Chapter 43 The Immune System
Recognition & Response
 Pathogens, agents (virus, bacteria, fungi) that cause disease, infect lots of animals. For them, the
internal environment of the host animal is an ideal habitat.
o Animal body offers ready source of nutrients, protected setting for growth & reproduction
& means of transport to new environments
 Immune system- enables animal to avoid or limit many infections
2. Innate immunity- defense that’s active immediately
upon infection & is the same whether or not the
pathogen has been encountered previously
o Ex: outer covering that provides a significant
barrier to entry by microbes
 But sealing off entire body surface is
impossible because gas exchange,
nutrition & reproduction require
openings to the environment
o Ex: chemical secretion that trap or kill
microbes guard the body’s entrances & exits
o Ex: Linings of the digestive tract, airway, &
other exchange surfaces
 If a pathogen breaks through barrier defenses and
enters the body, an animal’s immune system must
detect foreign particles & cells within the body to fight
infections; a properly functioning immune system
distinguishes nonself from self
o Molecular recognition- receptor molecules bind specifically to molecules from foreign
cells or viruses; accomplishes detection of nonself
 A small preset group of receptor proteins bind to molecules that are absent from animal bodies but
present in antibodies. Binding of an innate immune receptor to a foreign molecule activates
internal defenses
1. Adaptive (acquired) immunity- a type of molecular recognition only found in vertebrates;
produce lots of receptors, each of which recognize a feature typically found only on a particular
part of a particular molecule in a particular pathogen, so recognition & response occur with
specificity
o Ex: synthesis of proteins that inactivate a bacterial toxin
o Ex: targeted killing of a virus-infected cell body
 Activated after the innate immune response & develops more slowly
 It is enhanced by previous exposure to the infecting pathogen
43.1 In Innate Immunity, Recognition & Response Rely on Traits Common to Groups of Pathogens
Innate Immunity of Invertebrates
 Insects in terrestrial & freshwater habitats filled with diverse microbes shows the effectiveness of
invertebrate innate immunity, as insects rely on their exoskeleton as a fist line of defense against
infection
o The exoskeleton is composed of the polysaccharide chitin & provides an effective barrier
defense against most pathogens.
a. Chitin-based barrier is also in insect’s intestine, where it blocks infection by many
pathogens ingested with food
i.
Lysozyme- enzyme that breaks down bacterial cell walls; also protects
insect digestive system
 If a pathogen breaches an insect’s barrier defenses, it encounters many internal immune defenses
o
Hemocytes are immune
o
Hemocytes, immune cells, travel throughout the body in the hemolymph (insect
circulatory fluid)
a. Some hemocytes carry out phagocytosis, a defense in which the cellular ingestion
& digestion of foreign substance (i.e. bacteria)
b. Other hemocytes trigger the production of chemicals that kill pathogens and help
entrap large parasites (i.e. Plasmodium, the parasite of mosquitoes that causes
malaria)
c. Encounters with pathogens in hemolymph causes hemocytes & certain other cells
to secrete antimicrobial peptides, short chains of amino acids that circulate
throughout the body of the insect & inactivate or kill fungi & bacteria by
disrupting their plasma membrane
 Immune cells of insects, which are not found in animal cells, bind to molecules
found only in outer layers of fungi or bacteria
o Fungal cell walls contain certain unique polysaccharides & bacterial cell
walls have polymers containing combos of sugars & amino acids
 These macromolecules serve as identity tags for pathogen
recognition
 Insect immune cells secrete specialized recognition proteins,
each of which binds to a macromolecule characteristic of fungi
or bacteria
 Innate immune responses are distinct for different classes of pathogens
a. Ex: when fungus Nerosporar craesa infects a fruit fly, pieces of the fungal cell wall bind to
a recognition protein. This complex activates the protein Toll, a receptor on the surface of
hemocytes
i.
Signal transduction from the Toll receptor to the cell nucleus leads to synthesis of
a set of antimicrobial peptides active against fungi
b. Ex: if fruit fly is infected by bacterium Microoccus luteus, a different recognition protein’s
activated, & the fly produces a different set of antimicrobial peptides
c. It’s hard to pinpoint and target the activity of a specific peptide because fruit flies secrete
many distinct antimicrobial peptides in response to a single infection
i.
Modern genetic techniques to reprogram the fly immune system helped discover
that the synthesis of a single type of antimicrobial peptide in the fly’s body could
provide an effective immune defense
i. Brybi Kenautre began with a mutant fly strain in which pathogens are
recognized but the signaling that would normally trigger innate immune
response is blocked. So, the mutant flies don’t make any antimicrobial
peptides.
ii. Then, they genetically modified some of the mutant flies to express lots of
a single antimicrobial peptide.
iii. They infected the flies with Neurospora crassa and monitored survival
over 5 days. They repeated with micrococcuss tuteus
iv. Conclusion: each of the 2 antimicrobial peptides provided a protective
immune response. The different peptides defended against different
pathogens.
Innate Immunity of Vertebrates
 Innate defenses that are common in both vertebrates & invertebrates are barrier defenses,
phagocytosis, & antimicrobial peptides.
