UNIT 5 NOTES
I.
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Communication Between Unicellular Organisms
Unicellular organisms gather information about their environment and respond to it
appropriately by using signaling pathways -- part of a complex system of communication that
governs basic cellular activities and coordinates cell actions. The basis of this communication is
releasing and accepting chemicals that trigger a set of actions inside the cell.
Cell communication in single celled organisms can be used
o To relay information about food sources
o Initiate sexual reproduction
o Sense the number and type of cells nearby (quorum sensing)
o Sense the location of favorable environment
o Communicate other information between organisms
Example: Bacterial quorum sensing – Vibrio Harvey a marine bacterium emits light only if there
is a high concentration of this bacterium present in the environment. The bacteria can do this
by releasing a signal molecule. This signal molecule floats away in low concentration. However,
in high concentration, it attaches to the membrane receptors of surrounding bacteria. The
receptor activates genes to become active. The genes stimulate the production of proteins that
will create bioluminescence.
The discovery of this process:
http://media.hhmi.org/biointeractive/click/Quorum_Sensing/01.html
So the main components of the signal transduction pathway of this bacteria are: Signal molecule
– receptor – gene action – active proteins – bioluminescence
These processes are the main source of communication in multicellular organisms as well. Out
nervous, endocrine and immune systems are all dependent on communication. Development is
also based on it. There are thousands of processes in our body that follow the steps of cell
signaling.
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The basics of all cell communication:
o Reception – a signal molecule or ligand binds to a receptor
o Transduction – the intracellular part of the receptor activates a set of proteins and
other molecules (signal transduction molecules) to send the message to various parts of
the cell.
o Response – the signal transduction molecules initiate a cascade that can lead to many
different cellular actions such as turning genes on or off, stimulating protein formation
etc.
II.
Types of Signal Molecules
 Signal molecules or ligands are the molecules that come from the outside and binds with the
receptors of the cells.
 These signal molecules are organized according to distance that they travel to their target cells
(cells that have the proper receptors to take respond to the signal molecule):
o Autocrine signals – signal molecules that have receptors on the cell that released them
o Paracrine signals – the target cells with the appropriate receptors are near the cells that
actually released the signal
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Endocrine signals – hormones that are carried by the blood stream to distant cells to
generate responses in those cells.
Signal molecules can also be classified by their polarity:
o Polar signal molecules have receptors on the surface of the cell membrane
o Nonpolar signal molecules have receptors inside of the cell in the cytoplasm or in the
nucleus
III.
Types of Receptors
 A receptor on or in the target cell will be able to detect the signal molecule by matching
(complementary) shapes. So receptors are usually activated by molecules but may be activated
by heat or light as well (photoreceptors in plants).
 Ligand binding usually causes a receptor to undergo conformation (shape) change. This change
usually directly activates the receptor to interact with other molecules inside the cell. In some
instances receptor binding causes the aggregation of two or more receptors and causes further
cellular changes.
 Most receptors are protein molecules.
A. Intracellular (Nuclear or Cytoplasmic) Receptors
 Intracellular receptor proteins are found inside the cytoplasm or in the nucleus of the target
cells. The signal molecules (ligands) in these cases must be able to pass through the cell
membrane to reach the receptor. Signal molecules can do this by being hydrophobic or small to
cross the phospholipids bilayer. Examples of ligands that can pass through the cell membrane
include steroids, thyroid, nitric oxide (NO).
 The signal-receptor complex is able to regulate gene expression by acting as a transcription
factor that turns on specific genes. In cases of receptors that get into the nucleus, the receptor
and ligand complex can carry out the entire reception and transduction process
 Many of the intracellular receptor proteins have similar structures that suggest their common
evolutionary origin.
B. Receptors in The Plasma Membrane:
 Water-soluble signal molecules bind to receptor molecules on the surface of the plasma
membrane. These receptors have to change shape or aggregate to perform transduction.
 Three major types of membrane receptors and their function:
o G-protein-linked receptor: these receptors work with a G-protein (a group of proteins
that are able to bind with and activated by GTP). The G-protein has two important
binding sites. One site binds with the G protein-linked receptor, the other binds with
GDP in its inactive form and GTP, when the protein is activated. Many bacteria cause
diseases by producing toxins that intervene with G-protein function. These receptors
work the following way:
1. The G-protein acts as a molecular switch which is either on or off, depending on which
of the two guanine nucleotides is attached, GDP or GTP.
2. When a matching signal molecule binds to the receptor molecule, the receptor is
activated and changes shape. The change in shape activates the G-protein, so it
replaces its GDP with a GTP.
3. The activated G-protein dissociates from the receptor, moves to an enzyme and alters it.
When the enzyme is activated, it triggers a cellular response.
4. The G protein changes back to its inactive form and returns to the receptor molecule.
https://www.youtube.com/watch?v=xT0mAQ4726s
https://www.youtube.com/watch?v=ZBSo_GFN3qI
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Protein kinase receptors (receptor tyrosine kinase) – This group of receptors attach
ATP to tyrosine, an amino acid. These receptors, once they bind to two ligand
molecules, form a dimer. The dimer formation pulls ATP molecules to the intracellular
portion of the receptor and tyrosine molecules get phosphorylated. The
phosphorylation will result in activating other inactive proteins intracellularly and
generating a response. Good example of a protein kinase receptor is an insulin receptor
in the target cells of the liver and muscles. Abnormal receptor tyrosine kinases that
function in the absence of signal molecules can contribute to some kinds of cancer.
http://www.youtube.com/watch?v=-iBb1sH-Eh4
https://www.youtube.com/watch?v=J_vdVcuzi1U
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Ion channel receptors – a type of membrane receptors that can act as a gate when the
receptor changes shape. When the signal molecule binds to the receptor protein, the
gate opens or closes, allowing or blocking the transfer of specific ions such as Na+ or
Ca2+. Each type of ion channel receptor has its ligand molecule (signal molecule) or
another sensory signal such as light, sound, electric charge etc. (Ex. Acetylcholine
receptors in nerve and muscle cells. These receptors open up when acetylcholine binds
with them and allows Na+ ions to rush into the cell to generate a nerve signal or contract
a muscle).
https://www.youtube.com/watch?v=Mc0rRLlVi6w
IV.
