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Human Biology Concepts and Current Issues
Seventh Edition
Michael D. Johnson
9
The Immune
System and
Mechanisms of
Defense
© 2014 Pearson Education, Inc.
Lecture Presentations by
Robert J. Sullivan
Marist College
Overview of the Body’s Defense Mechanisms
 Defense mechanisms include
– Barriers to entry of pathogens (disease-producing
microorganisms)
– Skin, stomach acid, tears, vomiting
– Nonspecific defense mechanisms
– Phagocytosis, inflammation
– Specific defense mechanisms
– Immune response enables body to recognize and
remove specific bacteria, other foreign cells, viruses
– Antibodies
– T cells
© 2014 Pearson Education, Inc.
Pathogens Cause Disease
 Disease-causing agents include
– Living organisms
– Bacteria: unicellular prokaryotes
– Fungi: unicellular and multicellular eukaryotes
– Parasites: unicellular and multicellular eukaryotes
– Nonliving infectious “particles”
– Viruses
– Prions
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Figure 9.1
SEM ( 2,000) of Streptococcus,
a spherical bacterium that
causes sore throats.
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SEM ( 5,600) of Escherichia
coli, a common intestinal
bacteria that is usually harmless.
SEM ( 12,000) of Campylobacter
jejuni, a spiral-shaped bacterium
that causes food poisoning.
Figure 9.2
Ribosomes
DNA
Cell wall
Relative size
of a bacterium
Plasma
membrane
Mitochondrion
Bacterial cell. Bacteria have a single strand
of DNA and free-floating small ribosomes within
their cytoplasm. Their plasma membrane is
surrounded by a rigid cell wall.
Nucleus
Golgi
apparatus
Plasma
membrane
Endoplasmic
reticulum
RNA
Relative size
of a virus
Protein
coat
Eukaryotic cell. Eukaryotic cells have a membrane-bound
Viruses. Viruses consist of a protein coat
nucleus and well-defined membrane-bound organelles.
surrounding either RNA or DNA.
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DNA
Bacteria: Single-Celled Living Organisms
 Characteristics
– Prokaryotic (lack a membrane-enclosed nucleus and
membranous organelles)
– Single-celled
– Use a variety of resources for growth and reproduction
 Infections
– Pneumonia, tonsillitis, tuberculosis, botulism, toxic
shock syndrome, syphilis, Lyme disease, etc.
 Generally treated with antibiotics
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Viruses: Tiny Infectious Agents
 Extremely small, much smaller than bacteria
 Living? Open to debate
– Unable to reproduce outside of a host cell
– No metabolic activity
 Structure
– Contain DNA or RNA, not both
– Nucleic acid is surrounded by a protein coat
 Diseases caused by viruses:
– AIDS, hepatitis, encephalitis, rabies, influenza, colds,
warts, chicken pox
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Prions: Infectious Proteins
 Infectious proteins
 Normal brain proteins that are not folded correctly
 The mis-folding becomes self-propagating, filling and
disabling the cell with protein debris
 Resist cooking, freezing, drying
 Diseases
– Bovine spongiform encephalitis (BSE, “mad cow
disease”)
– Variant Creutzfeldt-Jakob disease (vCJD)
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Transmissibility, Mode of Transmission, and
Virulence Determine Health Risk
 Transmissibility
– How easily a pathogen is passed from person to
person
 Mode of transmission
– Respiratory, fecal–oral, body fluids, direct contact
 Virulence
– How much damage is caused by the infection
© 2014 Pearson Education, Inc.
The Lymphatic System Defends the Body
 Functions
1. Maintenance of blood volume in cardiovascular
system
2. Transport of fats and fat-soluble material from
digestive system to cardiovascular system
3. Filtration of foreign material to defend against infection
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Figure 9.3
Nasal passages
Adenoids
Tongue
Thymus gland
Tonsils
Heart
Trachea
Tonsils protect
the throat.
Lymphocytes
mature in thymus.
Lymph flow
Blood
flow
Lymph node
Lymph
vessels
Red pulp
White pulp
Spleen
Macrophages cleanse lymph; lymphocytes
activate defense mechanisms.
Spleen removes damaged blood
cells and microorganisms from blood.
Blood capillary
Lymphatic
capillary
Cells
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Lymphatic vessels transport fluid,
bacteria, and viruses.
