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PowerLecture:
Chapter 10
Immunity
Learning Objectives




Describe typical external barriers that
organisms present to invading organisms.
Understand how the lymphatic system
contributes to the body’s defenses.
Understand how vertebrates (especially
mammals) recognize and discriminate
between self and nonself tissues.
Distinguish between antibody-mediated and
cell-mediated patterns of immune
responses.
Learning Objectives (cont’d)

Describe some examples of immune
failures and identify as specifically as you
can which weapons in the immunity arsenal
fail in each case.
Impacts/Issues
The Face of AIDS
The Face of AIDS
Viruses, such as HIV, have
wide ranging impacts on human
health.



At least 40 million people are
infected with HIV; 12 million
African children alone have been
orphaned by AIDS.
Rates of new HIV infection are
declining in some areas, but we
still have no effective vaccine to
prevent infection.
The Face of AIDS

The immune system is responsible for
protecting us from HIV and other infectious
agents; the more we learn about this
system, the more opportunities we have to
improve our health.
How Would You Vote?
To conduct an instant in-class survey using a classroom response
system, access “JoinIn Clicker Content” from the PowerLecture main
menu.
 Should
the federal government offer
incentives to companies to discount the
drugs for developing countries?


a. Yes, drug companies have a responsibility to
world health, not just their bottom line.
b. No, if drug companies must provide subsidies,
they won't be able to afford to develop new
drugs.
Section 1
Overview of Body
Defenses
Overview of Body Defenses
We are born with some general defenses
and acquire other, specific ones.


We have many defenses to protect us from
pathogens—those viruses, bacteria, fungi,
protozoa, and parasitic worms that cause
disease.
•
•
Antigens on these pathogens identify them as
nonself.
Antigens are usually proteins, lipids, or
oligosaccharides.
Overview of Body Defenses

Immunity is the body’s overall ability to resist
and combat anything that is nonself.
•
•
Innate immunity encompasses preset responses
that activate rapidly and in a generalized way to
detected damage or invasion.
Adaptive immunity responds to specific antigens on
specific pathogens; this response takes longer to
develop, but the body “remembers” what it sees and
responds quicker the next time the same pathogen is
seen.
Table 10.1, p.176
Overview of Body Defenses
Three lines of defense protect the body.




Intact skin and mucous membranes are
important first-line physical barriers.
Innate immunity forms the second line of
defense.
Adaptive immunity forms the third line of
defense.
Overview of Body Defenses
White blood cells and their chemicals are
the defenders in immune responses.


White blood cells are the core of the immune
system.
•
•
Phagocytes release chemicals called cytokines to
further defense responses.
Cytokines regulate different aspects of the immune
response; interleukins affect inflammation and fever,
interferons defend against viruses, and tumor
necrosis factor also affects inflammation and
stimulates tumor cell death.
Overview of Body Defenses


Complement is a group of about 30 blood
proteins that can kill microbes or identify them
for phagocytes to destroy.
White blood cells serve a variety of different
functions in the immune response:
•
•
•
Neutrophils make up two-thirds of all white blood
cells and work at the site of inflammation or damage.
Basophils and mast cells produce histamines in
response to antigens.
Macrophages are the predominant phagocytes that
patrol the bloodstream.
Overview of Body Defenses
• Eosinophils target pathogens that are too large for the
macrophages.
• Dendritic cells signal when antigens are present in
skin and body linings.
• B and T lymphocytes (B and T cells) function in
adaptive immunity.
• Natural killer cells (NK cells) are lymphocytes that
function in innate responses.
Table 10.2, p.177
neutrophil
eosinophil
Fig. 10.1, p.177
basophil
mast cell
Fig. 10.1, p.177
T lymphocyte
(T cell)
B lymphocyte
(B cell)
Fig. 10.1, p.177
dendritic cell
macrophage
Natural killer (NK) cell
Fig. 10.1, p.177
Animation: White Blood Cells
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Section 2
The Lymphatic System
The Lymphatic System