Signal Transduction
 Signal transduction pathways are a set of biochemical reactions that take place after a receptor
is activated and results in a cell response.
 Once these receptors are activated, one receptor can stimulate a cascade of one or multiple
processes inside of the cell. These pathways can be highly complex.
 The signaling pathway usually involves proteins. These proteins may not be active until
activated by the receptor or they may be active until they are shut down by the activation of the
receptor. The most common method of activating proteins is phosphorylation by ATP or other
nucleotide triphosphates. The phosphate groups give two negative charges to the protein and
modify its shape. As a result, the protein’s function is also modified.
 After the protein performed its function, dephosphorylation modifies it back to its original
shape by removing the phosphate groups by hydrolysis.
 A large group of enzymes that perform phosphorylation of proteins are called kinases. They are
specific to the proteins that they phosphorylate. Different enzymes are responsible for
dephosphorylation. Phosphate groups can also be added to multiple sites on the protein so
various levels of phosphorylation are possible.
 Phosphorylation cascade occurs when numerous sequential proteins are phosphorylated and
dephosphorylated one after the other.
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Signal transduction pathways sometimes also require small, nonprotein molecules called second
messengers – these molecules mediate the signal from the receptor to the proteins. These
second messengers usually modify the activity of enzymes that they bind with.
Important second messengers:
o Cyclic AMP – An enzyme in the plasma membrane to convert ATP to cAMP in response
to an extracellular signal (ex. Epinephrine). When the signal molecule binds to a
receptor, the receptor activates this enzyme to form many molecules of cAMP. This
way one signal molecule can induce the synthesis of many cAMP molecules. The cAMP
molecule usually activates a protein kinase molecule to phosphorylate various proteins.
After this activation, the cAMP disintegrates. Many diseases are caused by toxins that
interact with the second messenger system (ex. Cholera)
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Ca2+ ions – Many signal molecules, including neurotransmitters, growth factors, some
hormones induce responses that increase the cytosolic concentration of calcium ions.
Increased calcium ion concentration can cause muscle contraction, secretion of certain
substances or cell division. This system can work because the normal Ca2+ ion
concentration in the cytosol is a lot lower than in the smooth ER or in the extracellular
matrix. A small change in the absolute concentration can result in a substantial change
in the cytosol. A good example of Ca2+ as a second messenger is when the sperm cell
unites with the egg, results in a massive release of Ca ions into the egg cytoplasm that
starts the various changes that leads to the development of the embryo.
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V.
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Nitric oxide (NO) – this very unstable gas that can act as a short term, short distance
second messenger that is usually activated by Ca ions. NO generally result in muscle
relaxation that is important when increased blood flow is required. (See our case study)
IP3 is another second messenger that causes the release of other second messengers,
like Ca2+.
Cellular Responses
A single activated receptor can produce an exponential response due to signal amplification -the binding of a signal molecule triggers successively larger responses along the transduction
pathway.
A signal molecule eventually can stimulate a pathway into the nucleus and turn genes on or off.
They can do this by using transcription factors -- proteins that regulate RNA transcription from
the DNA molecule. These transcription factors attach to the DNA at the promoter site (TATA
box). If the transcription factor is an activator, it will stimulate transcription, if it is a repressor,
it will prevent or slow transcription down. The transcription factors also get activated by
phosphorylation.
Signal molecules can also open ion channels and stimulate transport of ions into or out of the
cell (you will see this in nerve signaling). They can also facilitate cell movement or synthesis or
breakdown of various organic molecules.
THE ENDOCRINE SYSTEM
I. Connections of endocrine signals to other signaling mechanisms
 Endocrine signaling – endocrine cells release hormones that usually travel in the blood stream
to the target cells. The network of hormone-secreting glands forms the endocrine system.
 There is a hybrid of the nervous and endocrine system that combines and interacts with both
the nervous and endocrine systems. This interaction is called neuroendocrine signaling – this
pathway uses nerve cells that are located at the edge of blood vessels. They release
neurohormones directly into the blood stream.
 Neuroendocrine signaling makes the nervous and endocrine system an interconnected
regulatory system.
 Pheromones are a special group of signaling molecules that signal between organisms not
within the same organism. These signals are released from the organisms into the air or water
and can be used to communicate mating availability, food sources, danger or the borders of a
territory. Pheromones can be species specific or colony specific.
II. Transmission of hormone signals
 Hormones are long-distance signals that are released by endocrine cells and travel to the target
cells in animals through the blood stream.
 Hormones are used to alter existing cell functions, regulate homeostasis, enhance growth and
development and regulate metabolism.
 Lipid-soluble hormones can enter the target cell’s nuclei and directly regulate genes. These
hormones cannot travel in the blood stream on their own, they need polar transport proteins to
carry them.
 While water-soluble hormones are not able to enter the cell membrane and must bind to
membrane-receptors to initiate a cell signaling pathway. These hormones also need to be
released by exocytosis because they cannot exit the cell membrane either.
 The response to the hormone in the target cell depends on the type of receptors the hormones
have on or in the target cells. Different receptor-hormone complexes can bind to different
genes and initiate the production of different proteins. In the case of water-soluble hormones
the response also depends on the type of cell signaling pathway that is initiated. So the same
hormone can have different effects on different target cells.
III. The Chemical Structure and Function of Hormones
 Hormones are all organic molecules that can be classified chemically into three groups:
o Amines – small organic molecules that contain amino groups Ex. Epinephrine,
norepinephrine, thyroxine (T4), dopamine
o Peptides or proteins – peptide is any compound that contains two or more amino acids
combined by peptide bonds. Ex.: insulin, glucagon, oxytocin,
o Steroids – made up of sterols. Ex. Cortisol, testosterone, estrogen
 In general, amines and polypeptides are usually polar while sterols are nonpolar.
