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BIOL 273 Exam
Introduction
• James England• 4th Year Biochemistry Student• Research focus on the molecular causes of aging in
yeast
2010 Outreach TripSummaryDate Aug 20 – Sept 4Location Cusco, Peru# Students 22Project Cost
$16,000Building ProjectsKindergarten Classroom provides free
educationSewing Workshop enables better job
prospectsELT Classroom enables better job prospectsMore info @
studentsofferingsupport.ca/blog
Cell to Cell CommunicationType DescriptionGap Junctions
-Connexons (bridge structure composed of proteins called “connexins”) join interior environments of adjacent cells-Can transmit electrical and chemical signals-Can open and close
Contact-Dependant Signal
-Interaction between membrane molecules on two cells-Membrane proteins can than activate a signal upon binding-Found in Immune cells and during development (neurons growing cell extensions from nervous system to distal parts of body)
Add Red Dye to left cell
Connexon
Cell to Cell CommunicationType DescriptionLocal Communication
-Communication between neighbouring cells using paracrine hormones as signalling molecules-Autocrine signalling is local communication where the cell that produces the molecule also receives it-Example of histamine vasodilator secreted by damaged cells which causes surrounding capillary cells to be more permeable to fluid (swelling) and white blood cells/antibodies
Long-Distance Communication
Nervous and endocrine system-Similar to paracrine hormone secretion, except signalling molecules travel large distances to target (hormone through blood stream or electrical signal down entire length of neuron)-Target cell needs receptor
Cell to Cell Communication
Cell
Target Cell
Paracrine
Autocrine
Blood
Endocrine
Receptors
• Signalling specificity depends on Receptor Proteins• Signalling molecule binds onto a specific receptor
found only on target cells transmembrane, cytosolic, or nuclear location
• Receptor protein is what brings about the response to signal
• Agonists Binds receptor and activates response• Antagonists Binds receptor and produces no
response (inhibitory activity)
ReceptorsBiological Signalling Molecule
Foreign “drug” molecule
Foreign “drug” molecule
Normal Signal Pathway With Response
Agonist Pathway With Response
Antagonist Pathway Without Response
Nervous System
• 1) Receives information Sensory neurons from external environment (light, sound, pressure etc)
• 2)Integrates Information Organizes new information, combines with stored information
• 3) Transmits Information Sends signals to muscles/glands to carry out action
Neurons
Ref: Wikipediahttp://en.wikipedia.org/wiki/File:Neuron_Hand-tuned.svg
Dendrites
Nucleus
Soma
Myelin Sheath/ Schwann Cell
Node of Ranvier
Axon
Axon Terminal
NeuronsComponent Description
Soma Nucleus & biosynthetic machinery (ribosomes protein synthesis)Helps keep cell Alive
Dendrite Receive information (from sensory cells, or other neurons)•Can be part of synapse (post synaptic)
Axon Cytoplasmic extension that sends out information (to other neurons/muscles/glands)
Axon Terminal Connection between neuron/other cells•Can be part of synapse (pre synaptic)
Nervous SystemComponents Central Nervous System Peripheral Nervous SystemMajor Structures •Brain
•Spinal Cord•Everything else•Connects brain/spinal cords to muscles/organs•Receptor CELLS (convert stimuli to electrical signals)
Cluster of Cell Bodies •Nuclei •Ganglia
Axon Bundles •Tracts •Nerves
Neuron Types Interneurons (96% of all neurons)•Integrate information from Afferent neurons & transmit to efferent neurons
Afferent Neurons Cell bodies in PNS (ganglia)•Transmit signals to CNS
Efferent (motor) Neurons Cell bodies in CNS•Transmit signals to Effectors (muscles, glands, etc)
Glial Types •Oligodendria, Astroglia, microglia, ependymal cells
•Schwaan, Satellite cells
Glial Cells
Neurons are the VIP’s of the nervous systems! They need other people to help do their laundry, cook food, act as bodyguards, etc etc so they can focus on their jobs
Neurons
Neurons
Ref: Wikipediahttp://en.wikipedia.org/wiki/File:Neuron_Hand-tuned.svg
Dendrites
Nucleus
Soma
Myelin Sheath/ Schwann Cell
Node of Ranvier
Axon
Axon Terminal
PNS Glial Cells
Schwann Cells form myelin sheath which acts as electrical insulator. Only wrap around 1 cell
• Structure has many layers of cell membrane with gap junctions connecting layers
Neuron
-Gap Junctions
PNS Glial Cells
• Satellite Cells non-myelinating, support nerve cells
CNS Glial Cells-4 Types
• 1) Oligodendrite Myelinating Cell (like Schwaan) but can wrap around more than one neuron
• 2) Astroglia Make contact with blood vessels and neurons; transfer nutrients, maintain microenvironment; Star Shaped.
CNS Glial Cells
• 3) Microglia Small, specialized immune cells -maintain microenvironment like astroglia-remove dead cells & foreign invaders, protect neurons
• 4) Ependymal Cells Epithelial cells, create semi-permeable barriers between brain compartments-produce cerebrospinal fluid
Electrical Properties of Neurons
• Difference between electrical charge on the inside of the cell and the outside environment creates an electrical gradient across the membrane
• There is also an osmotic gradient due to the differences in concentrations of solutes between the inside & outside of cell
Electrical Properties of Neurons
• Cell membranes are semi-permeable- Allow free diffusion of small, hydrophobic (non-
polar) molecules• Membranes are impermeable to most
molecules, Especially charged ions. • Specific protein transporters move these
molecules across the membrane
Resting Membrane Potential
• Resting Membrane Potential for a neuron is around -70 mV to -90 mV Negative charge compared to environment; mostly due to phosphate (HPO4
2- ,H2PO4
-), and negatively charged proteins & DNA
-70 mV- --
--- --
- -+ ++ +
+ ++
+ +
+
Resting Membrane Potential
• Know the relative ion concentrations for the neuron at rest:
• Na+, Cl-, and Ca2+ have concentrations higher in the extracellular fluid (outside cell)
• K+ has a higher concentration inside the cell
-70 mVK+
Na+
Ca2+Cl-
Na+/K+ ATPase
• Active transport of 3 Na+ out of the cell and 2 K+ into the cell powered by ATP
• Pumps ions against gradient (by consuming energy) to maintain cellular concentrations of K+ and Na+
• Compensates for ions leaking into/out of cell along their concentration gradient
Nernst Equation
• Equilibrium Potential (Eion) is the electrical potential of the Cell needed to generate an equilibrium state for a KNOWN concentration gradient The electrical gradient needed to balance the concentration gradient
• Compare this to known cell potential to predict where ions are likely to flow
Nernst Equation• Know that K+ is found at higher concentrations inside
of the cell Concentration gradient dictates K+ would flow out of the cell
• Calculated Equilibrium Potential for Potassium is -90 mV.
-90 mV
K+
---
-Neuron with membrane potential of -90 mV
No NET K+ movementNegative charges attract Positive K+ to balance concentration gradient
-70 mV
K+
--Neuron with membrane potential of -70 mV
K+ will flow (leak) out of cellNegative charges not enough to attract Positive K+ to remain in the cell
Nernst Equation• Know that Na+ is found at higher concentrations outside of
the cell Concentration gradient dictates Na+ would flow into the cell
• Calculated Equilibrium Potential for Na+ is +60 mV.