 Innate defenses unique to vertebrates only are natural killer cells, interferons, & the inflammatory
response
Barrier Defenses
 In mammals, epithelial tissues block the entry of many pathogens. They include skin and the
mucous membranes lining the digestive, respiratory, urinary, & reproductive tracts
 Certain cells of the mucous membranes produce mucus, a viscous (hard to flow) fluid that
enhances defenses by trapping microbes & other particles.
o In the trachea, ciliated epithelial cells sweep mucus & any entrapped microbes, upward,
helping prevent infection of the lungs
 Saliva, tears, & mucous secretions that bathe various exposed epithelia provide a washing action
that inhibits colonization by fungi & bacteria
 Body secretions also provide an environment that’s hostile to many microbes.
o Lysozyme in tears, saliva, & mucous secretions destroys the cell walls of susceptible
bacteria as they enter the openings around eyes or upper respiratory tract
o Microbes in food or water & those swallowed in mucus contend with the acidic
environment of the stomach, which kills most of them before they can enter the intestines
o Secretions from oil & sweat glands give human skin a pH ranging from 3 – 5, acidic
enough to prevent bacteria growth
Cellular Innate Defenses
 Pathogens entering the mammalian body are subject
to phagocytosis.
 Phagocytic cells detect fungal or bacterial
components, using several types of receptors. Each
Toll-like receptor (TLR) binds to fragments of
molecules characteristic of a set of pathogens. The
recognized macromolecule is normally absent from
the vertebrate body & is an essential component of
certain groups of pathogens
o Ex: TLR3 (located on the inner surface of
vesicles formed by endocytosis) is the
sensor for double-stranded RNA (form of
nucleic acid common in certain viruses)
o Ex: TLR 4 (located on immune cell plasma
membranes) recognizes lipopolysaccharide,
a type of molecule found on the surface of
many bacteria
o Ex: TLR5 recoginzes flagellin, the main
protein of bacterial flagella
 After detecting invading pathogens, a phagocytic
cell engulfs them, trapping them in a vacuole. The vacuole then fuses with a Lysozyme, leading to
destruction of the invaders. It can destruct in two different ways:
1. Gases produced in Lysozyme poison the engulfed pathogens
2. Lysozyme & other enzymes in the lysosome degrade the components of the pathogens
 The main types of phagocytic cells in the mammalian body are:
1. Neutrophils- circulate in blood; are attracted to signals from infected tissues & then
engulf & destroy the infecting pathogens
2. Macrophages (big eaters)- large phagocytic cells; some migrate throughout the body,
some reside permanently in organs & tissues where they’re likely to encounter pathogens
 There are two other types of phagocytic cells that provide additional functions in innate defense:
1. Dendritic cells- stimulate adaptive immunity against pathogens they encounter & engulf;
populate tissues (i.e. skin) that contact the environment
2. Eosinophils- have low phagocytic activity but are important in defending against
multicellular invaders (i.e. parasitic worms); found beneath mucosal surfaces;
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Natural killer cells circulate through the body & detect the abnormal array of surface proteins
characteristic of some virus-infected & cancerous cells. They DO NOT engulf stricken cells.
Instead, they release chemicals that lead to cell death, inhibiting further spread of the virus or
cancer
Many cellular innate defenses of vertebrates involve the lymphatic system, a network that
distributes the fluid, lymph, throughout the body.
o Some macrophages reside in lymph nodes, where they engulf pathogen that have flowed
from the interstitial fluid into the lymph
o Dendritic cells reside outside the lymphatic system but migrate to lymph nodes after
interaction with pathogens
 Within lymph nodes, dendritic cells interact with other immune cells, stimulating
adaptive immunity
Antimicrobial Peptides & Proteins
 In mammals, pathogen recognition triggers the production & release of a variety of peptides &
proteins that attack pathogens or impede their production.
o Some of these defense molecules damage broad groups of pathogens by disrupting
membrane integrity. These are common in invertebrates too.
o Others (i.e. interferons & complement proteins) are unique to vertebrate immune systems
I. Interferons- proteins that provide innate defense by interfering with viral infections.
o 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 (i.e. colds & influenza)
o some white blood cells secrete a different type of interferon that helps activate
macrophages, enhancing their phagocytic ability
II. complement system- infection fighting system that consists of ~30 proteins in the blood plasma
aaaaawhich circulate in an inactive state & are activated by substances on the surface of microbes
o
Activation results in a cascade of biochemical reactions that can lead to lysis of invading
cells
o Also functions in inflammatory response & adaptive defenses
Inflammatory Response
 Inflammatory response- changes brought about by signaling molecules released upon injury or
infection that result in the pain & swelling in the local area where the injury occurred
 Histamine- an important inflammatory signaling molecule, which is stored in granules (vesicles)
of mast cells, found in connective tissue.
o Histamine released at sites of damage triggers nearby blood vessels to dilate & become
more permeable (“leaky capillaries”) so that fluid containing antimicrobial peptides can
more easily enter the tissue
 cytokines- signaling molecules that are discharged from activated macrophages & neutrophils &
enhance the immune response by promoting blood flow to the site of injury.
o The increase in local blood supply causes the redness & increased skin temperature
 Blood-engorged capillaries leak fluid into neighboring tissues, causing swelling
 During inflammation, cycles of signaling & response transform the site
o Activated complement proteins promote further release of histamine, attracting more
phagocytic cells that enter injured tissues & carry out additional phagocytosis
o Simultaneously, enhanced blood flow to the site helps deliver antimicrobial peptides. This
results in an accumulation of pus, a fluid rich in white blood cells, dead pathogens, & cell
debris from damaged tissues
 A minor injury causes a local inflammatory response, but severe tissue damage may lead to a
systemic response
o Cells in injured tissue often secrete molecules that stimulate the release of additional
neutrophils from the bone marrow.
