Physiology
310 -- Oct. 20, 2007
STUDY/REVIEW
OUTLINE II
You may need to review the first lectures' basic concepts & mechanisms,
used ALL SEMESTER!
NOTE: Sample
exam does not have Endocrine or Immune, which WILL be covered on Exam II in
2007.
SELF-REGULATING: Principles &
Mechanisms
-A.
HOMEOSTASIS--Key concepts=Negative
feedback; variations=antagonistic, behavioral & tonic effectors
-B.
REGULATED CHANGE--Key concepts=RESET
Systems including temporary and cyclical work; and POSITIVE FEEDBACK
-C.
ENHANCED REGULATION--
Key
concepts=ANTICIPATION (feedforward) and ACCLIMATIZATION
HIERARCHY OF REGULATION
Local vs Higher regulation: know the logic/usefulness of this fundamental
design feature
EVOLVING--Principles--Proximate/mechanistic ("how it
works") vs. Evolutionary ("why it evolved") and Teleological
(purpose)--be able to apply! How this leads to less-than-logical features such as the
VERTEBRATE RETINA, possible
VESTIGES like the human Vomeronasal Organ.
|
MOLECULAR &
CELLULAR PHYSIOLOGY: BASICS TO REVIEW |
+Protein
Structure/Function--basic features of primary to quaternary structure (e.g.,
alpha-helix)
+PROTEIN
REGULATION:
allosteric
, phosphorylation,
voltage change,
and physical distortion as ways of regulating/changing protein functions
--KEY POINT:
MACROMOLECULES and WEAK BONDS lead
to WHOLE-ORGANISM HOMEOSTASIS
+GENE
REGULATION:
the response-element (=enhancer) and promoter aspects of gene regulation with
specific transcription-activating proteins
+MEMBRANES and movement
mechanisms: know key parts about Diffusion, Conductance and Active Transport
+INTERCELLULAR COMMUNICATION --basic mechanisms of receptor types (2nd
messenger
and internal receptor), types of signals, same-key-different-locks principle;
drug effects ([ant]agonists)!
NEURONAL PHYSIOLOGY
GLIAL CELLS: roles; how MYELIN speeds up transmission by
eliminating Capacitance except at Nodes.
|
NERVOUS SYSTEMS |
STUDY
METHODS: from
patch clamp
to fMRI
and TMS
EVOLUTION:
HIERARCHY: recall the logic
of local/intrinsic vs higher/extrinsic control. Here, all neural types are
EXTRINSIC, but at many levels. The more advanced animals have at least 2 neural
levels beyond intrinsic cell/organ regulation:
A. Simple
Reflexes with
few synapses: for common, crucial, simple homeostasis needs requiring 2 or more
organs (e.g., sensor and muscle). Advanced animals still have these-- e.g., our
withdrawal reflex
from heat/pain. Know locations/functions of reflex integrators in spine, brainstem,
hypothalamus
B.
"Higher" Regulation: Evolution of centralized brains at front end, and longitudinal
nerve cords;
with AFFERENT sensory nerves coming in and EFFERENT nerves going out to
Effectors. Brain can do anticipation, memory; coordinate multiple
sensors/effectors; but lower reflexes still retained for some functions to
reduce delays.
Vertebrate
NEURAL ANATOMY
PERIPHERAL (PNS)--know basics of SOMATIC and AUTONOMIC: a)
Parasympathetic: neurons
usually inhibitory except for digestion; "rest and digest"; b) Sympathetic: neurons usually excitatory for
"fight-or-flight" (supress digestion)
CENTRAL (CNS) includes SPINE
and BRAIN -- know difference
between GREY and WHITE matter, where found, and what PYRAMIDAL cells are
|
BRAIN--4 main regions: Know functions and major divisions of the 4 regions; basic layouts, relative sizes; |
More on
CNS EVOLUTION:
major
changes in vertebrate cortexes, and motor, sensory, associative areas
MORE on
PNS; CNS-PNS BASIC WIRING!
