their surface and
peripheral lymphocytes are NK cells.
NK cells are lymphocytes with some T-cell markers, but
therefore do not present antigen to helper T cells. This is in
they do not have to pass through the thymus in order to
present antigen to helper T cells.
mature. They have no immunologic memory and, unlike
Neutrophils can be thought of as a “two-edged” sword.
cytotoxic T cells, have no TCR; also, killing does not
The positive edge of the sword is their powerful microbici-
require recognition of MHC proteins. In fact, NK cells have
dal activity, but the negative edge is the tissue damage
receptors that detect the presence of class I MHC proteins
on the cell surface. If a cell displays sufficient class I MHC
caused by the release of degradative enzymes. An excellent
proteins, that cell is not killed by the NK cell. Many virus-
poststreptococcal glomerulonephritis. The damage is
infected cells and tumor cells display a significantly reduced
caused by enzymes released by neutrophils attracted to the
amount of class I MHC proteins, and it is those cells that
are recognized and killed by the NK cells. Humans who example of the latter is the damage to the glomeruli in acute
glomeruli by C5a activated by the antigen–antibody com-
plexes deposited on the glomerular membrane.
lack NK cells are predisposed to life-threatening infections
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with varicella-zoster virus and cytomegalovirus.
Eosinophils are white blood cells with cytoplasmic granules
TABLE 58–7 Important Features of Natural Killer
that appear red when stained with Wright stain. The red
(NK) Cells
color is caused by the negatively charged eosin dye binding
to the positively charged major basic protein in the gran-
I. Nature of NK Cells
ules. The eosinophil count is elevated in two medically
• Large granular lymphocytes
important types of diseases: parasitic diseases, especially
• Lack T-cell receptor, CD3 proteins, and surface IgM and IgD
• Thymus not required for development
• Normal numbers in severe combined immunodeficiency disease
sensitivity diseases, such as asthma and serum sickness
(SCID) patients
(see Chapter 65). Diseases caused by protozoa are typically
• Activity not enhanced by prior exposure those caused by nematodes (see Chapter 56), and hyper-
not characterized by eosinophilia.
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II. Function of NK Cells
The function of eosinophils has not been clearly estab-
• Kill virus-infected cells and cancer cells
lished. It seems likely that their main function is to defend
• Killing is nonspecific and is not dependent on foreign antigen
presentation by class I or II MHC proteins
loides and Trichinella. They attach to the surface of the lar-
• Produce gamma interferon that activates macrophages to kill
vae and discharge the contents of their granules, which in
ingested bacteria
turn damages the cuticle of the larvae. Attachment to the
Ig = immunoglobulin; MHC = major histocompatibility complex.
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