 Fever is another systemic response. In response to certain pathogens, substances released by
activated macrophages cause the body’s thermostat to reset to a higher temperature
o Benefits of elevated body temperature caused by fever: enhanced phagocytosis, speeding
up of chemical reactions, & accelerated tissue repair
 Certain bacterial infections can induce an overwhelming systemic inflammatory response, leading
to septic shock, a life-threatening condition characterized by very high fever, low blood pressure,
& poor blood flow through capillaries
Evasion of Innate Immunity by Pathogens
 Adaptations have evolved in some pathogens that enable them to avoid destruction by phagocytic
cells
o
Ex: streptococcus pneumoniaie, which helped the discovery that DNA can convey genetic
info
 Some bacteria, after being engulfed by a host cell, resist breakdown within lysosomes
o Ex: bacteria that causes tuberculosis. Rather than being destroyed within host cells, they
grow & reproduce, effectively hidden from the body’s innate immune defenses
43.2 In Adaptive Immunity, Receptors Provide Pathogen-Specific Recognition
 Only vertebrates have adaptive immunity, which relies on T and B cells, which are types of white
blood cells, lymphocytes, which originate in the bone marrow.
 Some lymphocytes migrate from the bone marrow to the thymus, an organ in the thoracic cavity
above the heart. They mature to T cells
 Lymphocytes that remain & mature in the bone marrow develop as B cells.
 Some lymphocytes remain in the blood & become natural killer cells active in innate immunity
 Antigen- any substance that elicits a response from a B or T cell
 Recognition occurs when a B or T cell binds to an antigen via a protein called an antigen
receptor, which is specific enough to bind to just one part of one molecule from a particular
pathogen
 All of the antigen receptors made by a single B or T cell are identical.
 Infection by a pathogen triggers activation of B & T cells with antigen receptors specific for parts
of that antigen.
 Antigens are foreign & are large macromolecules (i.e. proteins or polysaccharides)
o Many antigens protrude from the surface of foreign pathogens
o Other antigens (i.e. toxins secreted by bacteria) are released into extracellular fluid
 Epitope (antigenic determinant)- small, accessible portion of antigen that binds to an antigen
receptor
o Ex: a group of amino acids in a particular protein
 A single antigen usually has many different epitopes, each binding a receptor with a different
specificity
 Each B or T cell displays specificity for a particular epitope, enabling it to respond to any
pathogen that produces molecules containing the same epitope
Antigen Recognition by B Cells & Antibodies
 Each B cell antigen receptor is a Y-shaped
molecule consisting of 2 polypeptide chains: 2
identical heavy chains & 2 identical light
chains, with disulfide bridges linking the
chains together
 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
 The light & heavy chains each have a constant
(C) region where amino acid sequences vary
little among receptors of different B cells. The
C region includes the cytoplasmic tail &
transmembrane region of the heavy chain & all
of the disulfide bridges.
 Within the 2 tips of the Y shape, the light & heavy chains each have a variable (V) region, which
has amino acid sequence variation 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. Each B cell antigen receptor has two identical antigen-binding sites
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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 an antibody or immunoglobulin (Ig), a soluble,
protein form of the receptor
Antibodies have the same Y-shaped receptor as B cell antigen receptors, but they’re secreted, not
membrane bound
It is the antibodies, not the B cells themselves, that help defend against pathogens
The antigen-binding site of a membrane-bound receptor or antibody has a unique shape that
provides a lock-and-key fit for a particular epitope
Many noncovalent bonds between an epitope & the binding surface provide a stable & specific
interaction
Differences in amino acid sequences of V regions provide the variation in binding surfaces that
enables this highly specific binding
B cell antigen receptors & antibodies bind to intact antigens in the blood & lymph
Antibodies can bind to antigens on the surface of pathogens or free in body fluids
Antigen Recognition by T Cells

Structure of T cell antigen receptor:
o has 2 different polypeptide chains, an α and a
ϐ chain, linked by a disulfide bridge.
o Near the base is a transmembrane region that
anchors the molecule in the cell’s plasma
membrane.
o At the outer tip of the molecule, the V
regions of the chains together form a single
antigen-binding site.
o The remainder is made up of C regions.