+Efferent
PNS: know roles of ACh and NE in somatic,
parasympathetic and sympathetic neurons
+CNS-PNS
WIRING: SPINE: basic connections =Sensory afferents via dorsal branches into
spine/brainstem; Somatic Motor efferents via ventral output. BRAIN: know pathways from
sensors to thalamus to sensory cortex, then to associative cortex; from motor cortex to skel. muscles. NOTE
from LAB the implications of this as revealed by SYNAESTHESIA: Wiring is critical for
our perception of "reality"! Brain "knows" what to
sense/perceive according to thalamus relays to dedicated sensory cortexes, which perceive
specific modalities (taste, light, etc.) by unknown mechanisms. All sensors
except smell run signals first through thalamus (Smell also goes directly to
LIMBIC). If information runs into the wrong area, perception is altered
accordingly (Synaesthesia!)
HIERARCHY of
REGULATION -- all
are EXTRINSIC!!
A.
Lower Level = Spine, Brainstem, Hypothalamus
REFLEXES--simple ancient homeostasis needs; have relatively
low delay (though still some delay, as in breathing reflex during exercise if
there is no anticipation).
1) SIMPLE REFLEXES: EXAMPLES
--a) Withdrawal somatic reflex: using skin pain sensors, spinal
interneuron, muscle effector
--b) Position/Posture reflex: how stretch
sensors in muscles work via feedback to maintain posture with little delay
--c) Temperature reflex: how this
works from skin to hypothalamus to effectors
2) Reflex PATTERN GENERATORS
a) Walking, swimming etc.
Diagram of brain commanding lower Pattern Generator, which takes over to reduce
delays
b) Breathing reflex: rhythmic
in/out circuit in MEDULLA uses gas/pH sensors in arteries, breathing muscles as
effectors
3) Biological
CLOCK: SCN of hypothalamus:
anticipates regular environmental cycles. See ENDOCRINE
AN
IMPORTANT ASIDE ON MEMORY:
1) Sensory:
2) Short-term: about 7-10 active registers!
3) Long term:
•DECLARATIVE= Images,
names, facts, etc.--evolved for ANTICIPATION
of future events, faster reactions, planning, etc.
•NON-DECLARATIVE: i) PROCEDURAL--learning new non-reflex motor skills! Cerebellum,
etc.;
-- ii) EMOTIONAL--see Amygdala
below
**WORKING MEMORY: active
register, thinking area that accesses CURRENT sensory info, SHORT-TERM Memory,
and LONG-TERM memory to plan an action/decision.
B. MID_LEVEL=LIMBIC, CEREBELLUM
1. LIMBIC SYSTEM evolved for declarative memory short-term and some basic long-term, with
primitive emotional memory: basic
learning for mating & survival, anticipating basic future needs/crises.
Know **hippocampus** as basic
'ringmaster of memory' and the **amygdala** for fearful memories, Know
Neural PATHWAYS for amygdala & fight-or-flight!! How this aids survival.
2. CEREBELLUM--evolved for procedural
memory = learning non-reflex, skilled
movements. Learns then appears to anticipate (feedforward) each move in a skilled sequence to eliminate clumsiness-causing delays. Typically, MOTOR CORTEX makes the decision to move,
then the cerebellum takes over for fine control …understand the reason why
coaches often say "Don't think about it, just do it!"
C. TOP LEVEL=MAIN CORTEX:
MOTOR , SENSORY, ASSOCIATIVE
1. SENSORY CORTEXES: evolved
for complex sensory processing; example of BODY MAP in the SOMATOSENSORY CORTEX!
2. MOTOR CORTEX: evolved for initiating
motion, including new ones to be learned. EXAMPLES:
a) MOTOR Cortex CONTROL OF BREATHING vs REFLEX
--i) Anticipation to reduce delays by activating respiration just before muscle
activity begins: GLUTAMATE neuron from motor cortex to medulla-oblongata
respiratory reflex center. NO delay in oxygen delivery!!!!!
