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Bubble Boy Disease
Severe combined
immunodeficiency (SCID)
It is a genetic disorder in which
the adaptive immune system is
nonfunctional.
SCID is a severe form of
heritable immunodeficiency. It
is also known as the “bubble
boy” disease because its
victims are extremely
vulnerable to infectious
diseases and some of them,
such as David Vetter, become
famous for living in a sterile
environment.
The human immunodeficiency virus
(HIV) infects and destroys a particular
type of white blood cells.
HIV
white
blood cell
The human immunodeficiency virus
(HIV) infects and destroys a particular
type of white blood cells.
HIV
white blood cell
Over time, the immunity of the infected
person may be seriously weakened,
resulting in AIDS.
HIV
white blood cell
Patients usually die from infections that
are harmless in healthy people.
HIV
white blood cell
1
What is immunity
Immune System: Functions
• Protects from pathogens and foreign
molecules
–Parasites
–Bacteria
–Viruses
• Removes dead or damaged cells
• Attempts to recognize and remove
abnormal cells
Immune System dysfunction
• Incorrect responses
–Autoimmune disease (Type 1 diabetes)
• Overactive responses
–Allergies
• Lack of response
–Immunodeficiency disease (AIDS)
9
26.1 Non-specific defence
mechanisms
immune
system
(免疫系統)
pathogens
Immune system
• provides body defence
non-specific
defence
mechanisms
(非特異性防禦機制)
specific
defence
mechanisms
(特異性防禦機制)
Non-specific defence mechanisms
• provide general protection
against pathogens
• prevent the entry of all types of
foreign substances
 non-specific
Non-specific defence mechanisms
• include
physical and chemical barriers
first line of defence (第一道防線)
Non-specific defence mechanisms
• include
physical and chemical barriers
blood clotting
phagocytosis
inflammatory responses
Physical barriers
• physical structures that prevent
pathogens from entering the body
Physical barriers
1 Skin
• covers the whole body
layer of dead
cells
- constantly worn
away and
replaced by
new cells
Physical barriers
2 Ciliated epithelium of
the respiratory tract
ciliated epithelial
cell
physical barrier
closely packed cells
Physical barriers
2 Ciliated epithelium of
the respiratory tract
mucussecreting cell
produces sticky mucus
 traps dust and pathogens
26.1 Non-specific defence mechanisms
Physical barriers
2 Ciliated epithelium of
the respiratory tract
cilia
beating action
 moves dust
and pathogens in mucus up from
the bronchi to the pharynx
Physical barriers
2 Ciliated epithelium of
the respiratory tract
cilia
beating action
 dust and
pathogens
 are swallowed or coughed out
Chemical barriers
• chemical secretions that may kill or
stop the growth of pathogens
Chemical barriers
1 Sebum
• secreted by sebaceous glands
• a natural antiseptic
(消毒劑)
• kills pathogens on the skin
sebum
Chemical barriers
2 Gastric juice
• secreted by gastric glands
• contains
hydrochloric acid
• kills pathogens in the
food in the stomach
gastric juice
Chemical barriers
3 Tears and saliva
• secreted by tear glands
tears
Chemical barriers
3 Tears and saliva
• secreted by salivary glands
Chemical barriers
3 Tears and saliva
• contain lysozyme (溶菌酶)
breaks down the cell walls of
certain bacteria on the conjunctiva
and in the mouth cavity
Chemical barriers
4 Vaginal secretion
• acidic
 inhibits the growth of pathogens in
the vagina

Mucus is a chemical barrier
that kills pathogens.
mucus
In fact, mucus is a physical
barrier that only traps pathogens
without killing them.
mucus
26.1
Identifying features of mammalian skin
that are related to body defence
1 Examine a prepared slide of mammalian
skin under a microscope using low power
magnification or a skin model.
2 Identify the structures that are related to
body defence.
Blood clotting
• blood clot (血凝塊) seals the wound
and stops breeding
 prevents pathogens
from entering
through the wound
Blood clotting
• formation of a blood clot:
- a blood vessel damaged
- blood platelets attracted
to the wound
Blood clotting
• formation of a blood clot:
- blood platelets release
chemicals
soluble protein
fibrinogen
(纖維蛋白原)
insoluble fibrin
(纖維蛋白)
34
35
Blood clotting
• formation of a blood clot:
- blood cells trapped in the net of fibrin
blood
platelet
white blood cell
red blood cell
Blood clotting
• formation of a blood clot:
- blood clot dries to form
a scab (痂) covering the
wound
Phagocytosis
• carried out by phagocytes (吞噬細胞)
phagocyte
bacterium
Phagocytosis
phagocyte
pathogen
enzymes
nucleus
Phagocytosis
1 A phagocyte engulfs a pathogen.
Phagocytosis
2 The pathogen is digested by enzymes.
Phagocytosis
3 The digested pathogen is released.
Inflammatory responses
Animation
wound is
infected
pathogens
Inflammatory responses
1 Capillary increases its permeability.
capillary
Inflammatory responses
2 More phagocytes come out of
the capillary.
phagocyte
Inflammatory responses
3 Phagocytes engulf and digest the
pathogens in the tissue.
carrying
out phagocytosis
Inflammatory responses
• increased blood flow and accumulation
of tissue fluid
 infected area becomes red, hot,
swollen and painful
 inflammation (炎症)
Inflammatory responses
• pus (膿) may form inside the wound
- consists of the remains of killed
pathogens and dead phagocytes
The inflammatory response mobilizes
nonspecific defense forces

