The Immune System

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The Immune System

• Chapter 43

A macrophage engulfing bacteria
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The Bodys Defenses
Smallpox virus
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The Bodys Defenses
Anthrax bacteria
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The Bodys Defenses
Protozoan Trypanosoma (African sleeping sickness)
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The Bodys Defenses
Sac fungus Candida albicans (yeast infections)
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The Bodys Defenses
Heartworm nematodes...
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How does the human body defend against invaders?
Figure 43.2
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Skin is an inhospitable barrier of dead, dry
cells, secretions containing oil lactic acid
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Mucous membranes in respiratory, digestive
urogenital tracts secrete mucus antibiotic
chemicals (e.g., lysozyme, which digests
bacterial cell walls)
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How does the human body defend against invaders?
Figure 43.2
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If external defenses are not effective
nonspecific, innate response
Four types of phagocytic leucocytes (WBCs)
engulf invaders
E.g., macrophages, dendritic cells
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If external defenses are not effective
nonspecific, innate response
Microbes
Vacuole
Macrophage
Lysosome
Figure 43.4
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If external defenses are not effective
nonspecific, innate response

• Natural killer cells (WBCs) destroy infected
  cells cancer cells by inducing apoptosis
  (programmed cell death)

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If external defenses are not effective
nonspecific, innate response

• Antimicrobial proteins (e.g., lysozyme)
  produced by many cells of the body, often in
  response to infection actively destroy microbes

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If external defenses are not effective
nonspecific, innate response

• Local inflammatory response injury or pathogens
  can cause mast cells of connective tissues to
  release histamine, triggering dilation and
  increased permeability of capillaries

Fever systemic (widespread) response that
increases the bodys thermostat
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How does the human body defend against invaders?
Figure 43.2
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Immune system mounts attack on specific
disease agents
Circulatory System
Immune System
Lymphatic System
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Immune system mounts attack on specific
disease agents
2 main types of lymphocytes (WBCs)
B cells produced in bone marrow differentiate
in bone marrow
T cells produced in bone marrow differentiate
in thymus
Mature B and T cells are found throughout the
body in lymph and blood
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Immune system mounts attack on specific
disease agents
2 main types of lymphocytes (WBCs)
Bone marrow
Lymphoid stem cell
Thymus
B cell
T cell
Blood, lymph, and lymphoid tissues
Figure 43.10
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RECOGNITION
Lymphocytes recognize and respond to particular
microbes and foreign molecules, i.e., they
display specificity
A foreign molecule that induces an immune
response is known as an antigen
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RECOGNITION
Multiple antibodies may recognize the same
antigen by different epitopes (small accessible
portions of the larger molecule)
Fig. 43.7
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RECOGNITION
B cells produce antibodies, that are either
secreted out of the cells or remain embedded in
the B cell membranes, and that bind to antigens
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RECOGNITION
B cells produce antibodies, that are either
secreted out of the cells or remain embedded in
the B cell membranes, and that bind to antigens
T cells have T-cell receptors, embedded in their
cell membranes, that bind to antigens
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RECOGNITION
Even though many receptors (antibodies or T-cell
receptors) encounter a given type of antigen,
only the receptors that are compatible will bind
to them
Illustrated here for B cells, but the process for
T cells is similar
Fig. 43.12
This process is known as clonal selection
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RECOGNITION
Secreted antibodies con-stitute a group of
proteins called immunoglobulins
Antibodies have 2 heavy chain and 2 light chain
subunits
Each subunit has a constant region and a variable
region
The variable region can bind to an antigen
Fig. 43.8
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Construction of antibodies(and T-cell receptors)
RECOGNITION of non-self molecules

• Millions of antigens are recognized by randomly
  combining the protein products of hundreds of
  genes

Card analogy although there are only 52 cards
in the deck, random combinations can produce an
enormous number of different hands
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Construction of antibodies
B
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Construction of antibodies
B
B
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Construction of antibodies
B
B
B
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RECOGNITION of self molecules

• In a healthy immune system, as B and T cells
  mature they are destroyed by apoptosis if they
  attack self molecules

