PowerLecture: Chapter 10

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PowerLectureChapter 10

• Immunity

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Learning Objectives

• Describe typical external barriers that organisms
  present to invading organisms.
• Understand how the lymphatic system contributes
  to the bodys defenses.
• Understand how vertebrates (especially mammals)
  recognize and discriminate between self and
  nonself tissues.
• Distinguish between antibody-mediated and
  cell-mediated patterns of immune responses.

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Learning Objectives (contd)

• Describe some examples of immune failures and
  identify as specifically as you can which weapons
  in the immunity arsenal fail in each case.

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Impacts/Issues

• The Face of AIDS

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The Face of AIDS

• Viruses, such as HIV, have wide ranging impacts
  on human health.
• At least 40 million people are infected with HIV
  12 million African children alone have been
  orphaned by AIDS.
• Rates of new HIV infection are declining in some
  areas, but we still have no effective vaccine to
  prevent infection.

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The Face of AIDS

• The immune system is responsible for protecting
  us from HIV and other infectious agents the more
  we learn about this system, the more
  opportunities we have to improve our health.

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How Would You Vote?

• To conduct an instant in-class survey using a
  classroom response system, access JoinIn Clicker
  Content from the PowerLecture main menu.
• Should the federal government offer incentives to
  companies to discount the drugs for developing
  countries?
• a. Yes, drug companies have a responsibility to
  world health, not just their bottom line.
• b. No, if drug companies must provide subsidies,
  they won't be able to afford to develop new
  drugs.

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Section 1

• Overview of Body Defenses

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Overview of Body Defenses

• We are born with some general defenses and
  acquire other, specific ones.
• We have many defenses to protect us from
  pathogensthose viruses, bacteria, fungi,
  protozoa, and parasitic worms that cause disease.
• Antigens on these pathogens identify them as
  nonself.
• Antigens are usually proteins, lipids, or
  oligosaccharides.

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Overview of Body Defenses

• Immunity is the bodys overall ability to resist
  and combat anything that is nonself.
• Innate immunity encompasses preset responses that
  activate rapidly and in a generalized way to
• detected damage or invasion.
• Adaptive immunity responds to specific antigens
  on specific pathogens this response takes longer
  to develop, but the body remembers what it sees
  and responds quicker the next time the same
  pathogen is seen.

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Table 10.1, p.176
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Overview of Body Defenses

• Three lines of defense protect the body.
• Intact skin and mucous membranes are important
  first-line physical barriers.
• Innate immunity forms the second line of defense.
• Adaptive immunity forms the third line of
  defense.

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Overview of Body Defenses

• White blood cells and their chemicals are the
  defenders in immune responses.
• White blood cells are the core of the immune
  system.
• Phagocytes release chemicals called cytokines to
  further defense responses.
• Cytokines regulate different aspects of the
  immune response interleukins affect inflammation
  and fever, interferons defend against viruses,
  and tumor necrosis factor also affects
  inflammation and stimulates tumor cell death.

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Overview of Body Defenses

• Complement is a group of about 30 blood proteins
  that can kill microbes or identify them for
  phagocytes to destroy.
• White blood cells serve a variety of different
  functions in the immune response
• Neutrophils make up two-thirds of all white blood
  cells and work at the site of inflammation or
  damage.
• Basophils and mast cells produce histamines in
  response to antigens.
• Macrophages are the predominant phagocytes that
  patrol the bloodstream.

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Overview of Body Defenses

• Eosinophils target pathogens that are too large
  for the macrophages.
• Dendritic cells signal when antigens are present
  in skin and body linings.
• B and T lymphocytes (B and T cells) function in
  adaptive immunity.
• Natural killer cells (NK cells) are lymphocytes
  that function in innate responses.

