1
Q
Mechanisms of intercellular communication
A
- Direct communication
- gap junctions
- membrane (tunneling) nanotubules
-mechanosignals - Indirect communication
- chemical messengers
2
Q
Connexons
A
- subunits that form a channel (gap junctions)
- pore size is very small
- permits passage of sugars, amino acids and ions between cells
- found in all cells except mature skeletal muscle
3
Q
Gap junction
A
First type of direct intercellular communication
Includes connexons and intercalated disks
4
Q
Intercalated disks
A
Type of gap junction in cardiac muscle
- allows for rapid and propagation of action potentials for rhythmic contractions
- smaller than connexons
- can be acutely regulated (deactivated/activated) by dephosphorilation/phosphorylation
5
Q
Nanotubes
A
Membrane nanotubes are a form of direct intercellular communication
- formed from the plasma membrane
- longer than gap junctions
- have larger pore diameter
- transfer nucleic acids, even small organelles between cells
-might be a way to transfer cellular components from stressed to healthy cells 
6
Q
Mechanosignal transduction
A
Conversion of mechanical Stimuli into a cellular response 
Direct physical stress to cells, eliciting a chemical or metabolic response
Ex. mechanical stress to muscle fibres from weightlifting, resulting in increased protein synthesis
7
Q
Indirect intercellular communication via chemical messengers
A
When you have 2 cells but nothing is directly connecting them
- paracrine
- neurotransmitters
- hormones (hydrophilic and phobic messengers)
8
Q
Paracrine
A
Chemical messenger
- clotting factors, growth factors
- lots of chemical messengers can
Act in a paracrine manner, or endocrine manner 
- ex. Estrogen
9
Q
Neurotransmitters
A
Chemical messengers
Characteristics
1. Synapse distance is SHORT
Neurotransmitter signal must be tightly controlled.
- Not too many molecules released
- need an auto shut off.
10
Q
Hormones
A
 Chemical messengers
- can be water or lipid soluble must cross boundaries(membranes)
- have specific target receptors
11
Q
Hydrophilic messengers
A
- water loving
- ex. Insulin, epinephrine, serotonin
- stored in secretory cell
- dissolves in plasma
NO NEED FOR CARRIER!
Secreted by fusing secretory vesicles to membrane and releasing
12
Q
Hydrophobic messengers
A
- water hating or lipid living
Ex. Steroid and sex hormones
-storage is typically more limited - cannot dissolve in plasma
- NEEDS A CARRIER
crossing a lipid membrane is not a barrier
13
Q
Receptor specificity
A
- Cells express many types of receptors
- There may be 100s or 1000s receptors on a cell surface
- Amount of receptor is controllable(can be regulated up or down)
14
Q
Goal of chemical signal transduction
A
To change overall profile of cellular protein/enzymatic activity
15
Q
Components of CCN
A
Control and communication network includes
- the central nervous system (brain and spinal chord
- the peripheral nervous system
(Somatic nervous system, autonomic nervous system)
16
Q
Overview of the nervous system
A
Sensory input in peripheral nervous system to central nervous to motor output in peripheral nervous system
17
Q
Sensory input
A
- input from sensory receptors
- responding to external stimuli
- in skin, muscles and joints
- in internal organs
18
Q
Motor output
A
In peripheral nervous system
Somatic nervous system
And autonomic nervous system
19
Q
Autonomic nervous system
A
Regulates involuntary activities such as heart rate breathing
Parasympathetic
Sympathetic
20
Q
Parasympathetic
A
Governs body during restful conditions
Rest and digest
21
Q
Sympathetic
A
Prepares body for stressful or emergency situations
22
Q
5 major cell types in the adult human
A
- Neurons
- Oligodendrocytes and Schwann cells
- Astrocytes
- Microglia
- Epedymal cells
23
Q
Signal transduction Lipophilic/ hydrophobic messenger acting on cell
A
- Enters cell through diffusion
- binds to hormone receptor complex - Attached to hormone response element, which binds to dna
- One hormone receptor complex can cause many mRNA to be formed
- mRNA exits the nucleus into the cytoplasm of cell
- Many proteins are formed from each mRNA
24
Q
Signal transduction
Hydrophilic messenger
A
1- the first messenger binds to the receptor on cell surface
2- GDP to GTP
- GTP binds to adrnylate Cyclades
3- Atp to cAMP (the second messenger)
4- activates protein kinase, resulting in cascade of activations of another protein