Lymphatic Vessels Transport Lymph
 Lymphatic vessels transport lymph
– Begin as blind-ended lymphatic capillaries
– Network of vessels, similar to veins
– Eventually drain into cardiovascular system through
right lymphatic duct and thoracic duct
 Lymph is a milky fluid containing:
–
–
–
–
White blood cells
Proteins
Fats
Occasionally bacteria and viruses
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Lymph Nodes Cleanse the Lymph
 Lymph nodes are located at intervals along lymphatic
vessels
 Nodes remove microorganisms, debris, and
abnormal cells from lymph
 Small, 1mm to 2.5 mm in size
 Nodes are composed of connective tissue,
macrophages, and lymphoctyes
 Nodes act as filters, cleansing the lymph as it passes
through them
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The Spleen Cleanses the Blood
 Largest lymphatic organ
 Located in upper left abdominal cavity
 Two regions of spleen:
– Red pulp
– Removes old and damaged red blood cells
– Temporary blood storage
– White pulp
– Contains lymphocytes, searching for pathogens
 Diseases that cause spleen enlargement
– Infectious mononucleosis, leukemia
 Spleen can be removed with minor medical impact
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Thymus Gland Hormones Cause T Lymphocytes to
Mature
 Thymus gland
– Located behind sternum, above heart
– Site of maturation of T cells (T lymphocytes)
– Secretes two hormones that control T cell
development: thymosin and thymopoietin
– Largest, most active during childhood
– Atrophies with aging
 Tonsils
– Filter food and air entering the throat
 Adenoids
– Filter air, back of nasal passages
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Keeping Pathogens Out: The First Line of Defense
 Skin—an effective deterrent
 Tears and saliva—contain lysozyme (antibacterial
enzyme)
 Ear wax—entraps microorganisms
 Mucus—entraps microorganisms
 Stomach—highly acidic, inhibits microorganisms
 Vagina—slightly acidic, inhibits some
microorganisms
 Vomiting, urination, and defecation—remove
microorganisms
 Resident bacteria—outcompete pathogens
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Nonspecific Defenses: Second Line of Defense
 Phagocytic cells: white blood cells that surround
and engulf invading bacteria
– Neutrophils, macrophages, eosinophils
 Inflammation
– Redness, warmth, swelling, pain
 Natural killer cells: a type of lymphocyte that attacks
tumor cells and virus-infected cells
 Complement proteins: plasma proteins that invade
bacteria when activated
 Interferons: antiviral proteins
 Fever response
© 2014 Pearson Education, Inc.
Table 9.1
© 2014 Pearson Education, Inc.
Figure 9.6
1
Phagocyte approaches
and captures
bacterium.
2
Phagocyte surrounds
bacterium.
Bacterium
Vesicle
3
Bacterium becomes
enclosed in vesicle.
Lysosome
4
Vesicle fuses with
lysosomes.
An electron micrograph
of a macrophage (blue)
capturing several
bacteria (pink).
5
Lysosomal enzymes
digest bacterium.
Cytoplasm
of phagocyte
6
Wastes and debris are
discarded.
Steps in the process.
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Figure 9.7
Phagocyte
Site of injury
Mast cell
Complement
protein
Bacteria
Histamine
1
2
Damaged cells and mast cells
in the area release histamine
and other substances.
Histamine dilates blood
vessels and makes them leaky.
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3
Complement proteins from plasma
diffuse out of leaky capillaries.
They mark the bacteria for
destruction and sometimes kill
them.
Attracted by histamine and
other chemicals, phagocytes
squeeze through the leaky
capillary walls and begin
attacking and engulfing bacteria
and debris.
© 2014 Pearson Education, Inc.
Animation: The Inflammation Response
Right-click and select Play
Figure 9.8
1
2
Activated complement
proteins form complexes of
proteins that create holes
in the bacterial cell wall.
3
Water and salts diffuse
into the bacterium
through the holes.
Water and
salts
Complement
proteins
Bacterium
Cell wall of
bacteria
Photomicrograph
of an intact
bacterium
A bacterium after lysis by activated
complement proteins.
© 2014 Pearson Education, Inc.
The bacterium swells and
eventually bursts.