The lymphatic system has two key roles:
to work with the cardiovascular system to
cycle fluids back into the circulation; and to
circulate lymph from the spleen, lymph
nodes, and other lymphoid tissues
throughout the body.
Right Lymphatic Duct
Drains right upper portion of
the body
Thoracic Duct
Drains most of the body
Tonsils
Defense against bacteria
and other foreign agents
Thymus
Site where certain white
blood cells acquire means
to chemically recognize
specific foreign invaders
Spleen
Major site of antibody
production; disposal site for
old red blood cells and foreign
debris; site of red blood cell
formation in the embryo
Some of the
Lymph Vessels
Return excess interstitial
fluid and reclaimable
solutes to the blood
Bone Marrow
Marrow in some bones is
production site for infectionfighting blood cells (as well as
red blood cells and platelets)
Some of the
Lymph Nodes
Filter bacteria and many
other agents of disease
from lymph
Fig. 10.2, p.178
Animation: Lymphoid Organs
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The Lymphatic System
The lymph vascular system functions in
drainage, delivery, and disposal.


The lymph vascular system consists of lymph
capillaries and other vessels linking it to the
cardiovascular system.
•
•
•
Water and solutes that drain from the blood vessels
collect in the lymphatic vessels and are returned to
the blood via these vessels.
The lymphatic vessels pick up absorbed fats and
deliver them to the blood.
Lymphatic vessels also transport foreign material to
the lymph nodes for disposal.
The Lymphatic System

Lymph capillaries and vessels are structured
much like blood capillaries and veins.
blood
capillary bed
a Lymph capillaries
lymph
capillary
interstitial
fluid
flaplike “valve”
formed from
overlapping cells
at the tip of a
lymph capillary
Fig. 10.3a, p.179
The Lymphatic System
Lymphoid organs and tissues are
specialized for body defense.


Lymph nodes are located at intervals along
the lymph vessels; lymphocytes congregate in
these nodes, making them key battlefields in
fighting off pathogens.
lymph trickles past
organized arrays of
lymphocytes within
the lymph node
valve (prevents
backflow)
b A lymph node, cross section
Fig. 10.3b, p.179
Animation: Human Lymphatic System
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The Lymphatic System


The spleen filters blood and serves as a
holding station for large numbers of
lymphocytes.
T cells are produced and become specialized
in the thymus.
Section 3
Surface Barriers
Surface Barriers

The normal microorganisms living on your
skin help prevent the growth of unwanted
pathogens through competition.

Some microorganisms, such as the
Lactobacillus species of the vaginal tract in
women, lower the pH of their surroundings
to prevent growth of other microbes.
Figure 10.4
Surface Barriers
The mucus coating your lungs contains
enzymes such as lysozyme that can attack
and destroy many bacteria; cilia can also
sweep out pathogens.



Chemicals in tears, saliva,
and gastric fluid offer
similar protection.
The natural low pH of urine, as well as its
flushing action, helps protect the urinary tract.
Section 4
Innate Immunity
Innate Immunity

Once a pathogen enters the
body, macrophages engulf it
and release cytokines to
attract dendritic cells,
neutrophils, and more
macrophages.
Figure 10.5
Innate Immunity
Circulating complement proteins can detect
pathogens and become activated.



Activated complement attracts phagocytes,
which can destroy the pathogens.
Activated complement can also form
membrane attack complexes in the pathogen;
these are holes that cause the pathogen to
disintegrate.
one membrane
attack complex
(cutaway view)
lipid bilayer of
a pathogen
pore
Fig. 10.6, p.180
Animation: Membrane Attack Complexes
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Innate Immunity
Activated complement and cytokines
stimulate inflammation, characterized by
redness, swelling, warmth, and pain.


