IMMUNITY: A SUMMARY Chapter 39 AP Biology Spring 2011.

IMMUNITY: A SUMMARY

Chapter 39

AP BiologySpring 2011

Integrated Responses To Threats

Immunity: body’s capacity to resist and combat infection, began when multicelled eukaryotic species evolved from free-living cells


Mutations introduced molecular patterns in membrane proteins that were unique to cells of a given type

Mutations led to mechanisms of identifying those proteins as belonging self- one’s own body

And ability to identify nonself


Antigen: any molecule that the body recognizes as nonself that revokes an immune response Most are proteins, lipids, and oligosaccharides

Pattern receptors: used to detect patterns that are present mainly on pathogenic cells Anything that became bound to hem induced an

animal cell to release complement (a set of about 30 proteins) which circulate in blood and destroy microbes or tag them for phagocytes


The microbial pattern receptors and complement offered innate immunity- fast, off-the-shelf responses to a fixed set of nonself cues Does not protect against novel or unrecognized

threats , adapting to them isn’t possible in an individual’s lifetime


Evolution of cytokines and lymphocytes Lymphocytes: specialized class of WBCTogether these signals and cells could tailor

defenses to an astounding array of specific threats that an individual encountered during its lifetime Adaptive immunity

Three Lines of Defense

1. Pathogens cannot do damage unless they can enter the internal environment

Intact skin and lining of body tubes and cavities Physical and chemical protection

2. Innate immunity Starts immediately after antigen has been detected

or after a tissue has become damaged WBC, complement, acute inflammation, and fever

3. Adaptive immunity Large populations of WBC form, all sensitized to a

specific threat

The Defenders

Leukocytes: all WBC that arise from stem cells in bone marrow

The Defenders

Many kinds Neutrophils: most abundant of WBC, fast acting

phagocytes Macrophages: slower, bigger eaters, can get rid of as

many as 100 bacterial cells Dendrite cells: alert immune system to the presence

of antigen

The Defenders

Many kinds: Basophils and Mast Cells: circulate in blood (basophils)

and tissues (mast cells) and release enzymes and cytokines in response to antigen or injury

Eosinophils: secrete enzymes and toxic proteins that are good at punching holes in larvae of parasitic worms

B and T Lymphocytes: are central to adaptive immunity Natural killer cells: innate immune response, also

participate in adaptive immunity, directly kill body cells that are infected, stressed, or mutated, as by cancerous transformations

Immunalogy

http://www.youtube.com/watch?v=T_4TrNRa3v8&feature=related

Watch the video Draw a diagram to separate innate and

adaptive immunity

Surface Barriers- The First Line of Defense

Your skin is teeming with about 200 different kinds of microbes

Skin is waterproof covering of dead, keratin packed epithelial cell layers

Normal skin resident populations of microbes have neutral or helpful impacts on health

Staphylococcus epidermidis , the most common species on skin and a leading cause of bacterial infections

Linings of Tubes and Cavities

Body has defenses that normally keep microbes outside on the surface of linings

Mucus: coating on free surface of epithelial linings Consists of glycoproteins (mucins) and salts in water Lysozyme: enzyme that cleaves peptidoglycans in

bacterial cell walls and disrupts their structure Tears have lysozymes


Breathing in air: Mucus coated epithelial lining of airways Coughing expels many cells, lysozymes in mucus kill

others Lining has ciliated cells, cilia beat in synchrony at its

free surface, which sweeps the bacteria laden mucus to throat for disposal


In the mouth If microbes make it to the stomach, low pH kills most If make it to small intestine bile salts in intestinal

lumen usually kill them If make it to large intestine, must compete with 500 or

so established species and if they do displace the residents a flushing mechanism (diarrhea) usually gets rid of them


Urinary tract and vagina Lactic acid, byproduct of fermentation by

Lactobacillus Helps keep vaginal pH beyond range of tolerance for

most bacteria and fungi Flushing action of urination normally keeps most

pathogens from colonizing in urinary tract

Uneasy Balance

Must keep microbes outside bodySurface barriers are vulnerableWhen we become sick or weak with age,

changes in physiology may compromise them Examples:

Acne Plaque deposits, periodontitis

Innate Immune Response

Phagocytes: Macrophages arrive first: engulf and digest anything

other than undamaged body cells Their pattern receptors recognize and bind to

pathogen secreting cytokines which signal more macrophages and neutrophils


Complement Proteins: Also arrive first Bind to circulating microbes or to antigen being

displayed at phagocyte’s surface which causes a positive feedback mechanism

One bound molecule becomes activated then activates a few molecules of a different type of complement then activates some of a different type, etc.