B Cell antigen receptors
T cell antigen receptors
 Bind to epitopes of intact antigens circulating  Bind only to fragments of antigens that are
in body fluids
displayed/ presented on the surface of host cells
 Major histocompatibility complex (MHC) molecule- host protein that displays the antigen
fragment on the cell surface
Steps of recognition of protein antigens by T cells
1. Pathogen infects host cell or is taken in by the host cell
2. Inside the host cell, enzymes in the cell cleave the antigen into small peptides, called antigen
fragments
3. Each antigen fragment binds to an MHC molecule inside the cell
4. MHC molecule & bound antigen fragment moves to cell surface, resulting in antigen
aaaapresentation, the presentation of the antigen fragment in an exposed groove of the MHC protein
 Antigen presentation advertises the fact that a host cell contains a foreign substance
5. 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 the antigen fragment & the MHC molecule
 This interaction of an MHC molecule, an antigen fragment, & an antigen receptor is necessary
for a T cell to participate in an adaptive immune response
B Cell & T Cell Development – Four Major Characteristics of adaptive immunity
1. There’s an immense diversity of lymphocytes & receptors, enabling the immune system to detect
pathogens never before encountered
2. Adaptive immunity normally has self-tolerance, & the lack of reactivity against one’s own
molecules & cells
3. Cell proliferation triggered by activation greatly increases the number of B & T cells specific for
an antigen
4. There’s a stronger & more rapid response to an antigen encountered previously due to
immunological memory
 Receptor diversity & self-tolerance arises as a lymphocyte matures
 Proliferation of cells & the formation of immunological memory occurs later, after a mature
lymphocyte encounters & binds to a specific antigen
I. Generation of B & T Cell Diversity
 We can generate such a remarkable diversity in antigen receptors despite the fact that there are
only ~20,000 protein-coding genes because of combinations. By combining variable elements, the
immune system assembles any different receptors from a much smaller collection of parts
 to understand the origin of receptor diversity, consider an immunoglobulin (Ig) gene that codes for
light-chain of both secreted antibodies & membrane-bound B cell antigen receptors (this process is
also very similar for all B & T cell antigen receptor genes)
 the structure of the Ig genes allows the capacity to generate diversity. A receptor light chain is
encoded by 3 gene segments: a V segment, a joining (J) segment, and a C segment.
o The V & J segments together encode the V region of the receptor chain.
o The light-chain gene contains 1 C segment, 40 different V segments, & 5 different J
segments
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These alternative copies of V & J segments are arranged within the gene in a series
 Because a functional gene’s built from 1 copy of each type of segment, the pieces
can be combined in 200 different ways
Assembling a functional Ig gene requires rearranging the DNA
o Recombinase links one light-chain V gene segment to one J gene segment in early B cell
development
 This recombination eliminates the long stretch of DNA between the segments
(intron), forming a single exon that's part V & part J
o The J & C segments of the RNA transcript will be joined when splicing removes the
intervening RNA
Recombinase acts randomly, linking any one of the 40 V gene segments to any one of the 5 J
segments.
o In any given cell, only 1 allele of a light-chain gene & 1 allele of a heavy-chain gene are
rearranged
o The rearrangements are permanent & are passed on to the daughter cells when the
lymphocyte divides
After both the light & heavy chain genes have rearranged, antigen receptors can be synthesized.
o The rearranged genes are transcribed, & are processed for translation.
o After translation, the light & heavy chains assemble together, forming an antigen receptor
 Each pair of randomly rearrange heavy & light chains results in a different
antigen-binding site
II. Origin of Self-Tolerance
 Adaptive immunity distinguishes self from nonself
 Because antigen receptor genes are randomly rearranged, some immature lymphocytes produce
receptors specific for epitopes on organism’s own molecules, but they are eliminated or
inactivated. If they were not eliminated, the immune system would not be able to distinguish self
from nonself & begin attacking its own proteins, cells, & tissues
 As lymphocytes mature in the bone marrow or thymus, their antigen receptors are tested for
body’s own molecules & are destroyed by apoptosis
 The remaining self-reactive lymphocytes are made nonfunctional, leaving only the lymphocytes
that react to foreign molecules.
 Since the body normally lacks mature lymphocytes that can react against its own components, the
immune system exhibits self-tolerance
III. Proliferation of B & T Cells
III. Proliferation of a Lymphocyte into a Clone of Cells in Response to Binding an Antigen
1. An antigen is presented to a steady stream of lymphocytes in the lymph nodes until a match is
made
 Clonal selection- an encounter with an antigen selects which lymphocyte will divide to
produce a clonal population of thousands of cells specific for a particular epitope
2. A successful match triggers changes in cell number & activity for the lymphocyte to which the
antigen has bound to
3. The binding of an antigen receptor to an epitope initiates events that activate the lymphocyte.
Once activated, a B or T cell undergoes many cell divisions, resulting in clones
4. The clone cells differentiate
a. Some become effector cells, which are short-lived cells that take effect immediately
against the antigen & any pathogens producing that antigen.
i. B cell effector cells are plasma B cells, which secrete antibodies
ii. T cell effector cells are helper T cells & cytotoxic T cells
b. The remaining clone cells differentiate into memory cells, long lived cells that can give
rise to effector cells if the same antigen’s encountered again
 Ex: B cell clonal proliferation into a clone cell in response to binding to an antigen. In response to
a specific antigen & to immune cell signals, one B cell divides & forms a clone of cells. (The
remaining B cells, whose antigen receptors are not specific to the particular antigen don’t
respond.) The clone of cells formed by the selected B cell gives rise to memory B cells &
antibody-secreting plasma cells.