--ii) RESET: Breathholding for swimming by inhibiting
reflex homeostasis == GABA neuron from motor cortex to medulla-oblongata
respiratory reflex center. Why can't you kill yourself by this conscious
suppression???
b) CONTROL OF POSTURE vs
MOTION: Negative
feedback posture reflex: spindle stretch sensors put out certain
AP frequency to hold its own muscle in place; increase if muscle is stretched,
so reflex via spine contracts the muscle to bring back to original position:
but !! an inhibitory GABA-type interneuron MUST SUPPRESS the
opposing antagonistic muscle to PREVENT its reflex from interfering in the
opposite direction!
--MOTOR CORTEX must Reset this for locomotion: motor cortex nerve uses glutamate to activate a motor
neuron, which fires and contracts muscle. But this STRETCHES the antagonistic
muscle so: another neural branch triggers a GABA interneuron to the
motor neuron of the antagonistic muscle, to prevent its posture reflex from interfering.
What TETANUS
toxin does to cause locked-up muscles!!!!!!
3. ASSOCIATIVE AREAS--evolved for complex learning/memory, understanding,
planning, anticipation of future; "higher" emotions to reinforce
these.
SUMMARY Example--KNOW
DIAGRAM of typical PATHWAYS!! 1) Sensor
to 2) Thalamus to 3)
Sensory Cortex for perceiving to 4) Sensory Associative Area for understanding sensory info; may go to 5) WORKING memory for PLANNING then to 6) Motor
Cortex to act. MEANWHILE, from Thalamus, information may go to 3b) HIPPOCAMPUS
for short-term memory and 4b) Basal Forebrain for Long-term memory.; 5)
WORKING memory in frontal lobe can access current, short and long-term info
for making decisions!!!!
NEUROCHEMISTRY:
MOLECULAR MECHANISMS of MEMORY: much unknown, works by reprogramming or
"long-term potentiation"
[LTP] of synapses (increased sensitivities)
1. Aplysia seaslug and Short-term memory: seaslug "learns" about approaching threat
by sensitizing its gill-withdrawal mechanism when it is poked hard in the tail:
How serotonin does this via 2nd
messengers.
2. Mammal: a)
Short-term: Glutamate mechanism of fast AMPA channel AND slower NMDA channel with Ca++ as 2nd messenger, activates enzyme
for retrograde messenger NO. That enhances
pre-synaptic vesicle release in
nearby neurons, making that circuit easier to use (more sensitive).
--b. Long-term memory: Neuromodulators via receptors and 2nd Messengers
alter gene activity! How one version works:
cAMP-->protein-kinase-->CREB-->response element for genes ---> new
mRNAs and proteins. Leads to more receptors, more dendrite branches/spines, and
??
More on
NTs and NEUROMODULATORS
DEFINE Neurotransmitters (fast or slow; alter voltages) and Neuromodulators
(slow; alter functions other than voltage itself). IN
CNS: some NTs/NMs have general functions, some associated with specific
functions
**Serotonin: good mood, serenity;
helps with sleep; anti-anxiety: PROZAC and how it affects this!!!
**Endorphins
/ Enkephalins
--role in
analgesia and pleasure of the anti-pain type; what triggers this system
('runner's high'; wartime wounds; etc). How morphine affect this
**Endocannabinoids such as anandamide--appetite; some
pleasure; and clearing out some short-term memories, dreams and fear memories. How THC in
marijuana affects
this
**Dopamine: paying attention to
useful information/accomplishments and reward pleasure associated with that.
COCAINE, METHAPHETAMINE, and RITALIN drugs! NOTE dopamine is also used in motor
coordination/dampening circuits in basal nuclei; same-key-different-locks
principle. Human Mental disorders and Evolutionary History! a
"disorder" in modern society that might have been useful in the past
--ADHD example!!
**Histamine -- maintains arousal in
hypothalamus clock system; why some anti-histamines make you drowsy
FRONTIERS
of NEUROSCIENCE
*PLASTICITY: use-it-or-lose phenomenon; *GLIAL functions: new findings
in the text list and reading
*Perception, Memory, Consciousness: Neural Networks -- coordinated actions
of 1000s of neurons probably; Prions possible role; SPINDLE Cells and 'humanity'
--READING.
