Chapter 43

The Immune System

Overview: Recognition and Response

Immune system: recognition of foreign bodies and
response by production of immune

cells and proteins

Innate immunity
Defense active immediately upon infection
Present from birth
All animals (and plants)
Adaptive immunity
Specific targeted defenses after exposure
aka acquired immunity
Only in vertebrates

Figure 43.2

Pathogens
(such as bacteria,
fungi, and viruses)

INNATE IMMUNITY
(all animals)
Recognition of traits shared
by broad ranges of
pathogens, using a small
set of receptors
Rapid response

ADAPTIVE IMMUNITY
(vertebrates only)
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
Natural killer cells
Antimicrobial proteins
Inflammatory response
Humoral response:
Antibodies defend against
infection in body fluids.
Cell-mediated response:
Cytotoxic cells defend
against infection in body cells.

Concept 43.1: In innate immunity,

recognition and response rely on traits
common to groups of pathogens
Recognition of the bad guys is very important
Fungal & bacterial cell walls are ID tags
Response depends on class of pathogen
Basic innate defenses include:
Barrier defenses
Phagocytosis
Antimicrobial peptides

Innate Immunity of Invertebrates

First line of defense is exoskeleton made of chitin
Digestive system protected by:
a chitin-based barrier
Lysozymes: enzymes that break down bacterial
cell walls
Hemocytes: immune cells circulating in hemolymph
Activate chemicals to kill pathogens
Secrete antimicrobial peptides
Carry out phagocytosis
2011 Pearson Education, Inc.

Figure 43.3

Pathogen

PHAGOCYTIC
CELL

Vacuole

Lysosome
containing
enzymes

Innate Immunity of Vertebrates

Innate immunity
First response to infection
Basis of adaptive immunity
What is unique to vertebrates?
Natural killer cells
Interferons
Inflammatory response

Barrier Defenses
Skin
Mucous membranes of respiratory, urinary, and
reproductive tracts

Mucus traps microbes

Saliva, mucus, and tears are hostile to microbe
Lysozymes destroy

Acidic environment of stomach

Cellular Innate Defenses

Phagocytic cells
aka destroyers
aka good guys
Toll-like receptors, TLRs
Bind to molecules common to certain
pathogens
Trigger internal innate immune defense

Figure 43.6

EXTRACELLULAR
FLUID

Lipopolysaccharide

Helper
protein

TLR4

Flagellin

PHAGOCYTIC
CELL
TLR5

VESICLE
CpG DNA

TLR9
TLR3 Innate immune
responses

ds RNA

Cellular Innate Defenses

Types of phagocytic cells

Neutrophils engulf and destroy pathogens

Macrophages are found throughout the body
Dendritic cells stimulate development of

adaptive immunity
Eosinophils discharge destructive enzymes

Natural killer cells

Release chemicals to kill viral or cancer cells
Circulate and detect these abnormal cells

Figure 43.7

Blood
capillary

Interstitial
fluid

Adenoid
Tonsils
Lymphatic
vessels
Thymus
Tissue
cells
Peyers
patches
(small
intestine)
Appendix
(cecum)

Spleen

Lymphatic
vessel
Lymphatic
vessel

Lymph
nodes

Lymph
node

Masses of
defensive cells

Antimicrobial Peptides and Proteins

Attack pathogens and stop their reproduction
Interferons: proteins interfering with viral spread
Alert other cells of the baddies
Activate macrophages to eat up viral cells
Complement system
Infection-fighting system of 30 circulating proteins
Cause lysis of invading cells
Active in the inflammatory response

Inflammatory Responses
Mast cells: a type of connective tissue
Release histamine
Triggers blood vessel dilation
Cytokines promote blood flow
Redness, swelling, warm
temperature
Minor damage --- local response
Major damage --- systemic response

