43 Flashcards
innate immunity
All animals have innate immunity, a defense that is active immediately upon infection and is the same whether or
not the pathogen has been encountered previously. Innate
immunity includes an outer covering, such as a skin or shell,
that provides a significant barrier to entry by microbes. Sealing off the entire body surface is impossible, however, because gas exchange, nutrition, and reproduction require
openings to the environment. Chemical secretions that trap
or kill microbes guard the body’s entrances and exits, while
the linings of the digestive tract, airway, and other exchange
surfaces provide additional barriers to infection
- In innate immunity, a small preset group of receptor proteins bind to molecules or structures that are absent from animal bodies but common to a group of viruses, bacteria, or
other microbes. Binding of an innate immune receptor to a
foreign molecule activates internal defenses, enabling responses to a very broad range of pathogens.
adaptive immunity
- A different type of molecular recognition provides the basis
for adaptive immunity, a defense found only in vertebrates. Animals with adaptive immunity produce a vast arsenal of receptors, each of which recognizes a feature typically
found only on a particular part of a particular molecule in a
particular pathogen. As a result, recognition and response in
adaptive immunity occur with tremendous specificity. - The adaptive immune response, also known as the acquired
immune response, is activated after the innate immune response and develops more slowly
innate immunity in insects
insects rely on their exoskeleton as a first line of defense against
infection. Composed largely of the polysaccharide chitin, the
exoskeleton provides an effective barrier defense against most
pathogens. A chitin-based barrier is also present in the insect
intestine, where it blocks infection by many pathogens ingested with food. Lysozyme, an enzyme that breaks down
bacterial cell walls, further protects the insect digestive system.
hemocytes
Any pathogen that breaches an insect’s barrier defenses encounters a number of internal immune defenses. Immune
cells called hemocytes travel throughout the body in the hemolymph, the insect circulatory fluid. Some hemocytes carry
out a defense called phagocytosis, the cellular ingestion
and digestion of bacteria and other foreign substances
antimicrobial peptides
- innate immunity in insects
- short chains of amino acids.
The antimicrobial peptides circulate throughout the body of
the insect (Figure 43.4) and inactivate or kill fungi and bacteria by disrupting their plasma membranes. - the synthesis of a single type of antimicrobial
peptide in the fly’s body could provide an effective immune
defense. They also showed that particular antimicrobial peptides act against different kinds of pathogens.
Immune cells of insects
bind to molecules found only in
the outer layers of fungi or bacteria. Fungal cell walls contain
certain unique polysaccharides, whereas bacterial cell walls
have polymers containing combinations of sugars and amino acids not found in animal cells. Such macromolecules serve
as identity tags in the process of pathogen recognition. Insect
immune cells secrete specialized recognition proteins, each of
which binds to a macromolecule characteristic of fungi or a
broad class of bacteria.
barrier defenses in mammals
- In mammals, epithelial tissues block the entry of many
pathogens. These barrier defenses include not only the skin
but also the mucous membranes lining the digestive, respiratory, urinary, and reproductive tracts. Certain cells of the
mucous membranes produce mucus, a viscous fluid that enhances defenses by trapping microbes and other particles. In
the trachea, ciliated epithelial cells sweep mucus and any entrapped microbes upward, helping prevent infection of the
lungs. Saliva, tears, and mucous secretions that bathe various
exposed epithelia provide a washing action that also inhibits
colonization by fungi and bacteria. - Lysozyme in tears, saliva, and mucous secretions destroys the cell walls of susceptible bacteria as they
enter the openings around the eyes or the upper respiratory
tract. (First, gases produced in the lysosome poison the engulfed pathogens. Second, lysozyme and
other enzymes in the lysosome degrade the components of
the pathogens.) - Microbes in food or water and those in swallowed
mucus must also contend with the acidic environment of the
stomach, which kills most of them before they can enter the
intestines. Similarly, secretions from oil and sweat glands
give human skin a pH ranging from 3 to 5, acidic enough to
prevent the growth of many bacteria.
