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

THE INNATE IMMUNE SYSTEM
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inactive
activating
receptor
class I
MHC protein
NK cell
activated
inhibitory
receptor
inactive
inhibitory
receptor
activating
protein
virus
NK cell
active
activating
receptor
KILLING
Figure 24–10 How an NK cell recognizes
its target. An NK cell preferentially attacks
infected host cells and cancer cells
because these cells have on their surface
both activating proteins and, in some
cases, abnormally low levels of class I
MHC proteins. (A) The high levels of class
I MHC proteins found on normal host cells
activate inhibitory receptors on the NK cell
that suppress the killing activity of the NK
cell. (B) In contrast, the activating proteins
on infected cells and cancer cells bind to
activating receptors on the NK cell and
stimulate the killing activity of the cell.
healthy host cell
(A) HEALTHY HOST CELL NOT KILLED
apoptotic virus-infected host cell
(B) VIRUS-INFECTED HOST CELL KILLED
The reason that class I MHC protein levels are often low on virus-infected
cells is that many viruses have developed a variety of mechanisms to inhibit the
expression of these proteins on the surface of the host cells they infect, in order
to avoid detection by cytotoxic T cells: some viruses encode proteins that block
class I MHC gene transcription; others block the intracellular assembly of peptide–MHC
complexes; still others block the transport of these complexes to the
cell surface. By evading recognition by cytotoxic T cells in these ways, however,
a virus incurs the wrath of NK cells, which recognize the infected cells as being
different—both because the infected cells express little class I MHC protein and
because they express large amounts MBoC6 of other n24.102/24.11 surface proteins that are recognized
by the activating receptors on the NK cells (Figure 24–10).
Dendritic Cells Provide the Link Between the Innate and
Adaptive Immune Systems
Dendritic cells are crucially important components of the innate immune system.
They are a heterogeneous class of cells that are widely distributed in the tissues
and organs of vertebrates. They express a large variety of PRRs, which enable dendritic
cells to recognize and phagocytose invading pathogens and their products
and to become activated in the process. The activated dendritic cells cleave the
proteins of the pathogen into peptide fragments, which bind to newly synthesized
MHC proteins, which then carry the fragments to the dendritic cell surface. The
activated cells then migrate to a nearby lymphoid organ such as a lymph node
(also called a lymph gland), where they present the peptide–MHC complexes to
T cells of the adaptive immune system, activating the T cells to join in the battle
against the specific pathogen (Figure 24–11).
In addition to the complexes of MHC proteins and microbial peptides displayed
on their cell surface, activated dendritic cells also display cell-surface costimulatory
proteins that help activate T cells (see Figure 24–11). As we discuss
later, the activated dendritic cells also secrete a variety of cytokines that influence
the type of response that the T cells make, ensuring that it is appropriate to
fight the particular pathogen. In these ways, dendritic cells serve as crucial links
between the innate immune system, which provides a rapid first line of defense
against invading pathogens, and the adaptive immune system, which mounts
slower but more powerful and highly specific responses to attack an invader, as
we now discuss.
Summary
All multicellular organisms possess innate immune defenses against invading
pathogens; these defenses include physical and chemical barriers and various
defensive cell responses. In vertebrates, these innate defense responses can also