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Table 10.2, p.177
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eosinophil
neutrophil
Fig. 10.1, p.177
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basophil
mast cell
Fig. 10.1, p.177
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B lymphocyte (B cell)
T lymphocyte (T cell)
Fig. 10.1, p.177
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dendritic cell
Natural killer (NK) cell
macrophage
Fig. 10.1, p.177
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Section 2

• The Lymphatic System

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The Lymphatic System

• The lymphatic system has two key roles to work
  with the cardiovascular system to cycle fluids
  back into the circulation and to circulate lymph
  from the spleen, lymph nodes, and other lymphoid
  tissues throughout the body.

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Tonsils Defense against bacteria and other
foreign agents
Right Lymphatic Duct Drains right upper portion
of the body
Thymus Site where certain white blood cells
acquire means to chemically recognize specific
foreign invaders
Thoracic Duct Drains most of the body
Spleen Major site of antibody production
disposal site for old red blood cells and foreign
debris site of red blood cell formation in the
embryo
Some of the Lymph Vessels Return excess
interstitial fluid and reclaimable solutes to the
blood
Some of the Lymph Nodes Filter bacteria and many
other agents of disease from lymph
Bone Marrow Marrow in some bones is production
site for infection-fighting blood cells (as well
as red blood cells and platelets)
Fig. 10.2, p.178
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The Lymphatic System

• The lymph vascular system functions in drainage,
  delivery, and disposal.
• The lymph vascular system consists of lymph
  capillaries and other vessels linking it to the
  cardiovascular system.
• Water and solutes that drain from the blood
  vessels collect in the lymphatic vessels and are
  returned to the blood via these vessels.
• The lymphatic vessels pick up absorbed fats and
  deliver them to the blood.
• Lymphatic vessels also transport foreign material
  to the lymph nodes for disposal.

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The Lymphatic System

• Lymph capillaries and vessels are structured much
  like blood capillaries and veins.

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blood capillary bed
interstitial fluid
lymph capillary
flaplike valve formed from overlapping cells at
the tip of a lymph capillary
a Lymph capillaries
Fig. 10.3a, p.179
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The Lymphatic System

• Lymphoid organs and tissues are specialized for
  body defense.
• Lymph nodes are located at intervals along the
  lymph vessels lymphocytes congregate in these
  nodes, making them key battlefields in fighting
  off pathogens.

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lymph trickles past organized arrays
of lymphocytes within the lymph node
valve (prevents backflow)
b A lymph node, cross section
Fig. 10.3b, p.179
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The Lymphatic System

• The spleen filters blood and serves as a holding
  station for large numbers of lymphocytes.
• T cells are produced and become specialized in
  the thymus.

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Section 3

• Surface Barriers

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Surface Barriers

• The normal microorganisms living on your skin
  help prevent the growth of unwanted pathogens
  through competition.
• Some microorganisms, such as the Lactobacillus
  species of the vaginal tract in women, lower the
  pH of their surroundings to prevent growth of
  other microbes.

Figure 10.4
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Surface Barriers

• The mucus coating your lungs contains enzymes
  such as lysozyme that can attack and destroy many
  bacteria cilia can also sweep out pathogens.
• Chemicals in tears, saliva,
• and gastric fluid offer
• similar protection.
• The natural low pH of urine, as well as its
  flushing action, helps protect the urinary tract.

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Section 4

• Innate Immunity

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Innate Immunity

• Once a pathogen enters the body, macrophages
  engulf it and release cytokines to attract
  dendritic cells, neutrophils, and more
  macrophages.

Figure 10.5
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Innate Immunity

• Circulating complement proteins can detect
  pathogens and become activated.
• Activated complement attracts phagocytes, which
  can destroy the pathogens.
• Activated complement can also form membrane
  attack complexes in the pathogen these are holes
  that cause the pathogen to disintegrate.

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Fig. 10.6, p.180
one membrane attack complex (cutaway view)
lipid bilayer of a pathogen
pore
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Innate Immunity

• Activated complement and cytokines stimulate
  inflammation, characterized by redness, swelling,
  warmth, and pain.
• Tissue irritation causes mast cells to release
  histamine and cytokines that cause the blood
  vessels to dilate (tissue
• redness and warmth)
• and capillary walls to
• become leaky (edema).

