2. Body Defense Mechanisms
The body’s defense system
Three lines of defense
Distinguishing self from nonself
Antibody-mediated responses and
cell-mediated responses
Steps of the adaptive immune response
Active and passive immunity
Monoclonal antibodies
Problems of the immune system
3. The Body’s Defense System
Targets of the body’s defense mechanisms
• Pathogens
• Disease-causing bacteria, viruses, protozoans,
fungi, parasitic worms, prions
• Cancer cells
• Once normal body cells whose genetic changes
cause unregulated cell division
4. Overview of Body Defenses
Every day we encounter a vast number of health
threats
Body defenses include physical barriers and two
interacting sets of cells and proteins
5. Three Lines of Defense Protect the Body
Physical barrier to invasion
• Intact skin
• Linings of body cavities and tubes
Innate immune system
• General, immediate response to antigens
• Does not target specific intruders
Adaptive immune system
6.
7. We Are Born with Some General Defenses
and Acquire Other, Specific Ones (1)
Pathogens
• Viruses
• Bacteria
• Fungi
• Protozoa
• Parasitic worms
Antigens
• Proteins
• Lipids
• Oligosaccharides
8. We Are Born with Some General Defenses
and Acquire Other, Specific Ones (2)
Immunity
• Innate immunity
• Preset responses
• Immediate response
• Carried out by some white blood cells and
plasma proteins
• Adaptive immunity
• Slower response
• Carried out by lymphocytes and proteins
• Every adaptive response leaves behind cells that
“remember” a pathogen basis of immunizations
9. White Blood Cells
The defenders
Produced by stem cells in bone marrow
10. Phagocytes
Type of WBC
Releases several types of cytokines
• “Cell movers” that promote and regulate immunity
• Interleukines
• Interferons
11. White Blood Cells & Their Chemicals Are
the Defenders in Immune Responses (1)
Phagocytic white blood cells release chemical
signals and aid the immune system
• Cytokines
• Interleukins
• Interferons
• Tumor necrosis factor
• White blood cell enzymes
Another chemical weapon
• Complement system (proteins)
• ~30 proteins
• Act as antimicrobials- flag microbes for destruction!
12. White Blood Cells & Their Chemicals Are
the Defenders in Immune Responses (2)
Types of white blood cells:
Neutrophils (2/3rds of our WBC’s)
Basophils (release histamines)
Mast cells (release histamines)
Macrophages (engulf cells)
Eosinophils (target worms, fungi, etc)
Dendritic cells (alert immune system when antigen is in tissue
fluid in skin and body linings
B and T Lymphocytes
• B cells and T cells: only cells with specific receptors
Natural killer cells (NK cells- destroy cancer cells & cells
infected by viruses
13. The Lymphatic System
Lymphatic system
• Picks up fluid lost from the capillaries and returns
it to the blood
• Defense
• Consists of: drainage vessels, lymphoid organs,
and lymph tissues
Lymphoid organs
• Spleen
• Lymph nodes
• Others
Lymph
Fluid identical to interstitial fluid
14. Lymphatic System
Elephantiasis
• A condition in which
parasites block
lymphatic vessels,
preventing the return
of fluid to blood
• Results in massive
swelling, darkening,
and thickening of the
skin in the affected
area
15. Lymphatic System
Components of the lymphatic system
• Lymph
• Fluid identical to interstitial fluid
• Lymphatic vessels
• Vessels through which lymph flows
• Have one-way valves to prevent backflow
• Lymphoid tissues and organs
16. Tonsils
Defense against bacteria and other foreign agents
Right Lymphatic Duct
Drains right upper portion of the body
Thymus Gland
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 Lymph Vessels
Return excess interstitial fluid and reclaimable
solutes to the blood
Some 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 Stepped Art
cells and platelets) Fig. 9-2, p. 158
17.
18. The Lymph Vascular System Functions
in Drainage, Delivery, and Disposal
Lymph capillaries at the start of the drainage
network
• Collect water & solutes
Merge into larger vessels containing smooth
muscles and valves
Transport material to ducts of CV system
20. Lymph
Lymph fluid returns to blood via large lymph
vessels that drain into veins in the lower neck
21. Lymphoid Organs and Lymphatic Tissues
Are Specialized for Body Defense
Lymph nodes
• Lymphocytes and macrophages clear the lymph
of bacteria and other foreign substances
Spleen
• largest lymphatic organ
• Filters blood
• Major site of antibody production
• Storage reservoir of red blood cells and
macrophages
Thymus
• Site of T cell multiplication and specialization
24. Surface Barriers (1)
Bacteria are normal inhabitants of the body
• Roles of bacteria
• On the skin
• In the mucosal lining of the digestive tract
• In the vaginal mucosa, e.g., Lactobacillus
Effect of antibiotics on normal microbial
inhabitants, e.g., Lactobacillus
Athlete’s foot
26. Surface Barriers (2)
Inner walls of the respiratory airways
• Sticky mucus
• Cilia
• Lysozyme
• Enzyme that fights bacteria
More protection found in:
• Tears
• Saliva
• Gastric fluid
• Urine has low pH and flushing action
• Mild diarrhea
27.
