Chapter 15

Lecture Outline
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I. Defense Mechanisms

A.Introduction

Protect against disease-causing agents

called pathogens
Make up the immune system
Two types:
a.Innate (nonspecific) immunity - inherited
b.Adaptive (specific) immunity learned from
exposure to specific pathogens; function of
lymphocytes

B.Innate Immunity

Includes external and internal defenses

Serves as a first line of defense against
pathogens
a.Examples: epithelial membranes, high acidity in
stomach, cells that can engulf/kill pathogens, fever

Innate Immunity

3.Activation of Innate Immunity

a.Cells distinguish self from nonself

using pathogen-associated molecular
patterns (PAMPs) unique to the
pathogens.
1)Immune cells have pathogen recognition
receptors, such as toll-like receptors for PAMPs on
their surface.
2)These cells respond by secreting chemokines to
recruit more immune cells or activate specific
immune cells.

b.Complement System

1)Integrates innate and adaptive

immune responses
2)Consists of proteins in the plasma that
become activated when antibodies bind
to antigens
3)Complement proteins promote
phagocytosis, lysis of target cells, and
inflammation.

c.Local inflammation

1)Tissue damage that causes necrosis

2)Stimulates innate immune responses and
inflammation

4.Phagocytosis

Three types of phagocytic cells:

1)Neutrophils are the first to arrive at an infection.
2)Mononuclear phagocytic cells (monocytes in the blood
and macrophages and dendritic cells in the tissues)
arrive later.
3)Dendritic cells - antigen-presenting cells (also known
as accessory cells)

Phagocytotic Cells & Locations

Migration of white blood cells

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Bacteria

Phagocytosis of bacteria

Vessel wall

Rolling
Capture
Neutrophil

Spreading
Adhesion
and activation

Extravasation

5.Fever

a.Regulated by hypothalamus
b.A chemical called an endogenous
pyrogen sets the body temperature
higher.
1)Produced as a cytokine by leukocytes
2)Endotoxins from some bacteria stimulate leukocytes
to produce these cytokines.
3)Along with fever, they also induce sleepiness and a
fall in plasma iron concentration (which limits
bacterial activity).

6.Interferons

a.Antiviral polypeptides produced by

infected cells
b.Three types identified
1)Alpha and beta inhibit viral replication and assembly
2)Gamma helps fight infections and cancer

Effects of Interferons

C.Adaptive Immunity

The acquired ability to defend against specific

pathogens after exposure to these pathogens
a.Mediated by antigens and antibodies

2.Antigens

a.Cell surface molecules that stimulate the

production of specific antibodies and
combine with those antibodies
1)Foreign antigens illicit an immune response. The
immune system can distinguish self from nonself.
2)Antibodies bind to their specific antigens.
3)Large molecules can have several antigenic
determinant sites or epitopes, that stimulate the
production of and binding to antibodies.

3.Haptens

a.Smaller, nonantigenic molecules that can

become antigens when bound to other
proteins
b.These are useful for creating antigens for
research and diagnosis.

D.Lymphocytes & Lymphoid Organs

Lymphocytes
a.Derived from stem cells in the bone marrow.
b.These stem cells seed the thymus, spleen,
and lymph nodes.
1)The bone marrow and thymus are
considered primary lymphoid organs.
2)Everything else belongs to secondary
lymphoid organs

c.T Lymphocytes
1)Lymphocytes that seed the thymus become T
lymphocytes. These then seed the blood, lymph nodes,
and spleen.
2)T lymphocytes attack host cells that have become
infected with a virus or fungus, transplanted human
cells, and cancer cells.
3)T lymphocytes do not produce antibodies.
4)They must be in close proximity to the victim cell in
order to destroy it.
5)This is called cell-mediated immunity.

d.B Lymphocytes
1)Lymphocytes that come directly from bone
marrow to seed other organs (not the
thymus) are called B lymphocytes.
2)They combat bacterial and some viral
infections.
3)They secrete antibodies into blood and
lymph so can be far from the victim.
4) humoral immunity or antibody-mediated
immunity.