Cascading reactions yield high concentrations of activated complement in localized tissue region


Activated complement proteins have many effects Chemotactic: attract phagocyte cells (phagocytes

follow gradients to site of damage, where complement is most concentrated)

Some bind to microbes: microbes coated with complements will get recognized and engulfed faster by phagocytes

Some assemble into attack complexes in cell wall or plasma membrane and promote bacterium’s lysis

Also function in adaptive immunity


Acute Inflammation: swift response from to tissue irritation or tissue damage Cytokines secretions from macrophages and activated

complement trigger this

Symptoms: redness, warmth, swelling, pain


Steps of acute inflammation Mast cells respond to complement cascades or to

antigen Secrete histamine and cytokines into interstitial fluid Histamine makes arterioles in tissue dilate increases

blood flow to the area (causes warmth and redness) Histamine makes blood capillaries in the tissue “leaky”

to plasma proteins that usually do not leave blood Causes endothelial cells of capillary wall to shrink, cells

pull further apart at clefts between them Plasma proteins and phagocytes slip out


Steps of acute inflammation continued Osmotic pressure in interstitial fluid rises, fluid

balance across the capillary wall shifts, localized edema (swelling)

Swollen tissue cause free nerve endings to give rise to sensations of pain; suppresses voluntary movements (allows for tissue repair)

Other plasma proteins leaking into interstitial fluid include clotting factors, macrophage secretions activate them


Fever: rise in body temperature above the normal set point on a built in thermostat in hypothalamus

Macrophages bring about fever as innate immune response Secrete pyrogenic cytokines which stimulates brain to

synthesize and release several kinds of prostaglandins Prostaglandins act in hypothalamus to raise thermostat

set point Fever of 39 degrees C, enhances immunity by increasing

enzyme activity and speeding metabolism (formation and action of phagocytes accelerates, so does tissue repair)

Also pop. Of many microbes grow slowly at high temp.s

Features of Adaptive Immunity

Four characteristics of vertebrate active immunity1. Self/nonself recognition 2. Specificity 3. Diversity 4. Memory


Self versus nonself recognition Every cell or virus has its own identity Human cells have markers: human leukocyte antigens

(HLA), also known as MHC markers (major histocompatibility complex)

T cells have TCRs: antigen receptors at their surface T cells normally do not target body cell that has bare

MHC markers, but will act against it if those markers have antigen bits attached


Specificity New B or T cell makes receptors for one kind of

antigen

Diversity: Refers to collection of antigen receptors on all B and T

cells is the body Potentially billions of different antigen receptors,

gives potential to counter billions of different threats


Memory Immune system’s capacity to “remember” antigen that

it vanquished First time lymphocytes recognize an antigen, takes a

few days to for their populations to form When the same antigen shows up again, system

makes faster, hightened response

First Step: The Antigen Alert

Recognition stimulates repeated mitotic cell divisions

Result is large populations of B and T cells, primed to recognize antigen


Macrophages, B cells, dendritic cells are antigen presenting cells and find antigens and present them to T cell (receptors recognize antigens)

First engulf anything bearing antigen, vesicles move into the cytoplasm

Vesicle fuses with lysomes, enzymes digest antigens

Some fragments bind to MHC markers Antigen-MHC complexes shuttled to plasma

membrane and are displayed


When a cell’s MHC markers become paired with antigen fragments, it becomes a call to arms

Odds are at least one T cell has receptors that can bind

Binds, becomes activated and secretes cytokines that induce divisions of B or T cells sensitive to same antigen

Effector cells: differentiated lymphocytes that act immediately against antigen

Memory cells: long lived B and T cells that develop during first exposure and set aside for future encounters

Two Arms of Adaptive Immunity

Antibody Mediated Immune Response Pathogens in blood or interstitial fluid intercepted by

phagocytes and B cells B cells execute most of this response T cells support

Two Arms of Adaptive Immunity

Cell mediated immune response Intracellular pathogens Vulnerable only for brief time when they slip out of

one cell and infect another This response does not acquire antibodies Starts after antigen becomes positioned at surface of

infected or altered body cells where phagocytes and cytotoxic T cells detect it

Intercepting and Clearing Out Antigens

After engulfing antigen, dendritic cells and macrophages enter a lymph node

In lymph node, both kinds of phagocytes alert the T cells to the threat

Free antigen in interstital fluid enters lymph vessels which deliver it to lymph nodes where it passes B cells, macrophages, and dendritic cells that can bind, process, and present it to T cells

Lymph nodes trap most antigen- some could circulate to blood! Spleen helps filter again!