+60 mV Na+
Neuron with membrane potential of +60 mV
No NET Na+ movementPositive charges repel Positive Na+ to balance concentration gradient
-70 mV+
--Neuron with membrane potential of -70 mV
Na+ will leak into the cellNegative charges not enough to repel Positive Na+ to prevent movement into cell
Na+
++ + +
Resting Membrane Potential & Ion Permeability
• The relative permeability of these ions dictate how important their contribution is to the resting membrane potential (RMP)
• Ions that can move more easily through the membrane contribute greater to the RMP
• RMP can be calculated using the Goldman Equation which takes into account the relative permeability of ions
• Permeability can be increased by:1)opening gated protein channels for transport2) increasing the # of transport proteins
Gated ChannelsStretch
Channel Open
Channel Closed
Mechanically Gated- Respond to physical forces- Found in Sensory neurons
Chemically Gated- Respond to ligand binding (neurotransmitters, neuromodulators)- “most important” for neurons (located in synapses)
Voltage Gated- Respond to membrane potential changes- Involved in initiation and conduction of electrical signals
++
+ +Channel Open
Channel Closed
Channel Open
Channel Closed
Changes in Membrane Potential
Depolarization Hyperpolarization
Effect on cell charge Cell becomes less negative (more positive)
Cell becomes more negative
Effect on potential difference
Decreases membrane potential difference
Increases membrane potential difference
Occurs when Lose: Cl- K+, Na+, Ca2+
Occurs when Gain: K+, Na+, Ca2+ Cl-
Occurs (in general): Loss of negative (-)ions, or gain of positive (+) ions
Loss of positive (+) ions, or gain of negative (-) ions
Repolarization is any change in membrane potential which returns it to the Resting Membrane Potential
Graded & Action PotentialsGraded Action
Distance: Short Long
Polarization: Hyperpolization or Depolarization Wave of depolarization followed by repolarization & hyperpolarization
Initiated by: Ion channels opening; usually from neurotransmitters, or mechanically gated channels in sensory neurons
Threshold potential (minimum depolarization) reached at axon hillock (triggering zone) the sum of excitatory and inhibitory graded potentials-Usually Threshold is -55 mV
Strength of signal: Dependant # of ions that enter cell (proportional to strength of trigger); diminishes with distance; can be summed temporally or spatially
Identical strength for all action potentials fired; does not diminish along length of neuron
Location in neuron: Dendrites, cell body Axon
Neurons
Ref: Wikipediahttp://en.wikipedia.org/wiki/File:Neuron_Hand-tuned.svg
Dendrites
Nucleus
Soma
Myelin Sheath/ Schwann Cell
Node of Ranvier
Axon
Axon Terminal
Graded Potentials Activate Action Potentials
-55 mV
-70 mV
Depolarizing Graded Potential
Hyperpolarizing Graded Potential
Net Graded potential
Action Potential
-55 mV
-70 mV
01
2
3
4
5 6
+30 mV
Action Potential-Voltage Gates
++ +
Sodium (Na+) Channel with Activation Gate (opens at -55 mV), and Inactivation Gate (voltage activated but time delayed)
Inactivation Gate
Activation Gate
Na+
Action Potential-Voltage Gates
++
Potassium (K+) Channel with Voltage Gate which opens later than Na+ channels (fully open at +30 mV)
K+
Action Potential
-55 mV
-70 mV
01
2
3
4
5 6
+30 mV
Action Potential
+ +0
MP = Less than -55 mV
+ +1
MP = -55 mV
Action Potential
++
2MP = Between -55 mV and +30 mV
3 &4
MP = +30 mV to -70 mV
Na+
+
K+
+
Action Potential
-55 mV
-70 mV
01
2
3
4
5 6
+30 mV
Action Potential
+5
MP = Less than -70 mV
5.5+
K+
+
K+
+ MP = Less than -70 mV
ABSOLUTE REFRACTORY
RELATIVE REFRACTORY
Neurons
Ref: Wikipediahttp://en.wikipedia.org/wiki/File:Neuron_Hand-tuned.svg
Dendrites
Nucleus
Soma
Myelin Sheath/ Schwann Cell
Node of Ranvier
Axon
Axon Terminal
Refractory Periods
• Set directionality of Signal cannot activate membrane regions which have recently fired
++
Na+
Na+
Na+Na+
+
Synapses• Electrical Synapses Gap junctions connect 2
cells allowing direct electrical signalling- CNS; between 2 neurons, or neuron and glial cell- Nervous system development and transmission in adult brain
Action Potential Depolarization wave
Action Potential Depolarization wave
Chemical Synapse
Synaptic Cleft
Presynaptic cell Postsynaptic cell
Ca2+
Action Potential Depolarization wave
Ions
AP causes Ca+2 entry vesicles release neurotransmitter
Neurotransmitter Receptors can either open ion channel directly, or cause another (long lasting) signal cascade coupled to G proteins etc
Types of NeurotransmittersNeurotransmitter DescriptionAcetylcholine Synthesized from acetyl CoA & choline by Choline Acetyl Transferase (CAT)
at axon terminal.Degraded for deactivation and then recycling by Acetylcholinesterase-Used by cholinergic receptors: a) Muscarinic Slow, G protein coupled b) Nicotinic Fast, ACh binds directly to ion channel
Biogenic Amines Contain amine group (NH2) derived from amino acids, synthesized at axon terminal
Amino Acids Very abundant in CNSExcitatory Glutamate, aspartateInhibitory Glycine, gamma-aminobutyric acid (GABA)
Neuropeptides Synthesized the same as regular proteins, in rough ER, packaged by Golgi apparatus
Types of NeurotransmittersNeurotransmitter DescriptionPurines Nucleotides nucleotides bind purinergic receptors in CNS
e.g. Adenosine, AMP, ATP
Gases Nitric Oxide (NO) synthesized from oxygen and arginine by Nitric Oxide Synthase-Synthesized and then immediately used (not stored)-Unstable and degrades quickly
Peripheral Nervous SystemAutonomic Division Somatic division
Structure of Relay 2 neuron chain Single neuron
Controls Smooth and cardiac muscle, glands, smooth muscle, and adipose tissue
Skeletal Muscle Can only cause muscle excitation, not inhibition
Neurotransmitters -Acetylcholine & Norepinephrine -Acetylcholine (Ach) in vesicles
Subdivisions Parasympathetic (rest & digest), sympathetic (flight or fight)
N/A
Muscle Cell
CNS
ACh Nicotinic ACh receptors
Somatic neuron Always excitatory
Target CellTarget Cell
CNS
Ganglion
Sympathetic 2 Neuron Chain
Parasympathetic 2 Neuron chain
LegendAcetylcholine
Norepinephrine
Nicotinic ACh Receptors
Muscarinic ACh Receptors
Adrenergic Receptors
Swollen Terminals Varicosity; stores a lot of neurotransmitter
G Proteins & Ion ChannelsIONS
e.g. Nicotinic cholinergic receptors1 molecule of neurotransmitter opens 1 ion channel
G Proteins & Ion Channels
G Protein Trimer
G Protein Coupled Receptor
Open Ion Channels
Increase cAMP levels
Activate other proteins
G Protein Coupled Receptor
e.g. Adrenergic receptors1 molecule of neurotransmitter can have many effects
Cholinergic ReceptorsType of Cholinergic Receptor
Receptor located on:
Respond to: Pathway of Response
Nicotinic Muscles (somatic system), post ganglionic nerves of autonomic system
ACh, nicotine (agonist)
ACh binds Na+ channels intracellular [Na+] increases depolarization-Excitatory
Muscarinic Tissues of parasympathetic system
ACh, muscarine (agonist)
G proteins close/open ion channels-Inhibitory or excitatory
Adrenergic ReceptorsType of Adrenergic Receptor
Associated Tissues/ Neurons
Neuro-transmitter Secreted by:
Respond to: Pathway of Response
α Many tissues; post-ganglionic symp. Neurons
Norepinephrine better than Epinephrine
G protein Ca2+ channels increase in cellular [Ca2+]
β1 Heart, muscle, kidney;
post-ganglionic symp. Neurons
Norepinephrine and epinephrine equally
G protein cAMP production
β2 Blood vessels, smooth muscle;
post-ganglionic symp. neurons
Epinephrine better than Norepinephrine
G protein cAMP production
Muscles• Tissues specialized to convert biochemical
reactions into mechanical work• Generate force, motion, & heat1) Skeletal attached to skeleton, responsible for
movement; has striations2) Smooth internal organs; influences movement
of materials through body no striations3) Cardiac Heart muscles; pumps blood; has
striations
Skeletal Muscles
• Attach to bones via tendons at 2 points;- Origin at “least” moveable part of body-Insertion at “most” moveable part of body
• Flexor Muscles contraction brings bones closer together
• Extensor Muscles contractions moves bones away from another
• Flexor & Extensor are antagonistic pairs
Muscle StructureEpimysium- outer connective tissue
Fascicles- Bundles of individual Muscle Fibers each wrapped in a connective tissue sheath (Endomysium)
Perimysium- contains Nerves & blood vessels surround fasicles
Muscle Fibres
• Muscle Fibers = Muscle Cells• Contain mostly Myofibrils Functional unit of muscle• Energy from mitochondria (oxidative phosphorylation
ATP synthesis) and glycogen granules (glucose storage)
• Cell membrane SarcolemmaCytoplasm SarcoplasmModified Endoplasmic Reticulum Sarcoplasmic Reticulum Sequester Ca2+ for rapid release into cell
Muscle Fibres- ProteinsProtein Class DescriptionActin Contractile Individual subunits (Globular G-actin) form filamentous, F-Actin
2 F-Actin chains twist together to form “thin filament” with troponin and tropomyosin
Myosin Contractile 2 rigid regions (head and tail) connected by flexible “hinge”250 molecules join to form “thick filament”Myosin Heads bind onto F-Actin (form cross-bridges)Motor protein- Powered by ATP
Tropomyosin Regulatory Can either block (“off”) or allow (“on”)binding of myosin head on F-Actin
Troponin Regulatory -Made of 3 subunits, most important for regulation it troponin C-Can change position of tropomyosin to either “on”/”off”
Titin, Nebulin, alpha actinin, etc
Accessory Titin- Largest known protein, elastic, returns muscles to resting lengthNebulin- Helps align actin filaments, organizational role (?)
H Zone
Myofibril Structure
Myosin Thick FilamentThin Filament- Actin, troponin, tropomyosin
Sarcomere
Z Disk
TintinM Line
Half of I Band Half of I BandA Band
Myofibril StructureContraction: Thick Filaments remain same size, but thin filaments have slid closer to M line Z Discs closer together
1 2 3 4 5 6
Sliding Filament Theory
Myosin Head
F-Actin
Step 1: Crossbridge 45°Myosin tightly bound
Step 2: ATP binds to myosin head; Myosin dissociates from actin
ATP
1 2 3 4 5 6
Sliding Filament Theory
Step 3: ATP Hydrolyzes to ADP + Pi
Step 4: Myosin Head rotates, binds weakly to new actin molecule
ADPPi
1 2 3 4 5 6 1 2 3 4 5 6
ADPPi
Sliding Filament Theory
Step 5: Pi is released; Myosin head rotates 45° dragging actin filament with it; POWER STROKE; Still weakly bound
Step 6: ADP dissociates from myosin Tight binding of Myosin to Actin
ADP
Pi
1 2 3 4 5 6 1 2 3 4 5 6
ADP
Sliding Filament Theory
• Overall1 2 3 4 5 6
1 2 3 4 5 6
Myosin has not moved;Thin Filament (actin) has
BEFORE
AFTER
Regulation of Contraction
1 2 3 4 5 6
Tropomyosin
ADPPi
Relaxed Muscles have myosin heads mainly in step 4
Tropomyosin position allows for weak binding of myosin to actin, but prohibits the ability to perform the “Power Stroke”
Troponin- 3 Subunits
Regulation of Contraction
1 2 3 4 5 6
Tropomyosin
Troponin- 3 Subunits Contracting
Muscles troponin C subunit binds to Ca2+ which shifts the tropomysosin position allowing the myosin head to carry out the power stroke & bind tightly to actin
Calcium ; Ca2+
ADP
Excitation Contraction Coupling
+
Cholinergic ReceptorsNa+/ K+ channels
T Tubule
Dihydropyridine Receptor (DHP)
Ryanodine Receptor
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+
Sarcoplasmic Reticulum
Excitation Contraction Coupling
ACh
Na+Na+
Na+
Na+K+
+Ca2+
Ca2+
Ca2+
Ca2+
Ca2+Ca2+
Ca2+
Na+
Excitation Contraction Coupling
• Ca2+ is pumped back into the SR by Ca2+-ATPase How fast calcium is removed dictates how fast muscle relaxes
• Twitch Single contraction-relaxation cycle-Dependant on ATPase rate and
Ca2+ removal rate
Practice Questions
• The “Power Stroke” of a myosin molecule:a) Involves the release of ADPb) Requires Ca2+ to be bound to tropomyosinc) Moves consecutive Z discs further apartd) Requires the release of inorganic phosphate
Practice Questions
• The “Power Stroke” of a myosin molecule:a) Involves the release of ADPb) Requires Ca2+ to be bound to tropomyosinc) Moves consecutive Z discs further apartd) Requires the release of inorganic phosphate
Practice Questions
• The role of Troponina) Involves the binding of calcium ionsb) Involves the interaction with nebulinc) Activates contraction in the absence of Ca+2
d) Involves a direct interaction with ryanodine receptors
e) None of the above
Practice Questions
• The role of Troponina) Involves the binding of calcium ionsb) Involves the interaction with nebulinc) Activates contraction in the absence of Ca+2
d) Involves a direct interaction with ryanodine receptors
e) None of the above
Muscle Energy
• ATP Needed Myosin:Actin Interaction, ion pumps (Na+, K+, Ca2+)
• ATP generated from glycolysis (fast, 2 ATP, produces lactic acid), or oxidative phosphorylation (slow, 30 ATP, produces CO2)
• Creatine Phosphate can regenerate ATP from ADP (Creatine Phosphokinase) to maintain consistent ATP levels
Muscle Energy and Exercise
• Oxygen Debt Not enough O2 for oxidative phosphorylation, therefore use glycolysis by degrading glycogen stores
• Glycolysis produces pyruvate lactic acid which must be detoxified by liver after exercise ceases & oxygen is available
Muscle Fibre ClassificationSlow-Twitch Oxidative
Fast-Twitch Oxidative-Glycolytic
Fast Twitch Glycolytic
Speed to Max Tension
Slow Medium Fast
Myosin ATPase Activity
Slow Fast Fast
Diameter Small Medium Large
Contraction Duration
Long Short Short
Ca2+-ATPase Activity Moderate High High
Endurance Fatigue Resistant Fatigue Resistant Easily Fatigued
Metabolism Oxidative (aerobic) Glycolytic & some oxidative
Glycolytic (anaerobic)
Mitochondria Many Moderate Few
Colour Dark red Red White
Motor Unit
• Composed of a single motor neuron and all the fibres that it controls (can be branched multiple times)
• All muscle fibres in Motor Unit are the same type (e.g. all slow twitch)
• # of muscle fibres associated with a neuron determines if it is “fine” control (few) or “coarse” (many muscle fibres)
Fast Glycolytic
Motor Unit
Slow Oxidative
Slow Oxidative Slow Oxidative
Practice Questions
• The cheetah is the fastest land mammal on Earth. Its muscles are easily fatigued, produce high amounts of lactic acid and use glycogen as a primary source of energy. Cheetah muscles are likely made of what type of muscle fibres?