Healthy, mature B and T cells then have the
capacity to distinguish self from non-self
molecules
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RECOGNITION of self molecules

• Almost all cells in an individual humans body
  have major histocompatibility complex (MHC)
  glycoproteins embedded in their cell membranes

Class I MHC molecules are found on almost every
nucleated cell
Class II MHC molecules are restricted to a few
specialized cells, including macrophages,
dendritic cells, B cells, etc.
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RECOGNITION of self molecules

• MHC glycoproteins migrate to the cellmembrane
  after they are produced

MHC glycoproteins pick up molecules from the
cytosol that are presented at the cells surface
T cells bind to MHC glycoproteins and the
molecules they present
An individuals own MHC glycoproteins, and
molecules of its own body that the MHC
glycoproteins present, are treated as self
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RECOGNITION of non-self molecules

• However, T cells treat foreign molecules
  presented by MHC glycoproteins as antigens

Fig. 43.9
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RECOGNITION of non-self molecules

• Cytotoxic T cells bind to cells that carry Class
  I MHC glycoproteins

Fig. 43.9
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RECOGNITION of non-self molecules

• Helper T cells bind to cells that carry Class II
  MHC glycoproteins

Fig. 43.9
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ATTACK MEMORY
The B and T cells that recognize a given foreign
antigen produce two types of cloneseffector
cells (attackers) and memory cells
Illustrated here for B cells, but the process for
T cells is similar
Fig. 43.12
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ATTACK MEMORY
The B and T cells that first recognize a given
foreign antigen are short lived, whereas immune
memory cells can have long lifetimes
Illustrated here for B cells, but the process for
T cells is similar
Fig. 43.12
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ATTACK MEMORY
Memory cells help produce a secondary immune
response that is faster, of greater magnitude,
and of longer duration than the primary immune
response
Fig. 43.13
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ATTACK MEMORY
There are two types of immune response
Humoral response B cells and antibodies Attack
antigens that have not yet infected cells
(toxins, bacteria, and viruses in body
fluids) Deactivate, coat, and clump antigens
(which are then often engulfed and destroyed by
macrophages)
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ATTACK MEMORY
There are two types of immune response
Cell-mediated response T cells Attack antigens
after they have entered cells, as well as fungi,
protozoa, and parasitic worms Activated T cells
kill antigen-containing cells by creating pores
in their cell membranes
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RECOGNITION, ATTACK, MEMORY
Cell-mediated response
Humoral response
Involves the activation and clonal selection of B
cells
First exposure to antigen
Infected cells
Dendritic cells
Antigens
MHC I
MHC II
Activate
Activate
Activate
Results in the production of antibodies that
circulate in the blood and lymph
Cytokines activate
B cell
HelperT cell
CytotoxicT cell
Gives rise to
Gives rise to
Gives rise to
Active and memory helperT cells
Memory cytotoxicT cells
Active cytotoxicT cells
MemoryB cells
Plasmacells
Defend against infected cells, cancer cells, and
transplanted tissues
Secrete antibodies that defend againstpathogens
and toxins in extracellular fluid
Figure 43.14
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RECOGNITION, ATTACK, MEMORY
Cell-mediated response
Humoral response
Involves the activation and clonal selection of
cytotoxic T cells
First exposure to antigen
Infected cells
Dendritic cells
Antigens
MHC I
MHC II
Activate
Activate
Activate
Cytotoxic T cells directly destroy certain target
cells
Cytokines activate
B cell
HelperT cell
CytotoxicT cell
Gives rise to
Gives rise to
Gives rise to
Active and memory helperT cells
Memory cytotoxicT cells
Active cytotoxicT cells
MemoryB cells
Plasmacells
Defend against infected cells, cancer cells, and
transplanted tissues
Secrete antibodies that defend againstpathogens
and toxins in extracellular fluid
Figure 43.14
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RECOGNITION, ATTACK, MEMORY
Cell-mediated response
Humoral response
First exposure to antigen
A primary immune response begins with the first
exposure to an antigen
Infected cells
Dendritic cells
Antigens
MHC I
MHC II
Activate
Activate
Activate
Cytokines activate
B cell
HelperT cell
CytotoxicT cell
Gives rise to
Gives rise to
Gives rise to
A secondary immune response begins with a
re-exposure to an antigen, and stimulates memory
cells
Active and memory helperT cells
Memory cytotoxicT cells
Active cytotoxicT cells
MemoryB cells
Plasmacells
Defend against infected cells, cancer cells, and
transplanted tissues
Secrete antibodies that defend againstpathogens
and toxins in extracellular fluid
Figure 43.14
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Medical practices can augment our immune response
by inhibiting invaders or enhancing the immune
response