Tissue damage triggers the inflammatory response
Skin surface
Swelling
Pin
Phagocytes
Bacteria
Chemical
signals
White
blood cell
1 Tissue injury; release of
chemical signals such as
histamine
Phagocytes and
fluid move
into area
2 Dilation and increased leakiness
3 Phagocytes (macrophages and
of local blood vessels; migration
of phagocytes to the area
neutrophils) consume bacteria
and cell debris; tissue heals
The inflammation can disinfect tissues
and limit further infection
Lymphatic system
Lymphatic system = lymphatic ducts and lymph nodes
 The
lymphatic system becomes a
crucial battleground during infection
 It returns tissue fluid to the circulatory
system
 It fights infections
LYMPHATIC
VESSEL
Tonsil
Right lymphatic
duct, entering
vein
Thoracic
duct
VALVE
Lymph nodes
Thoracic duct,
entering vein
Blood
capillary
Tissue cells
Interstitial
fluid
Thymus
Appendix
Spleen
LYMPHATIC
CAPILLARY
Masses of
lymphocytes and
Macrophages
Bone
marrow
Lymphatic
vessels
Primary lymph organs : Thymus and bone marrow
Secondary lymph organs : lymph nodes

This lymphatic vessel is taking up fluid from
tissue spaces in the skin
• It will return it as lymph to the blood
– Lymph contains less oxygen and fewer
nutrients than interstitial fluid
LYMPHATIC
VESSEL
VALVE
Blood
capillary
Tissue cells
Interstitial
fluid
LYMPHATIC
CAPILLARY

Lymph nodes are key sites for fighting infection
They are packed with lymphocytes and
macrophages
Masses of
lymphocytes and
macrophages
Outer capsule of
lymph node
Macrophages
Lymphocytes
Figure 23.3C, D
1 Non-specific defence mechanisms
prevent the entry of all types of
foreign substances .
2a The first line of defence includes
physical and chemical
barriers that prevent pathogens
from entering the blood and other
tissues.
2b Possible entrance of pathogens:
Body surface
Barrier: Skin
Physical 
Chemical 
Method of prevention:
• Covers the whole body to
prevent the entry of pathogens
2b Possible entrance of pathogens:
Body surface
Barrier: Sebum
Physical 
Chemical 
Method of prevention:
• An antiseptic that kills
pathogens
2c Possible entrance of pathogens:
Respiratory tract
Barrier: Ciliated epithelium
Physical 
Chemical 
Method of prevention:
• Cells are closely packed to
prevent the entry of pathogens
2c Possible entrance of pathogens:
Respiratory tract
Barrier: Ciliated epithelium
Physical 
Chemical 
Method of prevention:
• Mucus traps pathogens
2c Possible entrance of pathogens:
Respiratory tract
Barrier: Ciliated epithelium
Physical 
Chemical 
Method of prevention:
Cilia beat to move the trapped
pathogens upwards
2c Possible entrance of pathogens:
Respiratory tract
Barrier: Ciliated epithelium
Physical 
Chemical 
Method of prevention:
• The trapped pathogens are then
swallowed or coughed out
2d Possible entrance of pathogens:
Stomach
Barrier: Gastric juice
Physical 
Chemical 
Method of prevention:
• Contains hydrochloric acid
to kill pathogens
2e Possible entrance of pathogens:
Eyes
Barrier: Tears
Physical 
Chemical 
Method of prevention:
• Contains lysozyme to kill
pathogens
2f
Possible entrance of pathogens:
Mouth
Barrier: Saliva
Physical 
Chemical 
Method of prevention:
• Contains lysozyme to kill
pathogens
2g Possible entrance of pathogens:
Vagina
Barrier: Vaginal secretion
Physical 
Chemical 
Method of prevention:
• Acidity inhibits the growth of
pathogens
3 Pathogens can get into the body
through a wound on the skin.
By blood clotting , a blood clot is
formed which seals the wound to
prevent the entry of pathogens.
4 Phagocytosis is the process by
which phagocytes engulf
pathogens.
5 In an inflammatory response,
arterioles in the infected area
dilate, and capillaries there
increase their permeability .
5 More blood flows to the area and
more phagoctyes come out of
the capillaries to engulf and kill the
pathogens in the tissues.
6 Signs of inflammation:
Redness and heat result from
the increased blood flow, and
swelling and pain result from
the accumulation of tissue fluid.
Non-specific vs specific immunity
The Nature of Immunity
Immunity was originally used to indicate
exemption from taxes and this meaning still
exits in the term "diplomatic immunity".
• adaptive immune response (應變性) / specific immunity
• Major characteristics of adaptive immune response
• 多樣性 (Diversity)
• 專一性（specificity）
• 記憶性（memory）
• 自我辨識（self/non-self recognition）
Characteristics of Adaptive immunity

A ntigenic specificity
 To distinguish subtle difference among
antigens
 I mmunologic memory
 A second encounter with the same antigen
induces a heightened state of immune
reactivity
 D iversity
 To recognize billions of uniquely different
structures on foreign antigens
 S elf/nonself recognition
 To respond only to foreign antigens
26.2 Specific defence
mechanisms
antigens (抗原)
activate
lymphocytes (淋巴細胞)
B cells
T cells
carry out
immune responses
(免疫反應)
Lymphocytes
BONE MARROW

