The Immune System: Powerpoint Lectures For

Principles of Biomedical
Science Unit 5
The Immune System
PowerPoint Lectures for

Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Overview: Reconnaissance, Recognition, and
Response
• An animal must defend itself
– From the many dangerous pathogens it may
encounter in the environment
• Two major kinds of defense have evolved that

counter these threats
– Innate immunity and acquired immunity

• Innate immunity
– Is present before any exposure to pathogens
and is effective from the time of birth
– Involves nonspecific responses to pathogens
3m

• Acquired immunity, also called adaptive
immunity
– Develops only after exposure to inducing
agents such as microbes, toxins, or other
foreign substances
– Involves a very specific response to pathogens

• A summary of innate and acquired immunity
INNATE IMMUNITY ACQUIRED IMMUNITY

Rapid responses to a Slower responses to
broad range of microbes specific microbes
External defenses Internal defenses
Skin Phagocytic cells Humoral response

Mucous membranes Antimicrobial proteins (antibodies)
Secretions Inflammatory response
Invading
microbes Natural killer cells Cell-mediated response
(pathogens) (cytotoxic
lymphocytes)
Figure 43.2

• Innate immunity provides broad defenses
against infection
• A pathogen that successfully breaks through
an animal’s external defenses
– Soon encounters several innate cellular and
chemical mechanisms that impede its attack
on the body

External Defenses
• Intact skin and mucous membranes
– Form physical barriers that bar the entry of
microorganisms and viruses
• Certain cells of the mucous membranes

produce mucus
– A viscous fluid that traps microbes and other
particles

• In the trachea, ciliated epithelial cells
– Sweep mucus and any entrapped microbes
upward, preventing the microbes from entering
the lungs 10m

• Secretions of the skin and mucous membranes
– Provide an environment that is often hostile to
microbes
• Secretions from the skin

– Give the skin a pH between 3 and 5, which is
acidic enough to prevent colonization of many
microbes
– Also include proteins such as lysozyme, an
enzyme that digests the cell walls of many
bacteria
Internal Cellular and Chemical Defenses
• Internal cellular defenses
– Depend mainly on phagocytosis
• Phagocytes, types of white blood cells

– Ingest invading microorganisms
– Initiate the inflammatory response

Phagocytic Cells
• Phagocytes attach to their prey via surface receptors
– And engulf them, forming a vacuole that fuses with a
lysosome
1 Pseudopodia
surround
Microbes microbes.
2 Microbes
are engulfed
into cell.
MACROPHAGE
3 Vacuole
containing
microbes
forms.
Vacuole Lysosome
containing 4 Vacuole
enzymes and lysosome
fuse.
5 Toxic
compounds
and lysosomal
enzymes
destroy microbes.
6 Microbial
debris is
released by
exocytosis.

• Macrophages, a specific type of phagocyte
– Can be found migrating through the body
– Can be found in various organs of the

lymphatic system

• The lymphatic system
– Plays an active role in defending the body from
pathogens 1 Interstitial fluid bathing the
tissues, along with the white
blood cells in it, continually
enters lymphatic capillaries. Lymphatic
Interstitial capillary
fluid 2 Fluid inside the
Adenoid lymphatic capillaries,
called lymph, flows
Tonsil through lymphatic
vessels throughout
4 Lymphatic vessels the body.
return lymph to the
blood via two large
ducts that drain into
Lymph
veins near the Blood
nodes
shoulders. capillary
Spleen
Lymphatic
Tissue
Peyer’s patches vessel
cells
(small intestine)
3 Within lymph nodes,

Appendix microbes and foreign
particles present in
the circulating lymph
encounter macro-
phages, dendritic cells,
and lymphocytes,
which carry out
Lymphatic Masses of various defensive
vessels Lymph lymphocytes and actions.
node macrophages

Antimicrobial Proteins
• Numerous proteins function in innate defense
– By attacking microbes directly or by impeding
their reproduction

