Download 24. The Body`s Defenses

Chapter 24
The Immune System
PowerPoint Lectures for
Biology: Concepts and Connections, Fifth Edition
– Campbell, Reece, Taylor, and Simon
Lectures by Chris Romero
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
An AIDS Uproar
• Acquired immune deficiency syndrome (AIDS)
is epidemic throughout much of the world
• HIV, the virus that causes AIDS, attacks the
immune system, destroying the body's ability
to fight infection
• Drug trials in developing nations revealed the
complex interconnectedness of science,
politics, and ethics
• The ravaging effects of AIDS demonstrates
how dependent we are on our body's built-in
defenses
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
40 million
people living with AIDS
3 million
died in 2003
5 million
newly infected in 2003
500,000
children under the age of 15 who
died
in 2003
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
INNATE DEFENSES AGAINST INFECTION
24.1 Innate defenses against infection include
the skin and mucous membranes, phagocytic
cells, and antimicrobial proteins
• Innate immunity is the body’s first line of
defense against all invaders
– Skin provides tough barrier and general
chemical defenses
– Mucous membranes
– Stomach acid
– Hairs, cilia
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Microbes that breach the body's external
defenses are confronted by innate defensive
cells
– Found in blood and interstitial fluid
– Macrophages are large phagocytic cells
– Natural killer cells release chemicals
– Specific proteins attack microbes or impede
their reproduction
• Interferons help cells resist viruses
• The complement system
– Initiated by microbes, can lead to lysis of
invaders
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Colorized SEM 3,800
LE 24-1a
Bacteria
LE 24-1b
Virus
Viral nucleic acid
Antiviral proteins block
viral reproduction
New viruses
Interferon
genes
turned
on
DNA
mRNA
Interferon
molecules
Host cell 1
Makes interferon;
is killed by virus
Interferon stimulates
cell to turn on genes
for antiviral proteins
Host cell 2
Protected against virus
by interferon from cell 1
24.2 The inflammatory response mobilizes nonspecific
defense forces
•
Tissue damage triggers the inflammatory response
–
•
Can disinfect tissues and limit further infection
Steps of the inflammatory response
1. Tissue injury releases chemical signals such as
histamine
2. Local blood vessels dilate and leakiness
increases; phagocytes migrate to the area
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
3. Phagocytes consume bacteria and cell
debris; tissue heals
•
The inflammatory response may be
widespread as well as localized
–
White blood cells may increase
–
Fever may stimulate phagocytosis
–
Septic shock
•
Overwhelming systemic inflammatory
response
•
May cause death
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-2
Skin surface
Pin
Bacteria
Chemical
signals
White blood cell
Swelling
Phagocytes
and fluid
move into area
Phagocytes
Blood vessel
Tissue injury; release of
chemical signals such as
histamine
Dilation and increased leakiness
of local blood vessels; migration
of phagocytes to the area
Phagocytes (macrophages and
neutrophils) consume bacteria
and cell debris; tissue heals
24.3 The lymphatic system becomes a crucial
battleground during infection
•
The lymphatic system is involved in both innate and
acquired immunity
– Branching network of lymphatic vessels
– Lymph nodes packed with macrophages and white
blood cells
– Tonsils and adenoids
– Appendix
– Spleen
– Bone marrow and thymus
– Lymph, similar to interstitial fluid
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Main functions of the lymphatic system
– Return tissue fluid to circulatory system
• Lymphatic vessels take up fluid from
tissue spaces
• Lymph reenters circulatory system
through two large lymphatic vessels
– Fight infection
• Microbes picked up from infection sites
travel in lymph through lymphatic organs
packed with white blood cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-3
Adenoid
Tonsil
Lymph nodes
Right lymphatic
duct, entering
vein
Thoracic duct,
entering vein
Lymph node
Masses of
lymphocytes and
macrophages
Thymus
Valve
Lymphatic vessel
Blood capillary
Tissue cells
Interstitial fluid
Thoracic
duct
Appendix
Bone
marrow
Spleen
Lymphatic
vessels
Lymphatic
capillary
ACQUIRED IMMUNITY
24.4 The immune response counters specific