5 - protein + ATP —> protein p + adp
6- this produces a response in cell
25
G-protein
Turn signal transduction on and off in hydrophilic messengers
Responsible for moving the signal from outside the cell to inside it
Each activates adenylatr Cyclase
26
Signal amplification and total products
Hydrophilic messenger
1. One messenger binds to the receptor = 1
2. Several G proteins are activated =10
3. Each G protein activated adenylatr cyclase =10
4. Each adenylatr cyclase activates hundreds of camp mlc =5000 (enzyme is phosphodiesterase)
5. Each camp activates a protein kinase = 5000
6. Each protein kinase S phosphorylation hundreds of proteins =2500000
27
Secretion mechanism lipophilic vs hydrophilic
Lipophilic- diffusion
Hydrophilic - secretory cells
28
Transport of hydrophobic vs hydrophilic messengers in blood
Hydrophilic- dissolved
Hydrophobic- bound to carrier protein
29
Location of receptor
Hydrophobic vs hydrophilic messenger
Hydrophobic- cytosine or nucleus
Hydrophilic - plasma membrane/cell surface
30
Signal transduction mechanisms for hydrophilic vs hydrophobic cells
Hydrophilic- open/close ion
- activate membrane bound enzymes
-G- proteins and second messenger systems
Hydrophobic-
Alter transcription of mRNA (alter protein synthesis
31
Relative time of onset response and duration of response for hydrophilic vs hydrophobic cells
Hydrophilic- fast time, short duration
Hydrophobic - slow time, long duration
32
Neuroendocrine signalling system
Combines neural and endocrine signalling using neurojormones ex. Norephinephrine and antidiuretic hormone
Secreted by neuron
Messenger- neurotransmitter
Pathway- bloodstream
Target cell- endocrine cells
Specificity- receptors in target endocrine cells
Time to onset- delayed
Duration of effect- longer
33
Secretory cells nervous vs endocrine system
Nervous- neuron
Endocrine- endocrine cell
34
Target cell nervous system vs endocrine system (signalling)
Nervous- neuron, muscle, gland
Endocrine- most cell types in the body
35
Messenger (chemical signalling) nervous vs endocrine
Nervous- neurotransmitter
Endocrine- hormone
36
Pathway of communication nervous vs endocrine signaling
Nervous- across synapse
Endocrine- via bloodstream
37
Classic endocrine tissues in the body
-hypothalamus
-anterior pituitary
-adrenal glands
-pancreas
Thyroid
Sex organs
Kidneys
But in fact most tissues have endocrine function
38
Fluid secretion in intestinal lumen
Maintaining normal fluid levels in the lumen is a matter of chloride and sodium secretion
Chloride and sodium pumps are regulated by a protein kinase (and camp)
39
Cholera toxin and life threatening diarrhea
Cholera toxin activates G protein for a prolonged period so signal doesn’t turn off
Causes efflux of Cl- and Na+ and loss of 20L/day of water
40
Cystic fibrosis and cholera
Cystic fibrosis might be evolutionary response to cholera toxin since it causes fluid retention
41
Neurons built for what
- information flow
- to signal specific target cells with a specific neurotransmitter
- speed
- to be excitatory or inhibitory
- to diverge, converge and form networks
42
Myelinated vs non myelinated neuron speed
Myelinated- 6-120m/s (quicker)
Non myelinated- 0.5-2m/s (slower) very few of these
43
What age does remodelling of brains neural network begin
Age 10
44
Why might teenager be more impulsive
There’s a massive remodelling period and increase in myelination=increase in transmission speeds of neurons)
45
Oligodendrocytes and Schwann cells
Produce myelin
Oligodendrocytes-
- Found in central nervous system cns
- spam multiple axons
Schwann cells
- do not spam multiple axons
- found in PNS
46
Astrocytes
Stellate (starlike) morphology
Very important for communication
Have 5 key functions
47
5 key functions of Astrocytes
1- coordinates overall function of the blood and brain barrier and provides nutrients to feed neurons
2- coordinates function of the brain network (epithelium)
3- coordinates function at the nodes of ranvier
4- participates in/forms tripartite synapses with neurons
5- serve as super hubs for neural network via syncardium formation and calcium signalling (propagated from Astrocyte to astrocyte by gap junctions)
48
Microglia
Mobile, macrophage like immune cells
49
Ependymal cells
Line ventricles to form a Barrier
Produce cerebrospinal fluid
50
The blood brain barrier
Very tight control over what gets through to the brain