• About 30 proteins make up the complement
system
– Which can cause lysis of invading cells and
help trigger inflammation
• Interferons
– Provide innate defense against viruses and
help activate macrophages

Inflammatory Response
• In local inflammation, histamine and other
chemicals released from injured cells
– Promote changes in blood vessels that allow
more fluid, more phagocytes, and antimicrobial
proteins to enter the tissues

• Major events in the local inflammatory response
Pathogen Pin Blood clot
Macrophage
Blood
Chemical signals clotting
Phagocytic cells elements
Phagocytosis
Capillary
Red blood cell

1 Chemical signals released 2 Fluid, antimicrobial proteins, 3 Chemokines released by various 4 Neutrophils and macrophages
by activated macrophages and clotting elements move kinds of cells attract more phagocytose pathogens and
and mast cells at the injury from the blood to the site. phagocytic cells from the blood cell debris at the site, and the
site cause nearby capillaries Clotting begins. to the injury site. tissue heals.
to widen and become more
permeable.

Natural Killer Cells
• Natural killer (NK) cells
– Patrol the body and attack virus-infected body
cells and cancer cells
– Trigger apoptosis in the cells they attack

Acquired Immunity
• In acquired immunity, lymphocytes provide
specific defenses against infection
• Acquired immunity
– Is the body’s second major kind of defense
– Involves the activity of lymphocytes

• An antigen is any foreign molecule
– That is specifically recognized by lymphocytes
and elicits a response from them
• A lymphocyte actually recognizes and binds
– To just a small, accessible portion of the antigen
called an epitope
Antigen-
binding Epitopes
Antibody A sites (antigenic
determinants)
Antigen
Antibody B
Antibody C

Antigen Recognition by Lymphocytes
• The vertebrate body is populated by two main
types of lymphocytes
– B lymphocytes (B cells) and T lymphocytes
(T cells)
– Which circulate through the blood
• The plasma membranes of both B cells

and T cells
– Have about 100,000 antigen receptor that all
recognize the same epitope

B Cell Receptors for Antigens
• B cell receptors
– Bind to specific, intact antigens
– Are often called membrane antibodies or membrane

immunoglobulins Antigen- Antigen-
binding binding site
site V Disulfide
bridge
V
V
Variable
V
Light
chain regions
C
C
Constant
C C regions
Transmembrane
region
Plasma
membrane
Heavy chains
B cell Cytoplasm of B cell
(a) A B cell receptor consists of two identical heavy

chains and two identical light chains linked by
several disulfide bridges.
T Cell Receptors for Antigens and the Role of the MHC
• Each T cell receptor
– Consists of two different polypeptide chains
Antigen-
Binding site
Variable
regions
V V
Constant
regions C C
Transmembrane
region
Plasma  chain
membrane  chain
Disulfide bridge
Cytoplasm of T cell T cell
(b) A T cell receptor consists of one

 chain and one  chain linked by
a disulfide bridge.

• T cells bind to small fragments of antigens
– That are bound to normal cell-surface proteins
called MHC molecules
• MHC molecules
– Are encoded by a family of genes called the
major histocompatibility complex

• Infected cells produce MHC molecules
– Which bind to antigen fragments and then are
transported to the cell surface in a process
called antigen presentation
• A nearby T cell
– Can then detect the antigen fragment
displayed on the cell’s surface

• Depending on their source
– Peptide antigens are handled by different
classes of MHC molecules

• Class I MHC molecules, found on almost all
nucleated cells of the body
– Display peptide antigens to cytotoxic T cells
Infected cell
1 A fragment of
foreign protein
Antigen (antigen) inside the
fragment cell associates with
an MHC molecule
and is transported
1 to the cell surface.
Class I MHC
molecule
2 2 The combination of
T cell MHC molecule and
receptor antigen is recognized
by a T cell, alerting it
to the infection.
(a) Cytotoxic T cell