Figure 10.8
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Innate Immunity

• Plasma proteins and phagocytes leave the blood
  vessels.
• Plasma proteins contain clotting agents that help
  wall off the pathogen and promote repair of
  tissues.
• Macrophages release cytokines that tell the brain
  to release prostaglandins, which in turn
  stimulates fever production moderate fevers
  inhibit pathogen growth.

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b
a
Mast cells in tissue release histamine, which
then triggers arteriolar vasodilation (hence
redness and warmth) as well as increased
capillary permeability.
Bacteria invade a tissue and directly kill cells
or release metabolic products that damage tissue.
e
d
a
c
b
Fluid and plasma proteins leak out
of capillaries localized edema (tissue
swelling) and pain result.
Plasma proteins attack bacteria. Clotting factors
wall off inflamed area.
Neutrophils, macrophages, and other phagocytes
engulf invaders and debris. Activated complement
attracts phagocytes and directly kills invaders.
c
d
e
Fig. 10.7, p.181
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Section 5

• Overview of
• Adaptive Defenses

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Overview of Adaptive Defenses

• Adaptive immunity has three key features.
• Adaptive immunity is the bodys third line of
  defense and has three defining features
• Adaptive immunity is specific each B and T cell
  only recognizes one antigen.
• Adaptive immunity is diverse B and T cells
  collectively can recognize at least a billion
  different threats.
• Adaptive immunity has memory.

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Overview of Adaptive Defenses

• Recognition of an antigen results in rapid cell
  division to produce huge numbers of identical B
  and T cells that recognize the stimulating
  antigen.
• Some of these new cells are effector cells that
  can immediately destroy pathogens.
• Others are memory cells, held in reserve for
  future battles against the same threat memory
  cells are what make you immune to various
  pathogens.

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Overview of Adaptive Defenses

• B cells and T cells become specialized to attack
  antigens in different ways.
• Both B and T lymphocytes arise in stem cells in
  the bone marrow.
• B cells continue to develop within bone marrow.
• T cells travel to the thymus to finish
  developing T cells divide into two
  populationshelper T cells and cytotoxic
  (killer) T cells.
• When mature, B and T cells can be found in the
  lymph nodes, spleen, and other lymphoid tissues
  where they remain naive until they recognize
  antigen.

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Overview of Adaptive Defenses

• B cells and T cells respond to pathogens in
  different ways.
• B cells produce antibodies (proteins) and are
  responsible for antibody-mediated
• immunity.
• T cells directly attack invaders their response
  is called cell-mediated immunity.

Figure 10.9
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Red blood cells Platelets Monocytes, others
Bone marrow
Stem cells
Thymus
T cells
B cells
Organs of lymphatic system
Foreign invasion
T cells
B cells
Cell-mediated immune response
Antibody-mediated immune response
Fig. 10.9, p.182
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Antibody-Mediated Immune Response
Cell-Mediated Immune Response
antigen-presenting cells
inactive B cells antigen complement activate
d B cells
inactive helper T cells
inactive cytotoxic T cells
effector helper T cells memory helper T cells
effector B cells memory B cells
effector cytotoxic T cells memory cytotoxic
cells
Fig. 10.10, p.183
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Overview of Adaptive Defenses

• Proteins called MHC markers label body cells as
  self.
• All body cells have MHC markers (from Major
  Histocompatibility Complex genes) to identify
  them as self.
• T cells have TCRs (T Cell Receptors) that see MHC
  in context with antigen and respond.

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Overview of Adaptive Defenses

• Antigen-presenting cells introduce antigens to T
  cells and B cells.
• T cells and B cells can only see antigens that
  have been processed by an antigen-presenting cell
  (APC).
• Macrophages, dendritic cells, and B cells can all
  present antigen.
• The antigen is ingested and digested then its
  fragments are linked with MHC markers and
  displayed on the cells surface as antigen-MHC
  complexes.