TLR
- Pathogens entering the mammalian body are subject to
phagocytosis. Phagocytic cells detect fungal or bacterial components using several types of receptors, some of which are
very similar to the Toll receptor of insects. Each mammalian
Toll-like receptor (TLR) binds to fragments of molecules
characteristic of a set of pathogens - In each case, the recognized macromolecule
is normally absent from the vertebrate body and is an essential component of certain groups of pathogens.
main types of phagocytic cells
The two main types of phagocytic cells in the mammalian
body are neutrophils and macrophages. Neutrophils, which
circulate in the blood, are attracted by signals from infected
tissues and then engulf and destroy the infecting pathogens.
Macrophages (“big eaters”), like the one shown in
Figure 43.1, are larger phagocytic cells. Some migrate throughout the body, whereas others reside permanently in organs
and tissues where they are likely to encounter pathogens.
other phagocytic cells
Two other types of phagocytic cells—dendritic cells and
eosinophils—provide additional functions in innate defense.
Dendritic cells mainly populate tissues, such as skin, that
contact the environment. They stimulate adaptive immunity against pathogens they encounter and engulf, as we’ll explore shortly. Eosinophils, often found beneath mucosal surfaces, have low phagocytic activity but are important in
defending against multicellular invaders, such as parasitic
worms. Upon encountering such parasites, eosinophils discharge destructive enzymes.
natural killer cells
Cellular innate defenses in vertebrates also involve natural
killer cells. These cells circulate through the body and detect
the abnormal array of surface proteins characteristic of some
virus-infected and cancerous cells. Natural killer cells do not engulf stricken cells. Instead, they release chemicals that lead to
cell death, inhibiting further spread of the virus or cancer.
lymphatic system
Many cellular innate defenses of vertebrates involve the
lymphatic system, a network that distributes the fluid called
lymph throughout the body (Figure 43.7). Some macrophages
reside in the structures called lymph nodes, where they engulf
pathogens that have flowed from the interstitial fluid into the
lymph. Dendritic cells reside outside the lymphatic system but
migrate to lymph nodes after interaction with pathogens.
Within the lymph nodes, dendritic cells interact with other
immune cells, stimulating adaptive immunity.
antimicrobial peptides in mammals
In mammals, pathogen recognition triggers the production
and release of a variety of peptides and proteins that attack pathogens or impede their reproduction. Some of these defense molecules function like the antimicrobial peptides of
insects, damaging broad groups of pathogens by disrupting
membrane integrity. Others, including the interferons and
complement proteins, are unique to vertebrate immune
systems
interferons
Interferons are proteins that provide innate defense by
interfering with viral infections. Virus-infected body cells secrete interferons, which induce nearby uninfected cells to
produce substances that inhibit viral reproduction. In this
way, interferons limit the cell-to-cell spread of viruses in the
body, helping control viral infections such as colds and influenza. Some white blood cells secrete a different type of interferon that helps activate macrophages, enhancing their
phagocytic ability.
complement system
- The infection-fighting complement system consists of
roughly 30 proteins in blood plasma. These proteins circulate
in an inactive state and are activated by substances on the
surface of many microbes. Activation results in a cascade of
biochemical reactions that can lead to lysis (bursting) of invading cells - also functions in inflammatory response and other adaptive defenses
inflammatory response
The pain and swelling that alert you to a splinter under your
skin are the result of a local inflammatory response, the
changes brought about by signaling molecules released upon
injury or infection
histamine
One important inflammatory signaling molecule is histamine, which is stored in the
granules (vesicles) of mast cells, found in connective tissue.
Histamine released at sites of damage triggers nearby blood
vessels to dilate and become more permeable.
cytokines
Activated
macrophages and neutrophils discharge cytokines, signaling
molecules that enhance an immune response. These cytokines
promote blood flow to the site of injury or infection. The increase in local blood supply causes the redness and increased
skin temperature typical of the inflammatory response. Blood-engorged capillaries
leak fluid into neighboring tissues, causing swelling.
pus
During inflammation, cycles of signaling and response
transform the site. Activated complement proteins promote
further release of histamine, attracting more phagocytic cells
that enter injured tissues (see Figure 43.8) and carry out additional phagocytosis. At the same time, enhanced blood flow
to the site helps deliver antimicrobial peptides. The result is
an accumulation of pus, a fluid rich in white blood cells, dead
pathogens, and cell debris from damaged tissue.
fever
Another systemic inflammatory response is fever. In response to certain pathogens, substances released by activated
macrophages cause the body’s thermostat to reset to a higher
temperature (see Chapter 40). The benefits of the resulting
fever are still a subject of debate. One of several competing
hypotheses is that an elevated body temperature may enhance phagocytosis and, by speeding up chemical reactions,
accelerate tissue repair.
septic shock
Certain bacterial infections can induce an overwhelming
systemic inflammatory response, leading to a life-threatening
condition called septic shock. Characterized by very high fever,
low blood pressure, and poor blood flow through capillaries,
septic shock occurs most often in the very old and the very
young.
