Page 506 - Review of Medical Microbiology and Immunology ( PDFDrive )

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CHAPTER 57 Immunity
receptors may become important in preventing endotoxin-
mediated septic shock, a leading cause of death in hospital-
masome is a multi-protein complex with protease activity
that enhances inflammation by producing IL-1 from its
ized patients.
precursor protein. Anti-inflammatory cytokines, such as
(2) Many bacteria and yeasts have a polysaccharide
IL-10 and transforming growth factor-β (TGF-β), restore
called mannan on their surface that is not present on
human cells. (Mannan is a polymer of the sugar, mannose.)
needed.
A pattern-recognition receptor called mannan-binding
lectin (MBL) (also known as mannose-binding protein) on
Some acute-phase proteins bind to the surface of bacte-
ria and activate complement, which can kill the bacteria.
the surface of dendritic cells and macrophages binds to the homeostasis after the inflammatory response is no longer
For example, C-reactive protein binds to a carbohydrate in
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mannan on the surface of the microbes, which then acti-
vates complement (see Chapter 63), resulting in death of
the cell wall of Streptococcus pneumoniae and, as men-
tioned earlier, MBL binds to mannan (mannose) on the
the microbe. MBL also enhances phagocytosis (acts as an
opsonin) via receptors to which it binds on the surface of
Defensins are another important component of innate
phagocytes, such as macrophages. MBL is a normal serum
protein whose concentration in the plasma is greatly
immunity. Defensins are highly positively charged (i.e.,
increased during the acute-phase response (see later).
cationic) peptides that create pores in the membranes of
bacteria and thereby kill them. How they distinguish
MBL is a member of a group of pattern receptors called
C-type lectin receptors. A different C-type lectin receptor
between microbes and our cells is unknown. Defensins are
recognizes beta-glucan in the cell wall of fungi such as
Candida albicans.
tory tracts. Neutrophils and Paneth cells in the intestinal
(3) Part of the peptidoglycan (cell wall) of bacteria is
crypts contain one type of defensin (α-defensins), whereas
the respiratory tract produces different defensins called
recognized by NOD receptors. These receptors are located located primarily in the gastrointestinal and lower respira-
β-defensins.
within the cytoplasm of human cells (e.g., macrophages,
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dendritic cells, and epithelial cells); hence they are impor-
α-Defensins also have antiviral activity. They interfere
tant in the innate response to intracellular bacteria such as
with human immunodeficiency virus (HIV) binding to the
Listeria.
(4) RIG-I helicase receptors recognize the nucleic acids
The production of α-defensins may explain why some
HIV-infected individuals are long-term “nonprogressors.”
of viruses in the cytoplasm of infected cells. For example,
APOBEC3G (apolipoprotein B RNA-editing enzyme) is
members of the orthomyxovirus, paramyxovirus, and rhab-
an important member of the innate host defenses against
dovirus families synthesize double-stranded RNA during
replication that are recognized by RIG-I helicase receptors.
retroviral infection, especially against HIV. APOBEC3G is
an enzyme that causes hypermutation in retroviral DNA by
Activation of these receptors results in the synthesis of alpha
and beta interferons that induce the antiviral state (see later).
thereby inactivating these molecules and reducing infectiv-
ity. HIV defends itself against this innate host defense by
Effector Mechanisms of Innate Immunity deaminating cytosines in both mRNA and retroviral DNA,
producing Vif (viral infectivity protein), which counteracts
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The important cellular effectors of innate immunity namely,
APOBEC3G, thereby preventing hypermutation from
macrophages, dendritic cells, and natural killer cells are dis-
occurring.
cussed in some detail in Chapter 58 starting on page 514. For
Alpha and beta interferons are important antiviral pro-
this discussion, it will suffice to say that macrophages and
dendritic cells ingest and kill various microbes whereas natu-
infected cells. They exit that cell, bind to the surface of an
ral killer cells primarily kill virus-infected cells.
adjacent cell, and induce an antiviral state in that adjacent
Innate immunity has noncellular effectors as well.
cell. The antiviral state is mediated by a ribonuclease and a
Complement, a cascade of approximately 20 proteins, is
protein kinase that, acting together, inhibit viral protein
described in Chapter 63. Other protein effectors are dis-
synthesis. See Chapter 33 for more information on the
cussed in the following paragraphs.
The acute-phase response, which consists of an increase
tant mediator of inflammation but has only modest antiviral
in the levels of various plasma proteins (e.g., C-reactive
activity. It acts primarily to enhance killing by macrophages
protein and mannose-binding protein), is an important action of these interferons. Gamma interferon is an impor-
and other phagocytes, and to increase the synthesis of class
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part of innate immunity. These proteins are synthesized by
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1 and class 2 MHC proteins. See pages 509 and 520 for more
the liver and are nonspecific responses to microorganisms
information on the action of gamma interferon.
and other forms of tissue injury. The liver synthesizes these
proteins in response to certain cytokines, namely, IL-1,
IL-6, and TNF, produced by the macrophage after exposure
Adaptive immunity occurs after exposure to an agent,
to microorganisms. These cytokines, IL-1, IL-6, and TNF,
improves upon repeated exposure, and is specific. It is
are often called the proinflammatory cytokines, meaning
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