NeuroTheology--can human
ethics and spirituality be localized to specific brain circuits? READING
|
SENSORY PHYSIOLOGY |
I. Basic Signal
Transduction: stimulus-dependent channels or receptors: convert graded stimuli into graded
currents = Receptor Potentials. Then
must convert into frequency-coded
APs
A. TYPES of sensors: --Primary type: neuron dendrites ARE the
sensors: know graded vs AP frequency parts. Secondary types have
separate sensory cells --know signaling steps here also via NT/synapse first
B. Sensor ROLES:
1) Exteroceptors: classic five senses, but with skin senses actually
having a lot more: monitor external environment and incoming stimuli
2) Interoceptors: monitor the internal environment for homeostasis
3) Proprioceptors: monitor the body and limb positions and motions
C. TYPES of
Transductions: chemo,
mechano, photo, thermo, noci; electro; magneto
D. "ADAPTATION" RESPONSES--important
evolutionary differences
-- i) Continuous = tonic sensors--e.g.,
pain, proprioceptors do not shut off as long as stimulus lasts
--ii) Adapting = phasic: shut off even if stimulus continues; know mechanisms
of INTRINSIC inhibitory protein in cell as in SMELL; vs. EXTRINSIC neural inhibition
by GABA neuron
---- Evolutionary reasons for sensors that shut off like this !!! why ignore
constant stimuli???
E. CONTRAST ENHANCEMENT: know how lateral
inhibition (GABA) in touch, eye and
cochlea neurons enhances contrast!!
Strongly stimulated sensors suppress weakly stimulated neighbors--sharpens up
the information.
II. SPECIFIC SENSOR TYPES--Uses
& Mechanisms:
A. MECHANO-RECEPTION:
pressure, touch, stretch, vibration, gravity/position, acceleration
=Primary sensor type: mechanogated channels-- "pull-chain"
protein pops open gate.
=>Interoceptors for blood pressure; also stretch in the stomach,
bladder
=>Exteroceptors in SKIN for touch, pressure: high area of
dendritic branching for
sensitivity/leverage
=> PROPRIOception: stretch sensors in muscles, tendons, joints;
B. MECHANOreception: HAIR CELLS: Hairs = cilia with PACEMAKER activity when upright--
how cilia bending gives directional "stereo" information by
increasing or decreasing gating; pull-chain protein on cilia hooked to channel gate.
Used in
1) FISH Lateral lines--current FLOW/pressure waves,
2) MAMMALIAN INNER EAR:
----a) Vestibule--Saccule/Utricle: Linear Acceleration & Position
sensors: how otoliths in gel work
by pushing hair cells
----b) Semicircular Canals: Rotational Acceleration sensors--how 3D motions
sensed (dizziness!)
----c) Cochlea: Hearing; how basilar membrane distinguishes sound frequencies with protein
fibers like piano wires; vibrates and pushes hair cells into tectorial membrane. Note also BRAIN can shut these off!
C.
CHEMO-RECEPTION:
chemicals
open channels via receptors/2nd messengers, except for ions
INTEROceptors: most of these are chemoreceptors; monitor hormones, blood
gases, glucose, etc.
EXTEROceptors=taste and smell
-1)
GUSTATORY=TASTE = chemosensing of
solid/liquid material in direct contact with sensors
Vertebrates: ciliated taste buds
--5 Primary tastes = salt, sour, bitter, sweet umami. Know teleological
purposes for these; and the basic Mechanisms: direct channel for ions, and 2nd
messenger type for organic molecules
--Also know the Hot/spicy TRPV1 channel for capsaicin and heat
--Much detail still unsolved-- mysteries e.g. FAT TASTE; How artificial
sweeteners
work. See the READINGs
-2) OLFACTORY=SMELL=chemosensing of distant sources; accounts for
most of "taste"
Mammals: i) olfactory bulb & limbic system; ii) vomeronasal organ--READING from lab
--MECHANISM--Nobel Prize 2004: receptors with specific binding sites; cAMP
system; shut-off mechanism
~900-1500 genes for unique receptors (many mutated OFF in humans =pseudogenes);
but can distinguish 10,000+ odors. HOW? Know COMPARATIVE-Binding Combinatorial
concept of odors binding to multiple receptors
D. PHOTO-
reception:
know basic vertebrate eye
anatomy from lab.