a) Fast Oxidativeb) Fast Glycolyticc) Slow Glycolyticd) Slow Oxidative
Practice Questions
• The cheetah is the fastest land mammal on Earth. Its muscles are easily fatigued, produce high amounts of lactic acid and use glycogen as a primary source of energy. Cheetah muscles are likely made of what type of muscle fibres?
a) Fast Oxidativeb) Fast Glycolyticc) Slow Glycolyticd) Slow Oxidative
Muscle Contraction
• Tension determined by sarcomere length at contraction start
Too Little Overlap Little Force
Muscle Contraction
Too Much Overlap Little Force (Actin Filaments hit each other)
Muscle Contraction
Even More Overlap Very Little Force (Thick Filaments hit z Disk)
Summation & Tetanus
• Summation Rapid stimulation means no time for muscles to relax (still contracted) before muscle contracts again. This generates even more force than one action potential alone
• Tetanus Maximum Force of contraction (as strong as you can be)Incomplete Max force, but muscle relaxes a bit between action potentialsComplete Muscles don’t relax
Summation and Tetanus
Single Twitch
Summation
TETANUS
Unfused Fused
Physics!......for bio students
• Muscles & bones work like levers (rigid part) and fulcrums (pivot point)
5 cm
25 cm
How much force required to keep weight stationary?
Torque Up = Torque DownF1 x D1=F2 x D2Force1 X Distance1 = Force2 X Distance2 F x 5 cm = 10 kg x 25 cmF = (10 kg x 25 cm) / 5 cmF = 50 kg
10 kg
Smoooooooth Muscle
Smoooothies are digested, where smooth muscles are involved as intestines, and bladder
Smoooooooth Muscle Cells
• 1) Single unit gap junctions connect muscle fibres so no need to stimulate all of them (signal transduction through gap junctions)– Intestine, Blood Vessels2) Multi Unit Each muscle fibre innervated- Iris & cilary body of eye, some reproductive organs
Uterus normally multi unit but becomes single unit at birth
Smoooooth Muscle Cells: Key FeaturesMuscle Features Cellular Features Molecular Features
Contraction changes muscle shape
Small Fibres Less myosin per actin (a lot of actin)
Generates force slowly No striations (no sarcomeres)
Longer actin& myosin filaments more overlap
Maintains force for long periods (fatigue resistant)
Actin & Myosin arranged diagonally anchored at “dense bodies”
Slower ATPase than skeletal muscles (key to its slow, consistent activity)
No T Tubules, less SR No troponin
Caveolae Vesicles for Ca2+ storgage
Contraction involves Myosin regulation
Force is proportional to amount of Ca2+ released
Smooooth Muscle Contraction
Voltage Gated
Stretch Activated
Chem. Gated
Ca2+ Channels
Ca2+
Ca2+
Ca2+Ca2+
Ca2+
Ca2+Ca2+
Ca2+
SR/caveolae
CaMPi
MLCK
Calmodulin Myosin Light Chain Kinase
Myosin- Inactive
Smooooth Muscle Contraction
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+ Ca2+Ca2+
Ca2+
CaM
Pi
MLCK!!!
Myosin- Active
Ca2+
Ca2+
Ca2+
Ca2+
+
ACTIVATES!!!!
ATP ADP
Phosphorylates
Smoooooth Muscle Relaxation
• Ca2+ removed from cytosol– Ca2+ ATPase, Ca2+ - Na+ antiport
• Whats the result of this?
