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Chapter 39
IMMUNITY: A SUMMARY
AP Biology
Spring 2011
Integrated Responses To Threats
 Immunity: body’s capacity to resist and combat
infection, began when multicelled eukaryotic species
evolved from free-living cells
Integrated Responses To Threats
 Mutations introduced molecular patterns in
membrane proteins that were unique to cells of a
given type
 Mutations led to mechanisms of identifying those
proteins as belonging self- one’s own body
 And ability to identify nonself
Integrated Responses To Threats
 Antigen: any molecule that the body recognizes as
nonself that revokes an immune response

Most are proteins, lipids, and oligosaccharides
 Pattern receptors: used to detect patterns that are
present mainly on pathogenic cells

Anything that became bound to hem induced an animal cell to
release complement (a set of about 30 proteins) which
circulate in blood and destroy microbes or tag them for
phagocytes
Integrated Responses To Threats
 The microbial pattern receptors and complement
offered innate immunity- fast, off-the-shelf
responses to a fixed set of nonself cues

Does not protect against novel or unrecognized threats ,
adapting to them isn’t possible in an individual’s lifetime
Integrated Responses To Threats
 Evolution of cytokines and lymphocytes
 Lymphocytes: specialized class of WBC
 Together these signals and cells could tailor defenses
to an astounding array of specific threats that an
individual encountered during its lifetime

Adaptive immunity
Three Lines of Defense
Pathogens cannot do damage unless they can enter
the internal environment
1.


Intact skin and lining of body tubes and cavities
Physical and chemical protection
2. Innate immunity

Starts immediately after antigen has been detected or after a
tissue has become damaged

WBC, complement, acute inflammation, and fever
3. Adaptive immunity

Large populations of WBC form, all sensitized to a specific
threat
The Defenders
 Leukocytes: all WBC that arise from stem cells in
bone marrow
The Defenders
 Many kinds
 Neutrophils: most abundant of WBC, fast acting phagocytes
 Macrophages: slower, bigger eaters, can get rid of as many as
100 bacterial cells
 Dendrite cells: alert immune system to the presence of antigen
The Defenders
 Many kinds:
 Basophils and Mast Cells: circulate in blood (basophils) and
tissues (mast cells) and release enzymes and cytokines in
response to antigen or injury
 Eosinophils: secrete enzymes and toxic proteins that are good
at punching holes in larvae of parasitic worms
 B and T Lymphocytes: are central to adaptive immunity
 Natural killer cells: innate immune response, also participate
in adaptive immunity, directly kill body cells that are infected,
stressed, or mutated, as by cancerous transformations
Immunalogy
 http://www.youtube.com/watch?v=T_4TrNRa3v8&
feature=related
 Watch the video
 Draw a diagram to separate innate and adaptive
immunity
Surface Barriers- The First Line of Defense
 Your skin is teeming with about 200 different kinds
of microbes
 Skin is waterproof covering of dead, keratin packed
epithelial cell layers
 Normal skin resident populations of microbes have
neutral or helpful impacts on health
Staphylococcus
epidermidis , the most
common species on
skin and a leading
cause of bacterial
infections
Linings of Tubes and Cavities
 Body has defenses that normally keep microbes
outside on the surface of linings
 Mucus: coating on free surface of epithelial linings


Consists of glycoproteins (mucins) and salts in water
Lysozyme: enzyme that cleaves peptidoglycans in bacterial cell
walls and disrupts their structure

Tears have lysozymes
Linings of Tubes and Cavities
 Breathing in air:
 Mucus coated epithelial lining of airways
 Coughing expels many cells, lysozymes in mucus kill others
 Lining has ciliated cells, cilia beat in synchrony at its free
surface, which sweeps the bacteria laden mucus to throat for
disposal
Linings of Tubes and Cavities
 In the mouth
 If microbes make it to the stomach, low pH kills most
 If make it to small intestine bile salts in intestinal lumen
usually kill them
 If make it to large intestine, must compete with 500 or so
established species and if they do displace the residents a
flushing mechanism (diarrhea) usually gets rid of them
Linings of Tubes and Cavities
 Urinary tract and vagina
 Lactic acid, byproduct of fermentation by Lactobacillus