Comparison of T and B Lymphocytes

2.Secondary Lymphoid Organs

a.Lymph nodes, spleen, tonsils, and Peyers

patches (in mucosa of intestines)
b.Capture and present pathogens to
macrophages and house lymphocytes
c.Lymphocytes migrate between lymphoid
organs to sample blood and lymph.
1)The spleen filters blood for pathogens.
2)Other organs filter lymph for pathogens.

E.Local Inflammation

Occurs when bacteria enter a break

in the skin
Initiated by nonspecific
mechanisms of phagocytosis by
toll-like receptors
a.Macrophages and mast cells release cytokines and
chemokines to attract phagocytic neutrophils.
b.Complement proteins are activated, which also attract
phagocytic cells.
c.More phagocytic cells arrive via extravasation from nearby
venules. T lymphocytes are the last to arrive.

Local Inflammation, cont

3.Mast cells degranulate and secrete

heparin, histamine, prostaglandins,
leukotrienes, cytokines
a.These produce warmth, swelling, and pain (classic
symptoms).
b.They also recruit more leukocytes.

Local inflammation, cont

4.Neutrophils
a.Kill microorganisms through phagocytosis
b.Release NETS (neutrophil extracellular traps) to trap
pathogens
c.Undergo programmed cell death and spill proteindigesting enzymes into the surrounding tissues,
causing pus
d.Release granule proteins that draw monocytes to the
area

Local inflammation, cont

5.Monocytes
a.Enlarge into macrophages
b.Phagocytose apoptotic neutrophils and release growth
factors and other agents that will end inflammation and
promote repair.

6.As inflammation progresses, B lymphocytes

produce antibodies against bacterial antigens.
a.Formation of antigen-antibody complexes amplifies
phagocytosis by neutrophils, monocytes, and macrophages,
a process called opsonization.

Infiltration of an inflamed site by leukocytes

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Leukocyte infiltration
T lymphocytes

Intensity

Neutrophils
Monocytes

12

18

24
Hours

30

36

42

48

Local Inflammation, cont

7.Symptoms of inflammation
a.Redness and warmth due to histamine stimulated
vasodilation
b.Swelling vasodilation
c.Pain release of PGE2
d.Pus - phagocytosis

Events of Local Inflammation

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Bacteria

Epidermis

Antibodies

Antibody-coated
bacterium
Dermis
2

B lymphocyte

Lysosomal
enzymes
Vacuole

Phagocytic cell
(neutrophil)

Phagocytic cell

Lysosome
4

Activation of
complement

Extravasation
3
Dilation, increased
permeability of capillary
Release of
histamine

Capillary

Mast cell

Summary of Events in Local Inflammation

II. Functions of B
Lymphocytes

A.Introduction

Exposure to the specific antigen

activates a B lymphocyte
Enters the germinal center of a
secondary lymphoid organ
Undergo multiple cell divisions
(cloning).
a.Some become memory cells, which are used in a
later infection by the same pathogen.
b.Others become plasma cells, which produce
2,000 antibodies/second.

B Lymphocytes Become Plasma

& Memory Cells
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Antibody
Endoplasmic
reticulum
+

Nucleus

1. Antigens bind
to antibody
receptors

Antigen

Mitochondrion

2. Proliferation
(mitosis) causes
formation of
a clone

Plasma cell

Plasma cell
Memory cell

Memory cell

3. Plasma cells and

memory cells are formed

B.Antibodies

Introduction
a.Also known as immunoglobulins
b.Five classes: IgG, IgA, IgM, IgD, and IgE

Types of Antibodies

2.Antibody Structure

a.Y-shaped protein
1)2 long, heavy (H) chains joined by 2 shorter, light (L) chains
2)The bottom (Fc) is constant across different antibodies,
whereas the top (Fab) varies and allows antigen specificity.

b.B lymphocytes have antibodies on the plasma

membranes that are receptors for antigens.
1)When the antigen bonds to the antibody, the B cell is
stimulated to divide and produce more antibodies

Antibodies bond to antigens on bacteria

3.Diversity of Antibodies

a.Everyone has 1020 antibody

molecules.
1)There are a few million different
specificities.
2)There should be an antibody for every
antigen you might encounter.