Specific Defense Mechanisms: The Third Line of
Defense
 The immune response
– Characteristics
– Recognizes and targets specific pathogens and foreign
substances
– Has “memory”—“remembers” initial exposure and
responds more quickly and aggressively on subsequent
exposures
– Able to distinguish between
– “Self” cells and foreign, “non-self” invaders
– Healthy cells and abnormal (tumor) cells
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The Immune System Targets Antigens
 Antigen: any substance that triggers an immune
response
– Usually protein or polysaccharide on outer surface of
invading cell or virus
– MHC (major histocompatibility complex) proteins
– Self-antigens that are on human cell surfaces enabling
recognition of “self”
– Enable immune system to distinguish “self” from “nonself”
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Lymphocytes Are Central to Specific Defenses
 B lymphocytes: Antibody-mediated immunity
– Antibodies: proteins made by B lymphocytes that
bind with and neutralize specific antigens
– Active against viruses, bacteria, and soluble foreign
molecules
 T lymphocytes: Cell-mediated immunity
– Directly attack foreign cells
– Coordinate the immune response
– Active against parasites, viruses, fungi, intracellular
bacteria, cancer cells, cells with “non-self” MHC
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B cells: Antibody-Mediated Immunity
 B cells activated when they recognize an antigen
 Divide into two cell types
– Memory cells—store information for future immune
responses
– Plasma cells—actively secrete antibodies, which will
bind to antigen
© 2014 Pearson Education, Inc.
Figure 9.9
Bacterium
with surface
antigens
Mature inactive B cells specific for different
antigens, found in lymphatic tissue
Binding, activation
Clone formation
Memory cells
Plasma cells
Antibodies
Memory cells store
information until the
next exposure to the
same antigen.
© 2014 Pearson Education, Inc.
Plasma cells
secrete antibodies
into circulation.
Figure 9.10
Pathogens
When antibodies encounter a
pathogen with the right surface
antigen, they bind to it, forming
an antigen-antibody complex.
Antibody
Antigen-antibody
complex
Some antibodies cause
pathogens to agglutinate
(clump together).
The formation of an antibody-antigen
complex marks the pathogen for attack
by phagocytes or complement proteins.
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The Five Classes of Antibodies
 Antibodies also known as immunoglobulins (Ig)
 Classes of antibodies
–
–
–
–
–
IgG: most prevalent in the blood
IgM: first antibody produced in an immune response
IgA: found in body secretions, including breast milk
IgD: function is unclear
IgE: plays a key role in allergic responses
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Figure 9.11
Antigen
Antigenbinding
site
Variable
regions
Light
chain
Constant
regions
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Heavy chain
T Cells: Cell-Mediated Immunity
 T cells
– Originate from stem cells in the bone marrow
– Mature in the thymus
 Types of T cells
– CD4 T cells
– Helper T cells and Memory T cells
– CD8 T cells
– Cytotoxic T cell
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T Cells: Cell-Mediated Immunity
 T cells must be presented with antigen by antigenpresenting cells (APCs)
 APCs include
– Macrophages
– B cells
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Figure 9.12
Antigen
Major
histocompatibility
complex protein
(MHC)
Pathogen
1
The macrophage engulfs
a pathogen.
Lysosome
Vesicle with
MHC molecules
2
Lysosomes partially digest
the pathogen.
3
A vesicle containing MHC
molecules binds to the
digestive vesicle.
4
The MHC molecules and a
fragment of the antigen form
an antigen-MHC complex.
5
Antigen-MHC
complex
© 2014 Pearson Education, Inc.
The antigen-MHC complex
is displayed on the surface
of the cell when the vesicle
fuses with the cell membrane
and releases its digestive
products.
T Cells: Cell-Mediated Immunity
 Helper T cells
– Secrete cytokines, which stimulate other immune
system cells
– Play a key role in directing the immune response
– Are targets of HIV infection
 Cytotoxic T cells
– Directly attack and destroy abnormal (tumor or viralinfected) cells and foreign cells
 Memory T cells
– Reactivate during later exposures
© 2014 Pearson Education, Inc.
Figure 9.13
MHC molecule
Antigen-presenting cell (APC)
Antigen
fragment
CD4 receptor
Inactive
helper T cell
1
Activation
Memory
T cells
2
Clonal
expansion
3
Cytokine
production
© 2014 Pearson Education, Inc.
Figure 9.14
MHC molecule
Antigen-presenting cell (APC)
Antigen
fragment
CD8 receptor
Inactive
cytotoxic T cell
1
Activation
Memory
T cells
2
Clonal
expansion
3
Attack on
target cell
© 2014 Pearson Education, Inc.