(Remember neurons are meant to be very long lived and usually don’t regenerate)
- very good at protection against most bacteria and toxins
51
What gets through BBB
Mostly very small lipid soluble compounds (fatty acids)
Caffeine
Alcohol
Glucose by specific glucose transporter GLUT1(not insulin sensitive)
52
Phineas Gage
(1823-1860)
Most of his left frontal lobe was destroyed in accident with tamping iron that went through his skull
He recovered but had a completely different personality
Early evidence that different areas of our brain network to form our personality
53
emergent properties of the brain examples
Personality, rational decision making, emotion processing
54
Imaging techniques for the brain
Provide insight to how our brain is organized
PET scans
FMRIs
55
PET scan
Positron emission tomography
Tracks glucose uptake by injecting glucose tracer in bloodstream and using gamma rays to detect which brain regions consume most glucose (active brain cells have more glucose uptake) these will light up
56
FMRI
Functional magnetic resonance imaging
Tracks blood flow (oxygenated blood vs deoxygenated blood) by hemoglobin’s magnetic properties
Active regions of brain get greater oxygen supply MRI picks up on these
57
Neurotransmitter driven networks
- norepinephrine
- serotonin
- acetylcholine
-dopamine
58
Norepinephrine network
Modulates
- attention
- arousal, memory, pain, learning, sleep wake, mood
59
Phychostimulants
Use norepinephrine network
- methamphetamine
- Ritalin/aderall
- caffeine
60
Nootropics
Smart drugs
61
Serotonin network
Modulates
- pain, sleepwake cycle, emotion
Most antidepressants work by increasing serotonin levels
Low seretonin levels also associated with migranes
62
Acetylcholine network
Modulates
Arousal, memory, learning, sensory information, sleepwake
Alzheimer’s disease patients have low acetylcholine levels
63
How do Alzheimer’s medications work
Cholesterase inhibitors
Cholesterase is an enzyme that breaks down acetylcholine in the synapse
64
Dopamine network
Modulates
Motor control
Reward pleasure centres
Parkinson’s is a disease where there’s a loss of dopamine network
Dopamine agonists are used to increase healthspan
Too much medication can cause gambling 🎰
65
Where is dopamine signal processed into pleasure
Prefrontal cortex
66
GABA
Inhibitory neurotransmitter and turns dopamine signal off
67
How do heroine and morphine work
By blocking the release of the enzyme that inhibits dopamine
68
How does cocaine work
Blocks the reuptake (backflow) of dopamine
69
PKU effects
People with pku experience drastic drops in serotonin and dopamine
Have a higher risk of depression and anxiety
Have to follow low protein/phenothalanine diet
70
Hormones of posterior pituitary
Oxytocin (OC)
Antidiuretic hormone (ADH)
These hormones are made in hypothalamus and released by posterior pituitary
71
Oxytocin
Uterine contraction
Milk ejection
Positive mood
Social cognition and behaviour
Has calming effect on the mother
Low levels associated with autism
72
Antidiuretic hormone
Retention of fluid by kidneys
Plays important role in blood pressure regulation
Increased ADH release with heart failure, leads to water retention and increased release in respiratory to severe blood loss or dehydration
73
Hormones of the anterior pituitary
See notes man
But like growth hormone, thyroid hormone, follicle stimulating hormone and prolactin inhibiting hormone as examples
74
Neurotransmitters vs neurohormones
Neurotransmitters- chemical messengers released by neurons that transmit signals to adjacent cells typically within the nervous system act as synapses, the junctions between nerve cells and their target, the cells, neuron, muscle, or other gland
Neurohormones- neurotransmitters that instead of acting as synapses are released into the bloodstream by neurons once in the bloodstream, they travel to distant cells or organs, where they exert their affects in this way neurohormones act more broadly on the body
75
The local support and defence system
Consists of the nonspecific defenses, and the specific defences 
76
Nonspecific defenses
Natural not learned through experience, also known as innate immune system includes the first and second line of defence 
77
First line of defence
Nonspecific, physical and chemical surface barriers examples tears wash away irritating substances skin is a physical barrier saliva acid in the stomach bladder. 