Tissue irritation causes mast cells to release
histamine and cytokines that cause the blood
vessels to dilate (tissue
redness and warmth)
and capillary walls to
become leaky (edema).
Figure 10.8
Innate Immunity

Plasma proteins and phagocytes leave the
blood vessels.
•
•
Plasma proteins contain clotting agents that help wall
off the pathogen and promote repair of tissues.
Macrophages release cytokines that tell the brain to
release prostaglandins, which in turn stimulates
fever production; moderate fevers inhibit pathogen
growth.
Animation: Inflammatory Response
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a Bacteria invade a tissue and
b Mast cells in tissue release histamine,
which then triggers arteriolar vasodilation
(hence redness and warmth) as well as
increased capillary permeability.
directly kill cells or release
metabolic products that damage
tissue.
e
a
c Fluid and plasma
c
b
d Plasma
proteins leak out of
capillaries; localized
edema (tissue swelling)
and pain result.
proteins attack
bacteria. Clotting
factors wall off
inflamed area.
d
e Neutrophils, macrophages, and
other phagocytes engulf invaders
and debris. Activated
complement attracts phagocytes
and directly kills invaders.
Fig. 10.7, p.181
Section 5
Overview of
Adaptive Defenses
Overview of Adaptive Defenses
Adaptive immunity has three key features.


Adaptive immunity is the body’s third line of
defense and has three defining features:
•
•
•
Adaptive immunity is specific; each B and T cell only
recognizes one antigen.
Adaptive immunity is diverse; B and T cells
collectively can recognize at least a billion different
threats.
Adaptive immunity has memory.
Overview of Adaptive Defenses

Recognition of an antigen results in rapid cell
division to produce huge numbers of identical B
and T cells that recognize the stimulating
antigen.
•
•
Some of these new cells are effector cells that can
immediately destroy pathogens.
Others are memory cells, held in reserve for future
battles against the same threat; memory cells are
what make you “immune” to various pathogens.
Overview of Adaptive Defenses
B cells and T cells become specialized to
attack antigens in different ways.


Both B and T lymphocytes arise in stem cells in
the bone marrow.
•
•

B cells continue to develop within bone marrow.
T cells travel to the thymus to finish developing; T
cells divide into two populations—helper T cells and
cytotoxic (“killer”) T cells.
When mature, B and T cells can be found in the
lymph nodes, spleen, and other lymphoid
tissues where they remain “naive” until they
recognize antigen.
Overview of
Adaptive Defenses

B cells and T cells respond to pathogens in
different ways.
•
•
B cells produce antibodies (proteins) and are
responsible for antibody-mediated
immunity.
T cells directly attack invaders; their response is
called cell-mediated immunity.
Figure 10.9
Red blood
cells
Platelets
Monocytes,
others
Bone marrow
Stem cells
Thymus
B cells
T cells
Organs of lymphatic system
Foreign
invasion
B cells
T cells
Antibody-mediated
immune response
Cell-mediated
immune response
Fig. 10.9, p.182
Animation: Immune Response
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Antibody-Mediated
Immune Response
Cell-Mediated
Immune Response
antigen-presenting cells
inactive B cells
+
antigen
+
complement
activated
B cells
effector B cells
+
memory B cells
inactive helper T cells
effector
helper T cells
+
memory
helper T cells
inactive
cytotoxic T cells
effector cytotoxic T cells
+
memory cytotoxic cells
Fig. 10.10, p.183
Overview of Adaptive Defenses
Proteins called MHC markers label body
cells as self.



All body cells have MHC markers (from Major
Histocompatibility Complex genes) to identify
them as “self.”
T cells have TCRs (T Cell Receptors) that see
MHC in context with antigen and respond.
Overview of Adaptive Defenses
Antigen-presenting cells introduce antigens
to T cells and B cells.


T cells and B cells can only “see” antigens that
have been processed by an antigenpresenting cell (APC).
•
•
Macrophages, dendritic cells, and B cells can all
present antigen.
The antigen is ingested and digested; then its
fragments are linked with MHC markers and
displayed on the cell’s surface as antigen-MHC
complexes.
Overview of Adaptive Defenses

Helper T cells see the antigen-MHC complex,
release cytokines, and trigger repeated rounds
of division to produce the large numbers of
activated B and T cells.
•
•
Specialization of activated cells into effector or
memory cells also occurs.
An effector B cell is called a plasma cell; it can flood
the bloodstream with antibodies.
Animation: Molecular Cues
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Table 10.3, p.192
Section 6
Antibody-Mediated
Immunity: Defending
Against Threats Outside
Cells
Antibody-Mediated Immunity: Defending
Against Threats Outside Cells
Antibodies develop while B cells are in bone
marrow.