Figure 43.8-1

Pathogen

Mast
cell

Splinter

Macrophage

Signaling
molecules

Capillary
Neutrophil
Red
blood cells

Figure 43.8-2

Pathogen

Mast
cell

Splinter

Macrophage

Signaling
molecules

Capillary
Neutrophil
Red
blood cells

Movement
of fluid

Figure 43.8-3

Pathogen

Mast
cell

Splinter

Macrophage

Signaling
molecules

Capillary
Neutrophil
Red
blood cells

Movement
of fluid
Phagocytosis

Inflammatory Responses
Fever is a systemic inflammatory response
Triggered by pyrogens released by
macrophages and by toxins from pathogens
Septic shock is a life-threatening condition
Caused by overwhelming inflammatory
response
of cases result in death

2011 Pearson Education, Inc.

Evasion of Innate Immunity by Pathogens

Pathogens may avoid destruction if:
surface is modified to prevent recognition
they resist breakdown after phagocytosis

Constancy of evolution
Good and bad...

Adaptive Immunity
The adaptive response relies on two types of
lymphocytes, or white blood cells
T Cells
Mature in the
thymus above the
heart
Cell mediated
response

B Cells
Remain and mature
in bone marrow
Humoral response
Produce antibodies

Antigens - substances eliciting responses from B

or T cells
Exposure to pathogen activates B and T cells
with antigen receptors specific for parts of that
pathogen (bind through epitope, small
accessible part of antigen)
Specificity: 1 lymphocyte for 1 antigen

Figure 43.UN01

Antigen
receptors

Mature B cell

Mature T cell

Outline
Pathogen recognition
Humoral immune response: antibodies help
neutralize or eliminate toxins & pathogens in the
blood and lymph
Cell-mediated immune response: specialized T
cells destroy infected host cells

Figure 43.20a

Humoral+ (antibody-mediated)

Cell-mediated
immune response

immune response

Key
+

Antigen (1st exposure)

Engulfed by
Antigenpresenting cell

Stimulates
Gives rise to

+
B cell

Helper T cell

Cytotoxic T cell

Antigen Recognition (in T Cells)

Each T cell receptor consists of two different
polypeptide chains
and
Tips of the chain form a variable (V) region; the
rest is a constant (C) region
T cell and B cell antigen receptors are
functionally different

Figure 43.11

Antigenbinding
site

T cell
antigen
receptor

Variable
regions

Constant
regions

Disulfide
bridge

chain

T cell

Transmembrane
region
chain
Plasma
membrane

Cytoplasm of T cell

 Antigen presentation
MHC molecules bind and transport antigen
fragments to cell surface
MHC (major histocompatibility complex)
Host proteins that display antigen fragments
on cell surface

Figure 43.12b

Top view
Antigen
fragment
MHC
molecule
Host cell
(b) A closer look at antigen presentation

 Antigen-presenting cells
Have class I and class II MHC molecules on
surfaces
Receptors on helper T cells bind to antigen &
class II MHC molecule; signals exchange
Helper T cell activated, proliferates, & forms
clones of helper T cells, which activate the
two responses & appropriate B cells

Figure 43.16

Antigenpresenting
cell

Antigen fragment

Pathogen
Class II MHC molecule
Accessory protein
Antigen receptor

Helper T cell
Cytokines
Humoral
immunity
B cell

+
3

+
2
+
Cytotoxic T cell

Cellmediated
immunity

Cell Mediated Response

Cytotoxic T cells proliferate into memory and
active cells
Antigen exposed to steady stream of
lymphocytes until match is made
Binding of mature lymphocyte to antigen
initiates its activation
Cell-mediated response uses antigen
presentation, but employs Type 1 MHC

Proliferation
Once activated, T cell undergoes multiple cell
divisions
This proliferation of lymphocytes is called clonal
selection and produces:
short-lived activated effector cells that act
immediately against the antigen
long-lived memory cells that can give rise to
effector cells if the same antigen is
encountered again

Figure 43.12a

Displayed
antigen
fragment
MHC
molecule
Antigen
fragment
Pathogen
Host cell
(a) Antigen recognition by a T cell