IV. The Interactions and Special Characteristics of the Nervous and Endocrine Systems
 There are major differences between the nervous and endocrine systems:
o The endocrine cells are not directly attached to the target cells that they regulate, so they
can regulate cells in multiple locations, far away from each other and from the endocrine
gland. However, nerve cells are directly attached to cells that they regulate.
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Because the hormones of the endocrine system travel in blood vessels to long distances, this
system generally is slower than neural signaling that carries the signal by electric impulses
within less than a second from one side of the nerve cell to the next.
o The endocrine system uses existing structures such as blood vessels for transmission while
nerve cells have their own structures called synapses to transmit signals.
There are also many overlapping areas between the two systems. For example, neurosecretory
cells are nerve cells that release hormones. These cells receive signals from both the nervous
and the endocrine systems and use those signals to release regulatory hormones. The
hypothalamus is one example where a part of the nervous system releases several different
hormones to directly control growth, development or child birth or to regulate other endocrine
organs.
V. Basic Components of a Hormone Signaling Pathway
 Hormones interact with the nervous system. We use our sensory organs for example to detect
changes in the environment. These changes will be received and processed by the nervous
system. For example to the hypothalamus. The hypothalamus can release hormones into the
blood stream while also release nerve signals into the body. Than when the target cells get the
signals from the hypothalamus and start their individual signal transduction pathways and
responses. This way the one organ can generate multiple responses in different types of cells.
 Example is the “fight or flight response”:
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Hormones also interact with other tissues of the body. A stimulus triggers endocrine cells to
release hormones. These hormones travel in the blood stream to the target cells. The target
cells with the right kind of receptors take in the hormone and generate a cell signaling pathway
in response. The response of the cell can change homeostasis, make the cell divide, change its
metabolism….
VI.
Hormones and Homeostasis
 Hormones actively participate in maintaining homeostasis by participating in positive or
negative feedback mechanisms. Their production can also be regulated by these feedback
mechanisms.
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An example of a negative feedback mechanism is the regulation of thyroid hormone production.
Thyroid hormones, T3 and T4 have an effect on most cells in the body by regulating important
processes such as metabolism, growth, development, heart rate, mental state, reproductive
functions and vasodilation. Thyroid hormone release is tightly regulated by the hypothalamus
by the following process:
o Stimulus, such as the drop of temperature is detected by nerve cells in the
hypothalamus.
o The neurosecretory cells of the hypothalamus release a stimulating hormone called
thyrotropin-releasing hormone (TRH), which travels to the anterior pituitary in the blood
stream.
o TRH stimulates the production of another stimulating hormone, called thyroidstimulating hormone (TSH).
o TSH travels in the blood stream into the thyroid gland and stimulates the production
and release of T3 and T4.
o T3 and T4 leave the thyroid gland and moves to the target cells in the blood stream.
There is a wide range of target cells with different receptors and very different
responses.
o Some of the thyroid hormones return to the hypothalamus and inhibit the production of
more TRH and TSH hormones. This is a negative feedback mechanism, which is
necessary to stop overproduction of all other hormones that are stimulated by TRH.
An example of positive feedback is observable during child birth with the effect of oxytocin
hormone:
o As labor progresses, the head of the fetus presses on the cervix. This pressure is a signal
to the nervous system that stimulates the hypothalamus.
o The hypothalamus produces and releases oxytocin into the pituitary gland.
o The pituitary gland may store this hormone, it starts to gradually release it into the
blood stream.
o Target cells in the uterus detect this hormone and start muscle contractions.
o These contractions push the fetus’s head even more to the cervix, so more hormone is
produced and released. This hormone also stimulates milk gland cells to produce and
release milk.
o Hormone levels return to low later, well after birth.
VII.
When Hormone Regulation Fails
 When hormone regulation fails, various disorders can occur. Some of them are debilitating or
even deadly.
 Example: The thyroid gland T3 and T4 production is too low (hypothyroidism), goiter forms from
the enlargement of the thyroid gland. This condition is more serious if the hypothyroidism
occurs in young age, short stunted growth, mental retardation can be the result. The
overproduction of the thyroid gland is hyperthyroidism, can result in a different kind of goiter,
very high metabolism, nervous temperament, high blood pressure, bulging eyes etc. Today,
both conditions can be treated with medication and diet (iodine containing salt).
You will receive a specific hormone or groups of hormones and you will need to determine where they
are released from, under what conditions, how they travel in the blood stream and how they change the
target cell. On the target cell, you will need to work out a specific cell signaling pathway.
THE NERVOUS SYSTEM
I. How do we know?
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Please study the given handout on brain imaging
Human Connectome – TED Talk: http://www.ted.com/talks/sebastian_seung -- I am my
Connectome from 2:00 – 12:00 or so.
Human Connectome Project: http://www.humanconnectomeproject.org/
II. The Division of the Nervous System
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The nervous system is composed of two main parts:
o Central nervous system (CNS) – includes the brain and the spinal cord
o Peripheral nervous system (PNS) – nerves and nodes that form a network outside of
the CNS and transmit messages into the CNS. A nerve is composed of the axons of
nerve cells bundled together.
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The basic unit of signal transmission in both the CNS and PNS is the neuron.
II. Cells of the Nervous System
A. Neuron
 We had the composition of the neuron before. Please review.
 The myelin sheath of the nerve cell is made up of Schwann cells in the PNS and
oligodendrocytes in the CNS. These cells serve as insulation over the axon. This insulation
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assures that only the exposed, in between sections (nodes of Ranvier) participate directly in the
signal transmission, making the transmission process a lot faster.
