AP Biology 2007-2008

Immune / LymphaticSystem

lymphocytesattackingcancer cell

phagocytic leukocyte

lymphsystem

Fighting theEnemy Within!

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Avenues of attack Points of entry

digestive system respiratory system urogenital tract break in skin

Routes of attack circulatory system lymph system

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Why an immune system? Attack from outside

lots of organisms want you for lunch! animals are a tasty nutrient- & vitamin-packed meal

cells are packages of macromolecules animals must defend themselves against invaders (pathogens)

viruses HIV, flu, cold, measles, chicken pox

bacteria pneumonia, meningitis, tuberculosis

Lyme disease fungi

yeast (“Athlete’s foot”…) protists

amoeba, malaria Attack from inside

cancers = abnormal body cells

Mmmmm,What’s in your

lunchbox?

Nonspecific vs. Specific Defenses Three cooperative lines of defense have

evolved to counter threats posed by bacteria and viruses.

Two of these are nonspecific - that is, they do not distinguish one infectious agent from another.

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Lines of defense 1st line: Non-specific barriers

broad, external defense “walls & moats”

skin & mucous membranes 2nd line: Non-specific patrols

broad, internal defense “patrolling soldiers”

leukocytes = phagocytic WBC 3rd line: True immune system

specific, acquired immunity “elite trained units”

lymphocytes & antibodies B cells & T cells

Bacteria & insectsinherit resistance.

Vertebratesacquire immunity.

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1st line: Non-specific barriers Mechanical Barriers that physically

block pathogens from entering the body. The skin is the most important mechanical barrier.

It is the single most important defense the body has.

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1st line: Non-specific barriers Chemical Barriers destroy pathogens on

the outer body surface, at body openings, and on inner body linings. Sweat, mucus, tears, and saliva all contain enzymes that kill pathogens. Urine is too acidic for many pathogens, and semen contains zinc, which most pathogens cannot tolerate.

In addition, stomach acid kills pathogens that enter the GI tract in food or water

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1st line: Non-specific barriers Biological Barriers are living organisms

that help protect the body. Millions of harmless bacteria live on the human skin. Many more live in the GI tract. The harmless bacteria use up food and space so harmful bacteria cannot grow.

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1st line: Non-specific External defense

Barrierskin

Trapsmucous membranes, cilia,hair,

earwax

Lining of trachea: ciliated cells & mucus secreting cells

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1st line: Non-specific External defense Elimination

coughing, sneezing, urination, diarrhea Unfavorable pH

stomach acid, sweat, saliva, urine Lysozyme enzyme

digests bacterial cell walls tears, sweat

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2nd line: Non-specific patrolling cells Patrolling cells

attack pathogens, but don’t “remember” for next time leukocytes

phagocytic white blood cells macrophages, neutrophils,

natural killer cells

Phagocyte & yeast

macrophage

bacteria

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2nd line: Non-specific patrolling cells Proteins

complement system proteins that destroy cells

inflammatory response increase in body temp. increase capillary permeability attract macrophages

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Leukocytes: Phagocytic WBCs Attracted by chemical signals released by

damaged cells ingest pathogens digest in lysosomes

Neutrophils most abundant WBC (~70%) ~ 3 day lifespan

Macrophages “big eater”, long-lived

Natural Killer Cells destroy virus-infected cells

& cancer cells

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Natural Killer Cells perforate cells release perforin protein insert into membrane of target cell forms pore allowing fluid to

flow in & out of cell cell ruptures (lysis)

apoptosis

Destroying cells gone bad!

perforin puncturescell membrane

cell membrane

natural killer cell

cell membrane

virus-infected cell

vesicle

perforin

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Anti-microbial proteins Complement system