invaders
•
The immune system recognizes and defends
against invading microbes and cancer cells
– Can distinguish one infectious agent from
another
•
Acquired immunity develops only after exposure to
a specific foreign substance (antigen)
– System produces a specific type of antibody
that helps counter the antigen's effects
– Primed system remembers the antigen and
reacts to it in the future
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• Immunity is usually acquired by natural exposure
to antigens but may be achieved by vaccination
– Active immunity
• Person's own immune system actively
produces antibodies
– Passive immunity
• Person receives premade antibodies, as a
fetus does from its mother
• Immunity lasts only as long as the
antibodies do
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
24.5 Lymphocytes mount a dual defense
• Lymphocytes originate from stem cells in the
bone marrow
• Humoral immunity
– B cells secrete antibodies that circulate in
blood and lymph to sites of infection
– Defends primarily against bacteria and
viruses present in body fluids
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Cell-mediated immunity
– In the thymus, immature lymphocytes
specialize into T cells
– T cells attack cells infected with pathogens,
fungi and protozoans, cancer cells
– T cells also promote phagocytosis and
production of antibodies
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Functioning of B and T cells
– Certain genes in the cell are turned on
– Cell synthesizes specific protein molecules,
which are incorporated into the plasma
membrane
– Antigen receptors sticking up from cell
surface recognize specific antigens and
mount a defense
• Millions of diverse B and T cells stand ready to
recognize and bind virtually every possible
antigen
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-5a
Bone marrow
Thymus
Stem cell
Via
blood
Immature lymphocyte
Antigen
receptors
T cell
B cell
Humoral
immunity
Cell-mediated
immunity
Via
blood
Lymph nodes, spleen, and
other lymphatic organs
Other parts of the
lymphatic system
Final maturation
of B and T cells in
lymphatic organ
24.6 Antigens have specific regions where
antibodies bind to them
• Antigens are usually molecules on the surface
of viruses or foreign cells
• Antigenic determinants are the specific regions
on an antigen to which antibodies bind
– Antigens may have several different
determinants
– Immune system may direct several distinct
antibodies against one antigen
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-6
Antibody A
molecules
Antigenbinding
sites
Antigenic
determinants
Antigen
molecule
Antibody B
molecule
24.7 Clonal selection musters defensive forces
against specific antigens
• Primary immune response: lymphocytes
exposed to antigen for the first time
– Antigen activates a small subset of
lymphocytes (B cells) bearing
complementary receptors
– The selected B cells multiply into clones of
effector and memory cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Effector (plasma) cells
– Combat the antigen
– Secrete antibody molecules that circulate in
blood and contribute to humoral immunity
– Last only 4 or 5 days
• Memory cells
– Remain in lymph nodes
– May last for decades, sometimes confer
lifetime immunity
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Secondary immune response
– Memory cells exposed to same antigen a
second time
– Second round of clonal selection ensues
– Secondary response is faster and stronger;
produces very high levels of antibodies
Animation: Role of B Cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-7a
Primary
immune
response
Antigen receptor
(antibody on cell
surface)
Antigen
molecules
First exposure
to antigen
Antibody
molecules
Endoplasmic
reticulum
Plasma (effector) cells secreting antibodies
Memory cells
Antigen
molecules
Second exposure
to same antigen
Secondary
immune
response
Antibody
molecules
Endoplasmic
reticulum
Plasma (effector) cells secreting antibodies
Memory cells
• Comparison of primary and secondary immune
response
– Primary response
• Takes several days to occur, during which
the individual may become ill
• Antibody level peaks in about two weeks,
effector cells die out
– Secondary response
• Occurs quickly
• Is of greater magnitude and is more
prolonged
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Acquired immunity is specific: the body's