However, not all neurons myelinated. The ones in the gray matter in the brain for example are
not. These neurons are short, have close connections so speed for them is not so important.
The width of the axon also improves signal transmission. The thicker the axon is, the faster the
conduction occurs because of the lower resistance of the thicker axon (Ohm’s law – physics).
There are three major types of neurons in the body based on the information that they transmit:
o Sensory neurons – transmit information from the body toward the central nervous
system
o Motor neurons -- these transmit information from the central nervous system to the
rest of the body
o Interneurons – found only within the central nervous system. Connect various parts of
the CNS to each other
Most neuronal pathways are composed of at least one of each of the neuron types: sensory
neuron interneuron motor neuron. The shape of these neurons can vary as well.
Within the structure of the neuron, the dendrites or nerve cell body receive signals from the
surroundings. This signal travels forward in the axon toward the axon terminals. The axon
terminals connect the neuron to other cells and forward the signal to them.
B. Glial Cells
 Glial cells are the other type of important cells of the nervous system. These cells provide
insulation, nourishment, regulation to the neurons. They help to regulate the contents of the
extracellular fluid around the neurons. Schwann cells in the PNS and oligodendrocytes in the
CNS that form the myelin sheath are glial cells.
 New research also suggests that glial cells are active in transmitting messages but this is not yet
conformed.
III. Nervous System Diversity
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Through the course of evolution, simple systems to detect environmental changes gradually
changed into more sophisticated systems.
Among animals, cnidarians have the simplest nervous system called a nerve net – a network of
interacting neurons.
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From flatworms on, a gradual increase of the number of nerve cells occurs around the head.
This is called cephalization. The regulatory functions also get more concentrated in the brain of
higher animals. This process is called centralization.
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The activity and behavior of animals is usually also related to the complexity of the nervous
system. Animals that are sessile (remain in one place) or slow moving with simple behaviors
tends to have simple nervous system. While organisms that are fast moving and have complex
behaviors and intricate senses have more advanced brains.
IV. Resting Membrane Potential
http://www.sumanasinc.com/webcontent/animations/content/electricalsignaling.html -- resting
potential
http://highered.mheducation.com/sites/0072495855/student_view0/chapter14/animation__the_nerve
_impulse.html -- resting and action potential
https://www.youtube.com/watch?v=SdUUP2pMmQ4 – action potential and reflex arc (coming later)
Great video that guides you through the entire process:
http://outreach.mcb.harvard.edu/animations/actionpotential_short.swf
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Neurons require changes in electrical and chemical signals to rapidly transmit information
At rest, when the neuron does not forward information, there is a higher concentration of
sodium ions and chlorine ions outside of the cell and a higher concentration of potassium ions
inside of the cell. The concentration difference also causes an electrochemical gradient that is a
source of potential energy. This potential energy at rest, when a nerve impulse is not running
across the neuron is called resting potential.
Microelectrodes are used to measure the charge and voltage difference between the inside and
outside of the cell membrane of a neuron. The unit used to measure the charge difference is
mV.
The resting potential between neurons and their outside environment is around -60 to -80 mV.
So the inner surface of the membrane is more negative than the outer surface.
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Cells can use ion channels and ion pumps to move ions across the membrane. Ion channels are
integral proteins that specialize in transporting only one type of ion across the membrane by
passive transport by using the concentration gradient of that ion. These ion channels open and
close as a response to specific stimuli. Voltage-gated ion channels open and close as a result of
changes in voltage/membrane potential. Ligand-gated ion channels open and close as a result
of a ligand (usually a neurotransmitter) attach to them.
Some potassium channels remain open at resting potential. This causes a small net movement
of potassium ions out of the cell. Partially, this is the reason why the outside of the cell
membrane is more positive compared to the inside of the cell membrane. However, voltagegated sodium ion channels are closed, so sodium ions rarely move into the cell at rest.
Ion pumps, like the Na-K ion pump, use active transport and ATP to move ions against their
concentration gradient.
V. Neurons respond to stimuli by changes in the membrane potential
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Neurons are able to detect various stimuli, such as neurotransmitters, pressure, sound, light,
heat, etc.
When a stimulus is detected by the neuron, it results in changes in the membrane potential.
Membrane potential changes, because various votage-gated channels open and close.
Resting potential is bw. -60-80 mV that is kept up by some potassium channels and the Na-K
ion pump.
Hyperpolarization is caused by the decrease of membrane potential compared to the outside,
usually caused by inhibitory neurotransmitters. Hyperpolarization results, when more K+ ions
exit the cell through open channel proteins or when Cl- ions enter the cell through other ion
channels.
Depolarization in contrast means that the charge of the cell inside increases (becomes less
negative or even positive) compared to the resting potential. This would be caused by
excitatory stimuli that open sodium ion channels, so sodium ions would move into the cell.
Changes in membrane potential can open or close other voltage-gated ion channels as well and
change the membrane potential even more. Originally, this change only affects a small segment
of the cell membrane, but it can generate changes in the neighboring segments as well and a
nerve impulse can run through the entire neuron.
VI. Action Potential
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Action potential – a sudden large change in the membrane voltage due to a very rapid opening
of sodium voltage-gated channels. This occurs whenever a depolarization process reaches a
particular value called a threshold (it is -55mV in mammals). Once this threshold is reached the
value of the action potential is independent from the stimulus that triggers it – all-or-none
response. However, these action potentials are very quick, 1-2 msec, so a cell can generate
several of these in a second. The frequency of the action potential depends on the signal
strength.
The steps of the action potential:
o At rest, most voltage-gated sodium channels are closed, some potassium channels are
open but most voltage-gated ones are closed. This results in the -70mV resting
potential.
o A stimulus opens some sodium channels and sodium ions flow into the cell from the
extracellular matrix – depolarization. If the depolarization reaches a threshold, it
triggers an action potential.
o Depolarization opens most voltage-gated sodium ion channels, while potassium
channels remain closed, so the inside becomes more positive than the outside – rising
phase of the action potential
o Voltage gated sodium channels inactivate shortly after opening, stopping Na+ influx.