T cell
T cell antigen
receptor

Active Cytotoxic T Cells

Recognize foreign protein fragments on
infected cells
Possess the accessory protein that binds to
class I MHC molecules
Secrete perforins, which make pores in
membrane
Secrete granzymes, which destroy the cell

Figure 43.17-1

Cytotoxic T cell

Accessory
protein
Class I MHC
molecule
Infected
cell
1

Antigen
receptor

Antigen
fragmen
t

Figure 43.17-2

Cytotoxic T cell

Accessory
protein
Class I MHC
molecule
Infected
cell
1

Antigen
receptor

Perforin
Pore

Antigen
fragmen
t

Granzymes

Figure 43.17-3

Cytotoxic T cell

Accessory
protein
Class I MHC
molecule
Infected
cell
1

Released
cytotoxic
T cell
Antigen
receptor

Perforin
Pore

Antigen
fragmen
t

Dying
infected cell

Granzymes

Humoral Response
B Cell Antigen binding site consists of:
2 identical heavy polypeptide chains
2 identical light polypeptide chains
disulfide bridges that link chains
Chains have constant (c) regions and
variable (v) regions
c regions have little variability
v regions differ greatly & contribute to
antigen specificity for B cells

V
C

B cell
antigen
receptor

Light
chain

Heavy
chains
B cell

Disulfide
bridge

Antigenbinding site

Antigen
binding
site

Figure 43.9

Cytoplasm of B cell

Variable
regions
Constant
regions

Transmembrane
region

Plasma
membrane

Response to Cytokines
B cell proliferates and differentiates into
memory B cells and antibody- secreting
effector cells called plasma cells

Figure 43.18-1

Antigen-presenting
cell

Class II
MHC
molecul
e
Antigen
receptor

Accessory
protein

Helper T cell

Pathogen
Antigen
fragment

Figure 43.18-2

Antigen-presenting
cell

Class II
MHC
molecul
e
Antigen
receptor

Pathogen
Antigen
fragment

B cell

Accessory
protein

Cytokines

Activated
helper T cell

Helper T cell

Figure 43.18-3

Antigen-presenting
cell

Class II
MHC
molecul
e
Antigen
receptor

Pathogen
Antigen
fragment

B cell

Accessory
protein

Cytokines

Activated
helper T cell

Helper T cell

Memory B cells

Plasma cells

Secreted
antibodies

 Plasma cells secrete soluble form of protein

called an antibody or immunoglobulin (Ig)
Secreted antibodies similar to B cell receptors
but lack transmembrane regions that
anchoring receptor to plasma membrane
Also happens by direct binding to an antigen

2011 Pearson Education, Inc.

Figure 43.10

Antigen
receptor

Antibody

B cell
Antigen

Epitope

Pathogen
(a) B cell antigen receptors and antibodies

Antibody C
Antibody A

Antibody B

Antigen
(b) Antigen receptor specificity

 Antibodies disable pathogens in three ways

Neutralization - antibodies bind to viral
surface proteins and block infection
Opsonization - antibodies bind to antigens
on bacteria, creating a target for
macrophages or neutrophils
Complement system and pore formation
- complexes bind to complement protein,
triggering a cascade of protein activation
Membrane attack complex forms pore in
foreign cell = lysis

Figure 43.19a

Neutralization
Antibody

Virus

Figure 43.19b

Opsonization

Bacterium

Macrophage

Figure 43.19c

Activation of complement system and pore

formation
Complement proteins
Formation of membrane
attack complex
Flow of water
and ions
Pore
Foreign
cell

Antigen

B cells can express five different classes of

immunoglobulin (Ig) with similar antigen-binding
specificity but different heavy chain C regions

IgD: Membrane bound

IgM: First soluble class produced
IgG: Second soluble class; most abundant
IgA and IgE: Remaining soluble classes