An antibody has a Y-shaped protein structure;
antigens are bound by the two “arms” of the
antibody.
No two B cells make antibodies that are alike;
this allows both diversity and specificity.
B cells make many copies of their antibodies,
which are inserted in the plasma membrane,
arms sticking out and ready to bind antigen.
binding site for antigen
binding site for antigen
Fig. 10.11a, p.184
antigen on bacterial cell
(not to scale)
binding site on one kind
of antibody molecule
for a specific antigen
Fig. 10.11b, p. 184
Animation: Antibody Structure
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Antibody-Mediated Immunity: Defending
Against Threats Outside Cells
Antibodies target pathogens that are
outside cells.


Prior to activation, B cells serve as antigenpresenting cells.
•
•
•
Antibodies on the B cell surface bind antigens,
internalize them, process them, and then display
antigen-MHC complexes.
TCRs of a helper T cell see the antigen-MHC
complex and bind; binding causes the cells to
exchange signals.
The T cell disengages, but the B cell is now
activated; when it recognizes unbound antigen, the B
cell will divide into plasma cells and memory cells.
Animation: Clonal Selection
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Animation: Antibody-Mediated
Immune Response
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bacterium
dendritic
cell
complement
inactive
B cell
inactive
T cell
cytokines
antigen-presenting cell
B cell
memory
B cell
effector
helper
T cell
memory
helper
T cell
effector
B cell
Fig. 10.12, p. 185
Antibody-Mediated Immunity: Defending
Against Threats Outside Cells

Plasma cells can release up to 2,000 antibodies
per minute into the bloodstream; these
antibodies “flag” invaders for destruction by
phagocytes and complement.
There are five classes of antibodies, each
with a particular function.


Collectively, antibodies are referred to as
immunoglobulins, or Igs.
Antibody-Mediated Immunity: Defending
Against Threats Outside Cells

The five different classes of Igs are the protein
products of gene shuffling that takes place as
the B cells mature:
•
•
IgM antibodies cluster into a structure with 10
binding sites, making them more efficient at binding
clumped targets; IgM is the first antibody produced in
a response.
IgA antibodies are present in secretions of exocrine
glands (tears, saliva, breast milk) and in the mucus
of the respiratory, digestive, and reproductive tracts.
Antibody-Mediated Immunity: Defending
Against Threats Outside Cells
•
•
•
IgG antibodies neutralize toxins, turn on
complement, are long lasting, can cross the
placenta, and are found in mother’s milk.
IgD is the most common antibody bound to naive B
cells; it may help activate T cells.
IgE antibodies are involved in allergic reactions; they
bind to basophils and mast cells where they act as
traps for antigen, causing the release of histamine.
IgG, IgD, and IgE
IgA
IgM
In-text Fig., p.184
Animation: Generating Antibody Diversity
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Video: Germs in Pakistan
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
From ABC News, Human Biology in the Headlines, 2006 DVD.
Section 7
Cell-Mediated
Responses—Defending
Against Threats Inside
Cells
Cell-Mediated Responses – Defending
Against Threats Inside Cells


Cell-mediated responses fight those
pathogens (viruses, bacteria, and some
fungi and protozoans) that can enter cells to
avoid antibody defenses; cell-mediated
responses also fight abnormal body cells
such as cancer cells.
APCs present antigen to T cells, similar to
their role in antibody-mediated immunity.
Cell-Mediated Responses – Defending
Against Threats Inside Cells


