AP Biology
Cell Communication and
Homeostasis
AP Biology
Dynamic Homeostasis
What is (dynamic) homeostasis?
Homeostasis = The property of a system that regulates its internal environment to maintain stable, (relatively) constant conditions In living things, often terms “dynamic
homeostasis” - what do you figure this indicates?
Feedback Control Homeostasis is often
maintained through the use of feedback systems (or loops).
A feedback system uses the consequences of the process (too much or too little produced) to regulate the rate at which the process occurs Consists of a sensor, a
control center, and an effector pathway
Positive vs Negative
Feedback loops may be positive or negative Negative feedback mechanism:
Maintains homeostasis by returning a changing condition back to its stable target point Discussion: although there are negative
and positive operons, both types are a negative feedback mechanism - why?
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Generalized Negative Feedback Model
high
low
hormone 1
lowersbody condition
hormone 2
gland
specific body condition
raisesbody condition
gland
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Controlling Body Temperature
high
low
nerve signals
sweat
nerve signals
body temperature(37°C)
shiver
dilates surfaceblood vessels
constricts surfaceblood vessels
Nervous System Control Feedback
hypothalamus
hypothalamus
AP Biology
liver
pancreas
liver
Regulation of Blood Sugar
blood sugar level(90mg/100ml)
insulin
body cells takeup sugar
from blood
liver storesglycogen
reducesappetite
glucagon
pancreas
liver releasesglucose
triggershunger
high
low
FeedbackEndocrine System Control
islets of Langerhans beta islet cells
islets of Langerhansalpha islet cells
Positive vs Negative
Alterations in negative feedback mechanisms -> deleterious consequences
Discussion: People who are diabetic produce minimal insulin. What effect does this have on the blood sugar control feedback loop?
Positive vs Negative Positive feedback mechanism: Does
not maintain homeostasis; instead, amplifies responses and processes, moving the system further and further away from starting conditions. Example: labor in childbirth
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Generalized Positive Feedback Model
high
hormone 1
raisesbody condition
gland
specific body condition
Or…
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Generalized Positive Feedback Model
low
hormone 1
lowersbody condition
gland
specific body condition
Discussion Describe a positive feedback loop in the case of
asthma, taking into account variables such as: airway swelling/narrowing aiway irritation blood oxygen levels cortisol increasing heart & breathing rates lung oxygen content nervous system recognition of blood oxygen levels oxygen available to brain panic release of stress hormones such as cortisol
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Maintaining Homeostasis The activities and stability of cells,
organisms, and also whole populations, communities, ecosystems etc. are affected by both biotic and abiotic factors Discussion: Think back through the course!
Can you come up with a biotic and abiotic factor that affects cell activities? Organism? Population or community?
AND, how does the cell/organism/population maintain homeostasis when that biotic or abiotic variable changes?
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Cell Signaling
AP Biology
Cell Signaling Every feedback loop in an organism that we
discussed, positive or negative, has one thing in common: cell signaling.
In a multicellular (and even unicellular!) organism, recognizing and responding to changes, internal or external, necessitates cell-to-cell communication
Cells do this by generating, transmitting, and receiving chemical signals
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Cell SignalingSignals can be
stimulatory…
or inhibitory.
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Cell Signaling Cell signaling (sometimes just called
“signal transduction”) has three general stages: Reception Transduction Response
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Cell Signaling - Reception RECEPTION
Signaling begins with the recognition of a chemical messenger by a receptor protein embedded in the cell membrane Chemical messenger = a ligand
Different receptors “recognize” different ligands due to fit, in a one-to-one relationship (think enzymes!)
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Cell Signaling - Reception The ligand binding to the receptor
changes the receptor’s conformation (shape), which initiates the next step, transduction
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Cell Signaling - Transduction Signal transduction is the process
by which a signal is converted to a cellular response.
The utility of signal transduction is signal amplification: through a cascade of chemical reactions, a single recognized ligand will be able to trigger a proportionally larger response
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Signal Transduction The receptor protein was an integral protein that
spanned the membrane When it changes conformation, the part of it
exposed to the cytoplasm changes conformation too
It does something new now in the cytoplasm, such as… Serving as an enzyme Opening up a channel between cell interior and exterior
(like ion channels in neurons!) Release a polypeptide from itself into the cytoplasm
…which is the first in what will be a series of chemical reactions, using a variety of second messengers inside the cell.
