HOW THE ANIMAL BODY
DEFENDS ITSELF
CHAPTER 27
SKIN: THE FIRST LINE OF DEFENSE
• The vertebrate body is defended from
infection by three lines of defense:
• The skin and mucous membranes are the first
defense against invasion.
• The body can mount a cellular counterattack if
an infection manages to get past the first
defense.
• Lastly, cells in the bloodstream circulate and look
for foreign cells as part of the specific immune
response.
SKIN: THE FIRST LINE OF DEFENSE
• The skin is the first defense
against invasion by
microbes.
• The skin has two layers
• An outer epidermis
• A lower dermis
• A subcutaneous layer lies
underneath the dermis.
• Cells of the outer epidermis are continually being
worn away and replaced by cells moving up from
below.
SKIN: THE FIRST LINE OF DEFENSE
• The dermis of the
skin is thicker than
the epidermis.
• It provides structural
support for the
epidermis.
• The subcutaneous
layer beneath the
dermis is comprised
of fat-rich cells that
act as shock
absorbers and
provide insulation.
SKIN: THE FIRST LINE OF DEFENSE
• The skin also provides chemical defense in
addition to the physical defense:
• Oil glands make the skin surface very acidic.
• Sweat contains the enzyme lysozyme, which
attacks and digests the cell walls of many
bacteria.
CELLULAR COUNTERATTACK:
THE SECOND LINE OF DEFENSE
• When an infection occurs, a host of cellular
and chemical defenses swing into action,
including:
•
•
•
•
Cells that kill invading microbes
Proteins that kill invading microbes
The inflammatory response
The temperature response
CELLULAR COUNTERATTACK:
THE SECOND LINE OF DEFENSE
• The central location
for the storage and
distribution for the
substances involved
in the second line of
defense is the
lymphatic system.
Tonsils
Lymph
nodes
Thymus
Lymphatic
vessels
Spleen
CELLULAR COUNTERATTACK:
THE SECOND LINE OF DEFENSE
• Cells that kill invading microbes
• There are three types of white blood cells that kill
microbes.
• Macrophages kill bacteria by ingesting them.
CELLULAR COUNTERATTACK: THE
SECOND LINE OF DEFENSE
• Neutrophils ingest bacteria but, more importantly,
secrete chemicals to neutralize everything living in
the infected area, including themselves.
• Natural killer cells attack body cells that are
infected.
Natural killer cell
Perforin
Vesicle
Plasma membrane
Nucleus
Target cell
CELLULAR COUNTERATTACK: THE
SECOND LINE OF DEFENSE
• Proteins that kill
invading microbes
Water Lesion
• The complement
system is a very
effective chemical
defense in
vertebrates.
Plasma membrane
Complement
of invading microbe proteins
• It is comprised of approximately 20 different proteins that
circulate freely in the until they encounter either a fungal or
bacteria cell wall.
• Complement proteins then form a pore in the foreign cell’s
membrane, causing water to rush in and burst the cell.
CELLULAR COUNTERATTACK:
THE SECOND LINE OF DEFENSE
• The inflammatory response
• Makes the aggressive cellular and chemical
counterattacks more effective.
• It occurs in a sequence of stages:
• The infected or injured cell first releases chemical
alarm signals, such as histamine.
• These chemicals cause the blood flow to the
area to increase and for capillaries to stretch and
be more permeable.
• Phagocytes migrate to the site of infection and
attack the invaders; many of these cells die and
form the pus associated with some infections or
wounds.
THE EVENTS IN A LOCAL
INFLAMMATION
Bacteria
Chemical
alarm signals
Blood
vessel
Phagocytes
CELLULAR COUNTERATTACK:
THE SECOND LINE OF DEFENSE
• The temperature response
• Human pathogenic bacteria do not grow well at
high temperatures.
• When macrophages attack, they send a signal
to the brain to raise the body’s temperature.
• The body’s thermostat rises above the normal
37°C to produce a state of fever.
• While the fever curbs microbial growth, it can
be dangerous because it might inactivate
critical cellular enzymes.
SPECIFIC IMMUNITY: THE THIRD
LINE OF DEFENSE
• Lymphocytes are white blood cells that are
critical to the specific immune response.
• T cell lymphocytes
• Originate in the bone marrow but migrate to
the thymus gland for maturation.
• They recognize microorganisms and viruses by
the chemical markers, or antigens, on their
surfaces.
• B cell lymphocytes
• Complete their maturation in the bone marrow
and, when an antigen is encountered, they
produce antibodies
• These antibodies coat the antigen and mark
the cell bearing that antigen for destruction.
SPECIFIC IMMUNITY: THE THIRD
LINE OF DEFENSE
• No invader can escape being recognized
by at least a few T cells because tens of
millions of different ones are made, each
specializing in a particular antigen.
• There are four main kinds of T cells.
• Helper T cells (TH), memory T cells, cytotoxic T cells
(TC), and suppressor T cells.
