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
Fig. 9-2, p. 158
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
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
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
Bone Marrow Marrow in some bones is production site for infection-fighting blood cells (as well as red blood cells and platelets)
Stepped Art
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 cellsand 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 105F or 40.6C) 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 cells1. 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
Fig. 9-12, p. 164
binding site for antigen binding site for antigen
antigen on bacterial cell (not to scale)
binding site on one kind of antibody molecule for a specific antigen
Stepped Art
Typical Y-shape of simple antibody
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?
Fig. 9-25a, p. 175
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
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