• Class II MHC molecules, located mainly on
dendritic cells, macrophages, and B cells
– Display antigens to helper T cells
Microbe Antigen-
presenting
1 A fragment of cell
foreign protein
(antigen) inside the Antigen
cell associates with fragment
an MHC molecule
and is transported
to the cell surface. 1
Class II MHC
molecule
2 The combination of 2
T cell
MHC molecule and receptor
antigen is recognized
by a T cell, alerting it
to the infection.
Helper T cell
(b)
Lymphocyte Development
• Lymphocytes
– Arise from stem cells in the bone marrow

• Newly formed lymphocytes are all alike
– But they later develop into B cells or T cells,
depending on where they continue their maturation
Bone marrow
Lymphoid Thymus
stem cell
B cell T cell
Blood, lymph, and lymphoid tissues

(lymph nodes, spleen, and others)

Generation of Lymphocyte Diversity by Gene
Rearrangement
• Early in development, random, permanent

gene rearrangement
– Forms functional genes encoding the B or T
cell antigen receptor chains

• Immunoglobulin gene rearrangement
V4–V39
DNA of
undifferentiated V1 V2 V3 V40 J1 J2 J3 J4 J5 Intron C
B cell
1Deletion of DNA between a V segment

and J segment and joining of the segments
DNA of differentiated V1 V2 V3 J5 Intron C
B cell
Transcription
2 of resulting permanently rearranged,
functional gene
pre-mRNA V3 J5 Intron C
RNA
3 processing (removal of intron; addition of cap
and poly (A) tail)
mRNA Cap V 3 J5 C Poly (A)
4 Translation
Light-chain polypeptide V C B cell receptor
Variable Constant
B cell
region region
Testing and Removal of Self-Reactive Lymphocytes
• As B and T cells are maturing in the bone and
thymus
– Their antigen receptors are tested for possible
self-reactivity
• Lymphocytes bearing receptors for antigens

already present in the body
– Are destroyed by apoptosis or rendered
nonfunctional

Clonal Selection of Lymphocytes
• In a primary immune response
– Binding of antigen to a mature lymphocyte
induces the lymphocyte’s proliferation and
differentiation, a process called clonal
selection

• Clonal selection of B cells
– Generates a clone of short-lived activated effector
cells and a clone of long-lived memory cells
Antigen molecules
Antigen molecules bind to the antigen
B cells that
receptors of only one
differ in
of the three B cells
antigen
shown.
specificity Antigen
receptor
The selected B cell

proliferates, forming
a clone of identical
cells bearing
receptors for the
selecting antigen.
Some proliferating cells Some proliferating

develop into long-lived cells develop into
memory cells that can Antibody short-lived plasma
respond rapidly upon molecules cells that secrete
subsequent exposure antibodies specific
to the same antigen. Clone of memory cells for the antigen.
Clone of plasma cells

• In the secondary immune response
– Memory cells facilitate a faster, more efficient
response
1 Day 1: First 3 Day 28: 4 Secondary response to anti-
2 Primary
exposure to Second exposure gen A produces antibodies
response to
antigen A to antigen A; first to A; primary response to anti-
antigen A
produces anti- exposure to gen B produces antibodies to B
bodies to A antigen B
104
Antibody concentration
103
(arbitrary units)
102 Antibodies Antibodies

to A to B
101
100
0 7 14 21 28 35 42 49 56
Time (days)

Adaptive Immunity
• Humoral and cell-mediated immunity defend
against different types of threats
• Acquired immunity includes two branches
– The humoral immune response involves the
activation and clonal selection of B cells,
resulting in the production of secreted
antibodies
– The cell-mediated immune response involves
the activation and clonal selection of cytotoxic
T cells

• The roles of the major participants in the
acquired immune response
Humoral immune response Cell-mediated immune response
First exposure to antigen
Antigens engulfed and Antigens displayed