ROD cell mechanism: i) retinene/opsin complex=RHODOPSIN: cis to trans change via photon
absorption; ii) opsin-G-amplifier cascade destroys cyclicGMP: Na channels close
=inhibition of GABA output!! --note that light REDUCES sensor voltage, but APs
increase in downline neurons due to less GABA! Then fresh cis-retinene must
enter opsin receptor to shut off the signal.
Color & CONES--how distinguished by comparative/combination
mechanism with only 2-5 CONE types (red, green, blue, UV; 3 in humans, 4-5
in birds; 2 in most mammals, 1 in cetaceans.
E.
Thermoreception:
graph of
warm TRP-V3 vs cold/menthol TRP-M8 receptor types with activations at different
temperatures; uses. Role of TRPV1 and 2 in pain
F. Nociception: 2
responses and 3 types of receptors (initial fast response = mechanical and
extreme temperature TRPV2 & V1 reception; later persistent response is
chemical and involves damage etc.)
G. Electroreception: how shark ampullae are used, how they work
H.
Magnetoreception:
possible
mechanism using magnetosomes, how used and in what animals
|
ENDOCRINE SYSTEMS |
Evolved
for slower regulation involving metabolism; mineral/water balance; growth and
reproduction;
I. BASIC REGULATORY SYSTEM AND SIGNALS
A. Complexity of Function: see list in
lecture and text
B. Three Signal Types: peptides/proteins such as insulin; amines such as epinephrine; Steroids such as cortisol: made from cholesterol.
C. Signaling MECHANISMS: 1. Lipophobic/hydrophilis ones by 2nd messenger system; lipohilic ones usually via internal receptor and gene response
element.
2. Active hormone levels depend on: secretion; activation; degradation;
binding to blood proteins
3. Receptor UP- and DOWNregulation:
see text pp259-260: example of overstimulated target cell!
II. Regulatory Patterns & Examples
EXO- VS. ENDOCRINE GLANDS: most EXOCRINE Glands are EFFECTORS, not regulators!!
Have ducts for effector chemicals. ENDOCRINE glands do not have ducts
FEEDBACK LOOPS
A) SIMPLE: example 1. PANCREAS : simple
negative feedback : From lecture and lab, know full Pancreatic Insulin-Glucagon
system!! All parts, including how glucagon works via 2nd
messenger-cAMP cascade, and insulin by tyrosine kinase system. How beta-cells
"sense" rise in blood glucose to integrate
B. Complex NEUROEndocrine: HYPOTHALAMUS-PITUITARY
i) Posterior pituitary: direct neuroendocrine nerves from
hypothalamus
ii) Anterior
pituitary: multistage, up to 3 hormones! #1Releasing hormones from neuroendocrine
hypothalamus neurons got to pituitary, stimulate classic endocrine cells to
release #2trophic hormone which stimulates either target organ or
another gland, which releasing a #3final hormone to target
organs.
-- Often monitoring of downline hormones, not always the
regulated state itself!
EXAMPLE 2: GROWTH HORMONE/Somatomedin: how this is stimulated via multiple steps for
energy/growth; what the brain monitors for feedback; how hGH injections build
the body but stop own system.
EXAMPLE 3: CORTISOL and CLOCK: how this is stimulated via multiple steps for STRESS;
what the brain monitors for feedback
; CLOCK control
Biological CLOCKS--all
eukaryotes have; even unicells; use clock genes.
