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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
Integrated Responses To Threats
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
Integrated Responses To Threats
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
Integrated Responses To Threats
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
Integrated Responses To Threats
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
Linings of Tubes and Cavities
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
Linings of Tubes and Cavities
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
Linings of Tubes and Cavities
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
Innate Immune Response
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
Innate Immune Response
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
Innate Immune Response
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
Innate Immune Response
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
Innate Immune Response
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
Innate Immune Response
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
Features of Adaptive Immunity
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
Features of Adaptive Immunity
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
Features of Adaptive Immunity
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
First Step: The Antigen Alert
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
First Step: The Antigen Alert
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
B Cells: The Antibodies
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
B Cells: The Antibodies
5 structural classes of antibodies called Immunoglobulins (Igs) IgG IgA IgM IgE IgD
B cell secretes them, circulate alone or in clumps
B Cells: The Antibodies
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)
B Cells: The Antibodies
IgA Main immunoglobulin in exocrine gland secretions Tears, saliva, milk In mucus of respiratory, digestive, and reproductive
tracts
B Cells: The Antibodies
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
B Cells: The Antibodies
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
B Cells: The Antibodies
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
B Cells: The Antibodies
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
THE CELL-MEDIATED RESPONSE
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
THE CELL-MEDIATED RESPONSE
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
THE CELL-MEDIATED RESPONSE
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
Defenses Enhanced or Compromised
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
Defenses Enhanced or Compromised
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
Defenses Enhanced or Compromised
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
Defenses Enhanced or Compromised
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