response to a second antigen is not influenced
by its response to the first one
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-7b
Antibody concentration
Second exposure
to antigen X,
first exposure
to antigen Y
Secondary immune
response to
antigen X
First exposure
to antigen X
Primary immune
response to
antigen X
Primary immune
response to
antigen Y
Antibodies
to Y
Antibodies
to X
0
7
14
21
28
35
Time (days)
42
49
56
24.8 Antibodies are the weapons of humoral immunity
•
Antibody molecules are secreted by plasma
(effector) B cells
•
Antibody molecule structure
– Y shaped, made of two identical "heavy" and
two identical "light" polypeptide chains
– A C (constant) and a V (variable) region on
each chain
– Antigen-binding sites specific to the antigenic
determinants that elicited its secretion
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Antibody functions in humoral immunity
– Binds its antigen at the antigen-binding site
– Assists in elimination of the antigen, at the
C region of the heavy chains
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-8b
Antigen-binding
sites
Light
chain
C
C
Heavy
chain
24.9 Antibodies mark antigens for elimination
• Effector mechanisms involve a specific
recognition-and-attack phase followed by a
nonspecific destruction phase
• Antibodies mark invaders by forming antigenantibody complexes
• Binding triggers mechanisms to eliminate the
invader
– Neutralization
– Agglutination of microbes
– Precipitation of dissolved antigens
– Activation of complement system
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-9
Binding of antibodies to antigens
inactivates antigens by
Neutralization
(blocks viral binding
sites; coats bacteria)
Agglutination
of microbes
Precipitation of
dissolved antigens
Complement
molecule
Bacteria
Virus
Antigen
molecules
Bacterium
Activation of
complement system
Foreign cell
Enhances
Leads to
Phagocytosis
Cell lysis
Macrophage
Hole
Animation: Antibodies
Anitbodies
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
CONNECTION
24.10 Monoclonal antibodies are powerful tools in
the lab and clinic
• Antibodies are used in clinical diagnosis,
treatment, and research
• Monoclonal antibodies
– All cells producing the antibodies are
descendants of a single cell
– Harvested from cell cultures rather than
from animals
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Production of monoclonal antibodies
– Animal injected with antigen that stimulates
its B cells to make specific antibodies
– B cells fused with tumor cells
– Hybrid cells make antibodies specific for the
desired antigenic determinant
• Can multiply indefinitely in culture
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-10a
Antigen injected
into mouse
Tumor cells grown
in culture
B cells
(from spleen)
Tumor cells
Cells fused to
generate hybrid
cells
Single hybrid cell
grown in culture
Antibody
Hybrid cell culture,
producing monoclonal antibodies
24.11 Helper T cells stimulate humoral and cellmediated immunity
• Cell-mediated immunity produced by T cells
battles pathogens that have entered body cells
• T cells respond only to antigens present on the
surface of the body's own cells
– Cytotoxic T cells attack infected cells
– Helper T cells
• Help activate T cells, B cells, and
macrophages
• Interact with antigen-presenting cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Precise interaction of antigen-presenting cells
and helper T cells
– Antigen-presenting cell self protein binds
antigen nonself molecules and displays
them on the cell surface
– Helper T cells recognize and bind to the
self-nonself complex
• Depends on highly specific receptors in
the T cell's plasma membrane
– Binding activates helper T cells
• Enhanced by other signals
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Activated helper T cells promote the immune
response, particularly secretion of stimulatory
proteins
– Make helper T cells grow and divide,
producing memory cells and additional
helper T cells
– Help activate B cells, stimulating humoral
immunity
– Stimulate activity of cytotoxic T cells
Animation: Helper T Cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-11
Self-nonself
complex
Microbe
Macrophage
B cell
T cell
receptor
Interleukin-2
stimulates
cell division
Helper
T cell
Interleukin-2
activates
other B cells
and T cells
Self protein
Antigen from microbe
(nonself molecule)