Definitions:
circadian; circannual; circalunadian; Fig 7-6 example of CORTISOL
--i)
TEST: constant environment shows persistence of rhythmic behaviors--human
example in mine shaft
--ii) Evolutionary Advantages/Teleological
purpose: synchronize with and anticipate regular environmental cycles --e.g., clock prepares
for daily or seasonal change ahead of time: Sleep/wake and CORTISOL
example
--iii) MECHANISMS: Clock genes in single cells can run on
their own, but need external signal to synchronize to outside world . Cell
mechanism = positive and negative feedback loops among clock genes and proteins
cycle up and down over 24 hrs. Clock genes have "clock response
element" (specific promoter).
--Retina via special nerve to SCN of hypothalamus; sends signals to the cortex, and
indirectly activate pineal gland,
which secretes melatonin for sleep;
these may activate adenosine-using
neurons
. Open evolutionary question on SLEEP: why is it necessary at all? Repair,
consolidate/delete memories, refuel?
|
DEFENSE:
IMMUNE SYSTEMS |
Overview: A. New view as a 3rd whole-body regulatory
system
B. Functions = Defense from Pathogens ; Clean-up
debris; Anti-cancer (own cells gone bad
C. REGULATION: INNATE vs ACQUIRED : know basic differences and delay vs memory issues
D. SELF vs NON-SELF:
--1. Pattern-recognition receptor proteins (PRPs!!!)
(called TOLL-like RECEPTORS [TLR]
in vertebrates) and phagocytes; and
--2. EFFECTOR PROTEINS: i) opsonins (tags), ii) antimicrobial peptides--often by pore formation
E. SENSORS-INTEGRATORS-EFFECTORS are
often Cells/Proteins
I. INNATE OR NON-SPECIFIC IMMUNITY
A. Barrier TISSUES/ORGANS: 1st Line of
Defense; have Passive and Active features!
-- 1) SKIN + glands (tear glands, antimicrobial dermcidin);
-- 2) RESPIRATORY: mucus membranes —cilia; coughing/sneezing!
--3) DIGESTIVE: mucus; vomiting; stomach acid--how kills; symb. Bacteria;
antimicrobial peptides
--4) UROGENITAL: mucus; symb. Bacteria; antimicrobial peptides
B. CELLS & PROTEINS:
*CELLS: 1) PHAGOCYTES (Neutrophils;
Monocytes/Macrophages)--mostly Effectors to kill invaders
---know how phagocytosis works
--2) Natural Killer Cells--innate
destroyers of 'bad' body cells
that have abnormal proteins on their membranes
--3) MAST CELLS--Integrators of inflammation
--4) Microglia-- BRAIN's own special immune cells --read 2005 article
* Defense PROTEINS: Complement series of
proteins: 1) act as OPSONINS=tags
of foreign objects to signal phagocytes; 2) Act as Antimicrobial Peptides --
see Attack Complex in text" make
pores in bacterial membranes, cause ion leak with subsequent water osmosis-->pop!
C. INTEGRATION--NON-SPECIFIC REGULATORY RESPONSES
--1) INFLAMMATION: general
reaction to attack/injury:
MAST CELLS (sensor/integrators!
like thermostats) release histamine to make capillaries dilate and leak so phagocytes and complement can get
into the wound; and release chemotaxins to attract phagocytes
(effectors). Complement tags (as opsonins) invaders for destruction by phagocytes. Positive
feedback! Activated phagocytes make signals that attract more phagocytes.
Step 5: mast cells, wounded cells release prostaglandins made by COX2 enzyme; these increase blood flow and
trigger pain sensors. NSAIDS like aspirin block this!
