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Chapter 43:The
Immune System
(Body’s Defense
Mechanisms)
Barriers help an animal to defend itself from
the many dangerous pathogens it may
encounter
The Immune System and its Responses
• The immune system recognizes foreign bodies and
responds with the production of immune cells and proteins
• Innate immunity is present before any exposure to
pathogens and is effective from the time of birth
– It involves nonspecific responses to pathogens
– Innate immunity consists of external barriers plus
internal cellular and chemical defenses
• Acquired immunity, or adaptive immunity, develops after
exposure to agents such as microbes, toxins, or other
foreign substances
– It involves a very specific response to pathogens
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Fig. 43-2
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
• Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
• Rapid response
ACQUIRED IMMUNITY
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
• Slower response
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.
INNATE IMMUNITY: Barrier Defenses
A. Skin
1. physical barrier
2. skin and oil: pH of 3-5
3. saliva and tears
a. wash away invaders
b. lysozyme- breaks down cell walls of
bacteria
B. Mucous
1. traps particles
2. lines digestive, respiratory and urinary tracts
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INNATE IMMUNITY: Cellular Innate Defenses
C.
Phagocytic Lymphocytes
1. Neutrophils
a. attracted by chemicals (chemotaxis), leave blood
stream by amoeboid movement
b. self destruct as they destroy invaders
2. Monocytes
a. migrate into tissues and enlarge to form macrophages:
effective, long-living phagocytes
b. some macrophages are specialized for specific organs:
1. lungs: alveolar macrophages
2. liver: Kupffer’s cells
3. lymph nodes
4. spleen
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INNATE IMMUNITY: Cellular Innate Defenses
3. Eosinophils
a. limited phagocytic activity
b. contain enzymes in granules
c. defense against parasitic invaders (worms)
4. Natural Killer Cells
1. destroy body’s own infected cells
2. also destroy cancer cells
3. attack cell membrane -> cell lyses
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INNATE IMMUNITY: Antimicrobial Proteins
E. Antimicrobial proteins
1. Complement system:
a. group of ~30 proteins
b. cascade of reactions -> lysis of invading
cell
2. Interferons:
a. chemicals secreted by virus-infected cells
b. interfere with viral replication
c. most effective with short-term infections
(ex- flu, cold)
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Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
INNATE IMMUNITY: Inflammatory Responses
F. Inflammatory Response (localized)
1. small blood vessels dilate -> redness & heat
2. fluids move from blood to tissues -> edema
3. initiated by chemical signals
a. basophils and mast cells release histamines
b. WBCs discharge prostaglandins
4. Enhances migration of phagocytes to injury site
5. pus= dead cells (neutrophils) and fluid
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Fig. 43-8-3
Inflammatory Response
Joe gets a Splinter : (
Pathogen
Splinter
Chemical Macrophage
signals
Mast cell
Capillary
Red blood cells Phagocytic cell
Fluid
Phagocytosis
INNATE IMMUNITY: Inflammatory Responses
G. Systemic Responses (ex. appendicitis)
1. Increase in number of WBCs
2. fever
a. WBCs release pyrogens which set body’s
thermostat higher
b. inhibits growth of microorganisms
c. speeds up body’s reactions -> quick repair
• Septic shock is a life-threatening condition caused
by an overwhelming inflammatory response
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43.2 Innate Immune System Evasion by Pathogens
• Some pathogens avoid destruction by
modifying their surface to prevent recognition
or by resisting breakdown following
phagocytosis
• Tuberculosis (TB) is one such disease and kills
more than a million people a year
http://www.youtube.com/watch?v=G7rQuFZxVQQ&feature=related&safety_mode=true&persist_safety_mode=1
http://www.youtube.com/watch?v=k_GPGrl5HDM&feature=related
http://www.youtube.com/watch?v=_bNN95sA6-8&feature=related&safety_mode=true&persist_safety_mode=1
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Fig. 43-2
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
• Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
• Rapid response
ACQUIRED IMMUNITY
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.