Helps keep vaginal pH beyond range of tolerance for most bacteria
and fungi
Flushing action of urination normally keeps most pathogens
from colonizing in urinary tract
Uneasy Balance
 Must keep microbes outside body
 Surface barriers are vulnerable
 When we become sick or weak with age, changes in
physiology may compromise them
 Examples:


Acne
Plaque deposits, periodontitis
Innate Immune Response
 Phagocytes:
 Macrophages arrive first: engulf and digest anything other
than undamaged body cells
 Their pattern receptors recognize and bind to pathogen
secreting cytokines which signal more macrophages and
neutrophils
Innate Immune Response
 Complement Proteins:
 Also arrive first
 Bind to circulating microbes or to antigen being displayed at
phagocyte’s surface which causes a positive feedback
mechanism
 One bound molecule becomes activated  then activates a few
molecules of a different type of complement  then activates
some of a different type, etc.
 Cascading reactions yield high concentrations of activated
complement in localized tissue region
Innate Immune Response
 Activated complement proteins have many effects
 Chemotactic: attract phagocyte cells (phagocytes follow
gradients to site of damage, where complement is most
concentrated)
 Some bind to microbes: microbes coated with complements
will get recognized and engulfed faster by phagocytes
 Some assemble into attack complexes in cell wall or plasma
membrane and promote bacterium’s lysis
 Also function in adaptive immunity
Innate Immune Response
 Acute Inflammation: swift response from to tissue
irritation or tissue damage

Cytokines secretions from macrophages and activated
complement trigger this
 Symptoms: redness, warmth, swelling, pain
Innate Immune Response
 Steps of acute inflammation
 Mast cells respond to complement cascades or to antigen
 Secrete histamine and cytokines into interstitial fluid
 Histamine makes arterioles in tissue dilate  increases blood
flow to the area (causes warmth and redness)
 Histamine makes blood capillaries in the tissue “leaky” to
plasma proteins that usually do not leave blood
 Causes endothelial cells of capillary wall to shrink, cells pull
further apart at clefts between them
 Plasma proteins and phagocytes slip out
Innate Immune Response
 Steps of acute inflammation continued
 Osmotic pressure in interstitial fluid rises, fluid balance across
the capillary wall shifts, localized edema (swelling)
 Swollen tissue cause free nerve endings to give rise to
sensations of pain; suppresses voluntary movements (allows
for tissue repair)
 Other plasma proteins leaking into interstitial fluid include
clotting factors, macrophage secretions activate them
Innate Immune Response
 Fever: rise in body temperature above the normal set
point on a built in thermostat in hypothalamus
 Macrophages bring about fever as innate immune
response




Secrete pyrogenic cytokines which stimulates brain to
synthesize and release several kinds of prostaglandins
Prostaglandins act in hypothalamus to raise thermostat set
point
Fever of 39 degrees C, enhances immunity by increasing
enzyme activity and speeding metabolism (formation and
action of phagocytes accelerates, so does tissue repair)
Also pop. Of many microbes grow slowly at high temp.s
Features of Adaptive Immunity
 Four characteristics of vertebrate active immunity
1.
Self/nonself recognition
2.
Specificity
3.
Diversity
4.
Memory
Features of Adaptive Immunity
 Self versus nonself recognition
 Every cell or virus has its own identity
 Human cells have markers: human leukocyte antigens (HLA),
also known as MHC markers (major histocompatibility
complex)
 T cells have TCRs: antigen receptors at their surface

