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Body Defenses
Immune System
Part 2
What do the specific defenses
include?
Third line of defense
Helps protect us against specific pathogens when
nonspecific defenses fail
Helps protect us against cancer
Depends on the action of B and T cells
(remember that these are lymphocytes)
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Adaptive Immune Defenses
When innate defenses have failed to prevent
an infection, the adaptive line of defense
comes into play.
How Adaptive Defenses Works
Adaptive defenses respond to antigens
Molecules the immune system recognizes as foreign
to the body.
Adaptive defenses primarily depend on the action
of B and/or T lymphocytes
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Lymphocytes B cells remain in the bone
marrow to mature
“B” for “bone marrow”
T cells migrate to the
thymus, to mature
“T” for “thymus”
Maturation of a B or T cell
involves becoming immuno-
competent, meaning that it
can recognize, by binding, a
specific molecule or antigen.
What are the types of B and T
cells?
• B cells produce plasma cells and memory
cells.
– Plasma cells produce specific antibodies.
– Memory cells are ready to produce
antibodies in the future.
What are the types of B and T
cells?
• T cells regulate immune response;
produce various types of T cells.
– Cytotoxic T (Tc) cells kill virus-infected and
cancer cells.
– Helper T (TH) cells regulate immunity.
– Memory T (Tc and TH) cells are ready to kill
in the future.
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Lymphocytes
During the maturation process, B and T cells that
bind too strongly to the body’s own cells are
eliminated in order to minimize an immune response
against the body’s own tissues (autoimmune
diseases)
Cells that react weakly to the body’s own cells, but have
highly specific receptors on their cell surfaces that allow
them to recognize a foreign molecule, or antigen, remain.
Process occurs during fetal development and continues
throughout life.
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Lymphocytes
The specificity of this receptor is determined by the
genetics of the individual.
Once they are immunocompetent, the T and B cells
will migrate to the spleen and lymph nodes where
they will remain until they are called on during an
infection.
B cells are involved in the humoral immune response,
which targets pathogens in blood and lymph.
T cells are involved in the cell-mediated immune response,
which targets infected cells.
Third line of defense: Antibody-
mediated immunity by B cells
Each B cell has a unique receptor called a BCR that binds a specific antigen.
This binding plus cytokines secreted by helper T cells result in clonal expansion in which this B cell makes copies of itself.
Most of the cells produced are plasma cells that secrete antibodies.
Memory cells are also made.
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B Cells and Antibody-Mediated
Immunity
The clonal selection model states that an
antigen selects, then binds to the B-cell
receptor of only one type of B cell, and then
this B cell produces multiple copies (clones)
of itself.
Memory Cells
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B Cells and Antibody-Mediated
Immunity
The receptor on a B cell is called a B-cell receptor.
Receptor is an antibody (immunoglobulin)
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B Cells and Antibody-Mediated
Immunity
B Cells Become Plasma Cells and Memory B Cells
After initially binding an antigen to the B cell receptor, a B
cell internalizes the antigen and presents it on MHC class II.
MHC major histocompatibility complex antigen (“self”)
A helper T cell recognizes the MHC class II- antigen
complex and activates the B cell by secreting cytokines.
As a result, memory B cells and plasma cells are made.
Plasma cells secrete antibodies and eventually undergo
apoptosis (programmed cell death).
Memory B cells remain in the body and rapidly initiate
maturation and antibody production if the same antigen
enters the body at a later date.
Antibody-mediated immunity by
B cells
antigens
B cell B-cell
receptor
(BCR)
a. Activation: When a B cell receptor binds to an antigen
activation occurs.
antigen cytokines
from T cells
b. Clonal expansion – During clonal expansion, cytokines secreted by
helper T cells stimulate B cells to clone mostly into plasma cells or memory cells.
c. Apoptosis – Apoptosis, or programmed cell death, occurs to plasma cells
left in the system after the infection has passed.
Apoptosis
Plasma cells
Memory B cells
Figure 7.7 B cell clonal selection.
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The basic unit that composes antibody molecules is a Y-shaped protein.
The trunk of the Y is a constant region that determines the class of the antibody.
The ends of the arms (Y) are the variable regions where specific antigens bind.
Structure of antibodies
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Antibodies
Structure of an Antibody
Antibodies = immunoglobulins.
