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Immunity
Chapter 38 Part 1
Impacts, Issues
Frankie’s Last Wish
 Infection with a common, sexually transmitted
virus (HPV) causes most cervical cancers –
including the one that killed Frankie McCullogh
38.1 Integrated Responses to Threats
 Immunity
• The capacity to resist and combat infection by
pathogens such as viruses, bacteria, and fungi
 In vertebrates, innate and adaptive immune
systems work together to combat infection and
injury
Evolution of the Body’s Defenses
 Proteins in eukaryotic cell membranes have
unique patterns that the body recognizes as self
 Cells of multicelled eukaryotes have receptors
that recognize nonself cues (PAMPs) on or in
pathogens, and trigger defense responses
Innate Immunity
 Binding of a receptor with a PAMP triggers
immediate, general defense responses that are
part of inborn innate immunity
 Complement
• Proteins that destroy microorganisms or flag them
for phagocytosis
• An innate immune response
Adaptive Immunity
 Adaptive immunity is a system of defenses that
specifically targets billions of different antigens
an individual may encounter during its lifetime
 Antigen
• PAMP or other molecule the body recognizes as
nonself that triggers an active immune response
Three Lines of Defense
1. Physical, chemical, and mechanical barriers
• Keep pathogens outside the body
2. Innate immunity
• General responses destroy invaders inside the
body before they become established
3. Adaptive immunity
• Huge populations of white blood cells form to
target and remember a specific antigen
Mucus and Cilia: Physical Barriers
Comparing Innate and Active Immunity
The Defenders
 White blood cells (leukocytes) specialized for
different tasks carry out all immune responses
• Phagocytes (neutrophils, macrophages,
dendritic cells)
• Secretory cells (eosinophils, basophils, mast
cells
• Lymphocytes (B and T lymphocytes, natural
killer cells)
The Defenders
 All white blood cells secrete chemicals, including
cell-to-cell signaling molecules (cytokines) that
coordinate all aspects of immunity
• Interleukins
• Interferons
• Tumor necrosis factors
White Blood Cells
Fig. 38-3a, p. 661
Fig. 38-3b, p. 661
Chemical Weapons of Immunity
38.1 Key Concepts
Overview of Body Defenses
 The vertebrate body has three lines of immune
defenses
• Surface barriers prevent invasion by ever-present
pathogens
• General innate responses rid the body of most
pathogens
• Adaptive responses specifically target pathogens
and cancer cells
38.2 Surface Barriers
 Normal flora
• Billions of microorganisms normally live on
human surfaces, including interior tubes and
cavities of digestive and respiratory tracts
 A pathogen can cause infection only if it enters
the internal environment by penetrating skin or
other protective barriers at the body’s surfaces
Some Normal Flora
Vertebrate Surface Barriers
 Physical, chemical, and mechanical barriers
keep microorganisms outside body tissues
•
•
•
•
•
•
Skin
Mucus and cilia
Lysozyme
Gastric fluid and bile salts
Normal flora
Urination
Vertebrate Surface Barriers
Skin
 Healthy, intact skin is an effective surface barrier
skin surface
epithelial
cells die and
become filled
with keratin
as they are
pushed toward
skin surface
epidermis
dividing
epithelial
cells
0.1 mm
Fig. 38-5, p. 663
38.3 Remember to Floss
 Dental plaque
• A thick, sticky biofilm of glycoproteins, bacteria,
and their products that contribute to tooth decay
and gum disease (periodontitis)
 Nine of every ten cardiovascular disease
patients have serious periodontal disease
 Oral bacteria associated with periodontitis are
also found in atherosclerotic plaque
Plaque
38.2-38.3 Key Concepts
Surface Barriers
 Skin, mucous membranes, and secretions at the
body’s surfaces function as barriers that exclude
most microbes
38.4 Innate Immune Responses
 Innate immune mechanisms nonspecifically
eliminate pathogens that invade internal tissues
before they become established
•
•
•
•
Phagocytes
Complement
Inflammation
Fever
Phagocytes
 Macrophages
• Large phagocytes that patrol interstitial fluid and
engulf and digest pathogens
• Secrete cytokines when receptors bind to antigen
• Cytokines attract more macrophages, neutrophils,
and dendritic cells to infection site
Complement
 Complement proteins become activated when
they encounter antigen
• Cascading enzyme reactions concentrate
activated complement at infection site
• Complement attracts phagocytes to infection site
and tags pathogens for destruction
• Forms attack complexes that puncture bacteria
• Helps mediate active immunity
Complement Attack Complexes
activated
complement
antibody
molecule
A In some responses, complement proteins become activated when
antibodies (the Y-shaped molecules) bind to antigen—in this case, antigen
on the surface of a bacterium.