28. Innate Immunity
Phagocytosis,
…inflammation,
…and fever…
…are the body’s “off-the-shelf” mechanisms that
act at once to counter threats in general and
prevent infection
30. Innate Immunity (1)
Once a pathogen enters the body:
Macrophages arrive 1st (usually)
• Release cytokines if they detect antigen
• Cytokines are chemical signals that attract
dendritic cells, neutrophils, and more
macrophages
Complement molecules activated
• Attract phagocytes (such as macrophages &
neutrophils)
• Bind to the pathogen
• May form membrane attack complexes
• Trigger inflammation
31. Inflammatory Response
Inflammatory response
• Destroys invaders and helps repair and restore
damaged tissue
• Four signs
• Redness
• Heat
• Swelling
• Pain
32. Inflammatory Response
Redness
• Mast cells release histamine, which causes blood
vessels to dilate
• Blood flow to the area increases, delivering
defensive cells and removing dead cells
and toxins
33. Inflammatory Response
Heat
• Temperature rises as a result of increased blood
flow
• Speeds healing and activities of
defensive cells
34. Inflammatory Response
Fever
• An abnormally high body temperature
• Caused by pyrogens
• Chemicals that reset the brain’s thermostat to a
higher temperature
• A mild or moderate fever helps fight bacterial
infection
• A very high fever (over 105°F or 40.6°C) is
dangerous
35. Inflammatory Response
Swelling
• Histamine causes capillaries to become leaky
and fluid seeps into tissues
• Fluid brings clotting factors, oxygen,
and nutrients
37. Acute sudden inflammation
Activated complement and cytokines trigger this
fast, general response to tissue invasion
Symptoms are redness, swelling, warmth, and
pain, all caused by this series of internal events
39. Innate Immunity (2)
Symptoms of inflammation include redness, swelling,
warmth, and pain
Internal events of inflammation
• Mast cells release histamine
• Arteriole vasodilation
• Fluid and plasma leak out of capillaries leading to
edema (swelling)
• Bacteria attacked
• Clotting factors- wall off inflamed area
• Fever- develops when cytokines stimulate brain to
release prostaglandins
• Prostaglandins are signaling molecules that raise set point on
hypothalamic thermostat
41. Overview of Adaptive Defenses
When physical barriers and inflammation don’t
prevent an invasion, the adaptive immune
system is mobilized
42. Adaptive Immunity Has Three Key
Features
Adaptive immunity mobilizes B and T cells
1. Specificity- receptors for 1 kind of antigen form
2. Diversity- collectively, these cells may have
receptors for ~a billion different specific threats
3. Memory- some of the B and T cells are held in
reserve for future battles
Effector cells
• Respond immediately to destroy pathogen
Memory cells
• Set aside for a second or third encounter
43. Distinguishing Self from Nonself
T cells and B cells
• B cells and T cells that respond to a particular
antigen divide repeatedly, forming two cell lines
• Effector cells
• Short-lived cells that attack the invader
• Memory cells
• Long-lived cells that remember the invader and
mount a quick response when it is next
encountered
46. B Cells and T Cells Attack Invaders in
Different Ways
B cells
• Produced in bone marrow, sent to lymphatic
system
• Produce antibodies; antibody-mediated
immunity- instead of direct engagement, produce protein
antibodies
T cells
• Produced in bone marrow and go to the thymus
gland for development
• Cytotoxic T cells; cell-mediated immunity-
involves direct engagement
• Helper T cells- have both types of responses
47.
48. Steps of the Adaptive Immune Response
1. Threat
• Foreign organism or molecule (an antigen) enters
the body
2. Detection
• Macrophage detects foreign organism or
molecule and engulfs it
49. Steps of the Adaptive Immune Response
3. Alert
• Macrophages present antigens to helper
T cells
• Macrophages are antigen-presenting cells
• Helper T cells are the main switch for the adaptive
immune response
50.