T cells normally do not target body cell that has bare MHC
markers, but will act against it if those markers have antigen bits
attached
Features of Adaptive Immunity
 Specificity
 New B or T cell makes receptors for one kind of antigen
 Diversity:
 Refers to collection of antigen receptors on all B and T cells is
the body
 Potentially billions of different antigen receptors, gives
potential to counter billions of different threats
Features of Adaptive Immunity
 Memory
 Immune system’s capacity to “remember” antigen that it
vanquished
 First time lymphocytes recognize an antigen, takes a few days
to for their populations to form
 When the same antigen shows up again, system makes faster,
hightened response
First Step: The Antigen Alert
 Recognition stimulates repeated mitotic cell
divisions
 Result is large populations of B and T cells, primed
to recognize antigen
First Step: The Antigen Alert





Macrophages, B cells, dendritic cells are antigen
presenting cells and find antigens and present
them to T cell (receptors recognize antigens)
First engulf anything bearing antigen, vesicles
move into the cytoplasm
Vesicle fuses with lysomes, enzymes digest antigens
Some fragments bind to MHC markers
Antigen-MHC complexes shuttled to plasma
membrane and are displayed
First Step: The Antigen Alert
 When a cell’s MHC markers become paired with antigen




fragments, it becomes a call to arms
Odds are at least one T cell has receptors that can bind
Binds, becomes activated and secretes cytokines that
induce divisions of B or T cells sensitive to same antigen
Effector cells: differentiated lymphocytes that act
immediately against antigen
Memory cells: long lived B and T cells that develop
during first exposure and set aside for future encounters
Two Arms of Adaptive Immunity
 Antibody Mediated Immune Response
 Pathogens in blood or interstitial fluid intercepted by
phagocytes and B cells
 B cells execute most of this response
 T cells support
Two Arms of Adaptive Immunity
 Cell mediated immune response
 Intracellular pathogens
 Vulnerable only for brief time when they slip out of one cell
and infect another
 This response does not acquire antibodies
 Starts after antigen becomes positioned at surface of infected
or altered body cells where phagocytes and cytotoxic T cells
detect it
Intercepting and Clearing Out Antigens
 After engulfing antigen, dendritic cells and
macrophages enter a lymph node
 In lymph node, both kinds of phagocytes alert the T
cells to the threat
 Free antigen in interstital fluid enters lymph vessels
which deliver it to lymph nodes where it passes B
cells, macrophages, and dendritic cells that can bind,
process, and present it to T cells
 Lymph nodes trap most antigen- some could
circulate to blood! Spleen helps filter again!
Intercepting and Clearing Out Antigens
 During infection:
 Antigen-presenting T cells become trapped briefly in lymph
nodes
 Swollen lymph nodes sign of illness and lymphocyte activity
 Immune response subside once antigen is cleared away
B Cells: The Antibodies
 Antibodies: proteins synthesized only by B cells
that encounter and bind antigen



Many Y shaped
Most circulate in blood and enter interstitial fluid during
inflammation
Each acts spcifically against the antigen that promoted its
synthesis
B Cells: The Antibodies
 Structure of Antibodies:
 Four polypeptide chains
 Two identical “light” ones
 Two identical “heavy” ones
 Each chain has constant region, forms molecules backbone
 One end of each chain has variable region- domain for one
antigen
B Cells: The Antibodies
 5 structural classes of antibodies called
Immunoglobulins (Igs)





