Transcript The Living World - Chapter 27 - McGraw Hill Higher Education

Essentials of
The Living World
First Edition
GEORGE B. JOHNSON
22
How the
Animal Body
Defends Itself
PowerPoint® Lectures prepared by Johnny El-Rady
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22.1 Skin: The First Line of Defense
The vertebrate is defended from infection the same
way knights defended medieval cities
1. Walls and moats
Skin and mucous membranes provide a first
barrier
2. Roaming patrols
Cellular counterattack should first barrier be
breached
3. Sentries
Specific immune response scans for foreign
cells or viruses
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Skin
Our largest organ (about 15% of our total weight)
Provides the first line of defense against microbes
Has two distinct layers
Outer epidermis
Inner dermis
A subcutaneous layer lies underneath the dermis
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Fig. 22.2 A section
of human skin
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Epidermis
10-30 cells thick
Stratum corneum – Outermost layer
Cells continuously being replaced by others from below
Basal layer – Innermost layer
Dermis
15-40 times thicker than the epidermis
Provides structural support for the epidermis
Subcutaneous layer
Fat-rich cells that act as shock absorbers and insulators
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Other External Surfaces
Digestive tract
Lysozyme in saliva breaks down bacterial cell walls
Acidic environment of the stomach kills microbes
Respiratory tract
Cells of the small bronchi and bronchioles secrete mucus
Traps microorganisms
They also possess cilia
Sweep the mucus towards the glottis
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22.2 Cellular Counterattack:
The Second Line of Defense
Lymphatic system
Central location
for storage and
distribution of
immune cells and
proteins
A network of
capillaries, ducts,
nodes and organs
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Fig. 22.3
Cells That Kill Invading Microbes
Three types of white blood cells
Macrophages
Neutrophils
Natural Killer Cells
All three can distinguish between body cells
(self) and foreign cells (nonself)
Failure to make this distinction correctly
results in autoimmune diseases
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Macrophages
Fig. 22.4
Ingest bacteria
Most patrol the byways
of the body as precursor
cells called monocytes
Neutrophils
Fig. 22.5
Release chemicals
killing bacteria and
themselves in the process
Natural killer cells
Attack virus-infected body
cells and cancer cells
Puncture membranes
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Proteins That Kill Invading Microbes
Complement system
~ 20 different proteins
Circulate freely in blood
plasma in inactive form
Aggregate to form a
membrane attack
complex
Form holes in the
invading microbe
Can augment the
effects of other body
defenses
Fig. 22.7
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Proteins That Kill Invading Microbes
Interferons
Three major categories
Alpha
Beta
Prevent viral replication
and protein assembly
Defends against infection
Gamma
and cancer
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The Inflammatory Response
Can be broken down into three stages
1. Infected or injured cell releases chemicals
Histamine and prostaglandins
2. Chemicals cause blood vessel to expand
and become more permeable
Redness and swelling
3. Phagocytes migrate to the site of infection or
injury
Neutrophils, then monocytes/macrophages
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Fig. 22.8 The events in a local inflammation
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The Temperature Response
When macrophages counterattack, they send a
message to the brain to raise body’s temperature
Fever inhibits microbial growth
However, very high fevers are dangerous
because they can inactivate cellular enzymes
Fevers greater than 40.6oC (105oC) are
often fatal
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22.3 Specific Immunity:
The Third Line of Defense
Specific immunity involves the actions of white
blood cells (WBC)
WBC are very numerous
Two out of every 100 body cells
WBC come in different types
Lymphocytes
T cells and B cells
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T cells
Originate in bone marrow and migrate to Thymus
Develop ability to identify foreign agents by antigens
present on their surface
An antigen is a molecule that provokes a specific
immune response
Four main types of T cells
Helper (TH) – Initiate the immune response
Cytotoxic (TC) – Lyse virus-infected cells
Memory – Provide a quick response on re-exposure
Suppressor – Terminate the immune response
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B cells
Originate and mature in the bone marrow
The B refers to a region of chicken called Bursa, where