1. Antigens bind to the antigen receptors of only one specific B cell, whose antigen receptor
matches the particular epitope
2. The selected B cell proliferates, forming a clone of identical cells bearing receptors for the
antigen
3. Some daughter cells develop into long-lived memory cells that can respond rapidly upon
subsequent exposure to the same antigen, while other daughter cells develop into short-lived
plasma cells that secrete antibodies for the antigen
IV. Immunological Memory
 Immunological memory’s responsible for the long-term protection that a prior infection or
vaccination provides against many diseases
 Prior exposure to an antigen alters the speed, strength, & duration of the immune response
 Primary immune response- production of effector
cells from a clone of lymphocytes during the first
time exposure to an antigen
o Peaks ~10 – 17 days after the initial
exposure. During this time, selected B & T
cells give rise to their effector forms
 Secondary immune response- if an individual is
exposed again to the same antigen, the response is
faster (peaks 2 – 7 days after exposure), of greater
magnitude, & more prolonged
o Because selected B cells give rise to antibody secreting effector cells, measuring the
concentrations of specific antibodies in blood
over time distinguishes the 1st & 2nd immune
responses
43.3 Adaptive Immunity Defends Against Infection of
Body Fluids & Body Cells
 This section discusses how lymphocytes help fight infections & minimize damage by pathogens
Both
Humoral immune response
Cell mediated immune
Include a primary & secondary
response
 occurs in blood & lymph;
 specialized T cells destroy
antibodies help neutralize or immune response (which is
enabled with memory cells)
eliminate toxins &
infected host cells
pathogens in the blood &
lymph
 produced by activity of B
lymphocytes
Helper T Cells: A Response to Nearly All Antigens
 Helper T cell- triggers both humoral & cell-mediated immune responses; they themselves don’t
carry out those responses; rather, they send signals that initiate production of antibodies that
neutralize pathogens & activate T cells that kill infected cells
 Two requirements must be met for a helper T to activate adaptive immune responses
1. Foreign molecule must be present that can bind specifically to the antigen receptor of the T cell
2. This antigen must be displayed on the surface of an antigen-presenting cell (APC), which can be
a dendritic cell, macrophage, or B cell
 When host cells are infected, they also display antigens on their surface.
 Antigen-presenting cells have class I & class II MHC molecules
o The class II molecules provide a molecular signature by which an APC is recognized
 A helper T & the APC displaying its specific epitope have a complex interaction
1. The antigen receptors on the surface of the helper T bind to the antigen fragment & to the
class II MHC molecule displaying that fragment on the APC. At the same time, an
accessory protein, CD4, on the helper T surface binds to MHC II, helping to keep the cells
joined
2. When the APC & helper T interact, signals in the form of interleukins (a type of
cytokines) secreted from a dendritic cell act in combo with the antigen to stimulate the
helper T, causing it to produce its own set of interleukins.
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The different types of APCs interact with helper Ts in distinct ways.
o If the APC is a dendritic cell or macrophage:
1. A helper T is activated
2. Helper T proliferates, forming a clone of activated helper Ts
3. B cells present antigens to already activated helper Ts, which activates the B cells
themselves
Cytotoxic T Cells: A Response to Infected Cells
 In cell-mediated immune response, the effector cells are cytotoxic T cells, which use their toxic
gene products to kill infected cells
 To become active, they require signaling molecules from helper T & interaction with a host cell
that presents an antigen.
 Once activated, cytotoxic T can eliminate cells that are infected by intracellular pathogens
1. Fragments of foreign proteins produced in infect host cells associate with class I MHC molecules
& are displayed on the cell surface, where they can be recognized by cytotoxic Ts.
2. Cytotoxic Ts bind with accessory protein CD8, which helps keep the 2 cells in contact while the T
cell is activated
3. The targeted destruction of an infected host cell by cytotoxic T involves the secretion of proteins
that disrupt membrane integrity & trigger apoptosis.
o The death of the infected cell deprives the pathogen of a place to reproduce & exposes cell
contents to circulating antibodies, which mark them for disposal
4. After destroying an infected cell, cytotoxic T can move on & kill other cells infected with the
same pathogen
B Cells & Antibodies: A Response to Extracellular Pathogens
Activation of B Cells
 Activation of humoral immune response involves B cells & helper T cells & proteins on the
surface of pathogens
1. B cell activation by an antigen is aided by cytokines (interleukin 1) secreted from helper Ts that
have encountered the same antigen.
2. Stimulated by both an antigen & interleukin 1, the B cell proliferates & differentiates into memory
B & antibody-secreting effector plasma cells
 The pathway for antigen processing & display in B cells differs from that in other APCs.
o A macrophage or dendritic cell can present fragments from a wide variety of protein
antigens
o B cell presents only the antigen to which is specifically binds
1. When an antigen first binds to receptors on the surface of a B cell, B cell takes in a few foreign
molecules by receptor-mediated endocyotsis.
