Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1298 Chapter 24: The Innate and Adaptive Immune Systems
THE INNATE IMMUNE SYSTEM
Adaptive immune responses are slow to develop when a vertebrate first encounters
a new pathogen. This is because the specific B cells and T cells that can respond
to a particular pathogen are initially few in number and must be stimulated to
proliferate and differentiate before they can mount effective adaptive immune
responses, which can take days. By contrast, a single bacterium that divides every
hour can generate almost twenty million progeny in a single day, producing a fullblown
infection. Vertebrates, therefore, rely on their innate immune system to
defend them against infection during the first critical hours and days of exposure
to a new pathogen. Plants and invertebrates lack adaptive immune systems and
therefore rely entirely on innate immunity for protection against pathogens.
In this section, we consider some of the strategies the innate immune system
uses to recognize pathogens and to provide a first line of defense against them.
innate immune
responses
virus
virus-infected
host cell
Epithelial Surfaces Serve as Barriers to Infection
In vertebrates, the first encounters with infectious organisms are typically at the
epithelial surfaces that form the skin and line the respiratory, digestive, urinary,
and reproductive tracts. These epithelia provide both physical and chemical barriers
to invasion by pathogens: tight junctions between epithelial cells bar entry
between the cells, and a variety of substances secreted by the cells discourage the
attachment and entry of pathogens. The keratinized epithelial cells of the skin,
for example, form a thick physical barrier, and the sebaceous glands in the skin
secrete fatty acids and lactic acid, which inhibit bacterial growth. In addition, epithelial
cells in all tissues, including those in plants and invertebrates, secrete antimicrobial
molecules called defensins. Defensins are positively charged, amphipathic
peptides that bind to and disrupt the membranes of many pathogens,
including enveloped viruses, bacteria, fungi, and parasites.
The epithelial cells that line internal organs such as the respiratory and digestive
tracts also secrete slimy mucus, which sticks to the epithelial surface and
makes it difficult for pathogens to adhere. The beating of cilia on the surface of the
epithelial cells lining the respiratory tract and the peristaltic action of the intestine
also discourage the adherence of pathogens. Moreover, as we discuss in Chapter
23, healthy skin and gut are populated by enormous numbers of harmless (and
often helpful) commensal microbes, collectively called the normal flora, which
compete for nutrients with pathogens; some also produce antimicrobial peptides
that actively inhibit pathogen proliferation.
Pattern Recognition Receptors (PRRs) Recognize Conserved
Features of Pathogens
Pathogens do occasionally breach the epithelial barricades, in which case underlying,
nonepithelial cells of the innate immune system provide the next line of
defense. These cells sense the presence of pathogens largely through the use of
receptor proteins that recognize microbe-associated molecules that either are not
present or are sequestered in the host organism. Because these microbial molecules
often occur in repeating patterns, they are called pathogen-associated
molecular patterns (PAMPs), even though they are not unique to microbes that
can cause disease. PAMPs are present in various microbial molecules, including
nucleic acids, lipids, polysaccharides, and proteins.
The special receptor proteins that recognize PAMPs are called pattern recognition
receptors (PRRs). Some PRRs are transmembrane proteins on the surface
of many types of host cells, where they recognize extracellular pathogens; on
professional phagocytic cells (phagocytes) such as macrophages and neutrophils
(discussed in Chapter 22), they can mediate the uptake of the pathogens into phagosomes,
which then fuse with lysosomes, where the pathogens are destroyed.
Other PRRs are located intracellularly, where they can detect intracellular pathogens
such as viruses; these PRRs are either free in the cytosol or associated with
B cell
antibody
response
antibody
uninfected
host cell
T-cell-mediated
response
T cell
dead virus-infected
host cell
Figure 24–2 The two main classes
of adaptive immune responses.
Lymphocytes carry out both classes of
adaptive responses—shown here as
responses to a viral infection. In one class,
B cells secrete MBoC6 antibodies m25.02/24.02 that specifically
bind to and neutralize extracellular viruses,
by preventing the viruses from infecting
host cells. In the other, T cells mediate
the response; in this example, they kill the
virus-infected host cells. In both cases,
innate immune responses help activate
the adaptive immune responses through
pathways that are not shown.