SPECIFIC IMMUNITY: THE
THIRD LINE OF DEFENSE
• Both B and T cells produce memory cells.
• These provide the body with the ability to recall a
previous exposure to an antigen and to mount an
attack against that antigen very quickly.
• The initial immune response to an antigen
encountered for the first time is delayed.
• The second infection is halted much earlier due
to the presence of memory cells.
INITIATING THE IMMUNE
RESPONSE
• Macrophages initiate the immune response.
• They inspect the surfaces of all cells they
encounter.
• Every cell in the body carries special marker
proteins on its surface called major
histocompatibility proteins, or MHC proteins.
• The MHC protein is exactly the same on all cells in
that body.
• These serve as “self” markers that enable the
individual’s immune system to distinguish its cells
from foreign cells.
INITIATING THE IMMUNE
RESPONSE
• When a foreign particle infects the body, it is
taken in by cells and partially digested.
• Within the cells, the antigens are processed and
moved to the surface of the plasma membrane.
• Cells that perform this function are called antigenpresenting cells and are usually macrophages.
Antigen
MHC protein
•
Macrophage
Lymphocyte
(a) Body cell
(b) Foreign microbe
Processed
antigen
INITIATING THE IMMUNE
RESPONSE
• Macrophages that encounter a pathogen,
identified as anything which lacks the
proper MHC protein, respond by secreting a
chemical alarm signal which stimulates
helper T cells.
• The helper T cells activate two lines of immune
system defense.
• Cellular response carried out by T cells.
• Humoral response carried out by B cells.
T CELLS: THE CELLULAR
RESPONSE
• Macrophages process the foreign antigens
and trigger the cellular immune response.
• The activated helper T cells that are bound to an
antigen-presenting cell stimulate the proliferation
of cytotoxic T cells.
• These cells recognize and destroy infected
body cells.
T CELLS: THE CELLULAR
RESPONSE
• Any cytotoxic T cell whose receptor fits the
particular antigen-MHC complex present in the
body begins to multiply rapidly.
• This quickly eliminates large numbers of infected cells.
• The cytotoxic T cells kill by puncturing a hole in the
plasma membrane of the infected cell.
• Following an infection, some of the activated T
cells give rise to memory cells that remain in the
body, ready to mount an attack quickly if the
antigen is encountered again.
THE T CELL IMMUNE DEFENSE
MHC protein
Processed
viral antigen
Interleukin-1
Virus
Helper
T cell
1
Macrophage
T cell
receptor
that fits the
2
particular
antigen
Interleukin-2
5
Memory T cell
MHC protein
Viral antigen
4
3
Antigen-presenting cell
Proliferation
Infected cell
destroyed by
cytotoxic T cell
Cytotoxic T cell
B CELLS: THE HUMORAL
RESPONSE
• B cells also respond to activated helper T
cells.
• B cells do not attack infected cells, rather,
they mark the pathogen for destruction.
• Early in the humoral immune response, the
markers placed by B cells alert complement
proteins to attack the cells carrying them.
• Later, the markers activate macrophages and
natural killer cells.
B CELLS: THE HUMORAL
RESPONSE
• B cells produce markers, or antibodies.
• B cells can bind to free, unprocessed antigens
and antigen particles enter the B cell by
endocytosis.
• The antigens are then processed and placed
on the surface complexed with MHC proteins.
• Helper T cells that are able to recognize the
specific antigen bind to the antigen-MHC
protein complex.
B CELLS: THE HUMORAL
RESPONSE
• Helper T cells stimulate the B cell to divide
• Also, free, unprocessed antigens stick to
antibodies on the B cell surface, triggering even
more B cell proliferation.
• The B cells divided to produce
• Plasma cells that serve as short-lived antibody
factories.
• Memory cells that remain in the body after the
initial infection and mount a quick attack if the
antigen enters the body again.
THE B CELL IMMUNE DEFENSE
Interleukin-1
Invading
microbe
Helper T cell
Memory cell
T cell receptor
MHC protein
Processed antigen
Antigen
Macrophage
1
2
Processed
antigen
Helper T cell
4
Plasma cell
Plasma cell
Interleukin-2
B cell
3
B cell receptor
(antibody)
B cell
Antibody
Microbe
marked for
destruction
B CELLS: THE HUMORAL
RESPONSE
• Antibodies are proteins in a class called immunoglobulins
(abbreviated Ig).
• There are 5 different immunoglobulin subclasses:
•
•
•
•
•
IgM promotes agglutination (clumping) reactions.
IgG is the major form in the blood plasma.
IgD serves as antigen receptors on the B cell.
IgA is the form of antibody in external secretions.
IgE promotes the release of histamine.
Antigen-binding
site
Heavy chains
Light chains
Antigen-binding
site
Carbohydrate
chain
B CELLS: THE HUMORAL
RESPONSE
• The plasma cells that are derived from B
cells produce lots of the same antibody that
was able to bind to the antigen.
• These antibodies flood the bloodstream and stick
to antigens on any cells and microbes that
present them, flagging those foreign bodies for
destruction.