Intact antigens displayed by dendritic cells by infected cells
Activate Activate Activate
Secreted
cytokines
B cell activate
Helper Cytotoxic
T cell T cell
Gives rise to Gives rise to Gives rise to
Active and
Plasma Memory Memory Active
memory
cells B cells cytotoxic cytotoxic
helper
T cells T cells
T cells
Secrete antibodies that defend against Defend against infected cells, cancer
pathogens and toxins in extracellular fluid cells, and transplanted tissues

Helper T Cells: A Response to Nearly All Antigens
• Helper T cells produce CD4, a surface protein
– That enhances their binding to class II MHC
molecule–antigen complexes on antigen-
presenting cells
• Activation of the helper T cell then occurs

• Activated helper T cells
– Secrete several different cytokines that
stimulate other lymphocytes

• The role of helper T cells in acquired immunity
1 After a dendritic cell engulfs and degrades a bacterium, it displays
bacterial antigen fragments (peptides) complexed with a class II
MHC molecule on the cell surface. A specific helper T cell binds
to the displayed complex via its TCR with the aid of CD4. This
interaction promotes secretion of cytokines by the dendritic cell.
Cytotoxic T cell
Dendritic Peptide antigen
cell Helper T cell Cell-mediated
Class II MHC
Bacterium molecule immunity
(attack on
TCR infected cells)
2 3
Humoral
1 CD4
immunity
(secretion of
Dendritic Cytokines B cell antibodies by
cell plasma cells)
2 Proliferation of the T cell, stimulated 3 The cells in this clone
by cytokines from both the dendritic secrete other cytokines
cell and the T cell itself, gives rise to that help activate B cells
a clone of activated helper T cells and cytotoxic T cells.
(not shown), all with receptors for the
same MHC–antigen complex.

Cytotoxic T Cells: A Response to Infected Cells and
Cancer Cells
• Cytotoxic T cells make CD8

– A surface protein that greatly enhances the
interaction between a target cell and a
cytotoxic T cell

• Cytotoxic T cells
– Bind to infected cells, cancer cells, and
transplanted tissues
• Binding to a class I MHC complex on an

infected body cell
– Activates a cytotoxic T cell and differentiates it
into an active killer

• The activated cytotoxic T cell
– Secretes proteins that destroy the infected target
cell 2 The activated T cell releases perforin
1 A specific cytotoxic T cell binds to a 3 The granzymes initiate apoptosis within the
class I MHC–antigen complex on a molecules, which form pores in the target cells, leading to fragmentation of the
target cell via its TCR with the aid of target cell membrane, and proteolytic nucleus, release of small apoptotic bodies,
CD8. This interaction, along with enzymes (granzymes), which enter the and eventual cell death. The released
cytokines from helper T cells, leads to target cell by endocytosis. cytotoxic T cell can attack other target cells.
the activation of the cytotoxic cell.
Cytotoxic T cell Released

cytotoxic
Perforin T cell
Cancer
cell
Granzymes
Apoptotic
1 TCR CD8 3
target cell
Class I MHC 2
Pore
molecule
Target
cell Peptide
antigen Cytotoxic
T cell

B Cells: A Response to Extracellular Pathogens
• Activation of B cells
– Is aided by cytokines and antigen binding to
helper T cells

• The clonal selection of B cells
– Generates antibody-secreting plasma cells, the
effector cells of humoral immunity

1 After a macrophage engulfs and degrades 2 A B cell that has taken up and degraded the 3 The activated B cell proliferates
a bacterium, it displays a peptide antigen same bacterium displays class II MHC–peptide and differentiates into memory
complexed with a class II MHC molecule. antigen complexes. An activated helper T cell B cells and antibody-secreting
A helper T cell that recognizes the displayed bearing receptors specific for the displayed plasma cells. The secreted
complex is activated with the aid of cytokines antigen binds to the B cell. This interaction, antibodies are specific for the
secreted from the macrophage, forming a with the aid of cytokines from the T cell, same bacterial antigen that
clone of activated helper T cells (not shown). activates the B cell. initiated the response.
Bacterium
Macrophage
Peptide
antigen
Class II B cell
MHC
molecule
2 Secreted antibody
3 Clone of plasma cells
1 molecules
TCR CD4 Endoplasmic
reticulum of
plasma cell
Cytokines
Helper T cell Activated

helper T cell Clone of memory
B cells

Antibody Classes
• The five major classes of antibodies, or
immunoglobulins
– Differ in their distributions and functions within
the body