Evasion of Innate Immunity by Pathogens
- For example,
the outer capsule that surrounds certain bacteria interferes
with molecular recognition and phagocytosis - Some bacteria, after being engulfed by a host
cell, resist breakdown within lysosomes. An example is the
bacterium that causes tuberculosis (TB).
lymphocytes
Vertebrates are unique in having adaptive immunity in addition to innate immunity. The adaptive response relies on T cells and B cells, which are types of white blood cells called lymphocytes
lymphocytes location
Like all
blood cells, lymphocytes originate from stem cells in the bone marrow. Some lymphocytes
migrate from the bone marrow to the thymus, an organ in the
thoracic cavity above the heart (see Figure 43.7). These lymphocytes mature into T cells. Lymphocytes that remain and mature in the bone marrow develop as B cells. (Lymphocytes of a
third type remain in the blood and become the natural killer
cells active in innate immunity.)
antigen
Any substance that elicits a response from a B cell or T cell is
called an antigen.
- Antigens are usually foreign and are typically large molecules, either proteins or polysaccharides. Many antigens protrude from the surface of foreign cells or viruses. Other
antigens, such as toxins secreted by bacteria, are released into
the extracellular fluid.
antigen receptors
In adaptive immunity, recognition occurs
when a B cell or T cell binds to an antigen, such as a bacterial
or viral protein, via a protein called an antigen receptor. An
antigen receptor is specific enough to bind to just one part of
one molecule from a particular pathogen, such as a species of
bacteria or strain of virus.
- Although the cells of the immune system produce millions of different antigen receptors, all of
the antigen receptors made by a single B or T cell are identical.
- Infection by a virus, bacterium, or other pathogen triggers activation of B and T cells with antigen receptors specific for parts
of that pathogen.
- there are actually about 100,000 antigen
receptors on the surface of a single B or T cell.
epitope
The small, accessible portion of an antigen that binds to
an antigen receptor is called an epitope, or antigenic determinant. An example is a group of amino acids in a particular
protein. A single antigen usually has several different epitopes, each binding a receptor with a different specificity. Because all antigen receptors produced by a single B cell or T
cell are identical, they bind to the same epitope. Each B cell
or T cell thus displays specificity for a particular epitope, enabling it to respond to any pathogen that produces molecules
containing that same epitope.
- Many noncovalent bonds between
an epitope and the binding surface provide a stable and specific interaction. Differences in the amino acid sequences of
variable regions provide the variation in binding surfaces
that enables this highly specific binding.
B cell antigen receptor structure
Each B cell antigen receptor is a Y-shaped molecule consisting
of four polypeptide chains: two identical heavy chains and
two identical light chains, with disulfide bridges linking
the chains together (Figure 43.9). A transmembrane region
near one end of each heavy chain anchors the receptor in the
cell’s plasma membrane. A short tail region at the end of the
heavy chain extends into the cytoplasm.
- each
B cell antigen receptor has two identical antigen-binding sites
B cell: C region
The light and heavy chains each have a constant (C) region,
where amino acid sequences vary little among the receptors
on different B cells. The C region includes the cytoplasmic
tail and transmembrane region of the heavy chain and all of
the disulfide bridges.
B cell: V region
Within the two tips of the Y shape, the
light and heavy chains each have a variable (V) region, so
named because its amino acid sequence varies extensively
from one B cell to another. Together, parts of a heavy-chain
V region and a light-chain V region form an asymmetrical
binding site for an antigen.
antibody/Ig
The binding of a B cell antigen receptor to an antigen is
an early step in B cell activation, leading eventually to formation of cells that secrete a soluble form of the receptor
(Figure 43.10a). This secreted protein is called an antibody, or immunoglobulin (Ig). Antibodies have the same
Y-shaped organization as B cell antigen receptors, but they
are secreted rather than membrane bound. It is the antibodies, rather than the B cells themselves, that actually help defend against pathogens.
