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