Two kinds of
lymphocytes carry out
the immune response
 B cells secrete
antibodies that attack
antigens
 T cells attack cells
infected with
pathogens
Stem cell
THYMUS
Via
blood
Immature
lymphocytes
Antigen
receptors
T cell
B cell
HUMORAL
IMMUNITY
OTHER PARTS
OF THE
LYMPHATIC
SYSTEM
Via
blood
Lymph nodes,
spleen, and other
lymphatic organs
CELLMEDIATED
IMMUNITY
Final
maturation of
B and T cells
in lymphatic
organ
Antigens
• stimulate immune responses
• two groups:
foreign antigens and self antigens
- come from outside of the body
e.g. cell surface proteins of viruses
or toxins from bacteria
surface proteins
virus
Antigens
• stimulate immune responses
• two groups:
foreign antigens and self antigens
- produced by the person’s own body
e.g. surface proteins on red blood cells
surface
proteins
red blood cell
Antigens
• immune system can usually recognize
self antigens and does not attack them
Antigens
foreign antigens not yet
entered the host cells
activate
B cells
carry out
humoral immune responses
(HIR) (體液免疫反應)
Humoral immune responses
• B cells are formed and mature in the
bone marrow
• B cells have antigen receptors that
only bind with a specific antigen
B cells -- humoral immunity
Triggered by a specific antigen, a B cell
differentiates into an effector cell
 The effector cell is called a plasma cell
 The plasma cell secretes
antibodies
Humoral immune responses
activated by antigens
and helper T cells
multiplies and differentiates into
memory B cell
B cell
plasma cell
Humoral immune responses
Antibodies to act
against antigens
produces
plasma cell
Humoral immune responses
• antibody is a Y-shaped protein
molecule
antigenbinding site
polypeptide
chains
disulphide bond
Antigens have specific regions where
antibodies bind to them

Antigens are
molecules to
which
antibodies bind
Antibody A
molecules
Antigenbinding
sites
Antigens
Antigen
Antibody B
molecule
Humoral immune responses
antigen-antibody complex
antigen
Humoral immune responses
• production of antibodies is specific
- each type of antigen leads to the
production of only one type of antibody
3D animation
Humoral immune responses
Actions of antibodies
1 Lysis (溶菌)
a Antibodies attach to pathogen and
make holes in it.
Animation
antibodies
pathogen
(virus or bacterium)
Humoral immune responses
Actions of antibodies
1 Lysis (溶菌)
a Antibodies attach to pathogen and
make holes in it.
Humoral immune responses
Actions of antibodies
1 Lysis (溶菌)
b Pathogen is lysed (被溶解) and killed.
hole
Humoral immune responses
Actions of antibodies
2 Help in phagocytosis
a Antibodies attach to pathogen.
pathogen
antibody
phagocyte
Humoral immune responses
Actions of antibodies
2 Help in phagocytosis
b Phagocyte detects the antibodies
and engulfs the pathogen.
Humoral immune responses
Actions of antibodies
2 Help in phagocytosis
c Pathogen is killed by phagocytosis.
Humoral immune responses
Actions of antibodies
3 Stick pathogens into clumps
- pathogens stuck together by antibodies
and cannot reproduce or enter cells
antibodies
pathogens
Humoral immune responses
Actions of antibodies
3 Stick pathogens into clumps
- pathogens stuck together by antibodies
and cannot reproduce or enter cells
Humoral immune responses
Actions of antibodies
4 Neutralize toxins of pathogens
- antibodies act as antitoxins (抗毒素)
to neutralize toxins
toxins
antibodies
Humoral immune responses
Actions of antibodies
4 Neutralize toxins of pathogens
- antibodies act as antitoxins (抗毒素)
to neutralize toxins
Binding of antibodies to antigens
inactivates antigens by
Neutralization
Agglutination
Precipitation of
(blocks viral binding sites;
of microbes
dissolved antigens
coats bacterial toxins)
Make holes in
cell membrane
Complement
Bacteria
Virus
molecule
Antigen
Bacterium
molecules
Enhances
Phagocytosis
Macrophage
Foreign cell
Leads to
Cell lysis
Hole
Clonal selection musters defensive forces
against specific antigens

When an antigen enters the body, it activates
only lymphocytes with complementary
receptors
 B and T cells multiply into clones of specialized
effector cells that defend against the triggering
antigen
 This is called clonal selection
Antigen molecules
Variety of
B cells in a
lymph node
Antigen receptor
(antibody on
cell surface)
Cell growth
division, and
differentiation
Clone of many
effector cells
secreting
antibodies
Endoplasmic
reticulum
Antibody
molecules
Figure 24.7
The initial immune response results in a
type of “memory”

In the primary immune response, clonal
selection produces memory cells
 These cells may confer lifelong immunity