Ca2+ unbinds from CaM, MLCK inactivated, Myosin dephosphorylated (myosin light chain phosphatase)
Leads to Latch State
Practice Questions
• Multiunit smooth muscle cells are connected via gap junctions to conduct electric signals throughout the tissue:
a) Trueb) False
Practice Questions
• Multiunit smooth muscle cells are connected via gap junctions to conduct electric signals throughout the tissue:
a) Trueb) False
Cardiac Muscle
<3
<3 Cardiac Muscle
• Striated therefore organised into Sarcomeres• Single Nucleus per cell• Lots of mitochondria oxidative phosphorylation• Large, branched t-tubules fast signal
transduction• Cells joined by intercalated discs, & desmosomes
force transmission aids in contraction
Autorhythmic/Pacemaker cells
• Initiate Heartbeat (no need for nerves to control it)
• ~1% of myocardial cells• Use gap junctions to conduct electric signal to
other cardiac cells
Myocardial Contraction• Similar to skeletal muscle contraction
Ca2+
Ca2+
Ca2+
Ca2+
Ca2+Ca2+
Ca2+
Ca2+
Ca2+
Action Potential from neighbouring cells initially started by pacemaker cells
Ca2+
Binds to Troponin
Myocardial Contraction is Graded
• Force is proportional to # of active crossbridges
• # of active crossbridges depends on [Ca2+]• Force also proportional to length of muscle
fibre
Factors Affecting Contraction ForceStimulus Mechanism Final Effect
Epinephrine/Norepinephrine
Bind β1 Adrenergic receptors Phosphorylation of Ca2+ transporters increase their opening
Increased [Ca2+] more forceful contractions
Phosphorylation of phospholamban SR Ca2+ -ATPase activity increase
Increase SR [Ca2+] more forceful & shorter duration of contractions
Stretching Open Ca2+ channels Increase [Ca2+]
Cardiac Action Potentials
1
23
4
Cardiac Action Potentials
1- Na+ channels open (depolarization)2- Na+ channels Close, K+ channels open
(repolarization, but brief)3- Ca2+ channels open, some K+ channels close
(plateau to prevent tetanus) 4- Ca2+ channels close, K+ channels open
Practice Questions
• Which is true with regard to cardiac muscle fibres
a) They primarily undergo glycolysis for ATP production
b) The are no t-tubulesc) All cells are involved in contractiond) Undergo “all-or-none” style contractione) None of the above
Practice Questions
• Which is true with regard to cardiac muscle fibres
a) They primarily undergo glycolysis for ATP production
b) The are no t-tubulesc) All cells are involved in contractiond) Undergo “all-or-none” style contractione) None of the above
Practice Questions
• At the point marked “3”:a) Ca2+ channels are openb) Na+ channels are openc) Cardiac muscles are undergoing tetanusd) The cells are being rapidly hyperpolarized
1
23
4
Practice Questions
• At the point marked “3”:a) Ca2+ channels are openb) Na+ channels are openc) Cardiac muscles are undergoing tetanusd) The cells are being rapidly hyperpolarized
1
23
4
Cardiovascular System
• Cardiovascular System Heart, blood, and blood vessels
• Multicellular organisms <3 the Cardiovascular System for Nutrient and Waste exchange
• Transports nutrients, water, gas (O2, CO2), wastes, hormones, heat,
Venae CavaeAorta
Cardiovascular System Overview
Artery Vein
Capillaries
Nutrients Waste
Highest Pressure Lowest Pressure
Heart is 2 Pumps
• Pump #1 Blood leaves heart into lungs, red blood cells bind
to oxygen Small capillaries for fast O2 exchange, increased resistance
• Pump #2 Blood leaves heart to rest of the body Small capillaries for fast O2 exchange, increased resistance
External Heart Structure
Fluid
Pericardium
Coronary Arteries Supply oxygen for the heart itself
Internal Heart Structure
Right Atrium Left Atrium
Right Ventricle
Left Ventricle
Vena Cava
Lun gs
Bicuspid AV Valve
Tricuspid AV Valve
Chordae Tendinae
Pulmonary Semilunar Valve
Aortic Semilunar Valve
Cardiac CycleAtria and Ventricle RelaxedAV valves openBlood enters ventricles passively
Atria ContractsBlood enters VentricleSemiluminar (SL) valves closed, AV valves open
Ventricles Contract (isovolume)SL and AV valves closed AV closed (Lub)
Ventricular Ejection SL valves open
Ventricular relaxation SL, AV valves closed (dub)
Heart Contraction
• Autorhythmic/pacemaker cells in sinoatrial node (top of right atrium)
• Spontaneously generate action potentials which signal contraction for the whole heart
SA
Pacemaker Potentials
-60 mV
Open If Channels – K+ moves out, Na+ moves in
Ca2+
channels begin to open
Many Ca2+ channels open
Ca2+ channels close, K+ channels open
K+ Leaves the cell
Regulation of Heart RateHormone Mechanism Final Result
Norepinephrine, sympathetic stimulation, (great cardiac nerve)/Epinephrine, adrenal medulla
Bind β1 adrenergic receptors release of cAMP open If channels and Ca2+ channels increased depolarization rate
Increased heart rate
Acetylcholine- parasympathetic stimulation (vagus nerve)
Binds muscarinic receptors Increase K+ permeability Hyperpolarization
Slower heart rate
Pathway of Conduction
SA
AV
1)Pacemaker Cells in SA node generate Action Potential spreads to atrial cells via gap junctions
2) Internodal Pathways spread signal to AV node (AV junction is only place where current can pass to ventricle)
3) Bundle of His/ AV Bundle fibres transmit signal to bottom (apex) of ventricles (contraction starts at bottom)
4) Purkinje Fibres move signal upwards through ventricles
Disorders• Arrhythmia non-SA heart cells act as
pacemaker, SA node cells develop abnormal rate, conduction pathway is interrupted (signal not received in right order/time)
• Bradycardia slow heartbeat• Tachycardia Fast heartbeat • Ventricular Fibrillation Disorganized
contraction, no blood pumped• Atrial Fibrillation Disorganized contraction,
blood not pumped effectively blood pools/clots
ECG
• ECG uses electrodes on skin, need 3 for Einthoven’s Triangle
+
ECG
P-Wave: Atrial Depolarization
QRS complex: Ventricular Depolarization
T-Wave: Ventricular Repolarization
ECG
P-R Segment: Atrial Contraction S-T Segment:
Ventricular Contraction
ECG
ECG Info GainedFeature Information about Heart
Time for P wave to P wave Heart Rate
Arrhthmyia
Absent QRS complex Damage to heart, conducting pathway
P-R Interval Time for conduction from atria to ventricle
Cardiac Cycle AKA Heart Beat
• Systole Phase – Contraction of <3• Diastole Phase – Relaxation of <3• End Diastolic Volume (EDV) Maximum
volume (amount of blood) in ventricle• End Systolic Volume (ESV) minimum volume
of ventricle
Cardiac OutputCardiac Output = Heart rate x stoke volumeCardiac Output = Heart rate x [EDV – ESV]
Parasym. Stimulation (ACh) Decrease contraction of heart (lower stroke volume) by decreasing Ca2+
Sym. Stimulation (Norepinephrine) Increase contraction of heart by increasing Ca2+
Epinephrine Increase contraction of heart by increasing Ca2+
Frank-Starling Law Stroke volume is larger with greater EDV more myosin-binding sites on thin filament, Ca2+ enters cells more easily
Practice Questions
• The ______ Valve(s) help prevent backflow of blood into the atrium