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Overview of Adaptive Defenses

• Helper T cells see the antigen-MHC complex,
  release cytokines, and trigger repeated rounds of
  division to produce the large numbers of
  activated B and T cells.
• Specialization of activated cells into effector
  or memory cells also occurs.
• An effector B cell is called a plasma cell it
  can flood the bloodstream with antibodies.

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Table 10.3, p.192
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Section 6

• Antibody-Mediated Immunity Defending Against
  Threats Outside Cells

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Antibody-Mediated Immunity Defending Against
Threats Outside Cells

• Antibodies develop while B cells are in bone
  marrow.
• An antibody has a Y-shaped protein structure
  antigens are bound by the two arms of the
  antibody.
• No two B cells make antibodies that are alike
  this allows both diversity and specificity.
• B cells make many copies of their antibodies,
  which are inserted in the plasma membrane, arms
  sticking out and ready to bind antigen.

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binding site for antigen
binding site for antigen
Fig. 10.11a, p.184
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Fig. 10.11b, p. 184
antigen on bacterial cell (not to scale)
binding site on one kind of antibody molecule for
a specific antigen
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Antibody-Mediated Immunity Defending Against
Threats Outside Cells

• Antibodies target pathogens that are outside
  cells.
• Prior to activation, B cells serve as
  antigen-presenting cells.
• Antibodies on the B cell surface bind antigens,
  internalize them, process them, and then display
  antigen-MHC complexes.
• TCRs of a helper T cell see the antigen-MHC
  complex and bind binding causes the cells to
  exchange signals.
• The T cell disengages, but the B cell is now
  activated when it recognizes unbound antigen,
  the B cell will divide into plasma cells and
  memory cells.

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Fig. 10.12, p. 185
bacterium
dendritic cell
complement
inactive B cell
inactive T cell
cytokines
antigen-presenting cell
effector helper T cell
memory helper T cell
B cell
memory B cell
effector B cell
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Antibody-Mediated Immunity Defending Against
Threats Outside Cells

• Plasma cells can release up to 2,000 antibodies
  per minute into the bloodstream these antibodies
  flag invaders for destruction by phagocytes and
  complement.
• There are five classes of antibodies, each with a
  particular function.
• Collectively, antibodies are referred to as
  immunoglobulins, or Igs.

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Antibody-Mediated Immunity Defending Against
Threats Outside Cells

• The five different classes of Igs are the protein
  products of gene shuffling that takes place as
  the B cells mature
• IgM antibodies cluster into a structure with 10
  binding sites, making them more efficient at
  binding clumped targets IgM is the first
  antibody produced in a response.
• IgA antibodies are present in secretions of
  exocrine glands (tears, saliva, breast milk) and
  in the mucus of the respiratory, digestive, and
  reproductive tracts.

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Antibody-Mediated Immunity Defending Against
Threats Outside Cells

• IgG antibodies neutralize toxins, turn on
  complement, are long lasting, can cross the
  placenta, and are found in mothers milk.
• IgD is the most common antibody bound to naive B
  cells it may help activate T cells.
• IgE antibodies are involved in allergic
  reactions they bind to basophils and mast cells
  where they act as traps for antigen, causing the
  release of histamine.

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In-text Fig., p.184
IgG, IgD, and IgE
IgA
IgM
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Section 7

• Cell-Mediated ResponsesDefending Against Threats
  Inside Cells

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Cell-Mediated Responses Defending Against
Threats Inside Cells

• Cell-mediated responses fight those pathogens
  (viruses, bacteria, and some fungi and
  protozoans) that can enter cells to avoid
  antibody defenses cell-mediated responses also
  fight abnormal body cells such as cancer cells.
• APCs present antigen to T cells, similar to their
  role in antibody-mediated immunity.