When memory
cells are activated
by subsequent
exposure to an
antigen, they
mount a more
rapid and massive
secondary
immune response
Unstimulated lymphocyte
First exposure to antigen
FIRST CLONE
Memory cells
Second exposure to antigen
Effector cells
SECOND CLONE
More memory cells
New effector cells
Figure 24.8B
PRIMARY RESPONSE
(initial encounter
with antigen)
Antigen
Antigen receptor
on a B cell
Antigen binding
Cell growth,
to a B cell
division, and
differentiation
Clone of
cells
Memory B cell
Plasma cell
Antibody
molecules
Later
SECONDARY RESPONSE
(can be years later)
exposure
to
Cell division,
same
differentiation
antigen
Larger clone
Memory B cell
of cells
Plasma cell
Antibody
molecules
Figure 24.9
Cell-mediated immune response
infected cells or cancer cells
stimulate
T cells
carry out
cell-mediated immune responses
(CMIR)
Cell-mediated immune response
• T cells are formed in the bone
marrow and mature in the
thymus gland (胸腺)
• T cells have receptors on
their surface that fit
a specific antigen
Cell-mediated immune response
• several types: helper T cells,
killer T cells and memory
T cells
thymus gland
T helper cells activate HIR
activated by infected
cells or cancer cells
B cell
activates
helper T cell
carries out HIR
Cell-mediated immune response
activated by infected
cells or cancer cells
T cell
secretes
activates
helper T cell
activate
phagocytes
lymphokines
(淋巴激活素)
Cell-mediated immune response
T cell
multiplies and
differentiates
memory T cell
into
destroys cells
directly
killer T cell
(殺手 T 細胞)
Cytotoxic T / killer T cells bind to infected body
cells and destroy them by making hole in the cell membrane
1
Cytotoxic T cell binds
to infected cell
Foreign
antigen
2
Perforin makes holes
in infected cell’s membrane
3
Infected cell is destroyed
Hole
forming
INFECTED CELL
Perforin
molecule
Cytotoxic
T cell
Figure 24.13C
Killer T cells may help prevent
cancer
Killer T cells may
attack cancer cells
 The surface molecules
of cancer cells are
altered by the disease

Primary and secondary
immune responses
• immunological memory (免疫記憶):
the ability of memory B cells and
memory T cells to ‘remember’ the type
of antigen from the previous exposure
Primary and secondary
immune responses
• primary response occurs on the first
exposure to an antigen
• secondary response occurs when the
same antigen enters the body again
Primary and secondary
immune responses
• usually slow / longer latent period
• normally takes 3–14 days to
produce enough antibodies or cells
• antigens have time to cause damage
 disease symptoms
Primary and secondary
immune responses
• faster, stronger and lasts longer
• memory cells multiply and differentiate
quickly into a larger number of plasma
cells, killer T cells and memory cells
• kills the pathogen before it can
multiply and cause a disease
secondary
recovery response
concentration of
antibodies in blood
primary
response
0
7
14
first exposure
21
28
35
second exposure
days
concentration of
antibodies in blood
primary
response
secondary
recovery response
latent period
(潛伏期)
0
7
14
first exposure
21
28
35
second exposure
days
concentration of
antibodies in blood
primary
response
secondary
recovery response
concentration
of antibodies
0
7
14
first exposure
21
28
35
second exposure
days
secondary
recovery response
primary
response
concentration of
antibodies in blood
period of
existence of
antibodies
0
7
14
first exposure
21
28
35
second exposure
days
Principle of vaccination
• immunity can be enhanced by
vaccination
introduction of vaccines (疫苗)
into the body
Principle of vaccination
• four types of vaccines:
1 Live, weakened pathogens
e.g. vaccines of measles, mumps,
rubella
2 Killed pathogens
e.g. vaccines of poliomyelitis,
rabies (狂犬病)
Principle of vaccination
• four types of vaccines:
3 Viral proteins
e.g. vaccine of whooping cough
4 Inactivated bacterial toxins
e.g. vaccines of diphtheria, tetanus
Vaccines I
# Many exotoxins can
be modified chemically
so that they retain their
antigenicity but are no
longer toxic. Such a
modified exotoxin is
called a toxoid.
Vaccine II
# Most agents used for
immunization are either
attenuated or inactivated
pathogens or inactivated
forms of natural
microbial products.
Alternative immunization
strategies using
bioengineered molecules
eliminate exposure to
microorganisms and, in
some cases, even to
protein antigen.
Application of these
strategies may provide
safer and more targeted
vaccines.
Principle of vaccination
• vaccine contains an antigen
• introduced into the body
orally or by injection
Principle of vaccination
antigen in vaccine
stimulates
primary response
- production of some antibodies
and killer T cells
- production of memory cells
that ‘remember’ the type of
antigen
Principle of vaccination
invasion by the same antigen
stimulates
secondary response
- production of a larger amount
of specific antibodies and killer
T cells in a shorter time
Principle of vaccination
• makes use of the specificity and
immunological memory
• not completely without risk
• protects the health of the community if
a large number of people are vaccinated
Active and passive immunity
• given by antibodies produced by
our own plasma cells
• acquired naturally when
a person recovers
from an infection
• acquired artificially
by vaccination
Active and passive immunity
• start of the immunity is
relatively slow
• long lasting
Active and passive immunity
• given by direct transfer of antibodies
from immune persons
Active and passive immunity
• occurs naturally in babies when:
- antibodies diffuse from mother’s
blood to embryo’s blood in placenta
Active and passive immunity
• occurs naturally in babies when:
- babies are fed with breast milk
Active and passive immunity
• occurs artificially when:
- antibodies are injected for treatment
of diseases
• immunity starts immediately
• lost after a short period of time when
the antibodies break down
Connection: Monoclonal antibodies are
powerful tools in the lab and clinic

fusing B cells
specific for a single
antigenic
determinant with
easy-to-grow tumor
cells
Antigen injected
Tumor cells grown
into mouse
in culture
B cells
Tumor cells
(from spleen)
Cells fused to
generate hybrid
cells
Single hybrid cell
grown in culture
Hybrid cell culture,
producing monoclonal antibodies
Antibody

These cells are useful
in medical diagnosis
– Example: home
pregnancy tests
• They are also useful
in the treatment of
certain cancers
Connection: Malfunction or failure of
the immune system causes disease

Autoimmune diseases : The immune system turns against
the body’s own molecules, including SLE (紅斑狼瘡), RA (類風濕性關節
炎), type I diabetes, asthma, Crohn’s disease 孔羅氏症(消化道瘜肉),….