C.The Complement System

Part of the nonspecific defense system

a.Activity is triggered by binding of antibodies to
antigens (classic pathway) and by polysaccharides on
bacterial membranes (alternative pathway).

Binding of antibodies to antigens does not

destroy the pathogen.
a.This labels targets for attack by phagocytic cells and
stimulates opsonization.

The Complement System, cont

3.Complement is a group of plasma

proteins activated by the binding of
antibodies to antigens.
a.Proteins are designated C1C9.
b.C1 serves as a recognition protein.
c.C2, C3, and C4 serve as activators.
d.C5C9 attack by attaching to a cell membrane
and destroying it.

III. Functions of T
Lymphocytes

A.Killer, Helper, and Regulatory T Lymphocytes

Killer (cytotoxic) T Lymphocytes

a.Have surface molecules called CD8
b.Destroy body cells that harbor foreign antigens
1)Usually from a pathogen (virus or fungus), but can be
due to a malignancy (cancer)
2)Transplant cells
c.Cell-mediated destruction means the T cells must touch
the target victim.
1)Secrete perforins to create large pore in cell
2)to trigger apoptosis in cell through the action of enzymes

2.Helper T Lymphocytes

a.Surface molecule is CD4

b.Improve ability of B lymphocytes to
become plasma cells and enhance ability of
cytotoxic T cells to kill targets

3.Regulatory T Lymphocytes, T(reg)

a.Surface molecules CD4 and CD25
b.Previously called suppressor T lymphocytes
c.Inhibit response of B lymphocytes and killer T
lymphocytes
d.Activates the FOXP3 gene that codes for a transcription
factor needed for development of T (reg) lymphocytes
e.People with genetic deficiencies in regulatory T
lymphocyte production may develop autoimmune
diseases and allergies.

B.Interactions between antigen-presenting cells and

T cells
Classes of MHC molecules
a.Class 1 is made by all cells except RBCs.
1)Class 1 MHC molecules and foreign
antigens are presented together to activate
cytotoxic T cells.
b.Class 2 is made by antigen-presenting cells
and B cells
1)Class 2 MHC molecules and foreign
antigens are presented together to helper T
lymphocytes

IV. Active and Passive

Immunity

A.Active Immunity & the Clonal Selection Theory

Primary response
a.After infection, it takes 510 days before
antibodies are detected in the blood.
b.The person will get sick.
Secondary response
a.Later exposure to the same infection results in
maximum antibody production in less than 2 hours.
b.The person will likely never get sick.

Primary & Secondary Responses

3.Clonal Selection Theory

a.Explains how the secondary immune

response works:
1)A person inherits lymphocytes specific to
almost every pathogen, but there are few
of each type.
2)When exposed to foreign antigens,
immune cells respond by making many
copies of themselves.
3)Germinal centers in secondary lymphoid
organs develop to produce the clones

Clonal Selection Theory, cont

b.The primary response triggers a

massive production of cells that can
respond to that antigen.
c.These cells respond much quicker
after exposure a second time.

4.Active Immunity

a.Development of the secondary

response provides active immunity
b.Requires prior exposure to the antigen
and then protects the body from future
infections
c.Active immunity is also used to make
vaccines.
d.These vaccines include an antigen but
are not virulent (disease-causing).

Clonal Selection Theory & B cells

5.Vaccines

a.Stimulate a primary response and active

immunity without making the person sick.
b.Three ways to accomplish this:
1)Use a killed virus (Salk polio vaccine)
2)Use a live virus with attenuated virulencei.e., the
virus either cannot replicate or cannot infect target
tissues Sabin polio vaccine, MMR)
3)Use a genetically engineered recombinant virus
(hepatitis B)

c.Adjuvants molecules that boost

immune response when delivered with

B.Immunological Tolerance
Immunological competence (ability to mount an immune
response) develops during early postnatal life being able
to distinguish self-antigens from foreign antigens
Immunological tolerance continued recognition and
tolerance of self-cells
In some instances, self cells are attacked by antibodies
and autoreactive T cells:
a.If mutations occur in lymphocytes (usually good and adds
to what the body can defend against)
b.If cells in particular organs are never exposed to the
immune system
c.These lymphocytes are called autoreactive.