Figure 9.15
Cytotoxic T cell
Target cell
Cytotoxic T cells (blue)
attaching to a target cell
(pink).
Cytotoxic T cell
Vesicle
Perforin
Granzyme
Cytotoxic T
cell membrane
Intercellular
space
3
2
1
Intact target
cell membrane
Perforin pore
partially assembled
Completed pore;
granzyme
passing through
Target cell
How cytotoxic T cells kill a target cell.
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Table 9.2
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Immune Memory Creates Immunity
 Primary immune response
– Occurs on first exposure to antigen
– Characteristics
– Lag time of 3–6 days for antibody production
– Peak at 10–12 days
 Secondary immune response
– Occurs on second and subsequent exposure to
antigen
– Characteristics
– Lag time in hours
– Peak in days
– Much more antibody produced
© 2014 Pearson Education, Inc.
Figure 9.16
Secondary immune
response
Antibody concentration (units/ml)
Primary immune
response
100
10
1
0.1
0
7
14
1st exposure
21 28
0
7
14
21 28
2nd exposure
Time (days after exposure)
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35
42
Medical Assistance in the War Against Pathogens
 Immunization
– A strategy for causing the body to develop immunity to
a specific pathogen
– Active immunization
– Intentionally expose individual to a form of the antigen
that doesn’t produce disease (vaccine)
– Also known as vaccination
– Passive immunization
– Administer protective antibodies to an individual
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Medical Assistance in the War Against Pathogens
 Monoclonal antibodies
– Specific antibodies produced in the laboratory by a
hybrid B cell clone
– Commercial applications of monoclonal antibodies
– Home pregnancy tests
– Prostate cancer screening test
– Diagnostic testing for hepatitis, influenza, HIV
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Figure 9.17
1
Immunize mouse
with antigen.
2
Extract B cells from
the mouse’s spleen.
Myeloma
(cancer)
cells
3
Fuse antibody-producing
B cells with cancer cells to
produce fast-growing cells.
Hybridoma
cell
4
Select cells that produce
the desired antibody.
5
Hybridoma cells
multiply in culture
and produce
antibodies
Clone antibody-producing
hybridoma cells.
7
6
Grow large numbers
of the cells in
culture.
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Extract the
antibodies.
Medical Assistance in the War Against Pathogens
 Antibiotics combat bacteria
– Antibiotics kill bacteria or inhibit their growth
– Antibiotics are selectively toxic for bacteria by
targeting features of bacterial cells that are different
from eukaryotic cells
– Antibiotics are not effective against viruses
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Tissue Rejection: A Medical Challenge
 Tissue rejection
– May occur following tissue or organ transplant if
recipient’s immune system attacks the transplanted
tissue/organ
 To minimize risk of rejection
– Must match ABO and other blood group antigens and
MHC antigens
– 75% MHC match is essential
– MHC antigens allow body to distinguish “self” from
“nonself”
– Immunosuppressive drugs—prevent patient’s immune
system from attacking transplanted tissue
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Inappropriate Immune System Activity Causes
Problems
 Allergies are hypersensitivity reactions
– Inappropriate response to an allergen
– Allergen: any substance (antigen) that causes an
allergic reaction (not a pathogen, but the body reacts
as though it is a pathogen)
– Examples of allergens
– Pollen
– Bee venom
– Foods (nuts, seafood)
– Oil from poison ivy plan
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Inappropriate Immune System Activity Causes
Problems
 Allergies (cont’d)
– Excessive inflammatory response mediated by
– IgE
– Basophils and mast cells
– Histamine
– Reactions may be localized or systemic
– Localized: affect only the area exposed
– Systemic: affect several organ systems
– Anaphylactic shock: severe life-threatening systemic
reaction (difficulty breathing, circulatory collapse, drop in
blood pressure)
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Inappropriate Immune System Activity Causes
Problems
 Allergies (cont’d)
– Treatment of allergies
– Antihistamines—treatment of mild to moderate reactions
– Epinephrine injection—treatment of anaphylactic shock
– Allergy shots
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Figure 9.18
Allergen
B cell
1
Exposure to an allergen
causes B cells to produce
specific IgE antibodies.
IgE antibodies
Binding sites
for IgE
Mast
cell or
basophil
2
The IgE antibodies bind to mast
cells and basophils, sensitizing
them to future exposures to the
same allergen.