T cell structure
For a T cell, the antigen receptor consists of two different
polypeptide chains, an a chain and a b chain, linked by a
disulfide bridge (Figure 43.11). Near the base of the T cell
antigen receptor (often called simply a T cell receptor) is a
transmembrane region that anchors the molecule in the cell’s
plasma membrane. At the outer tip of the molecule, the
variable (V) regions of α and β chains together form a single
antigen-binding site. The remainder of the molecule is made
up of the constant (C) regions
T vs B cell antigen receptors
Whereas the antigen receptors of B cells bind to
epitopes of intact antigens circulating in body fluids, those of T cells bind only to fragments of antigens that are displayed,
or presented, on the surface of host cells. The host protein that
displays the antigen fragment on the cell surface is called an
MHC (major histocompatibility complex) molecule
Recognition of protein antigens by T cells
begins when a
pathogen or part of a pathogen either infects or is taken in by
a host cell (Figure 43.12a). Inside the host cell, enzymes in
the cell cleave the antigen into smaller peptides. Each peptide, called an antigen fragment, then binds to an MHC molecule inside the cell. Movement of the MHC molecule and
bound antigen fragment to the cell surface results in
antigen presentation, the display of the antigen fragment
in an exposed groove of the MHC protein.
- If the cell displaying an antigen fragment encounters
a T cell with the right specificity, the antigen receptor on the
T cell can bind to both the antigen fragment and the MHC
molecule. This interaction of an MHC molecule, an antigen
fragment, and an antigen receptor is necessary for a T cell to
participate in an adaptive immune response
four major characteristics of adaptive immunity
First, there is an immense diversity of lymphocytes
and receptors, enabling the immune system to detect
pathogens never before encountered. Second, adaptive immunity normally has self-tolerance, the lack of reactivity
against an animal’s own molecules and cells. Third, cell proliferation triggered by activation greatly increases the number of B and T cells specific for an antigen. Fourth, there is a
stronger and more rapid response to an antigen encountered
previously, due to a feature known as immunological memory.
gene segments coding for the chains
The capacity to generate diversity is built into the structure of Ig genes. A receptor light chain is encoded by three
gene segments: a variable (V) segment, a joining ( J) segment, and a constant (C) segment. The V and J segments together encode the variable region of the receptor chain,
while the C segment encodes the constant region. The lightchain gene contains a single C segment, 40 different V segments, and 5 different J segments. These alternative copies
of the V and J segments are arranged within the gene in a series (Figure 43.13). Because a functional gene is built
from one copy of each type of segment, the pieces can be
combined in 200 different ways (40 V 5 J 1 C). The
number of different heavy-chain combinations is even
greater, resulting in even more diversity.
recombinase
Assembling a functional Ig gene requires rearranging the
DNA. Early in B cell development, an enzyme complex called
recombinase links one light-chain V gene segment to one J gene
segment. This recombination event eliminates the long stretch
of DNA between the segments, forming a single exon that is
part V and part J. Because there is only an intron between the J
and C DNA segments, no further DNA rearrangement is required. Instead, the J and C segments of the RNA transcript will
be joined when splicing removes the intervening RNA (see
Figure 17.11 to review RNA splicing).
Recombinase acts randomly, linking any one of the 40 V
gene segments to any one of the 5 J gene segments. Heavychain genes undergo a similar rearrangement. In any given
cell, however, only one allele of a light-chain gene and one
allele of a heavy-chain gene are rearranged
formation of antigen receptr
After both the light- and heavy-chain genes have rearranged, antigen receptors can be synthesized. The rearranged
genes are transcribed, and the transcripts are processed for
translation. Following translation, the light chain and heavy chain assemble together, forming an antigen receptor (see
Figure 43.13). Each pair of randomly rearranged heavy and
light chains results in a different antigen-binding site
self tolerance
as
lymphocytes mature in the bone marrow or thymus, their
antigen receptors are tested for self-reactivity. Some B and
T cells with receptors specific for the body’s own molecules
are destroyed by apoptosis, which is a programmed cell death
(see Chapter 11). The remaining self-reactive lymphocytes
are typically rendered nonfunctional, leaving only those that
react to foreign molecules. Since the body normally lacks mature lymphocytes that can react against its own components,
the immune system is said to exhibit self-tolerance.