2. Class II MHC protein of the B cell then presents an antigen fragment to a helper T. This direct
cell-to-cell contact is critical to B cell activation.
 An activated B cell gives rise to thousands of identical plasma cells, which stop expressing a
membrane-bound antigen receptor & begin producing & secreting antibodies
 Most antigens recognized by B cells contain multiple epitopes, so an exposure to a single antigen
normally activates a variety of B cells, with different plasma cells producing antibodies directed
against different epitopes on the common antigen
Antibody Function
 Antibodies don’t kill pathogens. Instead, when they bind to antigens, they mark pathogens in
several ways for inactivation or destruction:
1. Neutralization- antibodies bind to viral surface proteins.
o The bound antibodies prevent infection of a host cell, neutralizing the virus.
o Antibodies sometimes bind to toxins released in body fluids, preventing the toxins from
entering the body
2. Opsonization- antibodies bound to antigens on bacteria present a readily recognized structure for
macrophages or neutrophils & increase phagocytosis
o
Because each antibody has 2 antigen-binding sites, antibodies sometimes also facilitate
phagocytosis by linking foreign substances into aggregrates
3. Antibodies sometimes work together with proteins of the complement system to dispose of
pathogens
o Binding of a complement protein to an antigen-antibody complex on a foreign cell or
enveloped virus triggers a cascade in which each protein of the complement system
activates the next protein
 Ultimately, activated complement proteins generate a membrane attack complex
that forms a pore in the membrane of the foreign cell. Ions & water rush into the
cell, causing it to lyse.
 This cascade of complement protein activity results in lysis of foreign cells &
produces factors that promote inflammation or stimulate phagocytosis
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When antibodies facilitate phagocytosis, they also help fine-tune the humoral immune response
o Phagocytosis enables macrophages & dendritic cells to present antigens to & stimulate
helper Ts, which then stimulate B cells whose antibodies contribute to phagocytosis
This is a positive feedback between innate & adaptive immunity
Antibodies can also bring about the death of infected body cells.
o When a virus uses a cell’s biosynthetic machinery to produce viral proteins, these viral
products can appear on the cell surface
o If antibodies specific for epitopes on these viral proteins bind to the exposed proteins, the
presence of bound antibody at the cell surface can recruit a natural killer cell, which then
releases proteins that cause the infected cell to undergo apoptosis
B cells can express 5 different forms of antibodies or immunoglobulin (Ig) For a given B cell,
each form or class has an identical antigen-binding specificity, but a distinct heavy-chain C region
1. IgD- the only B cell antigen receptor that's membrane bound. The other 4 classes consist
of soluble antibodies
2. IgM- first class of soluble antibody produced
3. IgG- follows next, is the most abundant antibody in blood
4. IgA
5. IgE
Summary of the Humoral & Cell-Mediated Immune Responses
 Both responses can include Io & IIo responses
 Memory cells of each type – helper T & B & cytotoxic T – enable the IIo response
o Ex: when body fluids are reinfected by a pathogen encountered previously, memory B &
T initiate a IIo humoral response
Active & Passive Immunization
 Active immunity- defenses that arises when a pathogen infects the body & prompts a Io or IIo
response
 Passive immunity- immunity that results when the IgG antibodies in the blood of a pregnant
female cross the placenta to her fetus. The transferred antibodies can immediately react with any
pathogens for which they’re specific; the antibodies provided by the mother guard against
pathogens that have never infected the newborn
o Because passive immunity doesn’t involve the recipient’s B & T cells, it persists only as
long as the transferred antibodies last
 After giving birth, a nursing mother continues to transfer protection against disease to her infant.
IgA antibodies present in breast milk provide additional passive immunity to the infant’s digestive
tract while the infant’s immune system develops.
o Later on, IgA functions in active immunity: IgA antibodies secreted in tears, saliva, &
mucus protect the mucous membranes
 Active & passive immunity can be introduced artificially.
 Immunization- allows active immunity to develop from intro of antigens into the body

In 1796, Edward Jenner used cowpox virus to induce adaptive immunity against the related
smallpox
 Many agents of antigens (i.e. inactivated bacterial toxins, killed pathogens, part of pathogens,
weakened pathogens that don’t cause illness, & genes encoding microbial proteins) are used today
to make vaccines. They induce a primary immune response & immunological memory, so an
encounter with the pathogen from which the vaccine was derived triggers a rapid & strong
secondary immune response)
Antibodies as Tools in Research, Diagnosis, & Therapy
 Some antibody tools are polyclonal: they’re products of many different clones of plasma cells,
each specific for a different epitope.
o Antibodies that an animal produces after exposure to a microbial antigen are polyclonal
 Monoclonal antibodies- prepared from a single clone of B cells grown in culture; identical &
specific for the same epitope on an antigen
 Medical diagnosis & treatment using monoclonal antibodies
o Ex: home pregnancy kits use monoclonal antibodies to detect human chorionic
gonadtrophin (hCG), which is produced as soon as an embryo implants in the uterus. The
presence of this hormone in her urine indicates for a very early stage of pregnancy
o Ex: for therapy to treat human diseases, researchers use mouse B cell clones to identify
antibodies specific for an epitope on diseased cells.
