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Immunity and Disease

The Lymphatic System
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
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
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
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
We Are Born with Some General Defenses
and Acquire Other, Specific Ones (1)
 Pathogens
  •   Viruses
  •   Bacteria
  •   Fungi
  •   Protozoa
  •   Parasitic worms

 Antigens
  • Proteins
  • Lipids
  • Oligosaccharides
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
White Blood Cells

           The defenders

Produced by stem cells in bone marrow
Phagocytes
 Type of WBC

 Releases several types of cytokines

  • “Cell movers” that promote and regulate immunity
     • Interleukines
     • Interferons
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!
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
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
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
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
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
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
Lymph Capillaries Collect Fluid and
Direct It through Lymph Nodes
Lymph
 Lymph fluid returns to blood via large lymph
  vessels that drain into veins in the lower neck
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
Take Home
• What are the functions of the
  lymphatic system?
Surface Barriers

Pathogens usually cannot get
past the skin or the linings of
other body surfaces such as
      the digestive tract
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
Vaginal Yeast Infection




http://yeastinfectionnomore.atarh.com/
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
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
The Mighty Macrophage!
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
Inflammatory Response
 Inflammatory response
  • Destroys invaders and helps repair and restore
    damaged tissue
  • Four signs
     •   Redness
     •   Heat
     •   Swelling
     •   Pain
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
Inflammatory Response
 Heat
  • Temperature rises as a result of increased blood
    flow
  • Speeds healing and activities of
    defensive cells
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
Inflammatory Response
 Swelling
  • Histamine causes capillaries to become leaky
    and fluid seeps into tissues
     • Fluid brings clotting factors, oxygen,
       and nutrients
Inflammatory Response
 Pain
  • Can be caused by
     • Excess fluid
     • Bacterial toxins
     • Prostaglandins
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 
Acute Inflammation Is a General
Response to Tissue Damage




    Histamines ↑
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
Adaptive Immunity
Overview of Adaptive Defenses
 When physical barriers and inflammation don’t
  prevent an invasion, the adaptive immune
  system is mobilized
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
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
Activated Lymphocytes Produce Effector
Cells and Memory Cells
Antibody-Mediated Responses
            and
  Cell-Mediated Responses
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
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
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
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
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
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
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
B and T Cells
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
How Do B & T Cells Learn?
 They study hard!
  • Study groups
  • Biojeopardy learning games


 Involves MHC markers
        • Major histocompatability complex genes
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
Antibody-Mediated Immunity: Defending
against Threats Outside Cells
 Different kinds of antibodies have roles in body
  defenses

 5 classes of antibodies
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’
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
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
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
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
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
T Cells Are the Warriors in Cell-Mediated
Immune Responses
T cell (orange) killing a cancer cell
(magenta).
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
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.
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
Immunological Memory
 The memory cells produced during an adaptive
  immune response can provide many years of
  immunity to a pathogen
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
Memory Cells Allow the Body to Mount a
Faster, Stronger Immune Response
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
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
Passive Immunity to Infectious Disease
1955
 http://www.youtube.com/watch?v=9Bm2fnCTaMg
WHO: Prevent. Protect. Immunize.
 http://www.youtube.com/watch?v=sGKrs1ED_rw
Disorders of the Immune System
 In allergies, harmless substances provoke an
  immune attack
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
The Basic Steps Leading to an Allergic
Response


                    Role of IgE antibodies
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
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??
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
HIV and AIDS
 HIV, the human immunodeficiency virus, cripples
  the immune system by destroying lymphocytes
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
Particles bursting the cell membrane
HIV Life Cycle
 http://www.youtube.com/watch?v=9leO28ydyfU
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
Many Infections Are Spread by Contact
or When a Pathogen Is Inhaled
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
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?
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
The Human Body’s Three Lines of Defense against
Pathogens
Introduction to how the immune system
works | Biology | Anatomy | Immunology
 http://www.youtube.com/watch?v=IWMJIMzsEMg
Cell Mediated Immune Response
 http://www.youtube.com/watch?v=1tBOmG0QMbA
Antibody Mediated Immune Response
 http://www.youtube.com/watch?v=hQmaPwP0KRI

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Ch11 or 13 body defenses & lymphatic system

  • 1. Immunity and Disease The Lymphatic System
  • 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
  • 19. Lymph Capillaries Collect Fluid and Direct It through Lymph Nodes
  • 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
  • 22. Take Home • What are the functions of the lymphatic system?
  • 23. Surface Barriers Pathogens usually cannot get past the skin or the linings of other body surfaces such as the digestive tract
  • 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
  • 36. Inflammatory Response  Pain • Can be caused by • Excess fluid • Bacterial toxins • Prostaglandins
  • 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 
  • 38. Acute Inflammation Is a General Response to Tissue Damage Histamines ↑
  • 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
  • 44. Activated Lymphocytes Produce Effector Cells and Memory Cells
  • 45. Antibody-Mediated Responses and Cell-Mediated Responses
  • 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
  • 55.
  • 56.
  • 57. B and T Cells
  • 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
  • 61.
  • 62. Antibody-Mediated Immunity: Defending against Threats Outside Cells  Different kinds of antibodies have roles in body defenses  5 classes of antibodies
  • 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
  • 70. T cell (orange) killing a cancer cell (magenta).
  • 71.
  • 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
  • 77. Memory Cells Allow the Body to Mount a Faster, Stronger Immune Response
  • 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
  • 81. WHO: Prevent. Protect. Immunize.  http://www.youtube.com/watch?v=sGKrs1ED_rw
  • 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
  • 90. Particles bursting the cell membrane
  • 91. HIV Life Cycle  http://www.youtube.com/watch?v=9leO28ydyfU
  • 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
  • 93.
  • 94. Many Infections Are Spread by Contact or When a Pathogen Is Inhaled
  • 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
  • 98. The Human Body’s Three Lines of Defense against Pathogens
  • 99. Introduction to how the immune system works | Biology | Anatomy | Immunology  http://www.youtube.com/watch?v=IWMJIMzsEMg
  • 100. Cell Mediated Immune Response  http://www.youtube.com/watch?v=1tBOmG0QMbA
  • 101. Antibody Mediated Immune Response  http://www.youtube.com/watch?v=hQmaPwP0KRI

Editor's Notes

  1. 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.
  2. 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.
  3. 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.