Immunodeficiency diseases : Immune components
are lacking, and infections recur.
 Innate immune deficiency : Severe combined immunodeficiency
(SCID)
 Acquired immune deficiency : AIDS

Physical and emotional stress may weaken the immune
system

Arthritis X-ray
RA is an autoimmune disorder in which your own body mistakenly attacks
healthy tissue, causing inflammation and damage to your joints.
About 1% of the US population suffers from RA. Patients usually develop
the signs and symptoms of the disease between the ages of 35 and 50,
with women affected 2 to 3 times more often than are men.
Connection: Allergies are overreactions to
certain environmental antigens

Allergies are abnormal sensitivities to
allergens in the surroundings
B cell
(plasma cell)
Histamine
Antigenic
Mast
determinant
cell
Allergen
B cells make
(pollen grain)
antibodies
Antibodies
Allergen binds to
Histamine is
attach to
antibodies on
released, causing
mast cell
mast cell
allergy symptoms
SENSITIZATION: Initial exposure to allergen
LATER EXPOSURE TO SAME ALLERGEN

Allergy-causing fungal spores
Figure 24.17x
Connection: AIDS leaves the body
defenseless

The AIDS virus attacks helper T Cells
 This cripples both cell-mediated and humoral
immunity

So far, AIDS is incurable
 Drugs and vaccines offer hope for the future

Practicing safer sex could save many lives
The Continuing Problem of HIV
Acquired immune deficiency syndrome (AIDS)
is epidemic throughout much of the world
 14,000 people are infected with the AIDS virus
every day

 HIV is the virus that causes AIDS
 HIV is transmitted mainly
in blood and semen

Former L.A. Laker Magic
Johnson is one of 900,000
Americans who are
HIV-positive
AIDS is an immunodeficiency disease
caused by a virus

In 1981, increased rates of two rare diseases,
Kaposi’s sarcoma, and pneumonia caused by a
protozoan P. carinii, were the first signals of a new
threat to humans, later known as acquired
immunodeficiency syndrome, or AIDS.
 Both conditions were previously known to occur
mainly in severely immunosuppressed individuals.
 People with AIDS are susceptible to opportunistic
diseases.
Kaposi’s Sarcoma
Unusual tumor arising
from blood or lymphatic
vessels in multiple
locations
 Tumor began to appear in
young men with HIV
○ 2000 time higher than period
before HIV
○ So common among AIDS
patients became AIDS-defining
condition
Pneumocystosis(肺孢子蟲病)

Causative agent - Pneumocystis carinii
 Tiny fungus formerly considered a
protozoan
 Differs from many fungi in cell wall
components
○ Consequently resistant to many fungal
medications

Pathogenesis
 Spores of organism are inhaled into lung
○ Attach to alveolar walls
 Alveoli fill with fluid, mononuclear cells
and organisms
 Alveolar walls become thickened and
scarred. Interferes with free passage of
oxygen

In 1983, a retrovirus, now called human
immunodeficiency virus (HIV), had been
identified as the causative agent of AIDS.

With the AIDS mortality close to 100%, HIV is
the most lethal pathogen ever encountered.
 Molecular studies reveal that the virus probably
evolved from another HIV-like virus in
chimpanzees in central Africa and appeared in
humans sometimes between 1915 and 1940.
○ These first rare cases of infection and AIDS went
unrecognized.

Two major strains HIV-1 and HIV-2.
 HIV-1 is the more widely distributed and more
virulent.

Both strains infect cells that bear CD4
molecules, especially helper T cells and also
macrophages, some lymphocytes and some
brain cells.
HIV infected cells: Among the susceptible
WBCs, what do they have in common?
 CD4 functions as the major receptor for the virus.
 Other HIV receptors present on the surface of some
WBCs are implicated:
• Clues:
Some people who are innately resistant
to HIV-1 owe their resistance to defective chemokine
receptors.
chemokines – chemicals secreted by WBC when signaling with
one another.
• What is your conclusion?
What is your conclusion?
The entry of the virus requires not only CD4 on the
surface of the susceptible cells but also a second
protein molecule, a co-receptor. Defective
chemokine receptor prevents HIV from binding and
infecting cells.

Once inside a cell, HIV RNA is reversetranscribed, and the product DNA is
integrated into the host genome.
 This directs the production of new virus particles.
 Because a retrovirus exists integrated in the host
genome of the infected cell, immune responses fail to
eradicate it from the body.
 Even more challenging : frequent mutational changes
that occur in each round of virus replication.
Give two reasons why it is difficult to remove
the virus from our body?
Give two reasons why it is difficult to
remove HIV from our body?
•Because a retrovirus exists integrated in
the host genome of the infected cell,
immune responses fail to eradicate it from
the body.
•Even more challenging : frequent
mutational changes that occur in each
round of virus replication.
Give two reasons why it is difficult to
remove HIV from our body?
Because a retrovirus exists integrated / hidden
in the host genome of the infected cell, immune
responses fail to eradicate it from the body.
Even more challenging : frequent mutational
changes occur in each round of virus replication
fools our immune system – render immunologic
memory and immune specificity ineffective.