• Slower response
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II. ACQUIRED IMMUNITY: An Overview
A. Immune System
1. Consists of:
a. lymph- fluid, WBCs, and wastes or antigens
b. lymph nodes- small masses of tissue that filter lymph
and destroy antigens
c. spleen- larger lymphatic organ that filters blood of
antigens and dead blood cells
d. tonsils- lymphatic organ that defends against antigens
in nose and mouth
e. thymus- most prominent in children- helps develop
immune response (T cells)
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Fig. 43-7
Interstitial fluid
Adenoid
Tonsil
Blood
capillary
Lymph
nodes
Spleen
Tissue
cells
Lymphatic
vessel
Peyer’s patches
(small intestine)
Appendix
Lymphatic
vessels
http://www.enile.co.uk/portfolio/cancer/lymph01.html
Lymph
node
Masses of
defensive cells
2. Qualities of the immune system
a. Specificity- ability to recognize and eliminate particular
microbes
1. antigen= foreign substance (ex- virus, bacteria,
parasite, pollen, foreign organs)
2. antibody= specific protein to recognize antigen
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b. Diversity- ability to respond to millions of kinds of
invaders due to enormous variety of lymphocytes
c. Self/Non-self recognition - ability to distinguish own
molecules from foreign molecules
d. Memory- ability to remember antigens and attack them =
acquired immunity
1. active immunity- body makes antibodies(ex- chicken
pox and vaccinations)
2. passive immunity- mother passes antibodies to fetus
across placenta or through breast milk
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B. Lymphocytes
1. All blood cells originate from stem cells in the bone
marrow
2. Lymph cells then differentiate
a. mature in thymus- T cell
b. mature in bone marrow- B cell
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3. B (bursa of Fabricius) cells
a. have antigen receptors
on cell membrane
b. humoral immunityproduction of antibodies
secreted by B cells and
circulated as soluble
proteins in blood and lymph
c. B cells activated by
antigens divide and give
rise to effector cells- secrete
antibodies
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4. T (thymus) cells
a. have receptors on cell
membrane
b. T cells activated by
antigens divide and give rise
to:
1. cytotoxic (killer) T
cells- destroy infected
cells and cancer cells
2. helper T cellsstimulate both humoral and
cell-mediated immunity
c. cell mediated immunity:
depends on the direct
action of cells (not
antibodies)
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Fig. 43-9
Antigenbinding
site
Antigenbinding site
Antigenbinding
site
Disulfide
bridge
C
C
Light
chain
Variable
regions
V
V
Constant
regions
C
C
Transmembrane
region
Plasma
membrane
Heavy chains
 chain
 chain
Disulfide bridge
B cell
(a) B cell receptor
Cytoplasm of B cell
Cytoplasm of T cell
(b) T cell receptor
T cell
C. Antigen-Antibody Specificity
1. epitope- region
on the surface of an
antigen that
antibody recognizes
2. Antibodies are a
class of proteins
called
immunoglobulins.
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3. Typical antibody
a. structure
C= constant region;
same amino acid sequence for all
antibodies
V= variable region= antigen-binding
site
b. association between antigen
binding site and epitope = lock &
key (like enzyme-subtrate)
c. 5 types of constant regions which
allow for different defense functions
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Fig. 43-10
Antigenbinding
sites
Antigen-binding sites
Antibody A Antigen Antibody C
C
C
Antibody B
Epitopes
(antigenic
determinants)
Fig. 43-20a
Class of Immunoglobulin (Antibody)
IgM
(pentamer)
Distribution
First Ig class
produced after
initial exposure to
antigen; then its
concentration in
the blood declines
J chain
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Function
Promotes neutralization and crosslinking of antigens;
very effective in
complement system
activation
Fig. 43-20b
Class of Immunoglobulin (Antibody)
IgG
(monomer)
Distribution
Most abundant Ig
class in blood;
also present in
tissue fluids
Function
Promotes opsonization, neutralization,
and cross-linking of
antigens; less effective in activation of
complement system
than IgM
Only Ig class that
crosses placenta,
thus conferring
passive immunity
on fetus
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Fig. 43-20c
Class of Immunoglobulin (Antibody)
IgA
(dimer)
J chain
Distribution
Present in
secretions such
as tears, saliva,
mucus, and
breast milk
Secretory
component
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Function
Provides localized
defense of mucous
membranes by
cross-linking and
neutralization of
antigens
Presence in breast
milk confers
passive immunity
on nursing infant
Fig. 43-20d
Class of Immunoglobulin (Antibody)
IgE
(monomer)
Distribution
Present in blood
at low concentrations
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Function
Triggers release from
mast cells and
basophils of histamine and other
chemicals that cause
allergic reactions
Fig. 43-20e
Class of Immunoglobulin (Antibody)
IgD
(monomer)
Distribution
Present primarily
on surface of
B cells that have
not been exposed
to antigens
Transmembrane
region
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Function
Acts as antigen
receptor in the
antigen-stimulated
proliferation and
differentiation of
B cells (clonal
selection)
D. Clonal Selection
1. Each lymphocyte’s antigenic target is
predetermined during embryonic development
2. Clonal selection- when antigen enters body,
lymphocyte is activated and divides to make
many effector cells = “clones”
http://student.ccbcmd.edu/courses/bio141/lecguide/
unit5/humoral/clonal/clonalan.html
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Fig. 43-14
Antigen molecules
B cells that
differ in
antigen
specificity
Antigen
receptor
Antibody
molecules
Clone of memory cells
Clone of plasma cells
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E. Cellular Memory
1. Primary Immune Response = clonal
selection
a. effector cells and memory cells made
b. 5-10 days lag time
2. Secondary Immune Response
a. 2nd exposure to the antigen ->
response faster (3-5 days)
b. memory cells- live long time & divide
quickly
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Fig. 43-15
Antibody concentration
(arbitrary units)
Primary immune response
to antigen A produces
antibodies to A.