C.Passive Immunity

Passing of antibodies from one

individual to another; person does
not make their own antibodies
Provides temporary protection:
a.From mother to fetus
b.From mother to child (in breast milk - colostrum)
c.Artificially via immunization (snake anti-venom)

Comparison of Active & Passive Immunity

3.Monoclonal antibodies

a.Animals are injected with an antigen

b.A single B lymphocyte that makes the
desired antibodies is extracted
c.The B cell is fused with a cancerous
myeloma cell in vitro
d.The hybridoma produces many clones
that produce antibodies specific for the
antigen

V. Diseases Caused by the

Immune System

A.Autoimmunity

Produced by failure of immune cells to

recognize and tolerate self antigens
a.Autoreactive T lymphocytes and
autoantibodies are produced, causing
inflammation and organ damage.
b.Common autoimmune diseases include
rheumatoid arthritis, type 1 diabetes,
multiple sclerosis, Graves disease,
pernicious anemia, thyroiditis, psoriasis,
and lupus

Some Examples of Autoimmune Diseases

2.Reasons why self-tolerance may fail

a.An antigen not normally exposed to the immune system

becomes exposed.
1)Hashimotos thyroiditis, most common thyroid disorder
(Hypothyroidism) in US
b.A normally tolerated antigen is combined with a foreign
hapten. This may occur when a drug such as aspirin
combines with platelets, resulting in the destruction of
platelets.
1)Thrombocytopenia

Reasons why self-tolerance may fail, cont

c.Antibodies are produced aimed at other

antibodies.
1)Cause of inflammation in rheumatoid arthritis

d.Antibodies produced against foreign

antigens cross-react with self antigens and
begin attacking self cells (can occur in the
heart or kidneys after a strep infection).
1)Rheumatic fever
2)Glomerulonephritis

Reasons why self-tolerance may fail, cont

e.Self antigens may be presented to T

helper cells
1)May occur after viral infection of cells
2)Occurs in diabetes type I
3)Graves Disease

f.Inadequate regulatory T cell activity.

Allergies

Abnormal response to allergens

(antigens)
a.Also called hypersensitivity
b.Two types:
1)Immediate hypersensitivity
2)Delayed hypersensitivity

2.Immediate Hypersensitivity

a.Abnormal B cell response to allergen

1)Effects seen seconds to minutes after
exposure
2)Can be caused by foods, bee stings, pollen,
etc.

Immediate Hypersensitivity, cont

c.These antibodies do not circulate in the blood but

attach to mast cells and basophils.
d.When re-exposed to the same allergen, these
antibodies bind with it and stimulate the production of
histamine, leukotrienes, and prostaglandin D, producing
allergy symptoms.

Mechanism of Immediate Hypersensitivity

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Allergen

B cell

Plasma cell

IgE antibodies

IgE receptor

Granule

Allergen

Mast cell

Histamine
and other
chemicals

Allergy

3.Delayed Hypersensitivity

a.Abnormal T cell response that produces

symptoms 2472 hours after exposure
b.Symptoms are caused by secretion of
lymphokines, not histamine, so taking
antihistamines has little effect.
c.Example: contact dermatitis caused by
poison oak, ivy

Comparison of Immediate & Delayed

Hypersensitivity Reactions

Hypo-immunity
Lymphocytopenia
Low lymphocytes
Low production, i.e. Aplastic anemia, leukemia
Too much destruction, i.e. hypersplenism

Infections
Viral, i.e. AIDS, West Nile encephalitis
Bacterial, i.e. TB,

Medication
Chemotherapy
Glucocrticoids

Radiation