Vesicles
containing
histamine
Allergens
specific
for IgE
3
The next exposure to the allergen
causes mast cells and basophils
to release histamine.
4
Histamine causes a localized or
systemic inflammatory response.
Histamine
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Inappropriate Immune System Activity Causes
Problems
 Autoimmune disorders
– Inability of immune system to distinguish “self” from
“non-self”
– Autoantibodies and cytotoxic T cells target the body’s
own tissues
– Examples
– Lupus erythematosis (LE or lupus)
– Inflamed connective tissue
– May affect a variety of organs
– Rheumatoid arthritis
– Inflamed synovial membrane
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Figure 9.19
© 2014 Pearson Education, Inc.
Immune Deficiency: The Special Case of AIDS
 AIDS: Acquired Immune Deficiency Syndrome
 Caused by infection with HIV (Human
Immunodeficiency Virus)
 HIV targets helper T cells
 HIV attaches to CD4 receptors of T helper cell, and
gains entry to the cell
 Transmission via body fluids (blood, semen, breast
milk, vaginal secretions)
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Figure 9.20
Protein spike
Phospholipid bilayer
RNA
(single stranded)
Enzyme
Outer protein coat
Inner protein coat
100–140 nm
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Figure 9.21
Retrovirus
Viral RNA
Single-stranded
DNA made from
RNA template
Double-stranded
DNA
Nucleus
Proteins
Viral coat
Core of virus
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© 2014 Pearson Education, Inc.
Animation: HIV: The AIDS Virus
Right-click and select Play
AIDS Develops Slowly
 Phase I
– May last a few weeks to a few years
– Brief period of flu-like symptoms
– Swollen lymph nodes
– Chills
– Fever
– Fatigue
– Body aches
– Most people don’t exhibit recognizable symptoms
– Virus is multiplying, antibodies are made but are
ineffective for complete virus removal
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AIDS Develops Slowly
 Phase II
–
–
–
–
Occurs within 6 months to 10 years
Characterized by opportunistic infections
Helper T cells affected, numbers are decreasing
If untreated, 95% will progress to next phase (AIDS)
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AIDS Develops Slowly
 Phase III: Clinical AIDS
– Helper T cells fall below 200 cells/mm3
– Opportunistic infections and cancers present
– Tuberculosis
– Pneumonia
– Meningitis
– Encephalitis
– Kaposi’s sarcoma
– Non-Hodgkins lymphoma
– If untreated, nearly always fatal
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Figure 9.22
Phase II
Phase I
Phase III
Connection of helper T cells in blood
(cells per mm3)
900
800
700
The time of transition
from Phase II to
Phase III is highly
variable between
individuals.
600
500
T cells
400
Antibodies
300
200
100
HIV in blood
0
0
1
2
3
4
Years after infection
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5
6
7
The AIDS Epidemic: A Global Health Issue
 Worldwide
–
–
–
–
More than 34 million infected with HIV
30 million dead so far
Most infections in sub-Saharan Africa
Increasing spread in Asia and India
 United States
– 16,000 deaths/year
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AIDS Deaths (thousands)
90
600
80
500
70
Living with AIDS
60
50
Deaths
400
300
40
200
30
20
100
10
0
0
Year
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Living with AIDS (thousands)
Figure 9.23
Risky Behaviors Increase Your Chances of Getting
AIDS
 Males (3/4 of cases)
– Sex with other men
– Sharing needles during intravenous drug use
– Heterosexual sex with HIV-infected female
 Females (1/4 of new cases)
– Sex with HIV-infected male
– Sharing needles during intravenous drug use
© 2014 Pearson Education, Inc.
Table 9.3
© 2014 Pearson Education, Inc.
Making Sex Safer




Abstinence
Reduce number of sexual partners
Choose sexual partners with low-risk behavior
Avoid high-risk sexual practices
– Anal-genital sex is a high-risk practice
 Use latex or polyurethane condoms or barriers
 Use nonoxynol-9 spermicide
 GET TESTED
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New Treatments Offer Hope
 Mechanisms of anti-HIV drugs
– Inhibit entry of HIV into host cell
– Reverse transcriptase inhibitors
– Block viral replication
– Integrase inhibitors
– Block insertion of viral genome into host cell DNA
– Protease inhibitors
– Block assembly of new viruses
 Early treatment with drug combinations may delay or
prevent clinical AIDS
 Vaccines: under development and testing
© 2014 Pearson Education, Inc.