Fig. 38-7a, p. 664
activated
complement
bacterial cell
B Complement also becomes activated when it binds directly to antigen.
Fig. 38-7b, p. 664
activated
complement
C By cascading
reactions, huge numbers
of different complement
molecules form and
assemble into structures
called attack complexes.
Fig. 38-7c, p. 664
attack complex
that causes a
pore to form
through the lipid
bilayer of the
bacterium
D The attack complexes
become inserted into the
target cell’s lipid envelope or
plasma membrane. Each
complex makes a large pore
form across it.
E The pores bring
about lysis of the cell,
which dies because
of the severe
structural disruption.
Fig. 38-7de, p. 664
Inflammation
 Inflammation
• A local response to tissue damage characterized
by redness, warmth, swelling and pain, triggered
by activated complement and cytokines
• Mast cells release histamine, increasing capillary
permeability
• Phagocytes and plasma proteins leak out, attack
invaders, form clots, and clean up debris
Inflammation Response
to Bacterial Infection
A Bacteria
invade a tissue
and release
toxins or
metabolic
products that
damage tissue.
B Mast cells in
tissue release
histamine, which
widens arterioles
(causing redness
and warmth) and
increases
capillary
permeability.
C Fluid and D Complement
proteins attack
plasma
proteins leak bacteria.
Clotting factors
out of
also wall off
capillaries;
inflamed area.
localized
edema (tissue
swelling) and
pain result.
E Neutrophils and
macrophages engulf
invaders and debris.
Macrophage
secretions kill
bacteria, attract
more lymphocytes,
and initiate fever.
Stepped Art
Fig. 38-8, p. 665
Fever
 Fever
• A temporary rise in body temperature – above the
normal 37°C (98.6°F) – that often occurs in
response to infection
• Cytokines stimulate brain cells to release
prostaglandins, which act on the hypothalamus
• Fever enhances the immune response by
speeding up metabolism and phagocyte activity
• Fever over 40.6°C (105°F) can be dangerous
38.4 Key Concepts
Innate Immunity
 Innate immune responses involve a set of
general, immediate defenses against invading
pathogens
 Innate immunity includes phagocytic white blood
cells, plasma proteins, inflammation, and fever
38.5 Overview of Adaptive Immunity
 Vertebrate adaptive immunity adapts to different
antigens it encounters during its lifetime
 Lymphocytes and phagocytes interact to effect
four defining characteristics: Self/nonself
recognition, specificity, diversity, and memory
Self/Nonself Recognition
 Self versus nonself recognition
• Each kind of cell or virus has a unique identity
 MHC markers
• Plasma membrane self-recognition proteins
 T cell receptors (TCRs)
• Antigen receptors that recognize MHC markers
as self, antigens as nonself
Specificity and Diversity
 Specificity
• Defenses are tailored to target specific antigens
 Diversity
• There are potentially billions of different antigen
receptors on T and B cells
Memory
 Memory
• The capacity of the adaptive immune system to
remember an antigen
• If the same antigen appears again, B and T cells
make a faster, stronger response
First Step – The Antigen Alert
 Once a B or T cell recognizes and binds to a
specific antigen, it begins to divide by mitosis
• All descendent cells recognize the same antigen
 T cells do not recognize an antigen unless it is
presented by an antigen-presenting cell
• Macrophages, B cells, and dendritic cells digest
particles and display antigen-MHC complexes
Cell Types
 Effector cells
• Differentiated lymphocytes (B and T cells) that act
at once to fight infection
 Memory cells
• Long-lived B and T cells reserved for future
encounters with the same antigen
Antigen Processing
Fig. 38-9a, p. 666
cell engulfs
an antigenbearing
particle
endocytic
vesicle forms
antigen–MHC complexes
become displayed on
cell surface
MHC markers
particle is bind fragments
digested
of particle
into bits
lysosome
fuses with
endocytic
vesicle
Stepped Art
Fig. 38-9b, p. 666
Two Arms of Adaptive Immunity
 Antibody-mediated immune response
• B cells produce antibodies that bind to specific
antigen particles in blood or interstitial fluid
 Cell-mediated immune response
• Cytotoxic T cells and NK cells detect and destroy
infected or altered body cells
Interactions Between Antibody-Mediated
and Cell-Mediated Responses
Intercepting and Clearing Out Antigen