Most voltage-gated potassium channels open, so K+ ions flow out of the cell very rapidly.
This brings the membrane potential back to negative inside again – falling phase of the
action potential.
o Most potassium channels close quickly but some remain open and the inside becomes
more negative than the resting potential – undershoot
o Sodium-potassium ion pumps return the resting potential.
During the time when the resting potential returns on the membrane, a second action potential
cannot be initiated – refractory period. However, this refractory period is due to the
inactivation of the sodium channels not to the change in ion gradients.
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The action potential triggers another action potential in the neighboring region of the axon. An
influx of sodium ions causes a depolarization of the membrane, while the previous segment of
the membrane is still going through the action potential. As a result, the action potential only
spreads in one direction, toward the axon terminals.
The stronger the stimulus, the more action potentials will be generated on the neuron because
the action potential always has the same strength once the threshold is reached.
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Because of the presence of the myelin sheath the action potential is only generated at the
nodes of Ranvier where the membrane is in contact with the extracellular matrix. In between
the nodes an intracellular current carries the impulse. This way of conduction (called saltatory
conduction) is common among vertebrate animals.
VIII.
Synapses
Animations:
 http://highered.mheducation.com/sites/0072495855/student_view0/chapter14/animation__tr
ansmission_across_a_synapse.html
 http://www.hhmi.org/biointeractive/molecular-mechanism-synaptic-function
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Cone snails and their toxicity: http://www.hhmi.org/biointeractive/motor-cabal-toxins-blockmotor-neuron-synapses
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Action potential only leads the nerve impulse to the end of one nerve cell. Synapse is used to
pass the information from one nerve cell to another nerve or muscle cell. There are two types
of synapses:
o Electrical synapse – forwards information really fast by using gap junctions between
cells. These gap junctions directly allow ions and neurotransmitters to flow from one
nerve cell to another. These types of synapses are used when repetitive, fast responses
are necessary, like animals escaping from a predator. Two-directional transport is also
possible with this kind of synapse. One nerve cell can activate multiple other nerve cells
once the threshold potential is reached all interconnected neurons will fire.
o Chemical synapse – a more common way of transmitting information. This synapse
uses neurotransmitters (simple chemicals) that are released from the presynaptic cell
and received by the postsynaptic cell to continue the impulse. This type of synapse is
one directional. The steps of this:
 An action potential travels down the axon to the axon terminals. The action
potential causes depolarization on the membrane of the terminal, which opens
voltage-gated calcium ion channels. Calcium ions flow into the cell by passive
transport.
 In small vesicles inside of the presynaptic cell, small vesicles store
neurotransmitters. These neurotransmitters serve as messengers.
 Calcium ions fuse with the vesicles and they start to release their
neurotransmitters into the synaptic cleft by exocytosis
 Neurotransmitters diffuse through the synaptic cleft and bind with ligand-gated
channel proteins to open them up. This will result in the intake of various ions
by the postsynaptic cell membrane.
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The types of ions that enter the postsynaptic membrane will determine what kind of response is
generated. If sodium ions flow into the postsynaptic cell, than the cell membrane gets
depolarized and a new action potential is generated on the cell – excitatory postsynaptic
potential (EPSP).
In other cases, different neurotransmitters bind to different kind of gated channels that are
permeable to only K+ or Cl-. In these cases the postsynaptic membrane hyperpolarizes and these
move the membrane further from the threshold – inhibitory postsynaptic potentials (IPSPs).
Unlike action potentials that are all-or-none, postsynaptic potentials are graded. Their
magnitude varies depending on many factors:
o The amount of neurotransmitters released
o Summation of various postsynaptic potentials – postsynaptic potentials get weaker as
they spread, because they are led on the nerve cell body or dendrite not the axon. For
that reason one EPSP is not enough to trigger an action potential alone. Spatial
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summation (summing EPSPs or IPSPs that come in at different locations but at the same
time), or temporal summation (EPSPs add together that come quickly one after the
other on the same axon) can initiate action potential.
IPSPs and EPSPs also may cancel each other out.
The axon hillock is the integrating center of the neuron, where all incoming IPSPs and
EPSPs are added up. Whenever the membrane potential on the axon hillock reaches the
threshold, a membrane potential is generated that runs all the way to the axon
terminal.
IX.
Types of Neurotransmitters
 There are more than 100 neurotransmitters have been discovered so far. By their functions
they can be classified as excitatory or inhibitory neurotransmitters. However, some of these can
be both, depending on the cell that they affect. They can also be classified by their chemical
structure.
 Some of the important neurotransmitters:
o Acetylcholine – this is the main neurotransmitter in neuromuscular synapses (synapse
that forms between nerve and muscle cells) except on the heart muscle cells. This
neurotransmitter generates an EPSP on the muscle cells that can result in muscle
contraction. The activity of this neurotransmitter is terminated by enzymes in the
synaptic cleft. In cardiac muscle, acetylcholine has inhibitory effects. Some chemicals
that interfere with acetylcholine are nicotine – binds to the same receptors as
acetylcholine and stimulates the postsynaptic muscle cells; botulism toxin – inhibits
acetylcholine release from the presynaptic cells.
o Dopanime – an amine neurotransmitter that is synthesized from amino acids. An
important neurotransmitter in the brain that connect various nerve cells. There are 5
different receptors that are used to detect dopamine on the postsynaptic cells.
Frequently associated with brain regions that are responsible for reward-driven
learning. As a result, several highly addictive drugs such as cocaine and
methamphetamine stimulate the same receptors and directly act on the dopamine
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system. Diseases, such as Parkinson’s disease that results in tremor, impairment of
muscle function is related to loss of dopamine secreting neurons.
o Gamma-aminobutyric acid (GABA) – is an amino acid which is the most important
inhibitory neurotransmitter, which produces IPSPs by increasing the permeability of the
postsynaptic membrane to Cl- ions.