 Then, the mouse antibody genes are altered to code for antibodies that appear less
foreign to the human adaptive immune defenses.
 Then, scientists use the humanized genes to produce large amounts of antibody
for injecting into patients
Immune rejection
 Cells from another person can be recognized as foreign & attacked by immune defenses. This is
the expected reaction of a healthy immune system exposed to foreign antigens
1. Blood Groups
 To avoid a blood transfusion being recognized as foreign by the recipient’s immune system, the
blood groups of the donor needs to have the same type carbohydrate on the surface of their RBCs
(i.e. both A & B carbohydrates are found on type AB RBCs & neither carbohydrate is found on O)
 Ex: immune response of male with type A blood
o Certain bacteria normally present in the body have epitopes very similar to the A & B
carbohydrates.
o By responding to the bacterial epitope similar to the B carbohydrate, a person with type A
blood makes antibodies that’ll react with the type B carbohydrate
o No antibodies are made against the bacterial epitope similar to the type A carbohydrate
because lymphocytes reactive with the body’s own molecules are inactivated or
eliminated during development
o If he receives a transfusion of type B blood, his anti-B antibodies cause an immediate
transfusion reaction. The transfused RBCs undergo lysis, which can damage health
2. Tissue & Organ (Graft) Transplants
 MHC molecules stimulate the immune response that leads to rejection
 Each vertebrate species has many alleles for each MHC gene, enabling presentation of antigen
fragments that vary in shape & electrical charge, guaranteeing that no two people have exactly the
same set, so in vast majority of graft & transplant recipients
 To minimize rejection, physicians use donor tissue bearing MHC molecules that match those of
the recipients very closely & the recipient needs to take meds that suppress immune responses
 Bone marrow transplants are used to treat leukemia & hematological (blood cell) diseases.
Transplants of bone marrow can cause immune reaction.
o Before receiving transplanted bone marrow, the recipient’s treated with radiation to
eliminate their own blood marrow cells, destroying the source of the normal cells

This treatment obliterates the recipient’s immune system, leaving little chance of graft
rejection
 But, lymphocytes in the donated marrow may react against the recipient’s
o This graft vs host reaction is limited if the MHC molecules of the donor &
recipient are well matched
43.4 Disruptions in Immune System Function can Elicit or Exacerbate Disease
Exaggerated, Self-Directed, & Diminished Immune Responses
Allergies
 Allergies are exaggerated (hypersensitive) responses to certain allergens, specific antigens.
 The most common allergies involve antibodies of the IgE class
o Ex: hay fever occurs when plasma cells secrete IgE antibodies specific for antigens on the
surface of pollen grains.
 Some IgE antibodies attach by their base to mast cells in connective tissues
 Pollen grains that enter the body attach to the antigen-binding sites of those IgE
bodies.
 This attachment links adjacent IgE molecules, inducing the mast cell to release
histamine & other inflammatory chemicals from granules (vesicles)
 Antihistamines diminish allergy symptoms &
inflammation by blocking receptors for histamine
 Anaphylactic shock- acute allergic response in
which the whole-body reacts in a life-threatening way
after exposure to an allergen; develops when
widespread release of mast cell contents triggers
abrupt dilation of peripheral blood vessels, causing a
huge drop in blood pressure & the constriction of
bronchioles
 People with severe hypersensitivities carry syringes
containing epinephrine, which counteracts this
allergic response
Autoimmune diseases

Autoimmune disease- caused by a person’s own immune system active against particular
molecules of their own body
 There are many forms of such a loss of self-tolerance:
1. Lupus- immune system generates antibodies against histones & DNA released by the
normal breakdown of body cells.