 After engulfing antigen-bearing particles,
dendritic cells or macrophages migrate to lymph
nodes, where T cells bind and initiate responses
 During an infection, lymph nodes swell due to
accumulation of T cells
 Antibody-antigen complexes bound by
complement are cleared by the liver and spleen
The Lymphatic System
lymph node,
midsection
(thymus
gland)
spleen
Fig. 38-11, p. 667
38.6 Antibodies
and Other Antigen Receptors
 Antigen receptors on B and T cells have the
potential to recognize billions of different antigens
 Antibody
• Y-shaped antigen receptor (protein), made only by
B cells, that binds only to the antigen that
prompted its synthesis
• Activates complement, facilitates phagocytosis, or
neutralizes pathogens or toxins
Antibody Structure
binding site for antigen
variable region
(dark green) of
heavy chain
binding site for antigen
variable region
of light chain
constant region
of light chain
constant region (bright
green) of heavy chain,
including a hinged region
Fig. 38-12b, p. 668
Five Classes of Antibodies
 Constant regions determine 5 classes of
antibodies (immunoglobins IgG, IgA, IgE, IgM,
and IgD), each with different functions
 B cell receptors are membrane-bound IgM or
IgD antibodies
Five Classes of Antibodies
Making Antigen Receptors
 Genes that encode antigen receptors occur in
several segments on different chromosomes
 Different versions are randomly spliced together
during B or T cell differentiation, producing about
2.5 billion different combinations
 T cells mature in the thymus, which stimulates
production of MHC and T cell receptors
Antigen Receptor Diversity
38.7 The Antibody-Mediated
Immune Response
 Antibody-mediated immune response
• Antigen activates naïve B cells and dendritic cells
• Naïve T cell binds to APC and differentiates into
effector and memory helper T cells
• Helper T cells bind antigen-MHC complexes on
activated B cell and secrete cytokines
• B cell differentiates into effector B cells, which
produce antibodies targeting a specific antigen,
and memory B cells
Antibody-Mediated Immune Response
A The B cell receptors on a naïve
B cell bind to a specific antigen on
the surface of a bacterium
naive
B cell
B The dendritic cell engulfs the
same kind of bacterium that the B
cell encountered.
C The antigen-MHC complexes on
the antigen-presenting cell are
recognized by antigen receptors on
a naïve T cell.
bacterium
complement
B
naive
T cell
A
D cytokines
antigenpresenting
dendritic
cell
C
effector
D Antigen receptors of one of the
B cell
helper T
effector helper T cells bind
cell
antigen-MHC complexes on the B
cell.
E
E The cytokines induce the B cell
to divide, giving rise to many
memory
effector
B cell
B cell
identical B cells.
F The effector B cells begin
making and secreting huge
numbers of IgA, IgG, or IgE.
dendritic
cell
memory
helper T
cell
F
Stepped Art
Fig. 38-14, p. 670
Clonal Selection and Memory Cells
 Only B cells with receptors that bind antigen
divide (clone) and differentiate into effector and
memory B cells
 First exposure (primary response) produces
memory B and T cells; secondary response is
stronger and faster
Clonal Selection and Memory Cells
antigen
Antigen binds only
to a matching B cell
receptor.
mitosis
clonal
population
of effector
B cells
Many effector B cells secrete many antibodies.
Fig. 38-15a, p. 671
B cell with bound antigen
mitosis
primary
immune
response
effector cells
memory cells
mitosis
secondary
immune
response
effector cells
memory cells
Fig. 38-15b, p. 671
Primary and Secondary
Immune Response
38.8 The Cell-Mediated Response
 Cell-mediated immune response
• Dendritic cell ingests altered body cell, displays
antigen-MHC complexes, migrates to lymph node
• Naïve helper T and cytotoxic T cells bind to APC
• Activated helper T divides and differentiates into
memory and effector cells; cytokines signal
division of activated cytotoxic T cells
• Cytotoxic T cells circulate and touch-kill altered
body cells
Primary Cell-Mediated Response
dendritic
cell
A A dendritic cell engulfs a
virus-infected cell.
A
B Receptors on a naïve helper T
cell bind to antigen-MHC
complexes on the dendritic cell.
naive
antigencytotoxic presenting
T cell
dendritic
cell
C
naive
helper T
cell
C Receptors on a naïve cytotoxic
T cell bind to the antigen-MHC
complexes on the surface of the
dendritic cell.
