Page 70 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 8 Host Defenses
PEARLS

• Host defenses against bacterial infections include both innate
caused by the production of granulocyte-stimulating factors
and adaptive (acquired) defenses. Innate defenses are non-
by macrophages.
specific (i.e., they are effective against many different organ-
isms). These include physical barriers, such as intact skin and
macrophages (and similar cells called dendritic cells) also pres-
mucous membranes; cells, such as neutrophils and macro-
ent antigen to CD4-positive (helper) T cells, whereas neutro-
phages; and proteins, such as complement and lysozyme.
phils do not. Dendritic cells are probably the most important
Adaptive (acquired) defenses are highly specific for the organ-
antigen-presenting cells in the body.
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ism and include antibodies and cells such as CD4-positive
helper T lymphocytes and CD8-positive cytotoxic T lymphocytes.
kines, they attach to the endothelium first using selectins on
the endothelium, then by the interaction of integrins (LFA
Innate Immunity
proteins) on the neutrophils with intracellular adhesion mole-
cule (ICAM) proteins on the endothelium. The concentration of
• Intact skin and mucous membranes provide a physical barrier
ICAM proteins is increased by cytokines released by activated
to infection. Loss of skin integrity (e.g., in a burn) predisposes
macrophages, which results in neutrophils being attracted to
to infection. The low pH of the skin, stomach, and vagina also
the infected site.
protects against infection.
• Neutrophils then migrate through the endothelium (diapedesis)
• The respiratory tract, a very important portal of entry for
and ingest the bacteria. IgG and C3b are opsonins, which
microbes, is protected by the ciliary elevator, alveolar macro-
enhance ingestion of the bacteria. There are receptors for the
phages, lysozyme, nose hairs, and the cough reflex.
heavy chain of IgG and for C3b on the surface of the neutrophils.
• The normal flora of the skin and mucous membranes occupy • Killing of the bacteria within the neutrophil is caused by hypo-
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receptors, which reduce the opportunity for pathogens to
chlorite, hydrogen peroxide, and superoxides. Lysosomes
attach–a process called colonization resistance. Suppression
contain various degradative enzymes and fuse with the phago-
of the normal flora with antibiotics predisposes to infec-
some to form a phagolysosome within which the killing occurs.
tion with certain organisms. Two important examples are the
suppression of colon flora predisposing to pseudomembra-
have inadequate neutrophils. For example, people with
nous colitis caused by C. difficile and the suppression of vaginal
defective neutrophils, people with fewer than 500 neutrophils/
flora predisposing to vaginitis caused by C. albicans.
μL, and those who have had a splenectomy or who have diabe-
• Inflammation (i.e., redness, swelling, warmth, and pain) is an
tes mellitus are at increased risk for pyogenic infections.
important host defense. Redness, swelling, and warmth are the
result of increased blood flow and increased vascular perme-
ability, which has the effect of bringing the cells and proteins of
our host defenses to the site of infection. The increased blood
• Passive immunity refers to protection based on the transfer of
flow and increased vascular permeability are caused by media- Adaptive Immunity
preformed antibody from one person (or animal) to another
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tors such as histamine, prostaglandins, and leukotrienes.
person. Passive immunity provides immediate but short-
• The predominant phagocytic cells in inflammation are neutro-
lived protection (lasting a few months). Examples of passive
phils and macrophages. Neutrophils are seen in the pyogenic
immunity include administration of antitoxin, passage of IgG
inflammatory response to bacteria such as S. aureus and S. pyo-
from mother to fetus across the placenta, and passage of IgA
genes, whereas macrophages are seen in the granulomatous
from mother to newborn through breast milk.
inflammatory response to bacteria such as M. tuberculosis.
• The acute-phase response consists of proteins (e.g., C-reactive
of both antibodies and cell-mediated immunity after expo-
protein, mannose-binding protein, and LPS-binding protein)
sure either to the microbe itself (with or without disease) or to
that enhance the host response to bacteria. Interleukin-6 is the
the antigens of the microbe in a vaccine. Active immunity pro-
main inducer of this response.
vides long-term protection but is not effective for days after
exposure to the microbe. In the primary response, antibody
• Neutrophils and macrophages are attracted to the site of infec-
appears in 7 to 10 days, whereas in the secondary response,
tion by chemokines, which are small polypeptides produced
by cells at the infected site. Interleukin-8 and C5a are impor- • The main functions of antibodies are to neutralize bacterial
antibody appears in approximately 3 days.
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tant chemokines for neutrophils.
toxins and viruses, opsonize bacteria, activate comple-
• In response to most bacterial infections, there is an increase in
the number of neutrophils in the blood. This increase is
ria, and interfere with attachment to mucosal surfaces.
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