The body is then engaged in a Prolonged
battle against HIV.
(1) The immune response diminishes the initial viral
load, but HIV continues to replicate in lymphatic
tissue.
(2) Viral load gradually rises as HIV is released from
lymphatic tissue and helper T cell levels decrease.
Consequence?

The body is then engaged in a Prolonged
battle against HIV.
(1) The immune response diminishes the initial viral
load, but HIV continues to replicate in lymphatic
tissue.
(2) Viral load gradually rises as HIV is released from
lymphatic tissue and helper T cell levels decrease.
Consequence?
This results in extensive loss of humoral
and cell-mediated immunity.
After an initial
peak, virus levels
in the blood fall as
anti-HIV
antibodies,
produced 1 to 12
months after
infection, rise.
After the early drop in HIV levels in the blood, the virus
continues to be produced by cells in the lymph nodes,
causing structural and functional damage.
In time, the concentration of HIV in the blood increases
as a result of :
the breakdown of lymphatic tissue function and
diminishing responses to the infection because of
the depletion of helper T cells.
The time required for
an HIV infection to
progress to severe
helper T cell
depletion and AIDS
varies greatly, but it
currently averages
about ten years.
 A person who is HIV-positive will have blood
tested positive for the presence of antibodies
to the virus.
 However, a HIV-negative blood test result does
not completely guarantee a safe blood supply,
WHY?
because an infected individual may
require several weeks to 6 months
(window period) before anti-HIV
antibodies become detectable.

After the early drop in HIV levels in the blood,
the virus continues to be produced by cells in
the lymph nodes, causing structural and
functional damage.
 In time, the concentration of HIV in the blood
increases as a result of :
 the breakdown of lymphatic tissue function and
diminishing responses to the infection because of
the depletion of helper T cells.

The time required for an HIV infection to
progress to severe helper T cell depletion
and AIDS varies greatly, but it currently
averages about ten years.
 During most of this time, the individual exhibits
only moderate hints of illness, such as swollen
lymph nodes and occasional fever.
 How do you think doctors can monitor the
progress of the disease?
by measuring changes in the level of T cells,
although measures of viral load are a better
indicator of disease prognosis and of the
effectiveness of anti-HIV treatment.

The time required for an HIV infection to
progress to severe helper T cell depletion
and AIDS varies greatly, but it currently
averages about ten years.
 During most of this time, the individual exhibits
only moderate hints of illness, such as swollen
lymph nodes and occasional fever.
 How do you think doctors can monitor the
progress of the disease?
by measuring changes in the level of T cells.
Or measures of viral load - a better indicator of disease prognosis
and of the effectiveness of anti-HIV treatment.

At this time, HIV infection cannot be cured, and
the progression to AIDS cannot be prevented.

New, expensive drug therapies can slow this
progression.
Suggest how these drugs might work:
slow viral replication by 1) inhibiting DNA synthesis,
2) inhibiting reverse transcriptase, and 3) protein
synthesis inhibitors
 Combinations of these drugs (a cocktail) decrease
viral load and therefore allow the number of helper T
cells to rise.

At this time, HIV infection cannot be cured, and
the progression to AIDS cannot be prevented.

New, expensive drug therapies can slow this
progression.
Suggest how these drugs might work:
slow viral replication by
•
- inhibiting DNA synthesis,
•
- inhibiting reverse transcriptase, and
•
- protein synthesis inhibitors
 Combinations of these drugs (a cocktail) decrease
viral load and therefore allow the number of helper T
cells to rise.
Highly Active Anti-retroviral therapy (HAART)

Reverse
transcriptase
inhibitors and
protease inhibitors,
provide a "one-two
punch," interrupting
HIV's replication
cycle at different
points and reducing
the virus in many
cases to
undetectable levels.
HOW ANTI-HIV DRUGS WORK
Entry inhibitors bind to the
proteins on the outside of the HIV
virus and stop it from entering the
target cell (Fuzeon only).
Nucleoside reverse transcriptase
inhibitors stop HIV copying its
genes into the cell. Nucleosides are
the building block for genes. The drugs
supply faulty versions of these building
blocks (drugs include abacavir, AZT,
ddI, 3TC).
Non-nucleoside reverse
transcriptase inhibitors also block
the gene-copying process. They
disable the enzyme that controls it
(drugs include nevirapine and
efavirenz).
Protease inhibitors disable
protease, an enzyme which plays a
key role in the formation of the
new virus (drugs include amprenavir,
lopinavir, ritonavir, nelfinavir).
HAART reduce the virus in many cases to
undetectable levels.
• Even though ARV
drugs are getting more
powerful in inhibiting
the effects of HIV, one
must remember that
these do not cure HIV
infection and AIDS.
• Individuals who are on
HAART can still
transmit the virus to
other people.
When the (HIV) replicates, it does not make perfect
copies of itself but rather, creates new strains in the
process. This means that an HIV+ person actually has
many different strains of the virus inside his/her
system.
Suggest why the ‘cocktail treatment’ is
preferred rather than a single drug?
Suggest why the ‘cocktail treatment’ is preferred rather
than a single drug?
• HIV evolve quickly because it has a very short life cycle and
high mutation rate.
• New strains of HIV which are resistant to the effects of a
particular antiretroviral (ARV) drug may appear and then
replicate quickly.
• For a treatment regimen to be effective over the long term,
it has to include more than one ARV drug at a time. Taking
two or more ARV drugs concurrently, known as combination
therapy, can vastly reduce the rate at which drug
resistance develops.
170
Transmission of HIV