Secondary immune response to
antigen A produces antibodies to A;
primary immune response to antigen
B produces antibodies to B.
104
103
Antibodies
to A
102
Antibodies
to B
101
100
0
7
Exposure
to antigen A
14
21
28
35
42
Exposure to
antigens A and B
Time (days)
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49
56
Fig. 43-16
Humoral (antibody-mediated) immune response
Cell-mediated immune response
Key
Antigen (1st exposure)
+
Engulfed by
Gives rise to
Antigenpresenting cell
+
Stimulates
+
+
B cell
Helper T cell
+
Cytotoxic T cell
+
Memory
Helper T cells
+
+
+
Antigen (2nd exposure)
Plasma cells
Memory B cells
+
Memory
Cytotoxic T cells
Active
Cytotoxic T cells
Secreted
antibodies
Defend against extracellular pathogens by binding to antigens,
thereby neutralizing pathogens or making them better targets
for phagocytes and complement proteins.
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Defend against intracellular pathogens
and cancer by binding to and lysing the
infected cells or cancer cells.
43.3 Self-Tolerance
1. There are no antigen receptors for animal’s own
molecules.
2. MHC (major histocompatibility complex): glycoproteins on
membrane = “self marker”
–
Class I MHC molecules are found on almost all
nucleated cells of the body
In infected cells, MHC molecules bind and transport
antigen fragments to the cell surface, a process called
antigen presentation
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Fig. 43-2
Pathogens
(microorganisms
and viruses)
INNATE IMMUNITY
• Recognition of traits
shared by broad ranges
of pathogens, using a
small set of receptors
•Rapid response
ACQUIRED IMMUNITY
• Recognition of traits
specific to particular
pathogens, using a vast
array of receptors
Barrier defenses:
Skin
Mucous membranes
Secretions
Internal defenses:
Phagocytic cells
Antimicrobial proteins
Inflammatory response
Natural killer cells
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic lymphocytes defend
against infection in body cells.
• Slower response
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
The acquired
immune system has
three important
properties:
1. Receptor
diversity
2. A lack of
reactivity
against host
cells
3.Immunological
memory
Fig. 43-16a
Humoral (antibody-mediated) immune response
Key
+
Antigen (1st exposure)
Stimulates
Gives rise to
Engulfed by
Antigenpresenting cell
+
+
B cell
Helper T cell
+
Memory
Helper T cells
+
Plasma cells
+
Antigen (2nd exposure)
Memory
B cells
Secreted
antibodies
Defend against extracellular pathogens
+
III. Humoral Response
A. Activating B cells (to make
antibodies)
1. Antigen binds to receptor on Bcell
or
2. Macrophage engulfs pathogens and
pieces displayed on cell membrane =
Antigen Presenting Cell
3. Helper T cells recognize self/non-self
combination of MHC & APC ->
activates T cells -> stimulate B cells to
mount a humoral response
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Fig. 43-19
Antigen-presenting cell
Bacterium
Peptide
antigen
B cell
Class II MHC
molecule
TCR
Clone of plasma cells
+
CD4
Cytokines
Secreted
antibody
molecules
Endoplasmic
reticulum of
plasma cell
Helper T cell
Activated
helper T cell
Clone of memory
B cells
2 µm
B. How Antibodies Work
1. Neutralization
a. attaching to antigen at site in which it binds to host
b. coating a bacterial toxin with antibody
2. Agglutination (opsonization)- bacteria clump
together; easier to engulf by phagocytosis
3. Work with Complements
a. complement bridges the gap between two
adjacent antibodies -> forms membrane attack
complex ->lesion -> cell lyses
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Fig. 43-21
Viral neutralization
Opsonization
Activation of complement system and pore formation
Bacterium
Complement proteins
Virus
Formation of
membrane
attack complex
Flow of water
and ions
Macrophage
Pore
Foreign
cell
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4. Monoclonal antibodies
a. all identical
b. technology to make large quantities of
pure antibody
c. can be used diagnostically (combat
microbes) or for treatment (possibly
cancer)
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Fig. 43-16b
Cell-mediated immune response
Key
+
Antigen (1st exposure)
Engulfed by
Antigenpresenting cell
Stimulates
Gives rise to
+
+
Helper T cell
Cytotoxic T cell
+
Memory
Helper T cells
+
+
Antigen (2nd exposure)
+
Active
Cytotoxic T cells
Memory
Cytotoxic T cells
Defend against intracellular pathogens
IV. Cell-mediated response
A. Respond to antigen epitope- MHC marker
complex