Y-shaped molecules with two arms.
Each arm has a heavy and a light polypeptide chain.
These chains contain variable and constant regions.
The antigen combines with the antibody in the variable
regions in a lock-and-key manner.
Structure of antibodies
Figure 7.8 The structure of an antibody. b: Courtesy Dr. Arthur J. Olson, Scripps Institute
C C
Antigen binds
to binding site.
heavy
chain
light
chain Shape of antigen fits
shape of binding site.
antigen
antigen-binding
sites
a.
b.
C = constant V = variable
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Classes of Antibodies
Classes of Antibodies
There are five different classes of circulating
antibodies:
IgG
IgM
IgA
IgD
IgE
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Monoclonal Antibodies
Every plasma cell derived from the same B
cell secretes antibodies against a specific
antigen.
These are monoclonal antibodies.
Monoclonal antibodies can be made outside
the body, and are being used to:
Diagnose certain conditions or infections
Deliver drugs
Treat cancers.
We make monoclonal antibodies (derived
from plasma cells that originated from the
same B cell) in glassware outside the body
(in vitro).
This is done through fusion of plasma cells
with myeloma cells that allow them to divide
indefinitely.
This fusion results in a cell called a
hybridoma.
How do we make monoclonal
antibodies?
Figure 7.9 The production of
monoclonal antibodies.
How do we make monoclonal
antibodies?
antibody plasmacell
antigen
cancerous myelomacell hybridomacell
monoclonal antibody
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Fig. 7.13
What are the characteristics of
T cells?
• Cell-mediated immunity against virus-infected
cells and cancer cells
• Produced in bone marrow, mature in thymus
• Antigen must be presented in groove of an HLA
(MHC) molecule
• Cytotoxic T cells destroy nonself antigen-
bearing cells
• Helper T cells secrete cytokines that control the
immune response
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T Cells and Cell-Mediated
Immunity
T cells:
Directly attack diseased cells and cancer cells.
Other T cells release cytokines that stimulate both
innate and adaptive defenses.
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Clonal Expansion
T cells have specific TCRs (T Cell Receptors).
An activated T cell undergoes clonal
expansion producing many copies of itself.
The two classes of MHC proteins are called
MHC I and MHC II.
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How T Cells Recognize an
Antigen
Each T cell bears a specific receptor. Antigen must be presented by an antigen-presenting cell
(APC), such as a macrophage.
A piece of a phagocitized pathogen is displayed in the
groove of a major histocompatibility (MHC) protein on the
APC’s surface.
Human MHC proteins are called human leukocyte
antigens (HLAs).
MHC proteins are self proteins that mark the cell as part
of a particular individual.
The T cell can compare the antigen and self protein side
by side in the plasma membrane of the antigen-
presenting cell and destroy cells carrying foreign
antigens.
Third line of defense: Cell-
mediated immunity by T cells
The T cell will specifically recognize the combination of the HLA protein and the piece of antigen.
Clonal expansion will occur leading to mostly helper T cells, cytotoxic T cells, and a few memory T cells.
After an infection has passed, helper and cytotoxic T cells undergo apoptosis, leaving memory cells.
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Fig. 7.14
Memory T cells remain in the
body to initiate an immune
reaction to a previous
antigen in the case of
another exposure.
Cell-mediated immunity by
T cells T-cell receptor (TCR)
bacterium
T cell
Activation
Clonal expansion Macrophage
Memory T cell
Cytotoxic T cell
Apoptosis
self antigen
(MHCI)
cytokines
Figure 7.10 The clonal selection model for T cells.
T cells
Helper T cells
Secrete cytokines that
help many immune
cells function.
HIV, the virus that
causes AIDS, infects
helper T cells, making
HIV-infected
individuals susceptible
to opportunistic
infections.
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T cells
Cytotoxic T cells
are responsible for cell-
mediated immunity,
causing virus-infected cells
or tumor cells to undergo
apoptosis and die.
have vacuoles containing
granzymes and perforins.
Perforins punch holes in
target cells, followed by
granzymes that cause the
cell to undergo apoptosis.
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Immunity
Immunity is the ability to combat diseases and cancer.
It can be brought about naturally through an infection or artificially through medical intervention.
There are 2 types of immunity, active and passive.