Helper T cells can be stimulated this way to
divide into effector and memory cells.
Effector helper T cells or APCs directly can
stimulate cytotoxic T cells to divide.
•
•
Cytotoxic T cells rapidly multiply and release
molecules that can “touch-kill” infected and abnormal
body cells.
Cytotoxic T cells also secrete chemicals that
stimulate apoptosis—the programmed cell death of
the infected cell.
cytotoxic T
cell
tumor cell
Fig. 10.14, p.187
Animation: Cell-Mediated
Immune Response
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Video: Cell-Mediated Response Overview
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dendritic
cell
virus particle
(red) infecting
a body cell
(yellow)
a
b
inactive
cytotoxic
T cell
inactive
helper
T cell
c
antigen-presenting
cell
d
activated
cytotoxic
T cell
memory
cytotoxic
T cell
cytokines
effector
cytotoxic
T cell
effector
helper
T cell
memory
helper
T cell
effector
cytotoxic
T cell
e
Fig. 10.13, p. 186
dendritic
cell
virus particle
( red) infecting
a body cell
( yellow)
a
b
inactive
helper
T cell
inactive
cytotoxic
T cell
c
antigen-presenting
cell
d
memory
cytotoxic
T cell
activated
cytotoxic
T cell
effector
cytotoxic
T cell
effector
helper
T cell
memory
helper
T cell
effector
cytotoxic
T cell
e
Stepped Art
Fig. 10.13, p. 186
Cell-Mediated Responses – Defending
Against Threats Inside Cells

Helper T cells can also stimulate NK cells; they
will attack any cell that has too few or altered
MHC, any cells that have been tagged by
antibodies, and cells showing “stress markers”
as indicators of infection or cancer.
Cytotoxic T cells cause the body to reject
transplanted tissue.


During organ transplants, donor tissues must
be matched to a recipient to ensure that the
MHC markers do not differ enough to stimulate
rejection by cytotoxic T cells.
Cell-Mediated Responses – Defending
Against Threats Inside Cells
•
•

Donor and recipient usually must share at least 75%
of their MHC markers for the transplant to succeed;
close relatives make the best donors because of this.
Recipients usually also take drugs to suppress the
immune system to prevent rejection; often they will
also take antibiotics to ward off potential infections.
Tissues of the eye and testicles do not
stimulate rejection; instead, cells of these
tissues secrete signals that cause lymphocytes
to undergo apoptosis, thus preventing the
lymphocytes from attacking.
Video: A Saving Graft
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
From ABC News, Human Biology in the Headlines, 2006 DVD.
Section 8
Immunological Memory
Immunological Memory


Memory cells form during the primary
(first) response to an antigen and remain
in the blood for years or decades.
Secondary responses to the same antigen
are much faster; plasma cells and effector T
cells form sooner and in greater numbers,
preventing infection.
Fig. 10.20, p.194
later exposure to
same antigen
Relative concentrations
of antibody
first exposure
to antigen
Response time (weeks)
Fig. 10.15b, p. 188
Animation: Immunological Memory
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First exposure
to antigen
provokes
primary
immune
response.
inactive T or B cell
effector cell
Later
exposure to
same antigen
provokes
secondary
immune
response.
memory cell
effector cells
memory cells
Fig. 10.15a, p. 188
Section 9
Applications of
Immunology
Applications of Immunology
Immunization gives “borrowed” immunity.



Immunization increases immunity against
specific diseases.
In active immunization, a
vaccine is given by injection or
is taken orally.
•
•
The first dose of vaccine elicits a primary immune
response; a second dose (“booster”) elicits a
secondary, and more long-lasting, response.
Vaccines are made from killed or very weak
pathogens, inactivated forms of toxins, or transgenic
(genetically engineered) viruses.
Figure 10.16
Applications of Immunology


Passive immunization involves injecting
antibodies into already infected individuals.
Vaccines are not risk free.
p. 188
Applications of Immunology
Monoclonal antibodies are used in research
and medicine.



Monoclonal antibodies
are antibodies made by
cells cloned from a single
antibody-producing B cell;
they are generally produced using genetically
altered bacteria or sometimes plants.
Monoclonal antibodies are being used
commercially in home pregnancy tests,
screening for prostate cancer, and other uses.
Figure 10.17
Applications of Immunology
Immunotherapies reinforce defenses.


