Summary to Chapter 1
Throughout their evolutionary history, multicellular animals have been colonized
and infected by microorganisms. To restrict the nature, size, and location of
microbial infestation, animals have evolved a series of defenses, which humans
still use today. The skin and contiguous mucosal surfaces provide physical and
chemical barriers that confine microorganisms to the external surfaces of the
body. When pathogens manage to breach the barriers and gain entry to the soft
tissues, they are sought out and destroyed by the immune system. The cells of
the immune system are principally the various types of lymphocyte or lymphoid
cells and the myeloid cells, which all derive from a
common stem cell in the bone marrow. In responding to infection, the immune
system starts with innate immune mechanisms that are fast, fixed in their mode
of action, and effective in stopping most infections at an early stage. The cells
and molecules of innate immunity identify common classes of pathogen and
destroy them. Four key elements of innate immunity are: pathogen receptors that
bind noncovalently to the surfaces of pathogens; proteins such as complement
that bond covalently to pathogen surfaces, forming ligands for receptors on
phagocytes; phagocytic cells that engulf and kill pathogens; and cytotoxic cells
that kill virus-infected cells. The defenses of adaptive immunity are brought into
play when innate immunity fails to stop an infection. Although slow to start, the
adaptive immune response eventually becomes powerful enough to terminate
almost all of the infections that outrun innate immunity. The mechanisms of
adaptive immunity
are ones that improve pathogen recognition rather than pathogen destruction.
They involve the T lymphocytes and B lymphocytes, which collectively have the
ability to recognize the vast array of potential pathogens. Adaptive immune
responses are initiated in specialized lymphoid tissues such as lymph nodes and
spleen, to which infections that elude innate immunity spread. In these
secondary lymphoid organs, small recirculating B lymphocytes and T
lymphocytes with receptors that bind to pathogens or their macromolecular
components are selected and activated. Because each individual B or T
lymphocyte expresses receptors of a single and unique binding type, a pathogen
stimulates only the small subset of lymphocytes that express receptors for the
pathogen, focusing the adaptive immune response on that pathogen. When
successful, an adaptive immune response terminates infection and provides long-
lasting protective immunity against the pathogen that provoked the response.
Failures to develop a successful response can arise from inherited
deficiencies in the immune system or from the pathogen’s ability to escape,
avoid, or subvert the immune response. Such failures can lead to debilitating
chronic infections or death. Adaptive immunity builds on the mechanisms of
innate immunity to provide a powerful response that is tailored to the pathogen
at hand and can be rapidly reactivated on future challenge with that same
pathogen, providing lifelong immunity to many common diseases. Adaptive
immunity is an evolving process within a person’s lifetime, in which each
infection changes the make-up of that individual’s lymphocyte population. These
changes are neither inherited nor passed on but, during the course of a lifetime,
they determine a person’s fitness and their susceptibility to disease.
Summary to Chapter 2
In confronting the microbial universe, the human body has several types of
defense, which must all be overcome if a pathogen is to establish an infection
and then exploit its human host for the rest of that unfortunate person’s life. First
and foremost are the protective epithelial tissues of the body—the skin and
mucosal surfaces—and their commensal microorganisms, which successfully
, prevent most pathogens from ever gaining entry to the rich resources of the
body’s interior. Any pathogen that successfully penetrates an epithelial surface is
immediately faced by the standing army of the innate immune response. These
troops are largely soluble peptides and proteins, which are made constitutively
and are present at mucosal surfaces or in the blood and
extracellular spaces. Families of antimicrobial peptides called defensins provide a
simple but effective mechanism for destroying some types of pathogen, but not
all. Much more elaborate is the complement system, which provides a general
means for tagging any pathogen with a molecular marker that ensures its
destruction by resident macrophages in the infected tissue. Pentraxins can
also consign pathogens to phagocyte-mediated destruction by simultaneously
binding to pathogens and to cell-surface receptors on phagocytes. Inhibiting the
pathogen’s progress in colonizing tissues and spreading infection are the
protease inhibitors, the blood-clotting cascade, and the kinin reactions. In total,
an army of plasma proteins and cell-surface molecules provide systems for
identifying microbiological invaders and distinguishing them from human cells.