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Cell-Mediated Responses Defending Against
Threats Inside Cells

• Helper T cells can be stimulated this way to
  divide into effector and memory cells.
• Effector helper T cells or APCs directly can
  stimulate cytotoxic T cells to divide.
• Cytotoxic T cells rapidly multiply and release
  molecules that can touch-kill infected and
  abnormal body cells.
• Cytotoxic T cells also secrete chemicals that
  stimulate apoptosisthe programmed cell death of
  the infected cell.

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cytotoxic T cell
tumor cell
Fig. 10.14, p.187
65
Fig. 10.13, p. 186
dendritic cell
virus particle (red) infecting a body
cell (yellow)
a
inactive helper T cell
inactive cytotoxic T cell
b
c
antigen-presenting cell
cytokines
effector helper T cell
memory helper T cell
activated cytotoxic T cell
d
memory cytotoxic T cell
effector cytotoxic T cell
effector cytotoxic T cell
e
66
Fig. 10.13, p. 186
a
b
c
antigen-presenting cell
d
e
Stepped Art
67
Cell-Mediated Responses Defending Against
Threats Inside Cells

• Helper T cells can also stimulate NK cells they
  will attack any cell that has too few or altered
  MHC, any cells that have been tagged by
  antibodies, and cells showing stress markers as
  indicators of infection or cancer.
• Cytotoxic T cells cause the body to reject
  transplanted tissue.
• During organ transplants, donor tissues must be
  matched to a recipient to ensure that the MHC
  markers do not differ enough to stimulate
  rejection by cytotoxic T cells.

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Cell-Mediated Responses Defending Against
Threats Inside Cells

• Donor and recipient usually must share at least
  75 of their MHC markers for the transplant to
  succeed close relatives make the best donors
  because of this.
• Recipients usually also take drugs to suppress
  the immune system to prevent rejection often
  they will also take antibiotics to ward off
  potential infections.
• Tissues of the eye and testicles do not stimulate
  rejection instead, cells of these tissues
  secrete signals that cause lymphocytes to undergo
  apoptosis, thus preventing the lymphocytes from
  attacking.

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Section 8

• Immunological Memory

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Immunological Memory

• Memory cells form during the primary (first)
  response to an antigen and remain in the blood
  for years or decades.
• Secondary responses to the same antigen are much
  faster plasma cells and effector T cells form
  sooner and in greater numbers, preventing
  infection.

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Fig. 10.20, p.194
72
Fig. 10.15b, p. 188
later exposure to same antigen
first exposure to antigen
Relative concentrations of antibody
Response time (weeks)
73
Fig. 10.15a, p. 188

First exposure to antigen provokes primary immune
response.
inactive T or B cell
effector cell
memory cell
Later exposure to same antigen provokes secondary
immune response.
effector cells
memory cells
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Section 9

• Applications of Immunology

75
Applications of Immunology

• Immunization gives borrowed immunity.
• Immunization increases immunity against specific
  diseases.
• In active immunization, a
• vaccine is given by injection or
• is taken orally.
• The first dose of vaccine elicits a primary
  immune response a second dose (booster)
  elicits a secondary, and more long-lasting,
  response.
• Vaccines are made from killed or very weak
  pathogens, inactivated forms of toxins, or
  transgenic (genetically engineered) viruses.

Figure 10.16
76
Applications of Immunology

• Passive immunization involves injecting
  antibodies into already infected individuals.
• Vaccines are not risk free.

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p. 188
78
Applications of Immunology

• Monoclonal antibodies are used in research and
  medicine.
• Monoclonal antibodies
• are antibodies made by
• cells cloned from a single
• antibody-producing B cell
• they are generally produced using genetically
  altered bacteria or sometimes plants.
• Monoclonal antibodies are being used commercially
  in home pregnancy tests, screening for prostate
  cancer, and other uses.

Figure 10.17
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Applications of Immunology

• Immunotherapies reinforce defenses.
• Immunotherapy alters the bodys own immune
  mechanisms to enhance defense against infections
  and cancer.
• Cytokines can be used to activate B and T cells
  to fight cancer.
• Monoclonal antibodies can be used to bind to
  proteins on cancer cells to draw NK cells to the
  tumor.