IgG
IgA
IgM
IgE
IgD
 B cell secretes them, circulate alone or in clumps
B Cells: The Antibodies
 IgG
 80% of all immunoglobulins in blood
 Induces complement cascades, neutralizes toxins
 Crosses placenta, protects fetus with mother’s aquired
immunities
 Secreted into early milk (colostrum)
B Cells: The Antibodies
 IgA
 Main immunoglobulin in exocrine gland secretions
 Tears, saliva, milk
 In mucus of respiratory, digestive, and reproductive tracts
B Cells: The Antibodies
 IgE
 Induces inflammation after pathogen invasions
 Constant regions of its heavy chains become anchored to mast
cells, basophils, monocytes, or dendritic cells
 Makes these cells release histamines and cytokines
 Factor in allergic reactions and HIV infection
B Cells: The Antibodies
 IgM
 First to be secreted in primary response and first made by
newborns
 Surface of each new B cell is covered with hundreds of
thousands of IgM or IgD antibodies, each of which recognizes
the same antigen
 Antibodies are B cell receptors, surface immunoglobulins that
function as B cell’s antigen receptors
The Making of Antigen Receptors
 B cells
 Before new B cell leaves bone marrow, already synthesizing
unique antigen receptors
 Constant region of each is positioned in lipid bilayer of B cell’s
plasma membrane
 Two variable arms project above it
 B cell will have 100,000 antigen receptors
 “naïve” B cell- has not yet met its antigen
B Cells: The Antibodies
 T cells:
 Form inside bone marrow
 Do not mature until they take a tour through thymus gland
 After exposure to thymic hormones, get receptors for MHC
proteins
 Also get TCR’s, unique antigen receptors by gene splicing
 These recombination’s are random , some TCRs end up
recognizing MHC markers rather than antigen, many will not
B Cells: The Antibodies
 To get a functional set of T cells
 Thymus cells produce small peptides that are derived from a
variety of the body’s proteins
 Peptides get attached to MHC markers, act as built in quality
controls to weed out “bad” TCRs
 Any T cell that binds too tightly to one of complexes, has TCRs
that recognize self peptide
 T cells that do not bind at all cannot recognize MHC markers
 Both types die
 By the time naïve T cells leave the thymus, their surface
contains functional TCRs
The Antibody Mediated Response
 Main targets of antibody mediated response are
extracellular pathogens and toxins freely
circulating in blood and interstitial fluid
 Nick your finger, staphlococcus aureus invades
 Complement in interstitial fluid latches on to
carbohydrates in their bacterial cell wall and activates
cascading reactions
 Complement coats bacteria
 Bacteria move through lymph vessels to lymph node,
where paraded past naïve B cells
The Antibody Mediated Response
 B cells bear immunoglobulins that bind to
peptidoglycan in bacterium’s cell wall
 Bears complement receptors that bind to complement
that coats the invading cell
 These 2 events provoke B cell to begin receptormediated endocytosis
 Bacterium enters B cell, which is no longer naïve, now
activated
The Antibody Mediated Response
 Meanwhile, more S. aureus cells have been secreting
chemotactic factors into interstitial fluid around cut
 Secretions attract phagocytes
 Dendritic cell engulfs some bacteria, then migrates to
the lymph node
 It has digested the bacteria cell and displays antigen
fragments bound to MHC markers on its surface
The Antibody Mediated Response
 Naïve T cells travel through the lymph nodes at all
times, inspect dendritic cells
 One of T cells has TCRs that tightly bind to S. aureus
antigen-MCH complexes on dendritic cell
 For the next 24h, two cells interact
 Transcription factors activated in T cell
 Two cells disengage, T cell returns to circulatory
system
The Antibody Mediated Response
 Theory of clonal selection
 S. aureus antigen “chose” that T cell because it bears a
receptor that can bind to it
 After T cell is activated, many descendents form by
mitotic cell divisions
 They are clones- one lineage of genetically identical
cells
 Differentiates into helper T cells, all with identical
TCRs specific for S. aureus antigen
The Antibody Mediated Response
 Back to the B cell in lymph nodes
 Fragments of S. aureus are bound to MHC markers
and displayed at the B cells surface
 Two cells latch on to each other and exchange
costimulatory signals
 Helper T cells secretes several interleukins- cytokines
that signal B cell to divide and differentiate
The Antibody Mediated Response
 When cells disengage, B cell divides, its clonal
descendents form huge populations, with identical
receptors
 Differentiate into effector and memory cells
The Antibody Mediated Response
 Effector cells work immediately in primary immune
response or against initial exposure to antigen
 Instead of making membrane bound IgM as B cell
receptors, they switch antibody classes
 Start making and secreting IgG, IgA, or IgE instead
 Each of secreted antibody molecules has same antigen
specificity as original B cell receptor
The Antibody Mediated Response
 Great numbers of antibody molecules specific for S.
aureus are now circulating through body
 Bind bacterial cells remaining in blood stream and
interstitial fluid
 Prevent them from attaching to body tissues and also
tag them for disposal for NK cells and complement
 Neutralize toxic agents
THE CELL-MEDIATED RESPONSE
As long as virus, bacteria, fungi, and protists hide
in host cell, antibody mediated response cannot
be initiated
 During acute inflammatory response, cell
mediated defenses against these menacing
threats get under way in interstitial fluid
 Usually plasma membrane of infected body cell
displays antigen- peptides of intracellular
pathogen or self proteins that were altered by
cancerous tranformation