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Signal Transduction The end result of the signal cascade
could be producing or destroying transcription factors, activating enzymes, cytoskeleton rearrangement… and often many related results from the same signal!
http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html
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Signal Transduction Signal transduction diagrams can
follow some slightly different conventions, but common ones are: A stimulates B A inhibits B Translocation/Relocation
B to C is a larger (amplified) response than A to B
A
A
A
B
B
B C
A
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Signal Transduction A and B subunits join to make C
A separates into subunits B and C
Multistep pathway from A to B with some steps not shown
B
B
B
A
A
A
C
C
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Discussion Consider this very simple diagram of a
signal cascade (bigger image on next slide), and answer: What’s happening? What is the ligand?
What are the second messengers? Does EGF trigger or inhibit gene regulation?
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Signal Transduction That example displayed a common signal
transduction method: a phosphorylation cascade A series of protein kinases adding a phosphate
group to the next protein in the sequence (protein kinase = acts like an enzyme activator using ATP)
Reception
Transduction
Response
mRNANUCLEUS
Gene
P
Activetranscriptionfactor
InactivetranscriptionfactorDNA
Phosphorylationcascade
CYTOPLASM
ReceptorGrowth factor
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Phosphorylation Cascade
AP Biology
Cell Signaling Specificity
Which receptors and secondary messengers a cell possesses determines which signals it will respond to, and how This is why a liver and a
heart cell will do two different things when activated by the same hormone, like epinephrin
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Short-Distance Signaling: Nervous System
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Discussion QUICK! NO NOTES!
What do you remember about how neurons signal each other??
AP Biology
Cells have voltage! Opposite charges on opposite sides of
cell membrane membrane is polarized
negative inside; positive outside charge gradient stored energy (like a battery)
+ + + + + + + ++ + + + + + +
+ + + + + + + ++ + + + + + +
– – – – – – – ––– – – – –
– – – – – – – ––– – – – –
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How does a nerve impulse travel? Stimulus: nerve is stimulated
reaches threshold potential open Na+ channels in cell membrane Na+ ions diffuse into cell
charges reverse at that point on neuron positive inside; negative outside cell becomes depolarized
– + + + + + + ++ + + + + + +
– + + + + + + ++ + + + + + +
+ – – – – – – –– – – – – – –
+ – – – – – – –– – – – – – –Na+
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Gate
+ –
+
+
channel closed
channel open
How does a nerve impulse travel? Wave: nerve impulse travels down neuron
change in charge opens next Na+ gates down the line “voltage-gated” channels
Na+ ions continue to diffuse into cell “wave” moves down neuron = action potential
– – + + + + + +– + + + + + +
– – + + + + + +– + + + + + +
+ + – – – – – –+ – – – – – –
+ + – – – – – –+ – – – – – –Na+
action potential
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How does a nerve impulse travel? Re-set: 2nd wave travels down neuron
K+ channels open K+ channels open up more slowly than Na+ channels
K+ ions diffuse out of cell charges reverse back at that point
negative inside; positive outside
+ – – + + + + +– – + + + + +
+ – – + + + + +– – + + + + +
– + + – – – – –+ + – – – – –
– + + – – – – –+ + – – – – –Na+
K+
action potential
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How does a nerve impulse travel? Combined waves travel down neuron
wave of opening ion channels moves down neuron signal moves in one direction
flow of K+ out of cell stops activation of Na+ channels in wrong direction
+ + – – + + + ++ – – + + + +
+ + – – + + + ++ – – + + + +
– – + + – – – –– + + – – – –
– – + + – – – –– + + – – – –Na+
action potential
K+
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Synapse
Impulse has to jump the synapse! junction between neurons has to jump quickly from one cell to next
What happens at the end of the axon?
How does the wave
jump the gap?