After the synaptic process is over, neurotransmitters are either broken down by enzymes or
recycled back into the presynaptic neurons by transport proteins. Some poisons can interfere
with this process.
X.
The Vertebrate Nervous System
 The central nervous system (CNS) consists of the brain and spinal cord. The brain that is located
in the cranium, processes sensory information coming from the internal and external
environment and integrates the new information with already stored info. Motor neurons
leaving the brain coordinate all kinds of responses in the body. The spinal cord in the vertebral
column carries information from the body into the brain and back. It is also responsible for
simple responses to external stimuli, such as the knee-jerk reflex.
 In cross section both the brain and spinal cord contains white matter which is a collection of
myelinated axons of neurons and gray matter which is made up of cell bodies, dendrites and
unmyelinated axons.
You need to be able to draw and label the parts of a cross section brain and spinal cord.
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The nerves of the peripheral nervous system can originate in the brain, these are called cranial
nerves. Or can originate from the spinal cord, these are called spinal nerves.
Different parts of the PNS control voluntary and involuntary movements. The somatic nervous
system senses the external environment and controls the voluntary muscles of the body. The
autonomic nervous system senses mostly internal stimuli and controls involuntary movements,
such as organ function and homeostatic responses.
The autonomic nervous system has two separate divisions, the sympathetic division activates
the body, generates the “fight-or-flight response”, while the parasympathetic division is
responsible for resting, relaxing the body.
During embryonic development, the brain differentiates into three main regions. These are the
forebrain, midbrain and hindbrain.
The forebrain is the most recent evolutionarily and develops to be the largest in mammals. This
section includes the cerebrum, hypothalamus and thalamus (region that coordinates
information going into the cerebrum, responsible for emotions, manages motor signals) and is
involved in basically every function of the nervous system.
The midbrain is an important switching station with coordinating some unconscious motor
responses.
The hindbrain contains the medulla oblongata, pons and cerebellum. The cerebellum is an
important motor coordinating and motor learning center. The pons and medulla oblongata with
the midbrain are responsible for vital process regulation such as heart rate, respiration and
forward information toward the upper regions of the brain.
XI.
The Reflex Arc
 Reflex – an involuntary and nearly instantaneous response to a stimulus usually to protect the
body from some sort of damage. These functions are frequently under the control of the spinal
cord and the brain only notified about the action after it was performed. However, there are
some cranial reflexes as well that are under the control of the brain.
 Reflex arc – the neuronal pathway that controls the reflex.
 The steps of this neuronal pathway are the following:
The Immune System
I. Overview -- http://www.npr.org/blogs/krulwich/2011/06/01/114075029/flu-attack-how-a-virusinvades-your-body
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We are exposed to microorganisms all the time. Most of these either live in mutualistic
relationships with us or they are harmless. However, there are microorganisms that can be very
harmful, even deadly for us. These microorganisms are called pathogens. Pathogens can be
bacteria, fungi, parasites and viruses. The immune system works to remove these pathogens by
using special molecules or specialized cells.
The immune system functions by recognizing special type of macromolecules like parts of
proteins. These special molecules are called antigens. The immune system is trained not to
respond to your own macromolecules.
If the recognition of the antigens is mistaken and the immune system recognizes your own
molecules as antigens, autoimmune diseases occur.
There are three basic lines of defense in the immune system:
o Physical barriers (all living organisms)
o Innate immunity (all living organisms)
o Adaptive immunity (vertebrates)
In vertebrate animals, major organs of the immune system are particularly rich in various cells of
the immune system. These organs are:
o Lymph nodes – microbes and foreign particles present in the circulating lymph get here
and encounter macrophages here that destroy them
o Lymph – fluid that is collected back from in between the cells
o Lymph vessels – collect lymph and lead it to large veins
http://www.as.wvu.edu/~sraylman/physiology/human_lymphatic.swf
II. Physical Barriers
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Physical barriers include the waxy cuticles of plants, the capsules of bacteria and the epithelial
cells of the human skin.
The human skin is made up of several layers of tightly packed cells with antimicrobial peptides
on their surface. The pH of the skin is also very acidic and hostile to pathogens. It is also very
dry, which limits bacterial growth and usually have a range of normal bacteria that live on the
skin and would compete with a potential pathogen for resources.
Mucous membranes also provide protection. The mucous traps pathogens, cilia can sweep the
pathogens out of respiratory ways and stomach acid also kills pathogens.
If this barrier is intact, very few pathogens can get into our body.
III. Innate Immunity
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The second line of defense after the barriers of the body is the innate immune system, which is
found in every organism to some extent.
This system has both cellular and molecular components to destroy pathogens. The response is
usually very fast, happens within minutes. The response is general to all kinds of pathogens
(antigens).
In vertebrates this system is also important in activating the third line of defense, the acquired
immune system.
In invertebrate organisms the following defenses are part of the innate immunity:
o Hemocytes – immune cells that circulate in the hemolymph and perform phagocytosis of
bacteria. Other hemocytes can also produce chemicals that destroy pathogenic bacteria
and multicellular parasites.
o Antimicrobial peptides – are also produced to punch holes on the cell membrane of
bacteria and fungi.
Vertebrate organisms also have various cells and molecules that are part of the innate immune
system. Look at a quick overview of the white blood cell types:
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Cellular Innate Defenses – phagocytic white blood cells (neutrophils and
macrophages) recognize microbes by using receptors called TLR (Toll-like receptor),
these recognize molecules that are typically found in some pathogens but not in
humans. There is a different type of TLR for molecules such as double stranded
RNA, various foreign proteins, liposaccharides etc. that can be found in some
bacteria, fungi and viruses. Once these receptors are activated, they trigger a series
of intracellular defenses, such as phagocytosis. Some of the phagocytic cells remain
in certain organs and tissues, while others migrate all over the body.
http://www.youtube.com/watch?v=iVa1swcEHDs (first half)
Dendritic cells – these cells are also called antigen-presenting cells, because they
recognize pathogens by using TLR’s and phagocytize these pathogens, degrade their
proteins into small pieces and present these small segments on their MHC class II
proteins for T and B cells to be activated. These cells originate from the monocyte
group of white blood cells, so these are a special subgroup of the phagocytic white
blood cells.