THE CELL-MEDIATED RESPONSE
Dendritic cells recognize, engulf, and digest these
antigens as bits of diseased or abnormal cells or
their remains
 Dendritic cells then travel to lymph nodes, where
antigen-MCH complexes on their surface are
presented to 2 different populations of naïve T
cells
 Both types are activated when their receptors
bind to antigen-MCH complexes on the dendritic
cells
 Clonal decendents of one population differentiate
into effector helper T cells, which secrete
interleukins and other cytokines
 These signal induce other type of T cell to divide
and differentiate into cytotoxic T cells

THE CELL-MEDIATED RESPONSE
Cytotoxic T cells circulate through body in blood
and interstitial fluid
 Bind to any cell bearing original antigen that is
complexed with MHC markers
 Inject it with perforin and proteases
 These toxins poke holes into cell and induce it to
die by apoptosis
 Cytotoxic T cells are body’s primary weapons
against infected body cells and tumors
 Also cause rejection of tissue and organ implants

THE CELL-MEDIATED RESPONSE
Cytokines secreted by some helper T cells
enhance macrophage action
 Stimulate these phagocytes to secrete more
inflammatory mediators and toxins that help kill
tumor cells and larger parasites
 Helper T cell cytokines also stimulate cell
divisions of NK cells

THE CELL-MEDIATED RESPONSE
Natural killer cells attack cells that are tagged
for destruction by antibodies
 Also detect
 Stress markers on infected or cancerous body
cells
 Cell that has normal MCH markers is not killed
 Cell with MCH markers that have been altered
will die
 NK cells and macrophages are crucial in killing
such cells; neither depends on presence of MCH
markers

Defenses Enhanced or Compromised
 Immunization: processes that may promote
immunity
 Active immunization: preparation that contains
antigen (a vaccine) is administered orally or injected
into body



First injection elicits primary immune response
Second one, booster, elicits secondary response
Additional effector and memory cells form for lasting
protection
Defenses Enhanced or Compromised
 Vaccines can be made from
 Weakened or killed pathogens or inactivated bacterial toxins
 Harmless viruses that have genes from other pathogens
inserted into their DNA or RNA
 Passive Immunization
 Helps if hepatitis B, tetanus, rabies, have already started
 Based on injections of antibody purified from blood of a
person who already fought disease
 Antibodies do not activate body’s immune system, memory
cells do not form
 Protection ends when body disposes of injected antibody
Defenses Enhanced or Compromised
 Allergies: hypersensitivity to an allergen
 Exposure to harmless proteins that stimulates immune
response
 Allergen: any substance that is ordinarily harmless yet
provokes immune response
 Antihistamines or anti-inflammatory drugs relieve symptoms
as can desensitization programs (allergy shots)
 Anaphylactic shock: life threatening response to allergen
Defenses Enhanced or Compromised
 Autoimmune Disorders
 When lymophocytes and antibody molecules fail to
discriminate between self and nonself
 Autoimmune response: misdirected attack against one’s own
tissues
 Ex. Rheumatoid arthritis, Graves disease, multiple sclerosis
Defenses Enhanced or Compromised
 Deficient Immune Responses
 Loss of immune function can have lethal outcomes
 Primary deficiencies, present at birth, are outcomes of
mutant genes or abnormal developmental steps


Ex. SCIDs, ADA
Secondary deficiencies are losses of immune function
after exposure to some outside agent

Ex. AIDS