~20 proteins circulating in blood plasma attack bacterial & fungal cells

form a membrane attack complex perforate target cell apoptosis

cell lysis

plasma membrane of invading microbe

complement proteinsform cellular lesion

extracellular fluid

complement proteins

bacterial cell

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Inflammatory response Damage to tissue triggers

local non-specific inflammatory response release chemical signals

histamines & prostaglandins capillaries dilate, become

more permeable (leaky) delivers macrophages, RBCs,

platelets, clotting factors fight pathogens clot formation

increases temperature decrease bacterial growth stimulates phagocytosis speeds up repair of tissues

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Fever When a local response is not enough

system-wide response to infection activated macrophages release interleukin-1

triggers hypothalamus in brain to readjust body thermostat to raise body temperature

higher temperature helps defense inhibits bacterial growth stimulates phagocytosis speeds up repair of tissues causes liver & spleen to store

iron, reducing blood iron levels bacteria need large amounts

of iron to grow

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Specific defense with memory lymphocytes

B cells T cells

antibodies immunoglobulins

Responds to… antigens

cellular name tags specific pathogens specific toxins abnormal body cells (cancer)

3rd line: Acquired (active) ImmunityB cell

Specific Defenses: The 3rd Line of Defense While microorganisms are under assault by

phagocytic cells, the inflammatory response, and antimicrobial proteins, they inevitably encounter lymphocytes, the key cells of the immune system.

Lymphocytes generate efficient and selective immune responses that work throughout the body to eliminate particular invaders: This includes pathogens, transplanted cells,

and even cancer cells, which they detect as foreign.

Humoral and Cell-Mediated Immunity The immune system can mount two types of

responses to antigens: a humoral response and a cell-mediated response. Humoral immunity involves B cell activation and

results from the production of antibodies that circulate in the blood plasma and lymph. Circulating antibodies defend mainly against free bacteria,

toxins, and viruses in the body fluids. In cell-mediated immunity, T lymphocytes attack

viruses and bacteria within infected cells and defend against fungi, protozoa, and parasitic worms. They also attack “nonself” cancer and transplant cells.

The humoral and cell-mediated immune responses are linked by cell-signaling interactions, especially via helper T cells.

B’s and T’s The vertebrate body is populated by two

main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells).

They are said to display specificity. A foreign molecule that elicits a specific

response by lymphocytes is called an antigen: Including molecules belonging to

viruses, bacteria, fungi, protozoa, parasitic worms, and nonpathogens like pollen and transplanted tissue or organs.

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Lymphocytes B cells

mature in bone marrow humoral response system

“humors” = body fluids attack pathogens still circulating

in blood & lymph produce antibodies

T cells mature in thymus cellular response system

attack invaded cells

“Maturation” learn to distinguish “self”

from “non-self” antigens if react to “self” antigens, cells

are destroyed during maturation

bone marrow

AP Biology“self” “foreign”

How are invaders recognized? Antigens

cellular name tag proteins “self” antigens

no response from WBCs “foreign” antigens

response from WBCs pathogens: viruses, bacteria, protozoa, parasitic worms,

fungi, toxins non-pathogens: cancer cells, transplanted tissue, pollen

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B cells Attack, learn & remember pathogens

circulating in blood & lymph Produce specific antibodies

against specific antigen Types of B cells

plasma cells immediate production of antibodies rapid response, short term release

memory cells continued circulation in body long term immunity

Antibodies One way that an antigen elicits an immune response

is by activating B cells to secrete proteins called antibodies.

This structure of a lymphocyte’s receptors is determined by genetic events that occur during its early development. As unspecialized cells differentiate into a B or T

lymphocyte, segments of antibody genes are linked together by a type of genetic recombination in the DNA, generating a single functional gene for each polypeptide of an antibody or receptor protein.

This process occurs before any contact with foreign antigens and creates an enormous variety of B and T cells in the body, each bearing antigen receptors of particular specificity.

This allows the immune system to respond to millions of antigens.