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axon terminal
synaptic vesicles
muscle cell (fiber)
neurotransmitteracetylcholine (ACh)receptor protein
Ca++
synapse
action potential
Chemical synapse Events at synapse
action potential depolarizes membrane
opens Ca++ channels neurotransmitter vesicles
fuse with membrane, release neurotransmitter to synapse diffusion
neurotransmitter binds with protein receptor Ligand-gated ion channels
open neurotransmitter
degraded or reabsorbed
We switched…from an electrical signal
to a chemical signal
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Nerve impulse in next neuron Post-synaptic neuron
triggers nerve impulse in next nerve cell Neurotransmitter = ligand opens ligand-gated ion channels Na+ diffuses into cell K+ diffuses out of cell
switch back to voltage-gated channel
– + + + + + + ++ + + + + + +
– + + + + + + ++ + + + + + +
+ – – – – – – –– – – – – – –
+ – – – – – – –– – – – – – –Na+
K+
K+K+
Na+ Na+
Na+
ion channel
binding site ACh
Here wego again!
AP Biology
Discussion How do neurons illustrate the basic principles
of signal transduction pathways?
“Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein. Different receptors recognize different ligands, which can be peptides, small chemicals, or proteins, in a one-to-one relationship. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal. Second messengers (hint: ions in this case) are often essential to the function of the cascade.”
AP Biology
Effects of Changes in Pathways Neurons illustrate what can happen when a
signaling pathway is tampered with!
SSRIs like Prozac and Zoloft block the channels that permit the presynaptic neuron to take the neurotransmitter serotonin back in.
Serotonin is used by neurons in the “happiness” pathways in the
brain. What’s the effect? Discuss using the terminology of cell
signaling.
AP Biology 2007-2008
Long-Distance Signaling:
Endocrine System
AP Biology
Why are hormones needed? chemical messages from one
body part to another communication needed to
coordinate whole body daily homeostasis & regulation of
large scale changes solute levels in blood
glucose, Ca++, salts, etc. metabolism growth development maturation reproduction
Regulation
growth hormones
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Regulation & Communication Animals rely on 2 systems for regulation
endocrine system system of ductless glands
secrete chemical signals directly into blood chemical travels to target tissue target cells have receptor proteins slow, long-lasting response
nervous system system of neurons
transmits “electrical” signal & release neurotransmitters to target tissue
fast, short-lasting response
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Nervous & Endocrine systems linked Hypothalamus = “master nerve control center”
nervous system receives information from nerves around body
about internal conditions releasing hormones: regulates release of hormones
from pituitary
Pituitary gland = “master gland” endocrine system secretes broad range
of “tropic” hormones regulating other glands in body
hypothalamus
pituitary
posterior
anterior
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How do hormones act on target cells Lipid-based hormones
hydrophobic & lipid-soluble diffuse across cell membrane & enter cells bind to receptor proteins in cytoplasm & nucleus bind to DNA as transcription factors
turn on genes
Protein-based hormones hydrophilic & not lipid soluble
can’t diffuse across cell membrane bind to receptor proteins in cell membrane trigger secondary messenger pathway activate internal cellular response
enzyme action, uptake or secretion of molecules…
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nucleus
target cell
DNAmRNA
protein
blood
proteincarrier
S
S
S
S
Action of lipid (steroid) hormones
binds to receptor protein
cytoplasm
becomes transcription factor
ex: secreted protein = growth factor (hair, bone, muscle, gametes)
2
4
6
cross cell membrane
1
steroid hormone
mRNA read by ribosome5
plasma membrane
protein secreted7
3
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Action of protein hormones
activatesenzyme
activatesenzyme
activates enzyme
ATP
produces an action
P1
2
3
cytoplasm
receptor protein
response
signal
secondarymessengersystem
signal-transduction pathway
acts as 2° messenger
target cell
plasma membrane
binds to receptor protein
proteinhormone
ATPactivatescytoplasmicsignal
cAMP
GTP
activatesG-protein
transduction
AP Biology
Effects of stress on a body
Spinal cord(cross section)
Nervesignals
Nervecell
Releasinghormone
Stress
Hypothalamus
Anterior pituitary
Blood vessel
ACTH
Adrenalgland
Kidney
adrenal medullasecretes epinephrine
& norepinephrineAdrenal cortexsecretesmineralocorticoids& glucocorticoids
(B) LONG-TERM STRESS RESPONSE(A) SHORT-TERM STRESS RESPONSE
Nerve cell
Effects of epinephrine and norepinephrine:
1. Glycogen broken down to glucose; increased blood glucose
2. Increased blood pressure3. Increased breathing rate4. Increased metabolic rate5. Change in blood flow patterns, leading
to increased alertness & decreased digestive & kidney activity
Effects of mineralocorticoids:
1. Retention of sodium ions & water by kidneys
2. Increased blood volume & blood pressure
Effects of glucocorticoids:
1. Proteins & fats broken down & converted to glucose, leading to increased blood glucose
2. Immune system suppressed
MEDULLA CORTEX
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adrenal gland
Ex: Action of epinephrine (adrenaline)
activatesprotein kinase-A
activatesglycogen phosphorylase
activates adenylyl cyclase
epinephrine
liver cell
releasedto blood
1
25
receptorproteinin cell membrane
cytoplasm
6glycogen
activatesphosphorylase kinase
GTP
cAMP
4
activatesG protein
ATP
glucose
activates GTP
3
signal
transduction
response7
GDP
http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html
AP Biology
Benefits of a 2° messenger system
Amplification!