Intercepting and Clearing Out Antigens

During infection: Antigen-presenting T cells become trapped briefly in

lymph nodes Swollen lymph nodes sign of illness and lymphocyte

activity Immune response subside once antigen is cleared

away

B Cells: The Antibodies

Antibodies: proteins synthesized only by B cells that encounter and bind antigen Many Y shaped Most circulate in blood and enter interstitial fluid

during inflammation Each acts spcifically against the antigen that

promoted its synthesis


Structure of Antibodies: Four polypeptide chains Two identical “light” ones Two identical “heavy” ones Each chain has constant region, forms molecules

backbone One end of each chain has variable region- domain for

one antigen


5 structural classes of antibodies called Immunoglobulins (Igs) IgG IgA IgM IgE IgD

B cell secretes them, circulate alone or in clumps


IgG 80% of all immunoglobulins in blood Induces complement cascades, neutralizes toxins Crosses placenta, protects fetus with mother’s

aquired immunities Secreted into early milk (colostrum)


IgA Main immunoglobulin in exocrine gland secretions Tears, saliva, milk In mucus of respiratory, digestive, and reproductive

tracts


IgE Induces inflammation after pathogen invasions Constant regions of its heavy chains become anchored

to mast cells, basophils, monocytes, or dendritic cells Makes these cells release histamines and cytokines Factor in allergic reactions and HIV infection


IgM First to be secreted in primary response and first

made by newborns Surface of each new B cell is covered with hundreds

of thousands of IgM or IgD antibodies, each of which recognizes the same antigen

Antibodies are B cell receptors, surface immunoglobulins that function as B cell’s antigen receptors

The Making of Antigen Receptors

B cells Before new B cell leaves bone marrow, already

synthesizing unique antigen receptors Constant region of each is positioned in lipid bilayer of

B cell’s plasma membrane Two variable arms project above it B cell will have 100,000 antigen receptors “naïve” B cell- has not yet met its antigen


T cells: Form inside bone marrow Do not mature until they take a tour through thymus

gland After exposure to thymic hormones, get receptors for

MHC proteins Also get TCR’s, unique antigen receptors by gene

splicing These recombination’s are random , some TCRs end

up recognizing MHC markers rather than antigen, many will not


To get a functional set of T cells Thymus cells produce small peptides that are derived

from a variety of the body’s proteins Peptides get attached to MHC markers, act as built in

quality controls to weed out “bad” TCRs Any T cell that binds too tightly to one of complexes,

has TCRs that recognize self peptide T cells that do not bind at all cannot recognize MHC

markers Both types die By the time naïve T cells leave the thymus, their

surface contains functional TCRs

The Antibody Mediated ResponseMain targets of antibody mediated response

are extracellular pathogens and toxins freely circulating in blood and interstitial fluid

Nick your finger, staphlococcus aureus invadesComplement in interstitial fluid latches on to

carbohydrates in their bacterial cell wall and activates cascading reactions

Complement coats bacteria Bacteria move through lymph vessels to lymph

node, where paraded past naïve B cells

The Antibody Mediated ResponseB cells bear immunoglobulins that bind to

peptidoglycan in bacterium’s cell wallBears complement receptors that bind to

complement that coats the invading cellThese 2 events provoke B cell to begin

receptor-mediated endocytosis Bacterium enters B cell, which is no longer

naïve, now activated

The Antibody Mediated ResponseMeanwhile, more S. aureus cells have been

secreting chemotactic factors into interstitial fluid around cut

Secretions attract phagocytes Dendritic cell engulfs some bacteria, then

migrates to the lymph nodeIt has digested the bacteria cell and displays

antigen fragments bound to MHC markers on its surface

The Antibody Mediated ResponseNaïve T cells travel through the lymph nodes

at all times, inspect dendritic cellsOne of T cells has TCRs that tightly bind to S.