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Antibodies Proteins that bind to a specific antigen

multi-chain proteins binding region matches molecular shape of antigens each antibody is unique & specific

millions of antibodies respond to millions of foreign antigens

tagging “handcuffs” “this is foreign…gotcha!”

each B cell has ~50,000

antibodies

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antigenantigen-binding site on antibody

variable binding region

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sss

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Structure of antibodies

lightchain

B cellmembrane

heavychains

lightchain

variable region

antigen-binding site

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What do antibodies do to invaders?

macrophageeating tagged invaders

invading pathogens tagged with antibodiesY

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First Exposure to antigen: The selective proliferation and differentiation of

lymphocytes that occur the first time the body is exposed to an antigen is the primary immune response. About 10 to 17 days are required from the initial

exposure for the maximum effector cell response.

During this period, selected B cells and T cells generate antibody-producing effector B cells, called plasma cells.

While this response is developing, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and plasma cells clear the antigen from the body.

Secondary Response A second exposure to the same antigen at

some later time elicits the secondary immune response. This response is faster (only 2 to 7 days), of

greater magnitude, and more prolonged. In addition, the antibodies produced in the

secondary response tend to have greater affinity for the antigen than those secreted in the primary response.

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macrophage

plasma cellsrelease antibodies

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B cell immune responsetested by

B cells(in blood & lymph)

10 to 17 days for full response

invader(foreign antigen) B cells + antibodies

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recognition

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clones1000s of clone cellsY

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“reserves”

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Ycapturedinvaders

Active Immunity Immunity conferred by recovering from an

infectious disease such as chicken pox is called active immunity because it depends on the response of the infected person’s own immune system. Active immunity can be acquired naturally or

artificially, by immunization, also known as vaccination.

Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but weakened microbes.

These no longer cause disease, but they can act as antigens, stimulating an immune response, and more important, immunological memory.

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Vaccinations Immune system exposed

to harmless version of pathogen stimulates B cell system to produce

antibodies to pathogen “active immunity”

rapid response on future exposure creates immunity

without getting disease!

Most successful against viruses

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Polio epidemics

1994: Americas polio free

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Obtaining antibodies from another individual maternal immunity

antibodies pass from mother to baby across placenta or in mother’s milk

critical role of breastfeeding in infant health mother is creating antibodies against pathogens baby

is being exposed to

Injection injection of antibodies short-term immunity

Passive immunity

AP Biology 2007-2008

What if the attacker gets past the B cells in the blood & actually infects (hides in) some of your cells?

You need trained assassins to recognize & kill off these infected cells!

T

Attackof the

Killer T cells!

But how do T cellsknow someone ishiding in there?

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How is any cell tagged with antigens? Major histocompatibility (MHC) proteins

proteins which constantly carry bits of cellular material from the cytosol to the cell surface

“snapshot” of what is going on inside cell give the surface of cells a unique label or

“fingerprint”

T or Bcell

MHC protein

MHC proteinsdisplaying self-antigens

Who goes there?self or foreign?

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How do T cells know a cell is infected? Infected cells digest some pathogens

MHC proteins carry pieces to cell surface foreign antigens now on cell membrane called Antigen Presenting Cell (APC)

macrophages can also serve as APC tested by Helper T cells

MHC proteins displaying foreign antigens

infected

cell

T cell with antigen receptors

TH cellWANTED

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T cells Attack, learn & remember pathogens hiding

in infected cells recognize antigen fragments also defend against “non-self” body cells

cancer & transplant cells Types of T cells

helper T cells alerts rest of immune system

killer (cytotoxic) T cells attack infected body cells

memory T cells long term immunity

T cell attacking cancer cell

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T cell response

stimulateB cells &

antibodies

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killerT cell

activatekiller T cells

or

interleukin 1

interleukin 2

interleukin 2

helperT cell

helperT cell

helperT cell

helperT cell

helperT cell

recognition

clones

recognition

APC:activatedmacrophage

APC:infected cell

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Attack of the Killer T cells