78
 Second line of defence 
Non-specific, internal cellular and chemical defence includes internal resident cells, proteins, inflammation, and fever, identifies foreign non-self matter, but isn’t specific and doesn’t develop a memory 
79
Specific defence
Aka the adaptive immune system
Activated if pathogen survives specific defences
Includes the third line of defence
80
Third line of defence
Immune response
81
Defensive cells examples and functions
From second line of defence
Examples- phagocytize cells such as neutrophils and macrophages, eosinophils, natural killer cells
Function: engulf invading organisms, kill parasites 🦠
82
Macrophage
Phagocyte
engulfs bacterium
83
Natural killer cells
Part of second line of defence defensive cells
Constantly circulate and patrol for non self
Target cancer cells
Release perforin and proteins to destroy cells
84
Phagocytes
Part of second line of defence defensive cells
Neutrophils- first on scene, consume bacteria
Macrophages- consume almost anything
85
Eosinophils
Part of second line of defence Discharge enzymes that digest target
86
Defensive proteins
Part of second line of defence Interferons
Complement system
Function: slow the spread of viruses in the body
Stimulates histamine release, promotes/kills bacteria, enhances inflammation
87
Inflammation
Part of second line of defence
Widening of blood vessels and increased capillary permeability leading to redness, heat, swelling and pain
88
Fever
Part of second line of defence
Abnormally high body temperature that slows growth of bacteria, speeds up body defences
89
Complement system
Protein based defence
Part of second line of defence
20+ proteins synthesized,
mainly in the liver
released in inactive form
normally deactivated by native proteins in the blood and surface of the body zone.
Enhances the ability of antibodies and phagocytic cells to clear microbes and damage cells from body
promotes inflammation
and attacks the pathogens cell membrane
90
Parenchyma cells
- functional portion of tissue(gland/organ)
-serve a purpose related to that cell
-most prominent in terms of mass
Ex. Muscle - myocyte
91
Parenchyma cell for liver, skeletal muscle, heart, brain
Liver- hepaticyte
Muscle- myocyte
Heart- cardio myocyte
Brain- neurons
92
Stromal cells
Aka non parenchyma cells
Support cells
Like a framework- support the parenchyma cells forming the LSDS through physical support and structure
Ex. Astrocytes- support neural functions, BBB
Cells of lymphoid origin - Tcells
Gap junctions- communicate between parenchyma cells
Often more branches in nature for structural support
93
LSDS
Local support and defence system
Does more than just defend against invading microbes
It’s always on
View it as watching and waiting for invaders
Has 3 main functions
94
Functions of LSDS
1) Local tissue damage by processes that are not due to infectious pathogens
2) normal tissue turnover: cell death, tissue repair, regeneration due to wound healing
3) looks out for appearance of transformed cell poplulations
95
Third line of defence
Aka the adaptive immune system
Activated in response to bacteria, viruses, cancer
Not born with it
96
MHC
Major histocompatibility complex
- markers are proteins expressed on the surface of cells
- used in the recognition of pathogens (attack!)
But also to recognize self (support!)
Like ID
Displays both self and non self antigens
97
Self MHC marker
Labels the body as self or friend (support)
98
Antigen
A molecule often in the surface of a pathogen that the immune system recognizes as a specific foe (ATTACK!)
Like a tag that says I’m a bad guy
99
Steps in the third line of defence
Step 1- threat
- an invader enters body (antigen)
Step 2- detection
- a macrophage encounters, engulfs and digests the invader
- macrophage places an antigen on its surface to identify invader
Step 3 - alert
- the macrophage presents the antigen to a helper T cell and secretes a chemical which activates helper T cell
Step 4 - antibody and cell mediated response
100
What set of signals activate helper T cells
Involves
1. Recognition
2. Verification (just to be sure it’s responding to non self
101
Cell mediated response
Final step of the third line of defence
Activated by effector T cells
Effector cytotoxic T cells target and kill infected cells by chemical means such as perforation
Memory T cells are stored for continued surveillance
102
Antibody based immunity
B cell route of attack
Effector helper T cells activate naive B cells
Cells divide to effector cytotoxic B cells which secrete antibodies!