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Antimicrobial Peptides and Proteins – these molecules attack pathogens or disable
their reproduction. The following two are specific peptides to vertebrates:
 Interpherons – proteins that are secreted by virus-infected body cells.
These act as local (paracrine) signals because they induce uninfected cells to
produce chemicals that inhibit viral reproduction and the spread of viruses.
Other types of interpherons activate macrophages to enhance their
phagocytic ability. Manufactured interpherons today are used as antiviral
drugs. http://www.youtube.com/watch?v=h1zjTImMuwY
 Complement system – These proteins are found in the blood plasma in
inactive form all the time. They get activated by the surface molecules of
pathogens. The activation of these proteins (frequently phosphorylation)
results in a cascade of protein activation that usually results in the lysing of
the invading cells. The complement system is also important in activating
inflammatory response.
Inflammatory responses – triggered by an injury or infection. On the site of an
infection, the following steps take place:
 The entry of pathogens activates special immune cells called mast cells that
release some inflammatory signaling molecules – histamines.
 The nearby blood vessels dilate as a response to the histamine signals.
During the dilation, the blood vessels also become more permeable and
release phagocytic white blood cells.
 The activated phagocytic cells start to destroy the bacteria in the area and
also release further signal molecules to further increase blood flow into the
area.
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More blood flow results in redness, heat and swelling – typical symptoms of
an inflammation
All this results in the formation of pus that is composed of fluid rich in white
blood cells, dead microbes and cell debris.
If the inflammation is caused by major tissue damage, the entire body may
respond with greatly increased white blood cell production, fever (caused
by the release of pyrogens).
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Natural Killer Cells – Normal cells express a surface protein called class I MHC (class
I major histocompatibility complex) on their surface. However, cells that are
infected by viruses or are cancerous, do not express this protein. NK cells patrol a
body and if they find cells without their proper MHC proteins, they attach to the
diseased cells and release chemicals that destroy these cells.
http://www.youtube.com/watch?v=HNP1EAYLhOs
ADAPTIVE IMMUNITY
I. Overview:
 This type of immunity is found only in vertebrate animals. The main cells to perform acquired
immunity are lymphocytes. These cells are produced in the red bone marrow from stem cells.
The lymphocytes that migrate to the thymus after production and mature there are called T
cells. The lymphocytes that mature in the bone marrow are called B cells.
 Both of these cells recognize foreign molecules and cells and inactivate them. Lymphocytes also
have immunological memory – recognize pathogens that they encountered previously and
respond to them faster. This memory can exist for decades for some pathogens.
 Acquired immunity is activated by the signaling molecules (like the complement system) of
phagocytic cells so the two types of immunity interact with each other.
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Each T and B cell has a set of surface receptors that can each bind to a particular foreign
molecule (an antigen). The receptors of one lymphocyte are all the same but different
lymphocytes have different receptors that recognize different foreign molecules. When a
molecule fits these receptors, the T and B cells become activated, undergo cell division to create
clones of themselves to fight the antigen. Some T cells alarm other lymphocytes, others detect
and kill the pathogen. Specialized B cells release proteins that attack pathogens in the body
fluids.
The following sections detail the cell’s types, behavior and activation during an immune
response generated by acquired immunity:
II.
ANTIGEN RECOGNITION BY LYMPHOCYTES
 Any foreign molecule that is recognized by a lymphocyte and starts a response is called an
antigen. Antigens can be macromolecules, such as proteins or polysaccharides.
 These antigens are recognized by antigen specific receptors on the surface of the T and B cells.
B cells also release these receptors into the plasma of the blood in soluble form. These released
receptors are called antibodies or immune globulins (Ig). The receptors recognize a small
portion of the antigen, this portion that is called an epitope. One single antigen can have
several different epitopes that are recognized by different lymphocytes. But all of the antigen
receptors of a single lymphocyte are the same, they recognize only one epitope.
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Each B cell receptor for an antigen is a Y-shaped protein, consisting of 4 polypeptide chains, 2
identical heavy chains and 2 identical light chains. These chains are linked together by disulfide
bridges. One end of the heavy chain anchors the receptor into the B cell's membrane. The
constant (C) region of the heavy and light chains varies very little among different B cells.
However, the V region of the light chain and the V region of the end of the heavy chain, vary
extensively among the B cells. These V-regions form binding site for antigens. Antibodies are
similar to the membrane receptors, but they are lacking the membrane binding sites.
T cell receptors for antigens consist of two different polypeptide chains, an α chain and a β
chain, linked by disulfide bridges. These receptors also have a membrane-binding region, a C
regions, and V regions.
Both the T and B cell receptors bind with antigens but have different functions. B cell receptors
bind with the antigen whether that antigen is free or on the surface of a pathogen. T cell
receptors only bind with antigen fragments if they are displayed on the surface of a host cell.
The host cell has a special group of genes called the major histocompatibility complex (MHC)
that produces host cell proteins that present the antigen fragments to T cell receptors.
Once a phagocytic cell engulfs a pathogen, it breaks down the pathogen proteins to small
peptides by using lysosomes. The small antigen fragments than bind to MHC molecules. The
MHC molecule binds to the surface membrane of the phagocytic cell where it can be recognized
by T cells. This process is called antigen presentation.
The antigen presentation can result in immune actions against the antigen or against the cell
that displays the antigen. Destroying the presenting cell may be necessary to stop the spread of
infection.