signal
receptor proteinActivated adenylyl cyclase
amplification
amplification
amplification
amplification
GTP G protein
product
enzyme
protein kinase
cAMP
Not yetactivated
1
2
4
35
6
7
FAST response!
amplification
Cascade multiplier!
AP Biology 2007-2008
Cell-to-Cell Signaling:Immune System
lymphocytesattackingcancer cell
phagocytic leukocyte
lymphsystem
Fighting theEnemy Within!
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Why an immune system? Chemical defense against infections that disrupt
dynamic homeostasis! (Animals aren’t the only organisms with defenses but we’re focusing on us)
Attack from outside lots of organisms want you for lunch! among other advantages, like shelter & reproduction, 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?
Immune System
Immune defenses may be non-specific or specific Non-specific = broad, defends against
many kinds of attackers Specific = targets one kind or a small
number of attackers
Three lines of defense…
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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
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1st line: Non-specific External defense Barrier
skin
Traps mucous membranes, cilia,
hair, earwax
Elimination coughing, sneezing, urination, diarrhea
Unfavorable pH stomach acid, sweat, saliva, urine
Lysozyme enzyme digests bacterial cell walls tears, sweat
Lining of trachea: ciliated cells & mucus secreting cells
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2nd line: Non-specific defenses Patrolling cells & proteins
attack many pathogens, but don’t “remember” for next time leukocytes
phagocytic white blood cells macrophages, neutrophils, natural
killer cells
complement system proteins that destroy cells
inflammation increase in body temp. increase capillary permeability attract macrophages
fever
yeast
macrophage
bacteria
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Discussion What are the advantages of the non-
specific defenses?
What are the disadvantages?
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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
AP Biology“self” “foreign”
How are invaders recognized? Antigens
Peripheral proteins - what does that mean? 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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Specific Immune Response Two “pathways” of response Cell-mediated immunity
Call in specialist cells to target the pathogen!
Humoral immunity Use antibodies!
Cell-mediated and humoral pathways use a variety of white blood cells, or lymphocytes…
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Lymphocytes B cells
mature in bone marrow humoral response system produce antibodies
T cells mature in thymus cellular response system
attack invaded cells
Macrophages Generalist cells from the 2nd
line of defense that can also interact with B and T cells in this 3rd line of defense, as you’ll see!
bone marrow
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Cell-Mediated Immunity Step 1: A generalist
macrophage engulfs an invader, including its antigens
Step 2: The macrophage “presents” the invader’s antigens - basically, it pops them out of its own membrane! It becomes an antigen-
presenting cell
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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
infectedcell
T cell with antigen receptors
TH cellWANTED
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Cell-Mediated Immunity Step 3: An immature T-cell binds to the antigen-
presenting cell; the presented antigens signal the T-cell, trigger it to: Release recruitment signals that, through signal
transduction, cause other immune cells to seek out and target that same antigen
Mature and proliferate into helper T-cells and cytotoxic T-cells
This is cell-to-cell signaling!