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Acquired Immunity
Immunity can be brought about artificially by
medical intervention.
Active Immunity
Sometimes develops naturally after infection with a
pathogen.
Ex. Chicken Pox, Mumps, Measles
Can also be induced.
Vaccines
Active immunity
The individual’s body makes antibodies against a particular antigen.
This can happen through natural infection or through immunization involving vaccines.
Primary exposure is shorter-lived and slower to respond while a secondary exposure is a rapid, strong response.
This type of immunity is usually long-lasting.
It depends on memory B and T cells.
Immunization: A type of active
immunity
Figure 7.12 How immunizations cause active immunity.
Pla
sm
a a
nti
bo
dy
co
nc
en
tra
tio
n
Time (days)
high
low
30 60 90 120 150 180 0
primary response secondary response
second exposure
to vaccine
first exposure
to vaccine
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Immunization: A type of
active immunity
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Table 7A
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Passive Immunity
Passive immunity occurs when an individual is
given antibodies from an outside source.
Nursing passes antibodies from mother to child.
Get shot of gamma globulins after exposure to
disease
Anti-venom for snake bite
Passive immunity is temporary.
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How can the immune system
harm the body?
Allergies
Tissue rejection
Immune system disorders
Allergies
Allergies are hypersensitivities to harmless substances such as pollen, food, or animal hair.
An immediate allergic response is caused by the IgE antibodies that attach to mast cells and basophils. When allergens attach to these IgE molecules, histamine is released and we see allergy symptoms.
An immediate allergic response that occurs when the allergen enters the bloodstream is anaphylactic shock, in which the blood pressure drops and is life-threatening.
Delayed allergic responses (such as the reaction to poison ivy) are initiated by memory T cells.
Tissue rejection
Tissue rejection can occur when cytotoxic T cells respond to tissue that is not recognized as “self.”
This can be controlled by giving patients immunosuppressive drugs and by transplanting organs that have the same MHC proteins in the donor and recipient.
Currently, we are trying to grow organs in the lab that can be transplanted with less rejection.
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Disorders of the immune system
Autoimmune disease A disease in which cytotoxic T cells or antibodies
attack the body’s own cells as if they were foreign
Examples
Myasthenia gravis -neuromuscular junctions do not
work properly.
Multiple sclerosis - the myelin sheath of the nerve
fibers is broken down.
Systemic lupus erythematosus - various symptoms
eventually leading to death from kidney damage.
Rheumatoid arthritis - the joints are affected.
Disorders of the immune system
Immunodeficiency disease A disease in which the immune system is
compromised and thus unable to defend the body against disease
Examples: AIDS and SCID
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Cytokines and Immunity
Cytokines, including interferon, are signaling
molecules produced by T lymphocytes,
macrophages and other cells which are used in an
attempt to promote the body’s ability to recover from
cancer.
Interferon and interleukins have been used as
immunotherapeutic drugs.
Interleukin antagonists are used to prevent
transplant rejection.
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Fig. 7.10
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Hypersensitivity Reactions
Sometimes the immune system responds in a
manner that harms the body.
Allergies
Allergic responses occur when the immune system
reacts vigorously to substances not normally recognized
as foreign.
Immediate allergic responses are due to the activity of
antibodies.
Symptoms can vary from mild, coldlike symptoms, to
anaphylactic shock, which is an immediate allergic
response that occurs because an allergen has entered
the bloodstream.
The immunoglobulin IgE appears to be responsible.
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Hypersensitivity Reactions
Allergies
Delayed allergic responses, such as contact dermatitis,
are due to the activity of T cells.
Skin test for TB is a classic example of a delayed
allergic response – redness and swelling don’t show
for a few days.
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Other Immune Problems
Transplant rejection
Occurs when cytotoxic T cells bring about the destruction
of foreign tissue in the body.
Immunosuppressive drugs act by inhibiting the response of
T cells to cytokines.
Xenotransplantation is the use of animal organs instead
of human organs in transplant patients.
Genetic engineering can make these organs less
antigenic to humans.
Laboratory grown urinary bladders have been
successfully used in human transplantations.
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Other Immune Problems
Transplant rejection
In individuals with severe combined immunodeficiency
disease (SCID), both antibody- and cell-mediated
immunity is lacking or severely reduced.
AIDS is an example of an acquired immune deficiency.
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