• The five classes of immunoglobulins
IgM First Ig class produced after initial exposure to
(pentamer) antigen; then its concentration in the blood declines
Promotes neutralization and agglutination of

J chain antigens; very effective in complement activation
(see Figure 43.19)
IgG Most abundant Ig class in blood; also present in

(monomer) tissue fluids
Only Ig class that crosses placenta, thus conferring
passive immunity on fetus
Promotes opsonization, neutralization, and agglutination

of antigens; less effective in complement activation than
IgM (see Figure 43.19)
IgA Present in secretions such as tears, saliva, mucus,

(dimer) and breast milk
Secretory J chain Provides localized defense of mucous membranes by

component agglutination and neutralization of antigens (see
Figure 43.19)
Presence in breast milk confers passive immunity on

nursing infant
IgE
(monomer) Triggers release from mast cells and basophils of
histamine and other chemicals that cause allergic
reactions (see Figure 43.20)
IgD Present primarily on surface of naive B cells that have

(monomer) not been exposed to antigens
Acts as antigen receptor in antigen-stimulated

proliferation and differentiation of B cells (clonal
Transmembrane
selection)
region

Antibody-Mediated Disposal of Antigens
• The binding of antibodies to antigens
– Is also the basis of several antigen disposal
mechanisms
– Leads to elimination of microbes by
phagocytosis and complement-mediated lysis

• Antibody-mediated mechanisms of antigen disposal
Binding of antibodies to antigens
inactivates antigens by
Viral neutralization Agglutination of

(blocks binding to host) antigen-bearing particles, Precipitation of Activation of complement system
and opsonization (increases such as microbes soluble antigens and pore formation
phagocytosis)
Bacteria Complement
Virus proteins
MAC
Pore
Bacterium Soluble
antigens Foreign cell
Enhances Leads to
Phagocytosis Cell lysis
Macrophage

Active and Passive Immunization
• Active immunity
– Develops naturally in response to an infection
– Can also develop following immunization, also

called vaccination

• In immunization
– A nonpathogenic form of a microbe or part of a
microbe elicits an immune response to an
immunological memory for that microbe

• Passive immunity, which provides immediate,
short-term protection
– Is conferred naturally when IgG crosses the
placenta from mother to fetus or when IgA
passes from mother to infant in breast milk
– Can be conferred artificially by injecting
antibodies into a nonimmune person

• The immune system’s ability to distinguish self
from non-self limits tissue transplantation
• The immune system
– Can wage war against cells from other
individuals
• Transplanted tissues
– Are usually destroyed by the recipient’s
immune system

Blood Groups and Transfusions
• Certain antigens on red blood cells
– Determine whether a person has type A, B,
AB, or O blood

• Antibodies to nonself blood types
– Already exist in the body
• Transfusion with incompatible blood

– Leads to destruction of the transfused cells

• Recipient-donor combinations
– Can be fatal or safe

• Another red blood cell antigen, the Rh factor
– Creates difficulties when an Rh-negative
mother carries successive Rh-positive fetuses

Tissue and Organ Transplants
• MHC molecules
– Are responsible for stimulating the rejection of
tissue grafts and organ transplants

• The chances of successful transplantation are
increased
– If the donor and recipient MHC tissue types
are well matched
– If the recipient is given immunosuppressive
drugs

• Lymphocytes in bone marrow transplants
– May cause a graft versus host reaction in
recipients