Summary of Humoral and Cell-Mediated

Immune Responses
Both responses can include primary and
secondary immune response
Memory cells allow for secondary response

B Cell and T Cell Development

Adaptive immune system has four major
characteristics
Diversity of lymphocytes and receptors
Self-tolerance
B and T cells proliferate after activation
Immunological memory

Generation of B and T Cell Diversity

Diverse variety of receptors results from
combination of variable elements
Immunoglobulin (Ig) gene encodes one chain of
the B cell receptor
Many different chains can be produced from the
same gene by rearrangement of the DNA

Figure 43.13

DNA of
undifferentiated
V37
B cell

V39

V38

J1 J2 J3 J4

V40

J5 Intron

1 Recombination deletes DNA between

randomly selected V segment and J segment
DNA of
differentiated
B cell

V37

V39 J5

V38

Intron

Functional gene
2 Transcription
pre-mRNA

V39 J5

Intron

3 RNA processing
mRNA Cap

V39 J5

Poly-A tail
V

4 Translation

V
C

Light-chain polypeptide

Variable
region

Consta
nt
region

Antigen receptor
B cell

Origin of Self-Tolerance
Antigen receptors generated by random
rearrangement of DNA
As lymphocytes mature they are tested for selfreactivity
B & T cells with receptors specific for the
bodys own molecules are destroyed or
rendered nonfunctional

Figure 43.14

B cells that
differ in
antigen
specificity

Antigen

Antigen
receptor

Antibody

Memory
cells

Plasma cells

Immunological Memory
Immunological memory allows for long-term
protection, due to prior infection or vaccination
Primary immune response - first exposure to
specific antigen
Selected B & T cells give rise to effector forms
Secondary immune response - memory cells
facilitate a faster, more efficient response

Figure 43.15

Antibody concentration
(arbitrary units)

Primary immune response Secondary immune response to

to antigen A produces
antigen A produces antibodies to A;
antibodies to A.
primary immune response to antigen
B produces antibodies to B.
104
103
Antibodies
to A

102

Antibodies
to B

101
100

Exposure
to antigen A

14

21

28

35

42

Exposure to
antigens A and B
Time (days)

49

56

Active and Passive Immunization

Active immunity - develops naturally when
memory cells form clones in response to an
infection
Can develop following vaccination
Immunization - a nonpathogenic form of a
microbe elicits an immune response to an
immunological memory

 Passive immunity - provides immediate,

short-term protection
IgG crosses placenta from mother to fetus
or IgA passes from mother to infant in
breast milk
Conferred artificially by injecting
antibodies into a non-immune person

Figure 43.20
Humoral (antibody-mediated) immune response

Cell-mediated immune response

Key

Antigen (1st exposure)

Engulfed by
Antigenpresenting cell

Stimulates
Gives rise to

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

Defend against
intracellular
pathogens and cancer

Figure 43.20b

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

Defend against
intracellular
pathogens
and cancer

Antibodies as Tools
Antibody specificity and antigen-antibody
binding are used in research, diagnosis, and
therapy
Polyclonal antibodies
Produced after exposure to antigen
Products of many different clones of plasma
cells, each specific for a different epitope
Monoclonal antibodies
Prepared from a single clone of B cells
grown in culture

Immune Rejection
Cells transferred from one person to another
can be attacked by immune defenses
Complicates blood transfusions or tissue &
organ transplants

Blood Groups
Antigens on red blood cells determine whether a
person has blood type A, B, AB, or O
Antibodies to nonself blood types exist in body
Transfusion with incompatible blood leads to
destruction of the transfused cells
Can be fatal, depending on type

Tissue and Organ Transplants

MHC molecules are different among individuals
Different MHC molecules stimulate rejection of
grafts or transplants
Donor & recipient MHC type must match well
Immunosuppressive drugs can help
Lymphocytes in bone marrow can cause
rejection