These immediate defenses of innate immunity are always available and do not
improve with repeated exposure to the same pathogen.
Summary to Chapter 3
The macrophages resident in an infected tissue are responsible for orchestrating
the induced innate response to infection. They express a variety of cell-surface,
endosomal, and cytoplasmic receptors that recognize the distinctive chemical
properties of the sugars, fats, proteins and nucleic acids of pathogens. After an
infection has been detected, the macrophages secrete inflammatory
cytokines and chemokines that alter the permeability of local blood vessels and
actively recruit neutrophils, monocytes, and NK cells into the infected tissue from
the blood circulation. This activity creates a localized state of inflammation with
associated heat, pain, redness, and swelling. The inflammatory cytokines also
induce the acute-phase response, which changes the patterns of protein
synthesis in the liver, the source of many plasma proteins. The overall effect is to
increase the production of proteins contributing to innate immunity at the
expense of other proteins. One such protein whose concentration rises markedly
is C-reactive protein, which recognizes pathogens and initiates complement
fixation by the classical pathway. In extracellular infections, the powerful but
short-lived neutrophil is the major effector cell that kills the pathogens. Disposing
of the numerous neutrophils that die at sites of infection is another challenge
faced by the resident macrophages.
Almost all cell types respond to viral infections by secreting type I interferons.
This general cellular response is complemented by the plasmacytoid dendritic
cell, which is dedicated to making huge quantities of these cytokines. Type I
interferons activate NK cells to kill virus-infected cells, thereby preventing viral
replication and the spread of infection. Killing involves the formation of a
synapse between NK cells and the virus-infected target cells; this synapse is the
conduit through which lethal poisons are accurately delivered. NK cells form
similar synapses with resident macrophages that result in their mutual activation
and the secretion of interferon-γ by the NK cells. Most infections that recruit an
induced innate immune response are terminated by its powerful
defense mechanisms. The minority of infections that are not resolved at this
stage then call up the adaptive immune response. The interactions between the
NK cell and the dendritic cell are implicated in making this decision.
Summary to chapter 4.1
Throughout their evolutionary history, multicellular animals have been colonized
and infected by microorganisms. To restrict the nature, size, and location of
microbial infestation, animals have evolved a series of defenses, which humans
still use today. The skin and contiguous mucosal surfaces provide physical and
chemical barriers that confine microorganisms to the external surfaces of the
body. When pathogens manage to breach the barriers and gain entry to the soft
tissues, they are sought out and destroyed by the immune system. The cells of
the immune system are principally the various types of lymphocyte or lymphoid
cells and the myeloid cells, which all derive from a
common stem cell in the bone marrow. In responding to infection, the immune
system starts with innate immune mechanisms that are fast, fixed in their mode
of action, and effective in stopping most infections at an early stage. The cells
and molecules of innate immunity identify common classes of pathogen and
destroy them. Four key elements of innate immunity are: pathogen receptors that
bind noncovalently to the surfaces of pathogens; proteins such as complement
that bond covalently to pathogen surfaces, forming ligands for receptors on
phagocytes; phagocytic cells that engulf and kill pathogens; and cytotoxic cells
that kill virus-infected cells. The defenses of adaptive immunity are brought into
play when innate immunity fails to stop an infection. Although slow to start, the
adaptive immune response eventually becomes powerful enough to terminate
almost all of the infections that outrun innate immunity. The mechanisms of
adaptive immunity
are ones that improve pathogen recognition rather than pathogen destruction.
They involve the T lymphocytes and B lymphocytes, which collectively have the
ability to recognize the vast array of potential pathogens. Adaptive immune
responses are initiated in specialized lymphoid tissues such as lymph nodes and
spleen, to which infections that elude innate immunity spread. In these
secondary lymphoid organs, small recirculating B lymphocytes and T
lymphocytes with receptors that bind to pathogens or their macromolecular
components are selected and activated. Because each individual B or T
lymphocyte expresses receptors of a single and unique binding type, a pathogen
stimulates only the small subset of lymphocytes that express receptors for the
pathogen, focusing the adaptive immune response on that pathogen. When
successful, an adaptive immune response terminates infection and provides long-
lasting protective immunity against the pathogen that provoked the response.