B. When activated, clones effector cells to
form:
1. Helper T cells -> activate B cells
2. Cytotoxic T cells
a. Bind to specific antigen-MHC marked cells
b. release perforin -> forms lesions -> lysis
1. destroys host cell
2. exposes pathogen to antibodies
3. defends against cancer
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Fig. 43-17
Antigenpresenting
cell
Peptide antigen
Bacterium
Class II MHC molecule
CD4
TCR (T cell receptor)
Helper T cell
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytokines
+
B cell
+
+
+
Cytotoxic T cell
Cell-mediated
immunity
(attack on
infected cells)
Fig. 43-18-3
Released cytotoxic T cell
Cytotoxic T cell
Perforin
Granzymes
CD8
TCR
Class I MHC
molecule
Target
cell
Dying target cell
Pore
Peptide
antigen
V. Self Versus Nonself
A. Blood Groups
1. Blood Type
Antigen
Antibodies
A
A
B
B
B
A
O
none
A&B
AB
AB
none
2. Rh factor=antigen (important during pregnancy)
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• Antibodies to non-self blood types exist in the body
• Transfusion with incompatible blood leads to destruction of the
transfused cells
• Recipient-donor combinations can be fatal or safe
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B. Organ Transplants
1. MHC responsible for rejection
2. Cytotoxic T cells mount a cell-mediated response
3. Immune system suppressed
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43.4 Disorders
1. Autoimmune diseases- don’t recognize own
MHC
a. rheumatoid arthritis (cartilage attacked)
b. Insulin-dependent diabetes (pancreas
attacked)
c. Grave’s Disease (thyroid attacked ->
excessive hormone)
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D. Allergies
1. hypersensitivities to environmental antigens = allergens
2. antibodies attach to mast cells -> histamines released
-> dilation of small blood vessels -> runny nose, sneezing,
breathing difficulty (smooth muscle contraction)
3. anaphylactic shock- histamines trigger rapid dilation of
capillaries -> low BP -> shock or death
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Antigenic Variation
• Through antigenic variation, some pathogens
are able to change epitope expression and
prevent recognition
• The human influenza virus mutates rapidly, and
new flu vaccines must be made each year
• Human viruses occasionally exchange genes
with the viruses of domesticated animals
• This poses a danger as human immune
systems are unable to recognize the new viral
strain
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E. Immunodeficiency
1. can be inborn- bone marrow transplant may help
2. Hodgkin’s disease- a type of cancer that depresses
the immune response
3. AIDS- Acquired Immunodeficiency Syndrome
a. HIV binds to CD4 markers on helper T cells, some
macrophages and a few B cells
b. Virus may remain dormant for many years
c. Virus replicates inside cell and GP 120 protein
starts
to appear on surface of helper T cells
d. Cytotoxic T cells and Natural killer cells attack and
destroy helper T cells marked with GP120
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http://highered.mcgrawhill.com/sites/0072495855/student_view0/chapter24/animation__how_the_hiv_infection_cycle_works.html
e. Why can’t body fight it?
1. dormancy- no antibodies formed
2. mutates QUICKLY!
3. number of viruses- number of T cells
f. death results from opportunistic diseases
g. transmitted through body fluids
h. life expectancy increased through drug
therapies (AZT/protease inhibitors)
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Fig. 43-26
AIDS
Helper T cell concentration
in blood (cells/mm3)
Latency
Relative antibody
concentration
800
Relative HIV
concentration
600
Helper T cell
concentration
400
200
0
0
1
2
3
4
5
6
7
8
Years after untreated infection
9
10
Attack on the Immune System: HIV
• Human immunodeficiency virus (HIV) infects
helper T cells
• The loss of helper T cells impairs both the
humoral and cell-mediated immune responses
and leads to AIDS
• HIV eludes the immune system because of
antigenic variation and an ability to remain
latent while integrated into host DNA
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• People with AIDS are highly susceptible to
opportunistic infections and cancers that take
advantage of an immune system in collapse
• The spread of HIV is a worldwide problem
• The best approach for slowing this spread is
education about practices that transmit the
virus
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•
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