a) AV b) Tricuspidc) Bicuspidd) All of the above
Practice Questions
• The ______ Valve(s) help prevent backflow of blood into the atrium
a) AV b) Tricuspidc) Bicuspidd) All of the above
Practice Questions• i. Purkinje Fibres• ii. AV Node• iii. Bundle of His• iv. SA Node• The correct pathway of conduction for cardiac cells to
contract is:a) i, ii, iii, ivb) iv, ii, i, iiic) iv, ii, iii, id) ii, iii, iv, i
Practice Questions• i. Purkinje Fibres• ii. AV Node• iii. Bundle of His• iv. SA Node• The correct pathway of conduction for cardiac cells to
contract is:a) i, ii, iii, ivb) iv, ii, i, iiic) iv, ii, iii, id) ii, iii, iv, i
Practice Questions
• The region marked as T corresponds to:a) Atrial contractionb) Ventricular depolarizationc) An irregular heart beat showing blocked AV conductiond) Ventricular repolarization
Practice Questions
• The region marked as T corresponds to:a) Atrial contractionb) Ventricular depolarizationc) An irregular heart beat showing blocked AV conductiond) Ventricular repolarization
Blood Vessels
Lumen
- Endothelial cells (all vessels)
- Vascular Smooth muscle Regulates diameter (vasoconstriction vs. vasodilator)
- Elastic Connective Tissue
- Fibrous Connective Tissue
Blood VesselsBlood Vessel Type Description
Artery Thick walled (endothelium, elastic fibre, smooth muscle, fibrous tissue), to withstand high pressure
Arteriole Smallest arteries: smooth muscles and endothelium
Capillary Smallest blood vessels: epithelium
Venule Smallest veins: epithelium and fibrous tissue
Vein Low pressure blood transport: (endothelium, elastic fibre, smooth muscle, fibrous tissue),
Blood Flow
Blood Flow• Flow is proportional to pressure difference (ΔP)
-Kinetic component of pressure (in direction of flow)-Static component of pressure (hydrostatics on walls of vessel)
• Myogenic Autoregulation- Stretch receptors in blood vessels cause constriction
• Paracrine Hormones – Endothelium cells affect cells around them
• Nerves of Sym. Nervous System: NE Bind α receptors for constrictionEpinephrine Bind α receptors to reinforce constriction
• Hormone Signals Epinephrine binds β2 receptors, vasodilation, smooth muscle of heart, live, muscles
Pressure
• Pressure Increases with decrease volume (the squeeze)
• Pressure decreases with friction (also known as resistance)
• R = 8Lη/πr4 Large impact of Radius, since L and η are normally constant
• Flow is inversely proportional to Resistance (proportional to r4)
Blood Pressure
• Systole Pressure Highest Arterial Pressure (when ventricles contract)
• Diastole Pressure Lowest Arterial Pressure (when ventricles relax)
• Sphygmomanometry Cuff inflates to cut off blood flow, then deflated
Cuff Pressure = Systolic pressure blood will flow, but will be turbulent (Korotkoff Sound)
Cuff pressure lowered still, when cuff pressure = diastolic pressure, no sound/turbulence
Mean Arterial Pressure
• Mean Arterial Pressure = Diastolic + 1/3 (systolic – diastolic)
• Affected by cardiac output, blood volume, peripheral resistance (radius change of blood vessel)
CNS regulation of Blood Pressure
• Baroreceptors stretch receptors in carotid artery (brain BP) and aorta (body BP)
• High BP- Stretch receptors increase in firing rate Action potentials to Medulla of CNS efferent pathway decreases sympathetic/increases parasym. output vasodilation, decrease heart contraction force, lowered heart rate, decreased cardiac output DECREASE in BP
CNS regulation of Blood Pressure
• Low BP- Stretch receptors Decrease in firing rate Fewer Action potentials to Medulla of CNS efferent pathway increases sympathetic/decreases parasym. output vasoconstriction, increase heart contraction force, increased heart rate, increased cardiac output INCREASE in BP
BloodComponent Decription
Plasma Fluid
Red Blood Cells
Erythrocytes, most abundant (37-54% of total blood volume hematocrit)Haemoglobin protein in cells binds Oxygen, CO2Lack nuclei and mitochondria
White Blood Cells
Leukocytes immune responseLymphocytes, Monocytes (macrophage), Granulocytes (neutrophils, eosinophiles, basophils/mast cells)
Platelets Thrombocytes blood clotting, made from megakaryocytes, no nucleus (more of a cell fragment)
Haemoglobin
• Protein that binds O2, made of 4 chains (globins),
• Fetal form binds O2 released by mother
• Iron (Fe) necessary for O2 binding (70% of iron in body)
• Sigmoidal Curve of O2 binding
O2 Concentration
% b
ound
hem
e gr
oups
Lungs
Body Tissues
Regulation of HemeFactors Effect on Haemoglobin-O2 binding
Temperature Increase in temperature decreases O2 binding
CO2 Increase decreases O2 affinity
pH (Bohr effect)
Low pH decreases O2 affinity
2,3-diphospho-glycerate (2,3-DPG)
-By-product of glycolysis (main energy source of RBC since no mitochondria)-Binds haemoglobin to decrease O2 affinity-Helps acclimatization to new environment
Haematopoiesis
• Blood cells produced in bone marrow from pluripotent haemapoetic stem cells
• Uncommitted stem cells many fates possible• Progenitor Cells Committed to 1 or 2 cell
fates
Cytokines
• Guide cell fate in haematopoiesis • Small peptide signals• E.g. Colony-stimulating factors
Interleukins- released by 1 WBC to act on another WBC
Thrombopoeitin –regulates formation of megakaryocytes
Erythropoietin- RBC development
Stem Cell FatesCell Type Factors Description
Leukocytes Colony Stimulating Factors released by endothelial cells, marrow fibroblasts and WBC
-CSF induce cell division an maturation-Leukocytes can release cytokines to produce more leukocytes (response to infection)
Megakaryocyte Thrombopoietin (TPO) Undergo mitosis up to 7 times without dividing (polyploid) produce platelets with no nucleus but have mitochondria, smooth ER, granules, clotting proteins and cytokines
Erythrocytes Erythropoeitin (EPO) glycoprotein made in kidneys
EPO synthesis signalled by low O2
Haemostasis
• 1) Vasoconstriction Decrease blood flow• 2) Platelet plug Platelets stick to exposed collagen;
cytokines promote platelet formation; activated platelets stick together to slow blood flow and begin clotting
• 3) Factor XII, collagen, tissue factor III activate plasma proteins thrombin activated and cleaves fibrinogen to fibrin and activates factor XIII fibrin cross-linked to long fibres by factor XIII clot forms
• Healing has plasmin dissolving clot (fibrinolysis)Thrombus is extensive clotting that blocks blood vessel
Practice Questions
• Which of the following promotes O2 binding to haemoglobin?
a) COb) High temperaturec) Replacing normal haemoglobin with fetal
haemoglobind) Low pH
Practice Questions
• Which of the following promotes O2 binding to haemoglobin?
a) COb) High temperaturec) Replacing normal haemoglobin with fetal
haemoglobind) Low pH
Practice Questions
• Which one of the cytokine:cell fate pairs is mismatched?
a) EPO:RBCb) Thromopoietin:megakaryocytesc) Colony Stimulating Factor:Leukocytesd) All of the above are correctly matched
Practice Questions
• Which one of the cytokine:cell fate pairs is mismatched?