--2) FEVER: interleukin-1
(= a cytokine, IL-1) released by
active phagocytes goes to
hypothalamus=>triggers local prostaglandin [made by Cox3, which
acetaminophen/Tylenol blocks]; this resets the brain's thermostat setpoint UP;
why this might be useful, but can be bad
--3) ANEMIA! phagocytes
release IL-6 which triggers the
liver to put out a hormone that reduces iron in the blood;; why this might be
useful but also can be bad
II. ACQUIRED or SPECIFIC IMMUNITY
A. Tissues/Organs:** Cell development: thymus, bone marrow; ** Filters,
traps: lymph and its nodes; spleen;
GALT --know functions of each
B. CELLS & PROTEINS: *CELLS: some in blood & spleen, lymph & node: 1) ANTIGEN-PRESENTING cells as SENSORS! 1) Dendritic cells in barrier tissues; 2) Macrophages in blood/lymph. How they act as key Sensors! 3) B-cells
--2) 3) Integrator/Effectors: B- and T-lymphocytes: have random unique receptors (PRPs, here called
Antigen or Ag receptors)!! Where
each matures, and nature of the Ag receptors. These are integrators and
effectors (see below)
• Defense PROTEINS:--i)
ANTIBODIES as opsonins
and antimicrobial peptides; and ii) PERFORINS as killer-pore peptides
|
Generating millions of Unique
Receptors/Antibodies: i) DNA
recombination: briefly how V,
J, C gene segments are
recombined to code for millions of unique Ag receptors and antibody proteins.
Ii) RNA editing and iii) hypermutation also contribute to variability |
C. INTEGRATION: SPECIFIC REGULATORY
RESPONSES... know all steps:
1) ANTIBODY-Mediated SYSTEM: Self vs Non-Self markers = MHCI
!!!
--a) Sensing by Antigen Presenting Cells!: Dendritic cells in barrier tissues (and , in the blood/lymph, phagocytes) eat objects
without self MHCI, and display
antigens with MHCII; migrate to nodes; "present" to inactive helper-T-cells with correct PRP receptor; also 'prime' a B-cell with the same receptor
--b) Helper T-cells are integrators: become active helper-Ts and quiescent/reserved memory-Ts
--c) Effector and memory B's:
active helper-Ts activate the 'primed' B-cells; B's clone themselves into plasma
= antibody-making effector B-cells, and into memory B-cells
--d) Antibodies made by effector ('plasma') B's; bind to, aggregate, and 'tag' antigens/pathogens;
attract phagocytes. Can kill directly with H-peroxide! [hypermutation
can increase diversity also]
NOTE that active B-cells can 'hypermutate' their antibody gene codes to make
slight variants of the antibody! Helps keep up with pathogen mutation
2) Cell-Mediated System = CYTOTOXIC
(killer) T-lymphocytes: kill infected
body cells presenting viral,
or parasite fragments, or cancer-related abnormal proteins on MHCI. Helper-T cells with correct receptor detect and
activate KILLER (CYTOTOXIC) T-cells, which kill the bad body cells, often using
PERFORINS which form pores in cells.
REVIEW Self- vs. Non-Self: MHC-I
alone says "I am you; leave me be"; MHC-I with foreign protein says
"I am bad; kill me"; MHCII on an APC says: "Go find and kill
other cells with this protein"
E. PROBLEMS, MALFUNCTIONS
_1) Initial time delay: why there is a
long delay in the acquired system the first time, and how memory cells help
with this later. Role of dendritic cells in new vaccination approach (IOMAI Corp.)
_2) Overreactions: allergies, high fever, prolonged anemia. AND
Uncontrolled Positive Feedback in inflammation may be lethal (anaphalactic
shock)
_3) Autoimmune disease: what is, examples
_4) Male vs female: latter have better immunity, but also more
autoimmune diseases--is this related??
_ 5) IMMUNITY and EVOLUTION
: Superbugs–reading
|
IV. NEURO-ENDOCRINE-IMMUNAL INTERACTIONS |
Psychoneuroimmunology! ANY one system can be in whole-body control under
certain circumstances
1. Neural-->Endocrine:
hypothalamus-pituitary!
2. Immune-->Neural: fever,
lethargy
3. Neural-->Immune:
1980s findings of autonomic nerves to immune organs; functions unclear, but
could explain 'mind-health' phenomena
4. Immune->Endocrine: anemia
5. All 3 systems together=STRESS SYSTEMS:
-- a) SHORT-TERM: = "anticipation" for FIGHT-or-FLIGHT ADRENAL
EPINEPHRINE system. Danger
sensed, amygdala triggers hypothalamus stress center-->sympathetic neurons to adrenal-gland medulla--> epinephrine to
blood--> effectors = heart (faster), lungs (dilate airways), muscle &
liver energy (increased glycogen
breakdown via cAMP cascade). Also
boosts the immune system!! Mobilize immune cells to barrier tissues in anticipation of wound.