There are two classes of MHC molecules:
o Class I MHC molecules -- are found in almost all cells of the body. After the cells are
infected by a pathogen, they displayed antigens will be recognized by cytotoxic T
cells and that will kill infected cells by releasing toxins into them. Some cells lose
their Class I MHC complex as a result of a viral infection. The loss of these molecules
activates natural killer cells to kill the virus infected or cancer cell.
o Class II MHC molecules -- made by only a few immune cells (macrophages, B cells)
that are commonly known as antigen presenting cells. After these cells phagocytize
the pathogen, the present the antigen on their surface. These antigens will be
recognized by cytotoxic T cells and helper T cells (cells that when activated, are able
to activate cytotoxic T cells and B cells for further action against the pathogen.)
VI. LYMPHOCYTE DEVELOPMENT
 Three major properties of the acquired immune system are:
o Diversity -- mostly recognizable by the number of different receptors that can be
displayed on the surface of lymphocytes. This ensures that all pathogens, even the
ones that we have never encountered before can be recognized.
o Self-recognition and tolerance -- even with the great diversity, under normal
conditions, lymphocytes do not attack the body's own cells.
o Immunological memory -- infections that we encountered previously, are
recognized and a stronger action is expressed against them.
 Lymphocyte diversity is enormous. Each human has about 1 million different B cells and about
10 million different T cells. This variety is due to the random combination of several different
segments of the C, J, and V region of the surface receptors and immunoglobulins. Once a B or T
cell is formed, it has to mature to become active. During the maturation process, the
lymphocyte DNA gets cut by enzymes. Some cut regions will not be expressed in the particular
maturing B or T cells. Other regions will become introns and will be cut out during RNA
modification. Only a few of the many genes that originally were present to form a surface
receptor will become genes that will be active in each cell. (Review transcription, translation and
RNA editing for this section)
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Because lymphocytes randomly generate new versions of surface receptors, they can always
generate receptors that would be active against the body's own surface receptors. However,
during maturation, the lymphocytes are tested for self-reactivity and if they are reactive against
the body's own surface receptors, they are destroyed by apoptosis or inactivated. If this system
fails, autoimmune diseases can occur. These diseases cause the body to destroy its own tissues.
Examples of autoimmune diseases are lupus, Type I diabetes and multiple sclerosis.
Clonal selection: The binding of an antigen to any mature lymphocyte will activate that
particular lymphocyte, because it alone is not able to fight off any pathogen. The activated B or
T cell divide many times, so in a short period of time we have thousands of two types of clones
(identical copies):
o Effector cells -- these are clones that directly attach the antigen or any pathogens
that produce the antigen. These cells are very short-lived.
o Memory cells -- long-lived cells (can survive for 10-15 years) but only a few of them
are produced. These cells bear the receptors for the antigen that we encounter.
These cells build our immunological memory.
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The first exposure to an antigen is slower because the immune system does not have memory
cells to that particular antigen yet. It takes longer to generate the clonal selection process and
produce the necessary effector cells and memory cells -- primary immune response.
Secondary immune response occurs when an antigen is encountered the second or multiple
times. This time the response is faster, greater in magnitude and longer. In this case a reservoir
of memory cells is activated.
VII. HUMORAL AND CELL-MEDIATED IMMUNE RESPONSES
 The two basic responses that are generated by lymphocytes are humoral immune response and
cell-mediated immune response.
 Humoral immune response -- involves the activation and clonal selection of B cells, which
secrete antibodies that circulate in the blood and lymph. The key players are antibodies
(basically free moving protein receptors), that are able to bind to antigens, with that neutralizing
pathogens and making them better targets for phagocytic cells and complement proteins. The B
cells get activated by cytokines that are released by helper T cells and by the presence of
antigens. The T cell binding results in a full scale activation of the B cell, that starts to divide and
forms antibody secreting plasma cells and memory B cells. The plasma cells can release as
many as 2000 antibody molecules/second for 4-5 days. These antibody molecules bind with the
antigen and destroy it.
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Cell-mediated immune response: Involves the activation and clonal selection of cytotoxic T
cells, which identify and destroy target cells. Helper T cells aid both of the humoral and cellmediated immune responses. The cytotoxic T cells become active when signals (cytokines)
come from helper T cells. Once the cytotoxic T cells are activated, they eliminate body cells that
are infected by viruses or other intracellular pathogens or they are cancerous. Class I MHC
proteins are displayed on the cell surface of these infected or cancerous cells that are
recognized by the cytotoxic T cells. The cytotoxic T cell releases proteins that cause the cell to
rapture. With this the pathogen loses its place to reproduce and also gets exposed to circulating
antibodies that will attack it.
Below is a summary of all processes related to the acquired immune response:
VIII. ACTIVE AND PASSIVE IMMUNIZATION:
 In response to infection, active immunity forms, which is the body produces its own memory
cells that can later respond by a secondary immune response a lot more efficiently when
exposed to the same antigen and/or pathogen.
 Passive immunity: forms when antibodies are transferred into a person either naturally by the
mother during pregnancy or breast feeding or by artificially when antivenin is given to a person
after a snake bite to neutralize the toxins.
 Immunization can also be active when antigens are given through a vaccine (smallpox, polio,
measles, whooping cough etc.)
Video resources:
Acquired immunity: http://www.youtube.com/watch?v=rp7T4IItbtM
Innate immunity:
http://www.youtube.com/results?search_query=innate+immunity&oq=innate+immunity&gs_l=youtube
-reduced.3...0.0.1.147.0.0.0.0.0.0.0.0..0.0...0.0...1ac.
Role of phagocytes: http://www.youtube.com/watch?v=O1N2rENXq_Y
Humoral and cell-mediated immune response: http://www.youtube.com/watch?v=YyCWm8WrZJU
All of the above: http://ocw.mit.edu/high-school/biology/structure-and-function-of-plants-andanimals/response-to-the-environment/