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Applications of Immunology

• Other monoclonal antibodies are bound to toxins
  to make immunotoxins these substances bind to
  cancer cells, enter them, and prevent growth.
• Gamma interferon, produced by T cells, stimulates
  NK cells and boosts activity of macrophages it
  is currently being used to treat hepatitis C.
• Beta interferon is being used to treat multiple
  sclerosis.
• Immunotherapies, as with vaccines, do not come
  without risks.

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Section 10

• Disorders of the Immune System

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Disorders of the Immune System

• In allergies, harmless substances provoke an
  immune attack.
• An allergy is an immune
• response to a normally
• harmless substance
• called an allergen.
• Allergens include pollen, some foods and drugs,
  dust mites, fungal spores, insect venom, and
  certain ingredients in cosmetics.
• Allergens trigger mild to severe inflammation of
  various tissues.
• A variety of causes, from genetic to emotional,
  lead to allergies.

Figure 10.18a
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Disorders of the Immune System

• Exposure to an allergen triggers production of
  IgE antibodies, which cause the release of
  histamines and prostaglandins from mast cells.
• Histamines and prostaglandins fuel inflammation.
• Hay fever manifests as stuffed sinuses, a drippy
  nose, and sneezing.
• In a few individuals, explosive inflammatory
  responses trigger life-threatening anaphylactic
  shock in which air passages constrict and fluid
  rushes out of the capillaries.

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Disorders of the Immune System

• Food allergies, such as peanut allergies, and
  wasp and bee venom allergies, can trigger
  anaphylactic shock.
• Rapid injections of the hormone epinephrine can
  prevent shock and save lives.
• Antihistamines are often used to relieve the
  short-term symptoms of allergies desensitization
  can be used to train the body not to see
  allergens.

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Fig. 10.18b, p. 190
allergen (antigen) enters the body
IgE antibodies
histamine granules
B cell
nucleus
mitochondrion
Allergen binds B cell receptors the sensitized
B cell now processes the antigen and, with the
help of T cells (not shown), proceeds through
the steps leading to cell proliferation
mast cell
Effector B cells (plasma cells) produce and
secrete IgE antibodies to the allergen
IgE antibodies attach to mast cells in tissues,
which have granules containing histamine molecules
86
Fig. 10.18b, p. 190
SECONDARY RESPONSE (allergy)
histamine granules
After the first exposure, when the allergen
enters the body it binds with IgE antibodies
on mast cells binding stimulates the mast cell
to release histamine and other substances
87
Disorders of the Immune System

• Autoimmune disorders attack self.
• In an autoimmune response, lymphocytes turn
  against the bodys own cells.
• Examples of autoimmune diseases include the
  following
• Rheumatoid arthritis, an inflammation of the
  joints caused by immune attack against collagen
  and antibodies in the joints
• inflammation, complement
• and faulty repair mechanisms
• contribute to the damage.

Figure 10.19
88
Disorders of the Immune System

• Type 1 diabetes, a type of diabetes mellitus,
  caused when the immune system attacks and
  destroys the insulin-secreting cells of the
  pancreas, impairing glucose absorption from the
  blood.
• Systemic lupus erythematosus, where patients
  develop antibodies to their own DNA and other
  self components.
• Autoimmune diseases tend to be more frequent in
  women than in men.

89
Disorders of the Immune System

• Immune responses can be deficient.
• Immunodeficiency is used to describe the state
  where a persons immune system is weakened or
  lacking under these conditions the body is
  vulnerable and infections that would normally not
  be serious become life threatening.

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Disorders of the Immune System

• In severe combined immune deficiency (SCID) both
  B and T cells are in low numbers infants born
  with SCID usually die early in life.
• In acquired immune deficiency syndrome (AIDS),
  the HIV virus attacks the bodys macrophages and
  helper T cells, crippling the immune response.