2. Rheumatoid arthritis- leads to damage & painful inflammation of the cartilage & bone of
joints
3. Type 1 diabetes mellitus- insulin producing beta cells of the pancreas are the targets of
autoimmune cytotoxic cells
4. Multiple sclerosis- most common; T cells infiltrate the central nervous system, resulting in
destruction of the myelin sheath that surrounds parts of many neurons, leading to muscle
paralysis through a disruption in neuron function
Exertion, Stress, & the Immune System
 Exercise to the point of exhaustion leads to more frequent infections & to more severe symptoms
o On average, marathon runners get sick less than their more sedentary peers during
training, but have a marked increase in illness in the period immediately following the
race
 Psychological stress can disrupt immune system regulation by altering the interplay of the
hormonal, nervous, and immune system
Immunodeficiency Diseases
 Immunodeficiency- disorder in which an immune system response to antigens is defective or
absent
1. Inborn immunodeficiency results from a genetic or developmental defect in immune system, ,
leading in impairment of innate and/or adaptive defenses
o Result from defects in development of various immune system cells or defects in
production of specific proteins (i.e. antibodies or proteins of complement system)
o In severe immunodeficiency (SCID), functional lymphocytes are rare or absent. Lacking
an adaptive immune response, SCID patients are susceptible to infections that can cause
death in infancy
 Treatments: bone marrow & stem cell transplantation
2. Acquired immunodeficiency develops later in life following exposure to chemical or biological
agents
o Drugs used to fight autoimmune diseases or prevent transplant rejection suppress the
immune system, leading to immunodeficient state
o Ex: Acquired immunodeficiency syndrome (AIDS), which is caused by human
immunodeficiency virus (HIV)
Evolutionary Adaptations of Pathogens that Underlie Immune System Avoidance
Antigenic variation
 Pathogen alters how it appears to the immune system
o Immunological memory is a record of the foreign epitopes previously encountered
 If the pathogen that expressed those epitopes doesn’t anymore, it can reinfect or remain in a host
without triggering the rapid response of memory cells
 Antigenic variation- such changes in epitope expression; regular events for viruses & parasites
o Ex: sleeping sickness periodically switches at random among 1000 different versions of
the protein found over its entire surface, so it can persist in the body without facing an
effective adaptive immune response
 Antigenic variation is the major reason why influenza virus remains a health problem
o As it replicates in one human host cell after another, the human influenza virus mutates
o Because any change lessens recognition by the immune system provides a selective
advantage, so the virus accumulates with alterations
 Human virus occasionally exchanges genes with influenza viruses that infect domesticated
animals.
o When this happens, influenza can take on such a radically different appearance that none
of the memory cells in humans can recognize the new strain
o Ex: H1N1 = flu viruses from pigs + humans + birds
Latency/ Lysogenic Cycle
 After infecting a host, some viruses enter a largely inactive state called latency
 Because such dormant viruses stop making most viral proteins & produce no free virus particles,
they don’t trigger an adaptive immune response
 But, the viral genome persists in the nuclei of infected cells, either as separate small DNA
molecule
 Latency persists until conditions arise that are favorable for viral transmission (i.e. when host’s
infected by another pathogen)
 Ex: herpes establish themselves in human sensory neurons.
o Because sensory neurons express few MHC I molecules, the infected cells are inefficient
at presenting viral antigens to circulating lymphocytes
o Stimuli like fever, stress, or periods reactivate the virus to reproduce & infect surrounding
epithelial tisses
Attack on the Immune System: HIV



HIV, the pathogen that causes AIDS, escapes & attacks the adaptive immune response
Once HIV is introduced into the body, it infects helper Ts with high efficiency.
To infect helper Ts, the virus binds specifically to the CD4 accessory protein and some cell types
that have low levels of CD4 (i.e. macrophages & brain cells)
 In the cell, the HIV RNA genome is reverse-transcribed, & the product DNA’s integrated into the
host cell’s genome. In this form, the viral genome can direct production of new virus particles
 Although the body responds to HIV with an immune response that can eliminate most viral
infections, some HIV escapes
 HIV persists because of antigenic variation. It mutates at a very high rate during replication.
Altered proteins on the surface of some mutated viruses reduce interaction with antibodies &
cytotoxic T cells.
o These viruses survive, proliferate, & mutate further; the virus evolves inside the body
 Latency also helps HIV persistence.
o When the viral DNA integrates into the chromosome of a host cell but doesn’t produce
new virus proteins, it’s shielded from the immune system of the host cell.
o This inactive viral DNA is protected from antiviral agents used against HIV because they
attack only actively replicating viruses
 Over time, an untreated HIV infection abolishes the adaptive immune response
 Viral reproduction & cell death triggered by the virus lead to loss of helper Ts, impairing both
humoral & cell0mediated immune responses. This results in progression to AIDS, characterized
by a susceptibility to infections & cancers that a healthy immune system would usually defeat
o These opportunistic diseases & nerve damage & body wasting are the primary causes of
death in AIDS patients, not HIV itself
 There is currently no cure to AIDS. Mutations that occur in each round of viral reproduction can
generate strains of HIV that are drug resistant.
 The impact of such viral drug resistance can be reduced by the use of a combo of drugs.
o But, the appearance of strains resistant to multiple drugs can reduce the effectiveness of
such multidrugs cocktails
 Transmission of HIV requires the transfer of virus particles or infected cells from person to person
via body fluids.
 People infected with HIV can transmit the disease in the first few weeks of infection, before they
express HIV-specific antibodies that can be detected in a blood test
Cancer & Immunity
 When adaptive immunity is inactivated, the frequency of certain cancers increases dramatically
 If the immune system recognizes only nonself, it should fail to recognize the uncontrolled growth
of self cells that’s the hallmark of cancer.
 Viruses are involved in 15 – 20% of all human cancers
 Because immune system can recognize viral proteins as foreign, it can act as a defense against
viruses that can cause cancer & against cancer cells that harbor viruses
o Kaposi’s sarcoma herpesvirus
o Hepatitis B virus, can trigger liver cancer. First vaccine to help prevent specific human
cancer
Vaccinating Against Cervical Cancer
 Human papillomavirus (HPV) can cause cervical cancer
 2 particular types of HPV from patients of cervical cancer were isolated, copied, leading to the
development