they were first characterized
Circulate in blood and lymph
Proliferate upon antigen exposure into
Plasma cells
Produce antibodies
Memory cells
Provide a quick response on re-exposure
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22.4 Initiating the Immune Response
Every cell in the body carries surface markers
called major histocompatibility (MHC) proteins
MHC proteins are different for each individual
So they act as “self” markers
Antigen-presenting cells
Ingest foreign particles and partially digest them
Process antigens and move them to surface of cell
membrane
There they are complexed with MHC proteins
T cell receptors can only interact with cells that
have this combination of MHC and antigen
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Fig. 22.9 How antigens are presented
Lymphocyte
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Antigenpresenting
cell
22.4 Initiating the Immune Response
Macrophages inspect the surface of cells looking for
“self” MHC proteins
If a cell displays “nonself” MHC protein-antigen
combinations
The macrophage will secrete an alarm signal,
the protein interleukin-1
Stimulates helper T-cells to initiate
Cellular immune response by T cells
Humoral immune response by B cells
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22.5 T-cells: The Cellular Response
Helper T cells get activated upon binding “nonself”
MHC protein-antigen complex of the macrophage
Helper T cells secrete interleukin-2
Stimulates proliferation of cytotoxic T cells
Recognize and destroy cells with the specific
antigen found on the antigen-presenting cell
Cytotoxic T cells will also attack transplanted tissue
and cause graft rejection
The drug cyclosporin inactivates cytotoxic T cells
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Fig. 22.10 The T cell immune defense
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22.6 B-cells: The Humoral Response
B cells recognize invading microbes, but do not go
on the attack themselves
Rather, they mark the pathogen for destruction by nonspecific immune defenses
B cells can bind to free and unprocessed antigens
Antigens are endocytosed, processed and presented on
the surface with an MHC protein
Helper T cells recognize this complex and stimulate B
cells to proliferate into
Memory cells
Plasma cells, which produce antibodies
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Fig. 22.11 The B cell immune defense
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Antibodies: Proteins in class immunoglobulins (Ig)
Five different subclasses
IgM
First to be secreted during the primary response
IgG
Major one secreted during the secondary response
IgD
Receptor for antigen on surface of B cells
IgA
Form in external secretions (saliva and milk)
IgE
Promotes release of histamine
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Plasma cells
Produce large
amounts of the
same antibody
that initiated the
immune response
Fig. 22.12
Antibodies bind to the antigens and flag the cells for
destruction by complement, macrophages or NK cells
Memory B cells
Circulate blood and lymph, waiting for future exposure
Second response is amplified about a millionfold
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Antibody Diversity
B cells can make an estimated 106 to 109 different
antibody molecules
Immune receptor genes are assembled by a
process called somatic rearrangement
DNA segments that code for different parts of
the receptor molecule are stitched together
Further antibody diversity is generated by
Imprecise DNA rearrangements
Random mutations
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Fig. 22.13 The
lymphocyte
receptor
molecule is
produced by a
composite
gene
Variable
region
Constant
region
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Diversity
region
Joining
region
22.7 Active Immunity
Through Clonal Selection
Fig. 22.15
The first encounter with a
foreign antigen is termed the
primary immune response
Only a few B cells or T cells
can recognize the antigen
Binding of antigen to its
receptor on lymphocyte
stimulates cell division
A clone is produced
This process is called
Clonal selection
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The second encounter with a foreign antigen is
termed the secondary immune response
This time, there is
a large clone of
lymphocytes that
can recognize the
antigen
The immune
response is
now swifter
and stronger
Fig. 22.15
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Fig. 22.16
How the
immune
response
works
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22.8 Evolution of the Immune System
Even bacteria can defend themselves from viruses
Use restriction endonucleases that cut foreign
DNA lacking a specific pattern of methylation
Mutlicellular organisms have to defend against
cellular invaders as well!