Killer T cellbinds toinfected

cell

Destroys infected body cells binds to target cell secretes perforin protein

punctures cell membrane of infected cell apoptosis

infected celldestroyed

cell membrane

Killer T cell

cell membrane

target cell

vesicle

perforin puncturescell membrane

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Immune response

free antigens in blood antigens on infected cells

humoral response cellular response

B cells T cells

macrophages(APC)

helperT cells

plasmaB cells

memoryB cells

memoryT cells

cytotoxicT cells

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skinskin pathogen invasionantigen exposure

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alert alert

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Human Immunodeficiency Virus virus infects helper T cells

helper T cells don’t activate rest of immune system: killer T cells & B cells

also destroys helper T cells AIDS: Acquired ImmunoDeficiency Syndrome

infections by opportunistic diseases

death usually from “opportunistic” infections

pneumonia, cancers

HIV & AIDS

HIV infected T cell

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AIDSThe HIV virus fools helper T-cells

into thinking its proteins are “self,” and so is able to infect the

cells that trigger specific immunity.

The virus forces T-cells to make more viruses, killing the T-cells when the new viruses burst

out.

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NATURAL COURSE OF HIV/AIDS

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Stage 1 - Primary Short, flu-like

illness - occurs one to six weeks after infection

Mild symptoms Infected person

can infect other people

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Stage 2 - Asymptomatic

Lasts for an average of ten years This stage is free from symptoms There may be swollen glands The level of HIV in the blood drops to

low levels HIV antibodies are detectable in the

blood

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Stage 3 - Symptomatic

The immune system deteriorates Opportunistic infections and cancers

start to appear.

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Stage 4 - HIV AIDS

The immune system weakens too much as CD4 cells decrease in number.

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Opportunistic Infections associated with AIDSCD4<500 Bacterial infections Tuberculosis (TB) Herpes Simplex Herpes Zoster Vaginal candidiasis Hairy leukoplakia Kaposi’s sarcoma

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Opportunistic Infections associated with AIDSCD4<200 Pneumocystic carinii Toxoplasmosis Cryptococcosis Coccidiodomycosis Cryptosporiosis Non hodgkin’s

lymphoma

HEALTH CARE FOLLOW UP OF HIV INFECTED PATIENTSFor all HIV-infected individuals:     CD4 counts every 3–6 months    Viral load tests every 3–6 months and 1 month following a change in

therapy    PPD    INH for those with positive PPD and normal chest radiograph    RPR or VDRL for syphilis   Toxoplasma IgG serology    CMV IgG serology    Pneumococcal vaccine    Influenza vaccine in season    Hepatitis B vaccine for those who are HBsAb-negative    Haemophilus influenzae type b vaccination     Papanicolaou smears every 6 months for women

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AIDS Prevention HIV is a fragile virus that cannot live

outside the human body for more than a few minutes.

Preventing HIV spread comes down to preventing exposure to body fluids of an infected person.

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How to protect yourself…

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Helping the immune system

Medical science has created to systems for augmenting the human immune system: Antibiotics (NOT the

same as antibodies) Vaccines

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How antibiotics work

Antibiotics help destroy bacteria (but not viruses).

Antibiotics work in one of several ways: Slowing bacteria

reproduction. Interfering with bacterial

cell wall formation.

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Antibiotic myths

Antibiotics are not antibodies. Antibiotics do not weaken our immune

system. They help it by weakening bacteria.

Humans do not become “immune” to antibiotics.

Bacteria that resist antibiotics and are not completely destroyed may multiply, producing more antibiotic-resistant bacteria.

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Immune system malfunctions Auto-immune diseases

immune system attacks own molecules & cells lupus

antibodies against many molecules released by normal breakdown of cells

rheumatoid arthritis antibodies causing damage to cartilage & bone

diabetes beta-islet cells of pancreas attacked & destroyed

multiple sclerosis T cells attack myelin sheath of brain & spinal cord nerves

Allergies over-reaction to environmental antigens

allergens = proteins on pollen, dust mites, in animal saliva

stimulates release of histamine

AP Biology 2009-2010

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