biol 273 exam

BIOL 273 Exam

Introduction

• James England• 4th Year Biochemistry Student• Research focus on the molecular causes of aging in

yeast

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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