Failures to develop a successful response can arise from inherited
deficiencies in the immune system or from the pathogen’s ability to escape,
avoid, or subvert the immune response. Such failures can lead to debilitating
chronic infections or death. Adaptive immunity builds on the mechanisms of
innate immunity to provide a powerful response that is tailored to the pathogen
at hand and can be rapidly reactivated on future challenge with that same
pathogen, providing lifelong immunity to many common diseases. Adaptive
immunity is an evolving process within a person’s lifetime, in which each
infection changes the make-up of that individual’s lymphocyte population. These
changes are neither inherited nor passed on but, during the course of a lifetime,
they determine a person’s fitness and their susceptibility to disease.
Summary to Chapter 2
In confronting the microbial universe, the human body has several types of
defense, which must all be overcome if a pathogen is to establish an infection
and then exploit its human host for the rest of that unfortunate person’s life. First
and foremost are the protective epithelial tissues of the body—the skin and
mucosal surfaces—and their commensal microorganisms, which successfully
, prevent most pathogens from ever gaining entry to the rich resources of the
body’s interior. Any pathogen that successfully penetrates an epithelial surface is
immediately faced by the standing army of the innate immune response. These
troops are largely soluble peptides and proteins, which are made constitutively
and are present at mucosal surfaces or in the blood and
extracellular spaces. Families of antimicrobial peptides called defensins provide a
simple but effective mechanism for destroying some types of pathogen, but not
all. Much more elaborate is the complement system, which provides a general
means for tagging any pathogen with a molecular marker that ensures its
destruction by resident macrophages in the infected tissue. Pentraxins can
also consign pathogens to phagocyte-mediated destruction by simultaneously
binding to pathogens and to cell-surface receptors on phagocytes. Inhibiting the
pathogen’s progress in colonizing tissues and spreading infection are the
protease inhibitors, the blood-clotting cascade, and the kinin reactions. In total,
an army of plasma proteins and cell-surface molecules provide systems for
identifying microbiological invaders and distinguishing them from human cells.
These immediate defenses of innate immunity are always available and do not
improve with repeated exposure to the same pathogen.
Summary to Chapter 3
The macrophages resident in an infected tissue are responsible for orchestrating
the induced innate response to infection. They express a variety of cell-surface,
endosomal, and cytoplasmic receptors that recognize the distinctive chemical
properties of the sugars, fats, proteins and nucleic acids of pathogens. After an
infection has been detected, the macrophages secrete inflammatory
cytokines and chemokines that alter the permeability of local blood vessels and
actively recruit neutrophils, monocytes, and NK cells into the infected tissue from
the blood circulation. This activity creates a localized state of inflammation with
associated heat, pain, redness, and swelling. The inflammatory cytokines also
induce the acute-phase response, which changes the patterns of protein
synthesis in the liver, the source of many plasma proteins. The overall effect is to
increase the production of proteins contributing to innate immunity at the
expense of other proteins. One such protein whose concentration rises markedly
is C-reactive protein, which recognizes pathogens and initiates complement
fixation by the classical pathway. In extracellular infections, the powerful but
short-lived neutrophil is the major effector cell that kills the pathogens. Disposing
of the numerous neutrophils that die at sites of infection is another challenge
faced by the resident macrophages.
Almost all cell types respond to viral infections by secreting type I interferons.
This general cellular response is complemented by the plasmacytoid dendritic
cell, which is dedicated to making huge quantities of these cytokines. Type I
interferons activate NK cells to kill virus-infected cells, thereby preventing viral
replication and the spread of infection. Killing involves the formation of a
synapse between NK cells and the virus-infected target cells; this synapse is the
conduit through which lethal poisons are accurately delivered. NK cells form
similar synapses with resident macrophages that result in their mutual activation
and the secretion of interferon-γ by the NK cells. Most infections that recruit an
induced innate immune response are terminated by its powerful
defense mechanisms. The minority of infections that are not resolved at this
stage then call up the adaptive immune response. The interactions between the
NK cell and the dendritic cell are implicated in making this decision.
Summary to chapter 4.1