Transmission of HIV requires the transfer of body
fluids containing infected cells, such as semen or
blood, from person to person:
• Unprotected sex (that is, without a condom)
among male homosexuals
• and transmission via nonsterile needles
(typically among intravenous drug users)
• However, transmission of HIV among
heterosexuals is rapidly increasing as a result
of unprotected sex with infected partners.
HIV is not transmitted by casual
contact.
 So far, only one case of HIV transmission by
kissing has been reported, and both individuals
had bleeding gums.
 Transmission of HIV from mother to child can
occur during fetal development or during
nursing. Mother-to-child transmission accounts
for more than 90% of all HIV infections in infants
and children worldwide.
 HIV screening has virtually eliminated blood
transfusions as a route of transmission in
developed countries.
河南爱滋病村
马深义一家住在中国河南上蔡县文楼村，他的家庭就是爱滋病的受害者。他们
一家五口人，有四人感染了艾滋病，只有9岁的大女儿是健康的。《好死不如赖
活着》没有故事、没有情节、没有背景音乐、没有字正腔圆的叙述、没有宏大
的场面，整部影片就是在纪录这个家庭的日常生活。影片的镜头从2001年的春
末夏初开始，历经盛夏、深秋、严冬，一直到春节，近距离地拍摄了马深义一
家面对爱滋病和死亡的人生经历。

As of 2000 the Joint United Nations
Program on AIDS estimates that 30 to 40
million people worldwide are living with
HIV or HIV/AIDS.
 Of these, approximately 70% reside in sub-
Saharan Africa.
 The number of people with AIDS is expected to
grow by nearly 20% per year.

The best approach for slowing the spread of
HIV is to educate people about the
practices that transmit the disease, such
as using nonsterile needles and having sex
without a condom.
Any individual who has sex with a
partner who had unprotected sex with
another person during the past two
decades risks exposure to HIV.
HIV on a lymphocyte
HIV budding collage (大雜燴)
Figure 24.18x2
HIV Prevention and Treatment
 No approved vaccine
 Most people infected are unaware
 Virus on surfaces can be inactivated with
commercially available disinfectants and heat at
56°C for more that 30 minutes
 Knowledge of transmission greatest tool for
control
 Use of condoms not 100% effective but have
been shown to decrease transmission
 Avoidance of practices that favor HIV
transmission
HIV vaccine prospects
Currently no approved vaccines
 In theory, vaccine could be used in two ways