51. Steps of the Adaptive Immune Response
4. Alarm
• Helper T cells activate appropriate B cells and T
cells to destroy the specific antigen
• When activated, these cells divide to form clones
of cells designed to eliminate the specific antigen
from the body
52. Steps of the Adaptive Immune Response
5. Building specific defenses
• B cells form plasma cells that secrete antibodies
into the bloodstream that bind to antigens
• T cells form cytotoxic T cells that attack
53. Steps of the Adaptive Immune Response
6. Defense: The cell-mediated response
• An effector cytotoxic T cell releases perforins,
which cause holes to form in cells with the
particular antigen
54. Steps of the Adaptive Immune Response
7. Continued surveillance
Immunological memory allows for a more rapid
response on subsequent exposure to the antigen
Primary response
Occurs during body’s first encounter with a
particular antigen
Antibody concentration rises slowly
Secondary response
Occurs during subsequent encounter with that
antigen
Strong and swift due to the large number of
memory cells programmed to respond to that
particular antigen
58. B & T Cells
When mature, most move into lymph nodes, the
spleen, and other lymphoid tissue
Remember- two different responses occur:
1) Antibody- mediated
2) Cell-mediated
59. How Do B & T Cells Learn?
They study hard!
• Study groups
• Biojeopardy learning games
Involves MHC markers
• Major histocompatability complex genes
60. MHC Markers Label Body Cells as Self
MHC markers
• Major Histocompatibility Complex genes code for
these proteins
• Some of these proteins stick out of cell
membranes
• T cells have receptors that recognize them
63. Antibodies Develop While B Cells Are in
Bone Marrow
B cell in bone marrow develops antibodies
Binding of antigens
• Copies of antibodies made by B cell, migrate to and
stick out of plasma membrane like ‘bristles’
64. Antibodies Can Bind to Antigens
antigen on bacterial
binding site for antigen binding site for antigen cell (not to scale)
binding site on one
kind of antibody
molecule for a
specific antigen
Typical Y-shape of simple antibody
Stepped Art
Fig. 9-12, p. 164
65. There Are Five Classes of Antibodies,
Each with a Particular Function
Immunoglobulins (Igs)
• Proteins produced by B cells; various shapes
• Result from gene shuffling while B cell matures
during immune response
• Antigen-binding sites; other sites with special
roles
Types of Igs (pg165)
• IgM
• IgD
• IgG
• IgA
• IgE
66. Cell-Mediated Responses: Defending
against Threats Inside Cells
Responses by antibodies can’t reach threats
inside cells
Accordingly, when cells become infected or
altered in harmful ways, other “warrior” cells
must come to the defense
67. Cell-Mediated Responses
Starts when an antigen presenting cell (APC) presents
an antigen to a T cell
Role of:
• Helper T cells and cytotoxic T cells specific response
• NK cells and macrophages more general response
Target: viruses, bacteria, some protozoa and some
fungi, and cancerous cells
Apoptosis
68. Protozoans
Giardiasis is an infection of the small
intestine caused by a microscopic
organism (protozoa), Giardia lamblia.
Abdominal pain, Diarrhea, Gas or bloating,
Headache, Loss of appetite, Low-grade
fever, Nausea, Swollen or distended
abdomen, Vomiting
69. T Cells Are the Warriors in Cell-Mediated
Immune Responses
72. Helper T Cells
Their cytokines stimulate NK cells
NK cells don’t need an antigen
They simply attack any body cell that has too
few or altered MHC markers, or that antibodies
have tagged for destruction
They also kill cells flagged with chemical “stress
markers” that develop when a cell is infected or
becomes cancerous
73. A Cytotoxic T Cell Touch-Killing a
Tumor Cell
Release chemicals that kill
on contact.
Also release chemicals that
cause genetically
programmed cell death-
apoptosis.