Concept 43.4: Disruptions in immune

system function can elicit or exacerbate
disease
Some pathogens have evolved to diminish
effectiveness of host response

If the delicate balance of the immune system is

disrupted, effects range from minor to fatal
Exaggerated, Self-Directed, and Diminished
immune responses

Allergies
Allergies - exaggerated responses to antigens
called allergens
In localized allergies such as hay fever, IgE
antibodies produced after first exposure to an
allergen attach to receptors on mast cells

Figure 43.22

Histamine

IgE
Allergen

Granule
Mast
cell

 The next time the allergen enters the body, it

binds to mast cellassociated IgE molecules
Mast cells release histamine, causing vascular
changes, leading to typical allergy symptoms
Acute allergic response can lead to anaphylactic
shock, a life-threatening reaction, within seconds
of allergen exposure
Develops when widespread release of mast
cell contents triggers abrupt dilation of
peripheral blood vessels, causing constriction
in bronchioles and drop in blood pressure
(EpiPens - epinephrine hormone that
counteracts allergic response)

Autoimmune Diseases
Autoimmune disease - immune system loses
tolerance for self and turns against certain
molecules of the body
Systemic lupus erythematosus
Rheumatoid arthritis
Insulin-dependent diabetes mellitus
Multiple sclerosis
Gender, genetics and environment all influence
susceptibility to autoimmune disorders

Figure 43.23

Exertion, Stress, and the Immune System

Moderate exercise improves immune system
function
Psychological stress has been shown to disrupt
immune system regulation by altering the
interactions of the hormonal, nervous, and
immune systems
Sufficient rest is very important for immunity

Immunodeficiency Diseases
Immunodeficiency - hereditary or
developmental defects that prevent proper
functioning of innate, humoral, and/or cellmediated defenses
Acquired immunodeficiency develops later in
life & results from exposure to chemical &
biological agents
Immunodeficiency can lead to frequent and
recurrent infections and increased susceptibility
to certain cancers
Acquired immunodeficiency syndrome
(AIDS) is caused by a virus

How Pathogens Avoid Arrest

If mechanisms against pathogens evolve, why

should pathogens not have evolved?
There are several different ways pathogens
escape your immune system

Antigenic Variation
Through antigenic variation, some pathogens are
able to change epitope expression and prevent
recognition
Ex:The human influenza virus mutates rapidly,
and new flu vaccines must be made each
year
Gene exchange between pathogens; immune
system does not recognize new strain
Ex: Between humans and domesticated
animals

Figure 43.24

Millions of parasites
per mL of blood

1.5

Antibodies
to
variant 1
appear

1.0

Variant 1

Antibodies
to
variant 2
appear
Variant 2

Antibodies
to
variant 3
appear
Variant 3

0.5

25

26
27
Weeks after infection

28

Latency
Some viruses may remain in a host in an
inactive state called latency
Ex: Herpes simplex viruses can be present in
a human host without causing symptoms
Lysogenic cycle

Attack on the Immune System: HIV

HIV escapes & attacks adaptive response
infects helper T cells
DNA of virus incorporates into host DNA
Humoral and cell-mediated immune responses
impaired
HIV eludes the immune system through antigenic
variation and latency through integration

Animation: HIV Reproductive Cycle

Helper T cell concentration

(in blood (cells/mm3)

Figure 43.25

Latency

AIDS

Relative anti-HIV antibody

concentration

800

Relative HIV
concentration

600

Helper T cell
concentration

400

200

3
7
8
2
4
5
6
Years after untreated infection

10

Attack on the Immune System: HIV

More susceptibility to infections and cancer
HIV alone not the primary cause of death
The spread of HIV is a worldwide problem
The best approach for slowing spread is
education about practices that transmit the
virus

Cancer and Immunity

Adaptive immunity impaired = cancer frequency up
20% of human cancers involve viruses!
Immune system can act to defend against viruses
that cause cancer & cancer cells that harbor
viruses
2006: HPV vaccine against cervical cancer