• Complement proteins, macrophages, or natural
killer cells then are the agents of destruction.
B CELLS: THE HUMORAL
RESPONSE
• Memory B cells circulate through the blood
and lymph for long periods of time
(sometimes the entire lifetime).
• It is estimated that human B cells can make
between 106 and 109 different antibodies.
ACTIVE IMMUNITY THROUGH
CLONAL SELECTION
• The first time a pathogen invades a body,
there are only a few B cells or T cells that
may recognize the antigens.
• Binding of the antigen to its receptor on the
lymphocyte surface stimulates cell division and
produces a clone.
• This process is called clonal selection.
• The result is the primary immune response,
which is slow to develop and produces both
plasma and memory cells.
• As a result of the first
infection, a large
clone of
lymphocytes that
can recognize a
pathogen remains.
• The secondary
immune response is a
more effective
response when the
pathogen is
encountered again.
Amount of antibody
ACTIVE IMMUNITY THROUGH
CLONAL SELECTION
This interval
may be years.
Exposure
to chicken pox
Exposure
to chicken pox
Time
Primary response
Secondary response
(Antibodies in 10–14 days (Antibodies in 3–5 days
1
Viruses infect the
cell. Viral proteins are
displayed on the cell
surface.
10
Antibodies bind to
viral proteins, some
displayed on the
surface of infected
cells.
Infected cell
6
11
2
Cytotoxic T cells
bind to infected cells
and kill them.
Macrophages destroy
viruses and cells tagged
with antibodies.
Viruses and viral
proteins on infected cells
stimulate macrophages.
Cytotoxic T cell
9
Other B cells
become antibodyproducing factories.
Macrophage
Memory T cells
B cell
7
Activated B
cells multiply.
5
Interleukin-2
activates B cells and
cytotoxic T cells.
5a
Some T
T cells
cells become
become
Some
memory T
T cells.
cells.
memory
3
Interleukin-2
Interleukin-1
8
Some B cells become
memory cells.
Helper T cell
4
Interleukin-1 activates
helper T cells, which
release interleukin-2.
Stimulated
macrophages
release interleukin-1.
VACCINATION
• Vaccination is the
introduction of a
dead or disabled
pathogen into a
body.
• The vaccination
triggers an immune
response against
the pathogen,
without an infection
occurring.
Edward Jenner (circa 1796)
VACCINATION
• Through genetic engineering, scientists can
routinely produce “piggyback,” or subunit,
vaccines.
• These vaccines are made of a harmless virus that
has a pathogen gene inserted so that the virus
displays the pathogen protein on its surface
• The body responds by making an antibody
against that antigen, as well as memory cells to
recall that antigen.
VACCINATION
• Some viruses change their antigen makeup
and prevent detection even after a
vaccination.
• Flu viral genes that code for surface proteins
mutate quickly.
• Efforts are being made to develop an
effective vaccine against HIV, using the
“piggyback” method.
ANTIBODIES IN MEDICAL
DIAGNOSIS
Type A
Agglutinated
Type AB
• If blood is mixed from two
incompatible sources, the
antibodies clump together
or agglutinate.
Agglutinated
Donor’s blood
Type B
• A person’s blood type
indicates the class of
antigens found on the
red blood cell surface ABO system.
Recipient's blood
Type A serum
Type B serum
(Anti-B)
(Anti-A)
Agglutinated
Agglutinated
ANTIBODIES IN MEDICAL
DIAGNOSIS
• Another group of antigens found in most red
blood cells is the Rh factor.
• People can be either Rh-positive or Rh-negative.
• This has significance when a mother and her fetus
have opposite Rh groups.
• Monoclonal antibodies are specific to one
antigen.
OVERACTIVE IMMUNE SYSTEM
• Many diseases reflect an overactive
immune system.
• An autoimmune disease is when the body attacks
its own tissues.
• For example, multiple sclerosis, type I diabetes,
rheumatoid arthritis, lupus, and Graves’ disease.
• An allergy occurs when the body mounts a major
defense against harmless antigens.
• For example, asthma is a form of an allergic
response in which histamines cause the
narrowing of air passages in the lungs.
AN ALLERGIC REACTION
Allergen
Plasma cell
IgE antibodies
Allergy
Histamine and
other chemicals
B cell
IgE receptor
Granule
Allergen
Mast cell
AIDS: IMMUNE SYSTEM
COLLAPSE
• AIDS (Acquired Immunodeficiency
Syndrome) is a disease caused by infection
with the human immunodeficiency virus
(HIV).
• the virus recognizes the CD4 surface
receptor on many human immune
cells, especially macrophages and
helper T cells
AIDS: IMMUNE SYSTEM
COLLAPSE
• HIV attacks the immune system by
inactivating cells that have CD4 receptors
(CD4+ cells), especially helper T cells.
• This leaves the immune system unable to mount a
response to any foreign antigen.
• HIV’s attack on CD4+ T cells progressively cripples
the immune system.