74. Cytotoxic T Cells Cause the Body to
Reject Transplanted Tissue
MHC markers on donor cells recognized as
antigens by recipient cells
Best donors have similar genetic makeup and
compatible blood type with recipient
Recipient takes immuno-suppressing drugs and
often antibiotics to control infections
Transplanted tissues of the eye and testicles do
not provoke an immune response
75. Immunological Memory
The memory cells produced during an adaptive
immune response can provide many years of
immunity to a pathogen
76. Immunological Memory
Memory cells form during primary (first) immune
response
• Circulate for years, even decades
• Patrolling battalions
Even more memory T and plasma cells form
during a second adaptive response
Memory cells determined by the type of antigen
exposure
78. Applications of Immunology
Modern science has developed powerful
weapons that can enhance the immune system’s
functioning or harness it in new ways to treat
disease
Vaccine primary immune response to antigen
Booster secondary immune response; more
effector & memory cells form that can provide
longer lasting protection
79. Immunization Gives “Borrowed”
Immunity
Immunization
• Vaccine: first injection + “booster shot”
• Killed or extremely weakened pathogens
• Inactive forms of natural toxins
• Transgenic viruses
Passive immunization
• Injections of purified antibodies
• Does not confer memory cells though
Adverse effects of vaccines
80. Passive Immunity to Infectious Disease
1955
http://www.youtube.com/watch?v=9Bm2fnCTaMg
82. Disorders of the Immune System
In allergies, harmless substances provoke an
immune attack
83. In Allergies, Harmless Substances
Provoke an Immune Attack (1)
Common allergens
• Pollen
• Variety of foods and drugs
• Dust mites
• Fungal spores
• Insect venom
• Ingredients in cosmetics
Allergy
• Response and severity
84. The Basic Steps Leading to an Allergic
Response
Role of IgE antibodies
85. In Allergies, Harmless Substances
Provoke an Immune Attack (2)
Symptoms of allergies vary
• Inflammation of mucus membranes
• Constriction of airways
• Stuffed sinuses, drippy nose, and sneezing in
hay fever
• Vomiting
• Diarrhea
Anaphylactic shock
• Whole-body allergic response
• Can be fatal
86. Autoimmune Disorders Attack “Self”
Autoimmune disorders
• Rheumatoid arthritis
• Type I diabetes
• Insulin secreting cells of pancreas attacked
• Systemic lupus erythematosus
Immune systems “weapons” unleashed upon
own body
More common in women- is receptor for
estrogen involved??
87. Immune Responses Can Be Deficient
Immunodeficiency
• Weakened or missing immune system
Severe combined immune deficiency (SCID)
• Short supply of B and T cells
• Usually inherited
• Usually infants die early
HIV and AIDS
88. HIV and AIDS
HIV, the human immunodeficiency virus, cripples
the immune system by destroying lymphocytes
89. HIV and AIDS
AIDS caused by infection with HIV
HIV kills lymphocytes
• Macrophages, dendritic cells, and helper T cells
• Can get in via certain type of surface receptor
Diagnostic signs of AIDS
• Severely depressed immune system
• Positive HIV test
• “Indicator disease”- types of pneumonia,
recurrent yeast infections, cancer, drug-resistant
TB
92. Pathogens Spread in Four Ways
Infections that can threaten health spread in 4
predictable ways and occur in 4 predictable patterns
1. Direct contact
2. Indirect contact
3. Inhaling pathogens
4. Contact with a vector
Nosocomial infection: acquired in a hospital
95. Diseases Occur in Four Patterns
Epidemic
• Disease rate increases to a level above what
we would predict
Pandemic
• When epidemics break out in several countries
around the world
Sporadic disease
• Irregularly breaks out and affects relatively few
Endemic disease
• Occurs more or less continuously
96. Virulence Is a Measure of Pathogen
Damage
Virulence of a pathogen
How fast can the pathogen invade the tissues?
How severe is the damage it causes?
Which tissues are targeted?
97. Respiratory tract
Preventative measures:
• Hand washing
• Cover mouth when coughing or
sneezing
• Proper disposal of used tissues
• Vaccination programs
GI tract
Preventative measures:
• Hand washing
• Proper food storage, handling, and
cooking
• Good public sanitation (sewage,
drinking water)
Blood
Preventative measures:
• Avoid/prevent needle sharing/ IV drug
abuse
• Maintain pure public blood supplies
• Vaccination programs against blood-
borne pathogens (e. g., hepatitis B)
Skin
Preventative measures:
• Hand washing
• Limit contact with items used by an
infected person
Fig. 9-25a, p. 175
Figure 9.2: Animated! The lymphatic system collects fluid and functions in defense. The small green ovals show where some of the major lymph nodes are located. The system also includes patches of lymphoid tissue in the small intestine and in the appendix.
Figure 9.12: Animated! Antibodies can bind to antigens. ( a ) The Y-shaped structure of many antibodies. ( b ) How an antibody binds to an antigen. Each kind of antibody can bind only one kind of antigen. The antigen fits into grooves and bumps on the antibody molecules.
Figure 9.25: It is helpful to know how pathogens spread and what their reservoirs are. ( a ) Some recommended strategies for preventing the spread of infectious disease.