Page 505 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
494
TABLE 57–4 Important Components of Innate Immunity
Factor
Factors that limit entry of microorganisms into the body
I.
Keratin layer of intact skin
Acts as mechanical barrier
Lysozyme in tears and other secretions
Elevate mucus-containing trapped organisms
Respiratory cilia
Retards growth of microbes
Low pH in stomach and vagina; fatty acids in skin Degrades peptidoglycan in bacteria cell wall
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Surface phagocytes (e.g., alveolar macrophages)
Ingest and destroy microbes
Defensins (cationic peptides)
Create pores in microbial membrane
Normal flora of throat, colon, and vagina
II.
Factors that limit growth of microorganisms within the body
Kill virus-infected cells
Natural killer cells
Ingest and destroy microbes
Neutrophils
Ingest and destroy microbes and present antigen to helper T
Macrophages and dendritic cells
cells
Interferons
C3b is an opsonin; membrane attack complex creates holes in
Complement
bacterial membranes
Transferrin and lactoferrin Inhibit viral replication
Sequester iron required for bacterial growth
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Elevated temperature retards bacterial growth
Fever
Inflammatory response
Limits spread of microbes
APOBEC3G (apolipoprotein B RNA-editing enzyme)
Causes hypermutation in retroviral DNA and mRNA
surface of microorganisms that are different from those on
humoral (antibody-mediated) response is produced against
human cells. Components of the innate arm have receptors
one type of bacteria, but a cell-mediated response occurs in
response to a different type of bacteria. The process that
called pattern-recognition receptors that recognize a
determines the type of response depends on the cytokines
molecular pattern called a pathogen-associated molecular
pattern (PAMP) that is present on the surface of many
microbes but—very importantly—is not present on human
which pattern-recognition receptor is activated by the
cells. By using this strategy, these components of the innate
Some important examples of this pattern recognition
arm do not have to have a highly specific receptor for every produced by the macrophages, and this in turn depends on
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are as follows:
different microbe but can still distinguish between what is
foreign and what is self.
There are two classes of receptors on the surface of cells
(1) Endotoxin is a lipopolysaccharide (LPS) found on
(Toll-like receptors and mannan-binding lectin receptors)
that recognize microbes outside of cells and two classes of
human cells). The lipid A portion of LPS is the most impor-
receptors in the cytoplasm of cells (NOD receptors and
tant cause of septic shock and death in hospitalized
RIG-I helicase receptors) that recognize microbes within
patients. When released from the bacterial surface, LPS
combines with LPS-binding protein, a normal component
cells. Mutations in the genes encoding these pattern recep-
tors result in a failure to recognize the pathogen and predis-
of plasma. This binding protein transfers LPS to a receptor
pose to severe bacterial, viral, and fungal infections.
a pattern-recognition receptor called Toll-like receptor 4
The most important of these pattern-recognition recep-
tors are the Toll-like receptors (TLR). This is a family of 10
(TLR4), which transmits a signal, via several intermediates,
receptors found mainly on the surface of three types of on the surface of macrophages called CD14. LPS stimulates
to the nucleus of the cell. This induces the production of
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cells: macrophages, dendritic cells, and mast cells. TLRs
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cytokines, such as IL-1, IL-6, IL-8, and tumor necrosis fac-
recognize various microbial components and then activate
tor (TNF), and induces the costimulator protein, B7, which
transcription factors that enhance the synthesis of several
is required to activate helper T cells and to produce anti-
proinflammatory cytokines. This initiates an immune
response appropriate to defend against that type of microbe.
nals the presence of gram-positive bacteria and yeasts
Note that the type of host defense mounted by the body
because they have a different molecular pattern on their
surface. Drugs that modify the action of these Toll-like
differs depending on the type of organism. For example, a
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