aureus antigen-MCH complexes on dendritic cell

For the next 24h, two cells interactTranscription factors activated in T cellTwo cells disengage, T cell returns to

circulatory system

The Antibody Mediated ResponseTheory of clonal selectionS. aureus antigen “chose” that T cell because

it bears a receptor that can bind to it After T cell is activated, many descendents

form by mitotic cell divisionsThey are clones- one lineage of genetically

identical cells Differentiates into helper T cells, all with

identical TCRs specific for S. aureus antigen

The Antibody Mediated ResponseBack to the B cell in lymph nodes Fragments of S. aureus are bound to MHC

markers and displayed at the B cells surface Two cells latch on to each other and

exchange costimulatory signals Helper T cells secretes several interleukins-

cytokines that signal B cell to divide and differentiate

The Antibody Mediated ResponseWhen cells disengage, B cell divides, its

clonal descendents form huge populations, with identical receptors

Differentiate into effector and memory cells

The Antibody Mediated ResponseEffector cells work immediately in primary

immune response or against initial exposure to antigen

Instead of making membrane bound IgM as B cell receptors, they switch antibody classes

Start making and secreting IgG, IgA, or IgE instead

Each of secreted antibody molecules has same antigen specificity as original B cell receptor

The Antibody Mediated ResponseGreat numbers of antibody molecules specific

for S. aureus are now circulating through body

Bind bacterial cells remaining in blood stream and interstitial fluid

Prevent them from attaching to body tissues and also tag them for disposal for NK cells and complement

Neutralize toxic agents

THE CELL-MEDIATED RESPONSE

As long as virus, bacteria, fungi, and protists hide in host cell, antibody mediated response cannot be initiated

During acute inflammatory response, cell mediated defenses against these menacing threats get under way in interstitial fluid

Usually plasma membrane of infected body cell displays antigen- peptides of intracellular pathogen or self proteins that were altered by cancerous tranformation

THE CELL-MEDIATED RESPONSE Dendritic cells recognize, engulf, and digest

these antigens as bits of diseased or abnormal cells or their remains

Dendritic cells then travel to lymph nodes, where antigen-MCH complexes on their surface are presented to 2 different populations of naïve T cells

Both types are activated when their receptors bind to antigen-MCH complexes on the dendritic cells

Clonal decendents of one population differentiate into effector helper T cells, which secrete interleukins and other cytokines

These signal induce other type of T cell to divide and differentiate into cytotoxic T cells


Cytotoxic T cells circulate through body in blood and interstitial fluid

Bind to any cell bearing original antigen that is complexed with MHC markers

Inject it with perforin and proteases These toxins poke holes into cell and induce

it to die by apoptosis Cytotoxic T cells are body’s primary weapons

against infected body cells and tumors Also cause rejection of tissue and organ

implants


Cytokines secreted by some helper T cells enhance macrophage action

Stimulate these phagocytes to secrete more inflammatory mediators and toxins that help kill tumor cells and larger parasites

Helper T cell cytokines also stimulate cell divisions of NK cells


Natural killer cells attack cells that are tagged for destruction by antibodies

Also detect Stress markers on infected or cancerous

body cells Cell that has normal MCH markers is not

killed Cell with MCH markers that have been

altered will die NK cells and macrophages are crucial in

killing such cells; neither depends on presence of MCH markers

Defenses Enhanced or Compromised

Immunization: processes that may promote immunity

Active immunization: preparation that contains antigen (a vaccine) is administered orally or injected into body First injection elicits primary immune response Second one, booster, elicits secondary response Additional effector and memory cells form for lasting

protection


Vaccines can be made from Weakened or killed pathogens or inactivated bacterial

toxins Harmless viruses that have genes from other pathogens

inserted into their DNA or RNA

Passive Immunization Helps if hepatitis B, tetanus, rabies, have already started Based on injections of antibody purified from blood of a

person who already fought disease Antibodies do not activate body’s immune system,

memory cells do not form Protection ends when body disposes of injected antibody


Allergies: hypersensitivity to an allergen Exposure to harmless proteins that stimulates

immune response Allergen: any substance that is ordinarily harmless yet

provokes immune response Antihistamines or anti-inflammatory drugs relieve

symptoms as can desensitization programs (allergy shots)

Anaphylactic shock: life threatening response to allergen


Autoimmune Disorders When lymophocytes and antibody molecules fail to

discriminate between self and nonself Autoimmune response: misdirected attack against

one’s own tissues Ex. Rheumatoid arthritis, Graves disease, multiple

sclerosis


Deficient Immune Responses Loss of immune function can have lethal outcomes Primary deficiencies, present at birth, are outcomes

of mutant genes or abnormal developmental steps Ex. SCIDs, ADA

Secondary deficiencies are losses of immune function after exposure to some outside agent Ex. AIDS

IMMUNITY: A SUMMARY Chapter 39 AP Biology Spring 2011.

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