• Concept 43.5: Exaggerated, self-directed, or
diminished immune responses can cause
disease
• If the delicate balance of the immune system is
disrupted
– The effects on the individual can range from
minor to often fatal consequences

Allergies
• Allergies are exaggerated (hypersensitive)
responses
– To certain antigens called allergens

• In localized allergies such as hay fever
– IgE antibodies produced after first exposure to
an allergen attach to receptors on mast cells

• The next time the allergen enters the body
– It binds to mast cell–associated IgE molecules
• The mast cells then release histamine and

other mediators
– That cause vascular changes and typical
symptoms

• The allergic response
IgE
Allergen Histamine
1
Granule
Mast cell
1 IgE antibodies produced in 2 On subsequent exposure to the 3 Degranulation of the cell,

response to initial exposure same allergen, IgE molecules triggered by cross-linking of
to an allergen bind to attached to a mast cell recog- adjacent IgE molecules,
receptors or mast cells. nize and bind the allergen. releases histamine and other
chemicals, leading to allergy
symptoms.

• An acute allergic response sometimes leads to
anaphylactic shock
– A whole-body, life-threatening reaction that
can occur within seconds of exposure to an
allergen

Autoimmune Diseases
• In individuals with autoimmune diseases
– The immune system loses tolerance for self
and turns against certain molecules of the
body

• Rheumatoid arthritis
– Is an autoimmune disease that leads to
damage and painful inflammation of the
cartilage and bone of joints

• Other examples of autoimmune diseases
include
– Systemic lupus erythematosus
– Multiple sclerosis
– Insulin-dependent diabetes

Immunodeficiency Diseases
• An inborn or primary immunodeficiency
– Results from hereditary or congenital defects
that prevent proper functioning of innate,
humoral, and/or cell-mediated defenses

• An acquired or secondary immunodeficiency
– Results from exposure to various chemical and
biological agents

Inborn (Primary) Immunodeficiencies
• In severe combined immunodeficiency (SCID)
– Both the humoral and cell-mediated branches
of acquired immunity fail to function

Acquired (Secondary) Immunodeficiencies
• Acquired immunodeficiencies
– Range from temporary states to chronic
diseases

Stress and the Immune System
• Growing evidence shows
– That physical and emotional stress can harm
immunity

• Acquired Immunodeficiency Syndrome (AIDS)
• People with AIDS

– Are highly susceptible to opportunistic
infections and cancers that take advantage of
an immune system in collapse

• Because AIDS arises from the loss of helper T
cells
– Both humoral and cell-mediated immune
responses are impaired

• The loss of helper T cells
– Results from infection by the human
immunodeficiency virus (HIV)
1µm

• The spread of HIV
– Has become a worldwide problem
• The best approach for slowing the spread of

HIV
– Is educating people about the practices that
transmit the virus

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Principles of Biomedical

The Immune System

PowerPoint Lectures for

Lectures by Chris Romero

• Two major kinds of defense have evolved that

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

INNATE IMMUNITY ACQUIRED IMMUNITY

External defenses Internal defenses

Skin Phagocytic cells Humoral response

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Certain cells of the mucous membranes

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• Secretions from the skin

• Phagocytes, types of white blood cells

– Initiate the inflammatory response

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– Can be found in various organs of the

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3 Within lymph nodes,

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Pathogen Pin Blood clot

Red blood cell

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– Involves the activity of lymphocytes

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

• The plasma membranes of both B cells

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– Are often called membrane antibodies or membrane

B cell Cytoplasm of B cell

(a) A B cell receptor consists of two identical heavy

(b) A T cell receptor consists of one

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

(a) Cytotoxic T cell

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Blood, lymph, and lymphoid tissues

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• Early in development, random, permanent

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1Deletion of DNA between a V segment

mRNA Cap V 3 J5 C Poly (A)

Light-chain polypeptide V C B cell receptor

• Lymphocytes bearing receptors for antigens

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

The selected B cell

Some proliferating cells Some proliferating

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102 Antibodies Antibodies

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