Prevention vaccine
Immunize uninfected individuals against disease
Therapeutic vaccine
Boost immunity of those already infected
Successful vaccine must
•get around HIV variability
•Be effective in preventing direct
spread of HIV from cell to cell
Successful vaccine must NOT
• Be capable of turning into disease-causing
strain
• Be oncogenic – cancer causing
• Stimulate an autoimmune response
Vaccine trial in humans has
been undertaken for at least 10
experimental vaccines
All have failed and
prospects do not look
favorable
A monumental safe-sex message in Paris
Pope says condoms are not the solution
to Aids - they make it worse
A monumental safe-sex message in Paris
Pope says condoms are not the solution
to Aids - they make it worse
Pope Benedict stressed that the Roman
Catholic Church is in the forefront of the
battle against Aids. The Vatican
encourages sexual abstinence to fight
the spread of the disease.
A monumental safe-sex message in Paris
14,000 people get infected
with HIV every day.
2 million people die of
Aids each year.
A monumental safe-sex message in Paris
Sub-Saharan Africa HIV & AIDS statistics (2010)
Country
People living
with
HIV/AIDS
Adult (1549) rate %
Women
with
HIV/AIDS
Children
with
HIV/AIDS
AIDS
deaths
Orphans
due to AIDS
Cameroon
610,000
5.3
320,000
54,000
37,000
330,000
Chad
210,000
3.4
110,000
23,000
11,000
120,000
Congo
77,000
3.4
40,000
7,900
5,100
51,000
Ghana
260,000
1.8
140,000
27,000
18,000
160,000
Kenya
1,500,000
6.3
760,000
180,000
80,000
1,200,000
Mozambique
1,400,000
11.5
760,000
130,000
74,000
670,000
Nigeria
3,300,000
3.6
1,700,000
360,000
220,000
2,500,000
South Africa
5,600,000
17.8
3,300,000
330,000
310,000
1,900,000
Total subSaharan Africa
22,500,000
5.0
12,100,000
2,300,000
1,300,000
14,800,000
Notes
Adults in this page are defined as men and women aged over 15, unless specified otherwise.
Children are defined as people under the age of 15, whilst orphans are children aged under 18
who have lost one or both parents to AIDS.
There is no single perfect solution to the
problem of Aids
Telling people to abstain doesn’t make
everyone abstain
Telling people NOT to use condom
undermines the effort of the fight against
AIDs and makes a serious global public
health problem in places where AIDs is
rapidly spreading e.g. Africa
Botswana, 23.9% of adults between 15 and 49 are HIV positive; Swaziland, where 26.1% of adults have HIV;
26.2 Specific defence mechanisms
1 Antigens are substances that
stimulate immune responses ,
activate the immune system to
produce antibodies , and combine
with specific antibodies.
26.2 Specific defence mechanisms
2 Humoral immune response uses
antibodies to act against specific
antigens that have not yet entered
host cells.
26.2 Specific defence mechanisms
3 How antibodies act against
pathogens:
a Antibodies may attach to the
antigens of pathogens and
lyse them.
26.2 Specific defence mechanisms
3 How antibodies act against
pathogens:
b Antibodies may help the
phagocytes engulf the
pathogens more easily.
26.2 Specific defence mechanisms
3 How antibodies act against
pathogens:
c Antibodies may help pathogens
stick into clumps , preventing
them from reproducing or
entering cells.
26.2 Specific defence mechanisms
3 How antibodies act against
pathogens:
d Antibodies may act as antitoxins
which neutralize the toxins
secreted by pathogens.
26.2 Specific defence mechanisms
4 Cell-mediated immune response
uses T cells to destroy cells
infected with specific antigens and
cancer cells.
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
Formed in
Mature in
B cells
T cells
Bone marrow
Bone marrow Thymus
gland
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
B cells give rise to:
- Plasma cells which produce
antibodies to act against
antigens that have not yet
entered host cells
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
B cells give rise to:
- Memory B cells which
‘remember’ the type of antigen
and are responsible for the
secondary response
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
T cells give rise to:
- Helper T cells which can
activate other T cells and B cells
- Killer T cells which destroy
infected cells or cancer cells
directly
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
T cells give rise to:
- Memory T cells which
‘remember’ the type of antigen
and are responsible for the
secondary response
26.2 Specific defence mechanisms
5 Compare B cells and T cells:
B cells
Responsible HIR
for
T cells
CMIR
26.2 Specific defence mechanisms
6 Distinguish primary and
secondary responses:
Primary response
Effected by
stimulation of
B cells and T cells
Secondary response
Effected by
stimulation of
memory B cells
and memory T cells
26.2 Specific defence mechanisms
6 Distinguish primary and
secondary responses:
Primary response Secondary response
Shorter
Longer
latent period
latent period
( slower response) ( faster response)
26.2 Specific defence mechanisms
6 Distinguish primary and
secondary responses:
Primary response Secondary response
Smaller amount
of antibodies and
killer T cells
produced
Larger amount of
antibodies and killer T
cells produced
26.2 Specific defence mechanisms
6 Distinguish primary and
secondary responses:
Primary response Secondary response
Lasts for a short Lasts longer
period of time
26.2 Specific defence mechanisms
7a Vaccination is the introduction of a
vaccine , which contains
an antigen , into the body.
A vaccine may contain live and
weakened pathogens, killed
pathogens, viral proteins or
inactivated bacterial toxins.
26.2 Specific defence mechanisms
7b Vaccination makes use of the
specificity and immunological
memory of the specific defence
mechanisms. The vaccine
produces a primary response.
26.2 Specific defence mechanisms
7b Any subsequent invasion by the
same antigen in the vaccine will
produce a secondary response,
giving enhanced immunity to the
disease.
26.2 Specific defence mechanisms
8 Distinguish active immunity and
passive immunity:
Active immunity
Passive immunity
Antibodies are
Antibodies are
produced by our
transferred from
own plasma cells immune persons
26.2 Specific defence mechanisms
8 Distinguish active immunity and
passive immunity:
Active immunity
Passive immunity
Acquired naturally Acquired naturally
when a person
through the diffusion
recovers from an of antibodies in the
and
placenta
infection
breast-feeding
26.2 Specific defence mechanisms
8 Distinguish active immunity and
passive immunity:
Active immunity
Acquired artificially
by vaccination
(for disease
prevention)
Passive immunity
Acquired artificially
by injection of
antibodies (for the
treatment of
diseases)
26.2 Specific defence mechanisms
8 Distinguish active immunity and
passive immunity:
Active immunity
Passive immunity
Start of immunity is Start of immunity is
slow
fast
26.2 Specific defence mechanisms
8 Distinguish active immunity and
passive immunity:
Active immunity
Passive immunity
Lasts longer
Lasts for a short
period of time
1
What is immunity?
Immunity is the ability of the body to
resist a disease.
2
Which type of white blood cell is
necessary to activate the defensive
reactions of the body?
Helper T cells are necessary to activate
the defensive reactions of the body.
3
How does a low level of those white
blood cells lead to weakened immunity?
With only a low level of helper T cells,
few B cells and T cells are activated to
carry out immune responses.
Body defence
consists of
non-specific
defence
mechanisms
specific defence
mechanisms
non-specific defence mechanisms
include
physical chemical
barriers barriers
blood
clotting
phagocytosis
inflammatory
response
physical
barriers
chemical
barriers
form
first line of
defence
phagocytosis
carried
out by
phagocytes
specific defence mechanisms
include
humoral immune
cell-mediated
response
immune response
carried out by
carried out by
T cells
some are
helper T cells
B cells
activate
T cells
can secrete
lymphokines
activate
phagocytes
T cells
multiply and
differentiate into
killer
T cells
memory
T cells
B cells
multiply and
differentiate into
memory
B cells
plasma
cells
produce
antibodies
memory
T cells
memory B
cells
responsible for
immunological
memory