• Antibiotics
• Inhibit microbial reproduction
• Potent agents of natural selection

Vaccines (weakened or dead microbes, or their
toxins) Stimulate development of memory cells
faster response to invasion Selectively effective
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The immune system and blood types
antigen
antigens
antigen
Table 43.1
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What happens when the immune system malfunctions?

• Allergies
• Exaggerated immune responses to otherwise
• benign substances

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What happens when the immune system malfunctions?
1. Antibodies are produced
Fig. 43.20
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What happens when the immune system malfunctions?
1. Antibodies are produced
2. Stems of antibodies attach to mast cells,
especially in the respiratory tract
Fig. 43.20
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What happens when the immune system malfunctions?
1. Antibodies are produced
2. Stems of antibodies attach to mast cells,
especially in the respiratory tract
Fig. 43.20
3. When antibodies attached to mast cells
bind antigens, the mast cells release histamine,
which causes inflammation
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What happens when the immune system malfunctions?

• Autoimmune diseases
• The immune system lacks or loses its ability to
  distinguish self vs. non-self molecules, i.e., it
  loses its self-tolerance and produces anti-self
  antibodies

• Rheumatoid arthritis (cartilage of joints)
• Multiple sclerosis (mylein sheaths of neurons)
• Insulin-dependent diabetes mellitus
  (insulin-secreting cells of the pancreas)

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What happens when the immune system malfunctions?
Immunodeficiency diseases Inhibit effective
immune response either inherited or acquired

• Severe Combined Immunodeficiency (SCID)
• An inherited disorder
• Acquired Immunodeficiency Syndrome (AIDS)
• Caused by retroviruses (Human
  Immunodeficiency Viruses HIV) that
  especially infect helper T cells

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Adults and children estimated to be living with
HIV as of the end of 2001
What happens when the immune system malfunctions?
Eastern Europe Central Asia 1 million
Western Europe 560,000
North America 940,000
East Asia Pacific 1 million
North Africa Middle East 440,000
South South-East Asia 6.1 million
Caribbean 420,000
Sub-Saharan Africa 28.1 million
Latin America 1.4 million
Australia New Zealand 15,000
Total 40 million
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Estimated number of deaths from AIDS during 2001
What happens when the immune system malfunctions?
Eastern Europe Central Asia 23,000
Western Europe 6,800
North America 20,000
East Asia Pacific 35,000
North Africa Middle East 30,000
South South-East Asia 400,000
Caribbean 30,000
Sub-Saharan Africa 2.3 million
Latin America 80,000
Australia New Zealand 120
Total 3 million
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What happens when the immune system malfunctions?
The global AIDS epidemic

• HIV destroy helper T cells
• Victims die from other diseases

• Transmission
• Direct contact between broken skin, mucous
  membranes body fluids

• No cure
• Treatments inhibitors of reverse-transcriptase
  and protease
• Problem virus evolves quickly

• How to reduce your risk
• Practice safe sex
• Avoid used needles

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What happens when the immune system malfunctions?

• Cancer

Malfunction in cell production combined with a
lack of recognition by the immune system of
aberrant cells or too many of them Uncontrolled
growth tumor
Causes Carcinogens, viruses, inheritance
No guaranteed cure Most treatments also destroy
healthy cells
How to reduce your risk Reduce exposure to
carcinogens