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Invertebrates
Mark cell surfaces with protein self labels
Employ a negative test
Special amoeboid cells engulf any invading cell that
lacks these labels
Fig. 22.17
In 1882, Elie Metchnikoff
discovered that invertebrates
have immune defenses
He pierced sea star larva with
a rose thorn
Next day tiny phagocytic
cells covered the thorn
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Invertebrates
The invertebrate immune response shares several
features with that of vertebrates
1.
2.
3.
4.
5.
Phagocytes
Distinguishing self from nonself
Complement
Lymphocytes
Antibodies
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Vertebrates
The modern vertebrate immune system first
appeared in jawed fishes
Sharks are the oldest surviving group
Have an immune response similar to that seen
in mammals
Most notable difference:
Antibody-encoding genes are arrayed
somewhat differently
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Fig. 22.18 How immune systems evolved in vertebrates
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22.9 Vaccination
The year 1796 marked the birth of immunology
Edward Jenner
observed that milkmaids
who got cowpox rarely
got smallpox
He inoculated
patients with cowpox
and thus protected
them from smallpox
Fig. 22.19
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Vaccination is the introduction into the body of a
dead or disabled pathogen
harmless microbe with pathogen proteins
displayed on its surface
Vaccination triggers an immune response without
causing an infection
Circulating memory B cells are produced
Elicit a quicker and larger immune response in
an actual infection
Vaccination may not provide effective defense in the
future, if pathogen’s surface proteins are altered
Example: Influenza virus
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Fig. 22.21 Researchers are attempting to construct an AIDS vaccine
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22.10 Antibodies in Medical Diagnosis
Blood typing
ABO system is the major group of RBC antigens
The immune system is tolerant to its own antigens
People who are Type A, make antibodies against the B
antigen
People who are Type B, make antibodies against the A
antigen
People who are Type AB, do not make either anti-A or
anti-B antibodies
People who are Type O, make both anti-A and anti-B
antibodies
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Clumping
of RBCs
Fig. 22.22
Blood typing
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Rh factor
A group of antigens found on RBC
Rh-positive people have them; Rh-negative people don’t
Of particular significance when Rh-negative mothers give
birth to Rh-positive babies
Mother may be exposed to fetal blood and thus produce
anti-Rh antibodies
A subsequent Rh-positive pregnancy leads to
erythroblastosis fetalis
Can be prevented by injecting the mother with
anti-Rh antibodies
Monoclonal antibodies
Antibodies specific to one antigen
Used in pregnancy tests to detect the hCG hormone
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22.11 Overactive Immune System
Autoimmune Diseases
Cytotoxic T cells and B cells lose their ability to
distinguish “self” cells from “nonself” cells
Body attacks its own tissues
Examples:
Mutliple sclerosis
Type I diabetes
Rheumatoid arthritis
Lupus
Graves’ disease
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22.11 Overactive Immune System
Allergies
Body mounts a major defense
against a harmless substance
Hay fever
House dust mite
Mast cells initiate the
inflammatory response
Release histamine
Fig. 22.23
Capillaries swell
Mucus production increases
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Fig. 22.24 An allergic reaction
In asthma, histamine causes the narrowing of air passages
in the lungs
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22.12 AIDS: Immune System Collapse
AIDS (acquired immunodeficiency syndrome) was
first recognized as a disease in 1981
Worldwide, 42 million have become infected
24 million have died
In the US, the total through the end of 2002 is
about 887,000 cases and 502,000 deaths
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Fig. 22.25 The AIDS epidemic in the United States
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AIDS is caused by HIV (human immunodeficiency
virus)
HIV attacks and cripples the immune system by
inactivating cells that have CD4 receptors
Found in macrophages and helper T cells
This leaves the immune system unable to
mount a response to any foreign antigen
A variety of otherwise commonplace
infections prove fatal
Death by cancer becomes far more likely
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