B
D
activated
cytotoxic
T cell
memory
cytotoxic T
cell
cytokines
effector
cytotoxic
T cell
memory
helper T
cell
effector
helper T
cell
E
D The activated cytotoxic T cell
recognizes cytokines secreted by
the effector helper T cells as
signals to divide.
E The new cytotoxic T cells
circulate through the body.
Stepped Art
Fig. 38-17, p. 672
Cytotoxic T Cells
 Cytotoxic T cells touch-kill cells displaying
antigen-MHC markers; perforin and proteases
puncture cells and kill them by apoptosis
cytotoxic
T cell
cancer
cell
Fig. 38-18b, p. 673
Natural Killer Cells
 Cytokines secreted by helper T cells also
stimulate natural killer (NK) cell division
 Unlike cytotoxic T cells, NK cells can kill infected
cells that are missing all or part of their MHC
markers
38.5-38.8 Key Concepts
Adaptive Immunity
 In an adaptive immune response, white blood
cells destroy specific pathogens or altered cells
 Some make antibodies in an antibody-mediated
immune response; others destroy ailing body
cells in a cell-mediated response
38.9 Allergies
 Allergy
• An immune response to a typically harmless
substance (allergen)
• First exposure stimulates production of IgE, which
becomes anchored to mast cells and basophils
• Later exposure stimulates secretion of histamine
and cytokines that initiate inflammation
• Anaphylactic shock is a severe and potentially
fatal allergic reaction
Allergies: Annoying or Life-Threatening
38.10 Vaccines
 Immunization
• The administration of an antigen-bearing vaccine
designed to elicit immunity to a specific disease
 Vaccine (active immunization)
• A preparation containing an antigen that elicits a
primary immune response
 Passive immunization
• Administration of antibodies; no immune response
Smallpox Vaccine
 Edward Jenner created the first vaccine against
smallpox, which has now been eradicated
Recommended Immunizations
38.11 Immunity Gone Wrong
 Misdirected or compromised immunity is
sometimes the result of mutation or
environmental factors
 The outcome is often severe or lethal
Autoimmune Disorders
 Sometimes lymphocytes and antibodies fail to
discriminate between self and nonself
 Autoimmune response
• An immune response that is misdirected against
the person’s own tissues
• Rheumatoid arthritis, Graves’ disease, multiple
sclerosis
Immunodeficiency
 In immunodeficiency, the immune response is
insufficient to protect a person from disease
 Primary immune deficiencies are present at birth
• SCIDs, ADA
 Secondary immune deficiency results from
exposure to an outside agent, such as a virus
• AIDS
Gene Therapy
 Primary immunodeficiency is the result of
mutation; Cindy Cutshwall was successfully
treated for ADA, a type of severe combined
immunodeficiency (SCID), using gene therapy
38.12 AIDS Revisited—Immunity Lost
 Acquired immune deficiency syndrome (AIDS)
• A group of disorders resulting from a failure of the
immune system due to HIV infection
• Includes rare cancers and infections caused by
normally harmless microorganisms
 Human immunodeficiency virus (HIV)
• A retrovirus that attacks specific cells of the
immune system, including helper T cells
T Cells and AIDS
Global HIV and AIDS Cases
Transmission and Treatment
 Common modes of HIV transmission
• Unprotected sex, mother to child, shared syringes
 HIV testing
• Antibodies are found in blood, saliva or urine
 Drugs
• There is no cure; protease inhibitors and reverse
transcriptase inhibitors can slow its progress
Prevention
 Vaccines
• Experimental vaccines are mostly ineffective or
risky; the virus’ high mutation rate is an obstacle
 Education
• The best option for preventing the spread of HIV
is teaching people how to avoid being infected
The Global AIDS Program
 The global battle continues; researchers are using
several strategies to develop an HIV vaccine
38.9-38.12 Key Concepts
Immunity In Our Lives
 Vaccines are an important part of any health
program
 Failed or faulty immune mechanisms can result
in allergies, immune deficiencies, or
autoimmune disorders
 The immune system itself is a target of human
immunodeficiency virus (HIV)
Animation: Inflammatory response
Animation: Complement proteins
Animation: Antibody-mediated response
Animation: Clonal selection of a B cell
Animation: Immune memory
Animation: Cell-mediated response
Animation: Antibody structure
Animation: Cell mediated response
Animation: Gene rearrangements
Animation: Human lymphatic system
Animation: Immune responses
Animation: Innate defenses
ABC video: Food Allergy Increase
Video: HPV vaccine
Video: Gene therapy