a) EPO:RBCb) Thromopoietin:megakaryocytesc) Colony Stimulating Factor:Leukocytesd) All of the above are correctly matched
Respiratory System
• Four functions1) Gas exchange between blood & atmosphere2) Homeostasis of blood pH3) Protection from foreign particles/pathogens4) Vocalization
Respiratory System-StructuresSystem Function
Conducting System
Airways which move gas through respiratory system1) Upper respiratory Tract: mouth, nasal cavity, pharynx, larynx2) Lower Respiratory Tract: trachea, primary bronchi, branches, lungs- Help condition the atmospheric air by warming it to body temp, adding
water vapour, and trapping foreign matter in mucusExchange Surface Alveoli Gas exchange with blood
-Made of tiny hollow sacs at ends of terminal bronchiole-covered by capillary network (circulatory system)Type I alveolar cells long and thin, good for gas exchangeType II alveolar cells small & thick, secrete surfactant (molecule which helps lungs expand by reducing surface tension)
Pumping system Thorax muscles and bones Force generate moves air through conducting system-pleural sac forms membrane around lungs which contains fluid that acts as a lubricant
Lungs
• Lung Volume depends on transpulmonary pressure (ΔP between alveolar pressure and intrapleural pressure) and elasticity of lungs (how easily they inflate)
• Boyles Law: P1V1 = P2V2
Lung Pressure
Lung Lung
Pleural Sac
Alveolar Pressure
Interpleural Pressure
Respiratory CycleInspiration Expiration
Somatic Motor Neurons Impulses signal contraction Impulses Stop
Thorax Expands Relaxes to original position
Muscles Diaphragm, external intercostals, scalene muscles contract
Relax (elastic recoil)/internal intercostals & abdominal muscles can force thorax contraction
Intrapleural Pressure Decreases Increases
Transpulmonary Pressure
Increases Decreases
Alveolar Pressure Decreases Increases
Lung Volume Increases Decreases
Air Flow Into lungs Out of Lungs
Lung Compliance and Elastance
• Compliance: Magnitude of lung volume change for given pressure change
• Lower Compliance Harder to Expand Lungs-Fibrotic Lung Disease Scar Tissue decreases lung
compliance-Low Surfactant Decreases Compliance Surfactant
produced by type II alveolar cells required to lower lung surface tension to make it easier to expand
Lung Elastance
• Elastance: Degree to which the lung will return to its original volume
• Low elastance Expiration must be active-Emphysema: Elastin fibres destroyed, low
elastance, breathing out must be forced
Practice Questions
• Disruption of Type II alveolar cell activity would result in:
a) Decreased gas exchange with bloodb) Lowered surfactant levelsc) Emphysema d) Low lung compliancee) B and Df) C and D
Practice Questions
• Disruption of Type II alveolar cell activity would result in:
a) Decreased gas exchange with bloodb) Lowered surfactant levelsc) Emphysema d) Low lung compliancee) B and Df) C and D
Airway Resistance
• Resistance depends on airway radius (R = 8Lη/πr4) can change bronchiole diameter with nervous system (parasym.)/hormones to alter pressure
• CO2, epinephrine (β2 receptors) can cause bronchodilation
• Histamine, parasym. nerves cause bronchoconstriction
Pulmonary FunctionLung Volumes Symbol Description
Tidal Volume VT Volume of air moved during normal inspiration/expiration
Inspiratory Reserve Volume
IRV Maximum volume of air that can be inspired above tidal volume
Exspiratory Reserve Volume
ERV Maximum volume of air that can be expired below tidal volume
Residual Volume
RV Amount of air left in lungs after maximum expiration
Vital Capacity VC Maximum amount of air that can be moved in/out of the respiratory system VC = IRV + ERV + Vt
Total Lung Capacity
TLC Total volume of air that can be in the lungsTLC=VC + RV
Efficiency of BreathingSymbol Description
Minute Volume/Total Pulmonary Ventilation
MV Rate of pulmonary ventilationMV= (VT)(Respiratory Rate in breaths/min)
Dead Space Volume of air not in contact with alveoli (in trachea, bronchi, bronchioles)
Alveolar Ventilation
Amount of air which reaches the alveoli per minuteAlveolar Ventilation = (Ventilation Rate )(VT-Dead Space)
Gas Transport• Oxygen transported bound to haemoglobin• CO2 transport through either binding to proteins (N-terminal
end) or conversion to carbonic acid (H2CO3) by carbonic anhydrase (lowers blood pH) HCO3
- exchanged with Cl- to transport molecules out of RBC until equilibrium shifts in lungs
CO2 + H2O ↔ H2CO3 ↔ HCO3- + H+
Gas Transport
O2
CO2
HCO3-
Cl-
In Capillaries
O2
CO2
HCO3-
Cl-
In Alveola
Plasma
RBC
Ventilation Control
• Contraction of respiratory muscles initiated in medulla by Central Pattern Generator– Dorsal Respiratory Group (DRG) Inspiratory
neurons control external intercostal muscles, diaphragm
– Ventral Respiratory Group (VRG) Active Expiration Neurons Control internal intercostal muscles, and abdominal muscles
Chemo-/Mechanoreceptor RegulationPeripheral Chemoreceptors
Located in carotid & aortic bodies; sense O2 and pH levels in bloodDecreased PO2, pH Increased ventilation
Central Chemoreceptors
Located in medulla oblongata; Increase PCO2 Increase ventilation; Decrease PCO2 Decrease ventilation
Irritant Receptors (mechanoreceptor)
Airway mucosa; stimulates parasym. nerves to cause bronchoconstriction
Stretch receptors(mechanoreceptor)
In lungs; sense over-inflation and terminate ventilation (Hering-Breuer Inflation Reflex)
Practice Questions
• The volume of air that can be voluntarily moved via respiration:
a) Is equivalent to the total lung capacityb) Is the total lung capacity minus the residual
volumec) Is less than the inspiratory and expiratory reserve
volumesd) Includes air left in lungs after maximum
expiration
Practice Questions
• The volume of air that can be voluntarily moved via respiration:
a) Is equivalent to the total lung capacityb) Is the total lung capacity minus the residual
volumec) Is less than the inspiratory and expiratory reserve
volumesd) Includes air left in lungs after maximum
expiration
Immune System
• 1) Protect body from microbes, parasites, allergens
• 2) Remove dead, damaged tissue• 3)Recognize and remove abnormal cells
Immune System Diseases
• Autoimmunity Immune system attacks the body’s own cells
• Overactive Responses Allergies• Lack of response immunodeficiency
Immune System Organs/Tissues
• Lymphoid Organs and Lymph carry lymph (Clear Fluid) which lymphocytes can travel through
• Lymphocytes = leukocytes that can access lymph system
• Lymph nodes in various places around body
Lymphoid OrgansLymphoid Organ Type
Examples Function
Primary Bone Marrow, Thymus Organs where lymphocytes Develop; all blood cells orginate in bone marrow, only B-Cells mature there; T- Cells mature in Thymus
Secondary Spleen, lymph nodes, tonsils, Gut Associated Lymphoid Tissue
where lymphocytes interact with each other and other leukocytes, coordinate and initiate responses; filter blood and lymph for pathogens-Afferent Lymph Vessel Brings lymphocytes from periphery (body)-Efferent Lymph Vessel Sends lymphocytes to periphery (body)
LeukocytesLeukocyte Subdivision DescriptionEosinophils Granulocyte (have granules),
Phagocyte (ingest pathogens), Cytotoxic (kills other cells)
-Bright pink staining granules; parasite defense, allergic response, 6-12 h lifespan; found in digestive tract, lungs, genital tract, skin-Granules are storage of cytotoxic molecules which is spewed at bound parasite