Memory Bcells are stored
103
Antibodies
Neutralize foreign proteins (toxins)
Trigger release of more complement
Attract more macrophages
Attack foreign antigens wherever they find them
But B cells themselves don’t engage
104
Types of memory cells
1. Memory helper T cells
2. Memory cytotoxic Tcells
3. Memory B cells
105
Where are memory cells stored
Bone marrow and thymus
106
How do memory cells help for future attack
Provide quicker more robust response in subsequent encounters
107
T suppressor cells
Provide negative feedback
Suppress activation of the immune system, particularly production of helper T cells
This is important in allowing tolerance to self antigens
108
Too little vs too much T suppressor response
Too little = autoimmune disease m, allergies, IBS
Too much= increased incidence of infectious disease
109
3components of cardiovascular system
Heart- muscle pump
Blood vessels - conduits for blood flow
Blood- fluid that circulates through the body and Carrie’s materials between cells
110
Affiliated tissues with cardiovascular system
MANY
Lymph, cerebrospinal fluid. Extracellular fluid
Kidney, lungs
Spleen, thymus tonsils bone marrow etc
111
Cardiovascular + lymphatic
= circulatory system
112
Examples of cardiovascular disease
Coronary artery disease
Stroke
Heart attack (myocardial infarction)
Heart failure
Hupertension
Diabetes
113
Blood vessels
Conduit blood in continuous loops
Veins
Venues
Capillaries
Arterioles
Arteries
114
Pathway of blood through the heart
Deoxygenated blood comes from veins in body to inferior vena cava, right atrium, right AV valve, right ventricle, right semilunar/pulmonary valve, pulmonary trunk, pulmonary arteries (one for each lung), pulmonary arterioles, capillaries where has exchange occurs then oxygenated blood goes to pulmonary ventless, then pulmonary veins, left atrium, left av valve, left ventricle, left semilunar valve/aortic valve, aorta, arteries and arterioles etc.
115
Main site of Blood Pressure regulation
Arterioles
Since lots of innervation to control muscle control
116
Capillaries
Blood vessel
No muscle, no control over tiny diameter, no ability to withstand high pressure, thin walled, movement of fluids is maximized here
Low velocity high surface area perfect for exchange of nutrients gases waste
117
Arteries
Carry blood away from heart
Thick muscular walls designed to handle high pressures
118
Main site of lymphocytes
Venules
(White blood cells) crossing from blood to lymph nodes
119
Veins
Blood vessel
Carry blood to heart
Thin walled, fairly muscular for easy expansion and recoiling
120
Dyslipidemia
Plaque/LDL cholesterol build up
Normal arteries are open, allow for efficient blood flow but not here
121
Atherosclerosis
Consistent build up of LDL cholesterol/plaque
122
Cardiac output
Amount of blood pumped by the heart per minute
Product of heart rate x stroke volume
123
Resting blood flow cardiac output
5L/min
124
Exercise blood flow/cardiac output
25L/min and most goes to skeletal muscles
125
How do veins move blood against gravity
Pressure gradient between left and right side of the heart
Facilitated by:
Valves (prevent blood flowing backwards)
- contracting skeletal muscle
- expansion of thoracic cavity during breathing
126
Varicose veins
One way valves malfunction
Allow backwards flow of blood and pooling
Generally occurred is in superficial veins of thigh and calf
127
Saphenpus vein
Longest vein in the body
128
Myocardium
Cardiac muscle tissue
129
What makes cardiac muscle tissue different from skeletal muscle?
Neural input- autonomic/involuntary
Neural conduction- gap junctions, very fast, contract as a unit
Metabolism- very high oxidative capacity
- lots of miochindria (35%) vs 5% in skeletal muscle
- fatigue resistant!
130
Lub sound
Generated by the closing of the AV valves as the blood goes from the atriums to ventricles
131
Dub sound
Closing of the semilunar valves (pulmonary and aortic valves- connecting ventricle to artery) makes dub sound
BIOL1080
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