Immunotherapy alters the body’s own immune
mechanisms to enhance defense against
infections and cancer.
•
•
Cytokines can be used to activate B and T cells to
fight cancer.
Monoclonal antibodies can be used to bind to
proteins on cancer cells to draw NK cells to the
tumor.
Applications of Immunology
•
•
•

Other monoclonal antibodies are bound to toxins to
make immunotoxins; these substances bind to
cancer cells, enter them, and prevent growth.
Gamma interferon, produced by T cells, stimulates
NK cells and boosts activity of macrophages; it is
currently being used to treat hepatitis C.
Beta interferon is being used to treat multiple
sclerosis.
Immunotherapies, as with vaccines, do not
come without risks.
Video: Polio Scare
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
From ABC News, Biology in the Headlines, 2005 DVD.
Section 10
Disorders of the Immune
System
Disorders of the Immune System
In allergies, harmless substances provoke
an immune attack.


An allergy is an immune
response to a normally
harmless substance
called an allergen.
•
•
•
Allergens include: pollen, some foods and drugs,
dust mites, fungal spores, insect venom, and certain
ingredients in cosmetics.
Allergens trigger mild to severe inflammation of
various tissues.
A variety of causes, from genetic to emotional, lead
to allergies.
Figure 10.18a
Disorders of the Immune System

Exposure to an allergen triggers production of
IgE antibodies, which cause the release of
histamines and prostaglandins from mast cells.
•
•

Histamines and prostaglandins fuel inflammation.
Hay fever manifests as stuffed sinuses, a drippy
nose, and sneezing.
In a few individuals, explosive inflammatory
responses trigger life-threatening anaphylactic
shock in which air passages constrict and fluid
rushes out of the capillaries.
Disorders of the Immune System
•
•

Food allergies, such as peanut allergies, and wasp
and bee venom allergies, can trigger anaphylactic
shock.
Rapid injections of the hormone epinephrine can
prevent shock and save lives.
Antihistamines are often used to relieve the
short-term symptoms of allergies;
desensitization can be used to “train” the body
not to see allergens.
allergen (antigen)
enters the body
IgE
antibodies
histamine
granules
B cell
Allergen binds B
cell receptors; the
sensitized B cell now
processes the antigen
and, with the help of T
cells (not shown),
proceeds through the
steps leading to cell
proliferation
mitochondrion
nucleus
mast cell
Effector B cells
(plasma cells)
produce and secrete
IgE antibodies to the
allergen
IgE antibodies attach to
mast cells in tissues,
which have granules
containing histamine
molecules
Fig. 10.18b, p. 190
SECONDARY RESPONSE
(allergy)
histamine
granules
After the first exposure, when
the allergen enters the body it
binds with IgE antibodies on
mast cells; binding stimulates
the mast cell to release
histamine and other
substances
Fig. 10.18b, p. 190
Disorders of the Immune System
Autoimmune disorders attack “self.”



In an autoimmune response, lymphocytes
turn against the body’s own cells.
Examples of autoimmune diseases include the
following:
•
Rheumatoid arthritis, an inflammation of the joints
caused by immune attack against collagen and
antibodies in the joints;
inflammation, complement
and faulty repair mechanisms
contribute to the damage.
Figure 10.19
Disorders of the Immune System
•
•

Type 1 diabetes, a type of diabetes mellitus,
caused when the immune system attacks and
destroys the insulin-secreting cells of the pancreas,
impairing glucose absorption from the blood.
Systemic lupus erythematosus, where patients
develop antibodies to their own DNA and other “self”
components.
Autoimmune diseases tend to be more frequent
in women than in men.
Disorders of the Immune System
Immune responses can be deficient.


Immunodeficiency is used to describe the
state where a person’s immune system is
weakened or lacking; under these conditions
the body is vulnerable and infections that would
normally not be serious become life
threatening.
Disorders of the Immune System


In severe combined immune deficiency
(SCID) both B and T cells are in low numbers;
infants born with SCID usually die early in life.
In acquired immune deficiency syndrome
(AIDS), the HIV virus attacks the body’s
macrophages and helper T cells, crippling the
immune response.