Basophils (Mast Cells)
Granulocyte Allergic response; Dark blue granules; Basophils in blood, mast cells in tissue; granules of histamine, heparin, cytokines;Found in digestive tract, lungs, skin
Neutrophils Granulocyte, Phagocyte , 50-70% of all leukocytes; 3-5 lobed nucleus (polymorphonuclear PMN); 1-2 day lifespan; in circulatory system or tissues; granules have cytokines to initiate fever/inflammatory response
LeukocytesLeukocyte Subdivision DescriptionMonocytes (macrophages)
Phagocyte , Antigen Presenting Cell (APC, display pathogen fragment on cell surface)
1-6% of leukocytes;Monocytes in blood (8 h) then move to tissues (machrophage); digest old RBC and dead neutrophils, can phagocytose 100 bacterial cells; digested pathogens have fragments placed on surface of phagocyte for APC function
Lymphocytes Cytotoxic (some), APC 20-30% of leukocytes; 5% found in blood, the rest in lymphoid tissue; acquired immune response (remember pathogens that have been encountered in the past)
Dendritic Cells Phagocyte, APC Phagocytes with long extensions; found in skin; digest pathogens and then present antigens (APC) to become activated move to 2ary lymphoid organs to activate lymphocytes
HaematopoesisProgenitor Cells Cells Derived
Erythrocyte progenitor Erythroblasts reticulocytes erythrocytesMegakaryocyte Progenitor Megakaryocyte thrombocytesGranulocyte Progenitor Eosinophils,
BasophilsNeutrophils
Macrophage Progenitor MonocytesDendritic cells
Lymphoid Progenitors Natural Killer Cells (innate immune response)B Lymphocytes (acquired immune response)T Lymphocytes (acquired immune response)
Practice Questions
• Monocytes:a) Will become macrophages in the tissueb) Will degrade dead cellsc) Are APC’sd) Are not granulocytese) All of the above
Practice Questions
• Monocytes:a) Will become macrophages in the tissueb) Will degrade dead cellsc) Are APC’sd) Are not granulocytese) All of the above
Immune Response
• Detect Foreign Substance• Communicate with Immune Cells• Recruit & coordinate response• Destruction of invader
• Antibodies molecules that bind antigens• Cytokines Molecules that differentiate
leukocytes
Innate Immune Response
• Rapid and Non-specific• Always present; clear 95% of all pathogens• Includes physical (skin), and chemical (mucus) barriers,
as well as patrolling non-specific leukocytes• Innate Leukocytes mostly phagocytes (macrophages,
neutrophils) ingest invaders, secret molecules to attract other immune cells
• Phagocytes can recognized foreign particles, or particles tagged (opsonized) by blood proteins (opsonin)
Innate Immune Response
• Natural Killer Cells Lymphocytes, can cause apoptosis in infected cells (viruses), or tumour cells, produce:– Interferons (Cytokines) α, β interferon prevent
viral replication γ interferon recruits macrophages, etc
Inflammation
• Part of Innate Immune Response• Swelling attracts immune cells, causes fever,
prevents pathogen spreading (barrier quarantine)
• Caused by Cytokines: Interleukin-1 acts on endothelial cells of blood vessel, liver cells (damage control blood proteins), induces fever, stimulate other cytokine production
Complement Proteins
• Opsonins, chemotaxins, Membrane Attack Complex (MAC)
• MAC proteins makes holes in pathogen membrane to introduce ions osmosis caused cell to swell/lyse
Ions, Water
Lyse
Acquired Immunity
• Antigen specific recognize specific pathogens• T, B-cells are mostly specific to certain antigen,
which when bound causes clonal replication (many cells that target the specific pathogen) that are either effector cells (destroy pathogen) or memory cells (remember pathogen)
B Cells• B cells: Develop in bone marrow (humans) or
Bursa of Fabricius (chickens); Produce Antibodies (immunoglobins)
• Activated B Cells become plasma cells (short lived) produce a LOT of antibodies
• Primary response naive cells become specialized for new antigen; response is slow and low Ab concentration produced
• Secondary response Rapid, many antibodies produced, mediated by memory cells
AntibodiesImmunoglobin Function
IgG 75% of plasma Ab (found in blood), secondary response Ab activates complement proteins , opsonizes
IgA In Secretions neutralize pathogens before it gets into the body; 2 Y unit dimer
IgE Allergic responses Recognized by Mast cells
IgM Primary response activates complement; linked Y units
IgD Found on B cell surface with IgM
Antibodies
Fc Region-Determines Ab class; elicit response
Fab Region
Ag Binding -Make up 20% of proteins in blood; good against extracellular pathogens
Antibody Functions
• 1)Act as opsonins• 2) Cause aggregation of pathogen• 3) Neutralize toxins• 4) Activate complement• 5) Activate B cells; have Ab that act as
receptors• 6) Activate NK cells; Fc receptors• 7) Activate Mast cells; Fc receptors
T Cells
• T Cells: Mature in thymus; bind Ag on Major Histocompatibility Complex
• Class I MHC Peptides are presented in MHC to Cytotoxic Tc cells - Tc cells kill cells infected with viruses since they present viral proteins
• Class II MHC present on surface of specialized immune cells (APCs); bound by Helper T cells
T Cells– Cytotoxic T Cells (Tc) Kills cells expressing certain
antigen (present on Class I MHC)
T CellInfected
CellAg MHC
Factor Effect on Target CellPerforin Forms pores in target cell
Granzymes Activates apoptosis
Fas Death receptor on target cell that can be activated by T Cell
T Cells– Helper T Cells; bind antigens on MHC class II on
APCs, secrete cytokines to activate B cells and other T cells
T CellInfected
CellAg MHC
Extracellular Bacteria• 1) Complement activates by bacterial cell wall
components chemotaxins attract leukocytes, MAC lyse bacteria, opsonize bacteria
• 2) Haemostasis if blood vessel breaks (swelling)• 3)Cytokines produced by complement/phagocytes,
activated lymphocytes present antigens• 4) TH Cells activate B cells (cytokines)• 5) B cells produce Ab
Viruses
• 1) Extracellular phase Ab opsonize, Phagocytes neutralize – prevent entry into cells
• 2) Infected Host cells produce Interferon β; macrophage produce interferon α Antiviral state
• 3) Cytokines secreted by host cells activate NK and Tc cells
• 4)Tc Cells recognize infected cells via MHC class I and kill it
Allergic Response• Inflammatory response caused by antigens• -Atopic individuals have excessive response which causes
more harm than antigen• Immediate Hypersensitivity Ab mediated• Delayed Type Hypersensitivity T cells and Macrophage
mediated• Sensitization first (Ag ingested by APC, activates TH cells, and
B cells memory cells• Re-Exposure: IgE on masts cells detects allergen Mast Cells
degranulate Histamines, cytokines inflammatory reaction
Practice Questions
• Which of the following is not a granulocyte?a) Neutrophilsb) Monocytesc) Mast Cellsd)Eosinophils
Practice Questions
• Which of the following is not a granulocyte?a) Neutrophilsb) Monocytesc) Mast Cellsd)Eosinophils
Practice Questions
• Cytotoxic T cells:a) Are part of the innate immune responseb) Recognize antibodies on the MHCc) Are lymphocytes that produce granzymesd)Develop in the Bursa of Fabriciuse) Bind to MHC found only on specialized
immune cells
Practice Questions
• Cytotoxic T cells:a) Are part of the innate immune responseb) Recognize antibodies on the MHCc) Are lymphocytes that produce granzymesd)Develop in the Bursa of Fabriciuse) Bind to MHC found only on specialized
immune cells