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Helper T-Cells Signal cytotoxic T-cells and B-cells (humoral
immunity pathway, up next) to seek out and target that antigen Some become “memory T-cells,” which hang out
in the body, ready to immediately respond if that antigen ever returns!
http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__t-cell_dependent_antigens__quiz_1_.html
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Cytotoxic 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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Humoral Response 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
Y
YY
YY
YY
Y
Y
YY
YY
YY
Y
Y
YY
YY
YY
Y
Y
YY
YYYY
Y
Y
Y
Y
Y
Y
Y
Y
YYY
Y
YY
Y Y
antigenantigen-binding site on antibody
variable binding region
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What do antibodies do to invaders?
macrophageeating tagged invaders
invading pathogens tagged with antibodiesY
Y
YY
YY
neutralize capture precipitate apoptosis
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Humoral Response Step 1: If triggered by a helper T-cell, B
cells, upon encountering the antigen, bind to the pathogen that bears it
Step 2: The bound B-cell proliferates into two new kinds of B cells…
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Humoral Respose Plasma B-Cells:
Produce antibodies against that antigen for a few days
Memory B-Cells: Long-lived, will rapidly proliferate into
fresh plasma cells for an instant counter-offensive if the antigen is ever re-encountered
AP Biology
AP Biology
Humoral Response The first ever encounter with the
pathogen = primary response (or primary immunity), moderately effective
Re-encounter in the future = secondary response. Immediate, powerful, decisive!
Copyright © 2006 Pearson Education, Inc., publishing as Benjamin Cummings
Discussion
Figure 12.19
http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__the_immune_response.html
Use the conventions of cell signaling diagrams that we learned to construct a flowchart of specific immunity
events! Include both humoral and cell-mediated immunity in the same diagram.
AP Biology
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
YYY
Y
YY
Y
YantibodiesY Y Y
skinskin pathogen invasionantigen exposure
YY
Y
Y
YY
Y
YantibodiesY Y Y
alert alert
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Vaccinations Immune system exposed
to harmless version of pathogen stimulates B cell system to produce
antibodies to pathogen rapid response on future exposure creates immunity
without getting disease!
Most successful against viruses
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Human Immunodeficiency Virus virus infects helper T cells
AIDS: Acquired ImmunoDeficiency Syndrome AIDS itself doesn’t kill HIV-positive patients.
Discussion: If AIDS doesn’t kill HIV-positive patients, what does? What is the specific effect of infected T-cells? How does this alter cell-mediated immunity? Humoral immunity?
HIV & AIDS
AP Biology 2007-2008
Cell Signaling: Wrap-Up
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Evolution of Homeostasis & Signaling Continuity of homeostatic mechanisms is a
means of studying shared ancestry A homeostatic mechanism can be thought of as
a “structure,” like an organ or a limb - it can show homology, analogy, vestigiality…
Changes to homeostatic mechanisms may occur in response to changes in environmental conditions Just like changes to a physical body structure!
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Evolution of Homeostasis
For example, the control of blood osmolarity has been basically the same from flatworms through vertebrates Excretory demands haven’t changed
much, so neither has the control mechanism:
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osmoreceptors inhypothalamus
nephron
nephron
Blood Osmolarity
blood osmolarityblood pressure
ADH
increasedwater
reabsorption
increasethirst
renin
increasedwater & saltreabsorption
high
FeedbackEndocrine System Control
pituitary
angiotensinogenangiotensin
adrenalgland
aldosterone
JuxtaGlomerularApparatus
nephron(JGA)
low
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Evolution of Homeostasis On the other hand, when environmental
demands change, so does the homeostatic mechanism that responds to them!
Consider control of blood oxygen. Water is liquid, low oxygen. Air is non-
liquid (and drying), high oxygen. So…
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Discussion What parts of fish,
amphibian, and mammal control of blood oxygen are homologous? What are the differences?
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Evolution of Homeostasis & Signaling
Correct and appropriate signaling mechanisms are under strong selective pressure A single simple change to a single
protein in a signaling pathway can have a massive effect, for better or for worse!
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Signaling in Prokaryotes Signaling isn’t just for the multicellular! Prokaryotes signal to each other in quorum
sensing Example: Signals passed between neighboring
bacteria trigger the expression of genes for forming attachment surface proteins And the more bacteria you’re surrounded by, the
more and more of that signal you’re getting Discussion: What’s advantageous about that?