Antigen-presenting Interleukin-1
cell
stimulates
helper T cell
Binding Binding
site for site for
antigen self protein
Humoral
immunity
(secretion of
antibodies by
plasma cells)
Cytotoxic
T cell
Cell-mediated
immunity
(attack on
infected cells)
CONNECTION
• 24.12 HIV destroys helper T cells,
compromising the body's defenses
• HIV (human immunodeficiency virus) causes
AIDS
– Most often attacks helper T cells
– Destruction of humoral and cell-mediated
immunity compromises body's ability to fight
infections
Animation: HIV Reproductive Cycle
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Mechanism of HIV action
– Transmitted through body fluids
– Inside the body, HIV binds to and enters
helper T cells
– RNA genome of HIV is reverse-transcribed
inside the T cells
– Newly produced DNA is integrated into host
T cell's genome, able to direct the
production of new viruses
– HIV in the bloodstream may infect and kill
other helper T cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Immune system impairment makes patients
with AIDS susceptible to opportunistic
infections and cancer
• So far, AIDS is incurable
– Certain drugs slow HIV reproduction and
the progress of AIDS
– Best way to stop AIDS is to prevent spread
of HIV
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
24.13 Cytotoxic T cells destroy infected body
cells
• Like helper T cells, cytotoxic T cells recognize
and bind with self-nonself complexes on
infected cells
• Mechanism of cytotoxic T cell action
– Binding to infected cell stimulates cytotoxic
T cell to synthesize perforin
– Perforin makes holes in infected cell's
membrane, and T cell enzymes enter
– Infected cell is destroyed
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-13
Cytotoxic T cell binds
to infected cell
Perforin makes holes in
infected cell’s membrane
and enzyme enters
Self-nonself
complex
Infected cell
Perforin
molecule
Hole
forming
Foreign
antigen
Cytotoxic
T cell
Enzyme that
can promote
apoptosis
Infected cell
is destroyed
Video: T Cell Receptors
Animation: Cytotoxic T Cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
24.14 Cytotoxic T cells may help prevent cancer
• Genetic changes leading to cancer can result
in new proteins displayed on cell surfaces
• T cells identify these tumor antigens as foreign
and destroy the affected cells
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
24.15 The immune system depends on our
molecular fingerprints
• Each person's cells have particular self protein
"fingerprints" that mark them as off limits to
attack by lymphocytes
• Self proteins are coded for by MHC (major
histocompatibility complex) genes
– Except for identical twins, two individuals
cannot have identical self proteins
• Transplanted organs may be rejected because
their cells lack the unique fingerprint of the
recipient's self proteins
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
DISORDERS OF THE IMMUNE SYSTEM
CONNECTION
24.16 Malfunction or failure of the immune
system causes disease
• In autoimmune diseases, the immune system
turns against some of the body's own
molecules
• In immunodeficiency diseases, immune
system components are lacking, and infections
occur frequently
• Physical and emotional stress may weaken the
immune system
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
CONNECTION
24.17 Allergies are overreactions to certain
environmental antigens
• Allergies are abnormal sensitivities to antigens
(allergens) in the surroundings
• Allergic reactions occur in two stages
– Sensitization: initial exposure to allergen
• Allergen enters bloodstream
• B cells make antibodies
• Antibodies attach to mast cells that produce
histamines and trigger the inflammatory
response
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– Later exposure to same allergen
• Allergen binds to antibodies on mast cell
• Histamine is released, causing allergy
symptoms
• Anaphylactic shock is a severe allergic
reaction
– Causes severe drop in blood pressure
– Potentially fatal
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
LE 24-17
B cell
(plasma cell)
Mast
cell
Antigenic
determinant
Allergen (pollen
grain) enters blood
stream
Histamine
B cells make
Antibodies
antibodies
attach to
mast cell
Sensitization: Initial exposure to allergen
Allergen binds
to antibodies
on mast cell
Histamine is
released, causing
allergy symptoms
Later exposure to same allergen