-- b) LONG-term: = REPAIR/Recovery
ADRENAL CORTISOL system.
Prolonged danger sensed, hypothalamus
triggered to release CRH to
anterior pituitary which secretes ACTH--->adrenal cortex-->glucocorticoid/cortisol steroid hormones to blood--> Effectors=liver
(glycogen breakdown), Adipose (fat breakdown), Muscle (protein breakdown). This
makes building-block molecules for tissue repair. Also if goes on awhile, this INHIBITs
the immune system! Why uncertain, but
may have evolved as antagonist to positive-feedback inflammation etc. in case
it gets out of hand. Thus medicine uses corticosteroid drugs at high levels to
reduce inflammation. See chart of ancient and modern stressors in lecture
handout! Unnatural stresses causes this system to turn on inappropriately.
|
SELF-SUPPORT/MOVEMENT: MUSCLE PHYSIOLOGY |
I. SKELETAL MUSCLE
(Striated)
A. Structure: 1) Organ [and Fascicles];2) Fibers=multinucleated
Cells; 3) Fibrils=organelles; 4). Sarcomeres with highly organized
filaments, Z-disc to anchor them; 5) Proteins filaments a) THICK = myosin in bipolar array: myosin head structure, 2 binding
sites for ATP, actin; b) THIN = actin,tropomyosin,troponins
----6) Transverse tubule (TT) &
7) Sarcoplasmic Reticulum (SR):
arrangement, uses
B. MECHANISM: RESTING: Tropomyosin blocks myosin from
binding actin : know molecular
arrangements!
CONTRACTING: synapse with ACh nicotinic receptor lets Na+ in; APs go down T-tubes;
& SR Ca++ channels open; Ca++ conducts in, binds to troponins, flip
tropomyosin out of the way; myosin head binds to actin = crossbridge; head does power stroke; head disconnects using ATP, which then reenergizes the head. REPEAT the myosin steps until:
Relaxation:
Ca++ ATPase pumps remove Ca++ back into SR;
troponin/tropomyosin flips back to blocking position
Key concepts: ATP use in detaching/energizing myosin; one-way aspect
opf bipolar myosin filament; why relaxation slower than contraction
C. NEURAL CONTROL: LAB!
--1. Fiber level: AP frequency
controls twitch or tetanus: how tetanus is a normal function or disease
--2. ORGAN level: MOTOR units provide graded contractions; HOW this works
D. Endocrine Control: temporary ENERGY RESET: epinephrine boosts muscle glucose via cAMP amplification
E. Energy: know
all pathways and ATP roles!! LOCAL Intrinsic fuels 1) Creatine-phosphate + 2)
muscle glycogen. External extrinsic fuels
= 3) liver glycogen, 4) adipose fat
-- Anaerobic vs. Aerobic uses!!! CP, local glycogen give fast energy with
minimal diffusion time; but burn out quickly due to low energy yield
--liver glycogen and fat give long-lasting energy, but are slow due to distance
to travel (and long breakdown pathways for fat) and oxygen diffusion limit
F. FIBER Specializations: compare three
main types; use TABLE from lecture/text
Physiological Genomics--Know the 4
types of myosin genes given, their uses and expression in different animals!!
E.g., IIb vs IIx
Fast Glycolytic (FG or IIx in humans, or IIb superfast in rodents); Fast Oxidative/Glycolytic (FO or FOG or IIa); Slow Oxidative (SO or I): --how each differs in color, energy
adaptations, usage & fatigue resistance; External energy sources for SO, local glycogen for FG
USAGE: Evolutionary
adaptation of Fibers: a muscle organ
can have up to all 3 types, depending on adaptive use. Some Examples to ponder:
bottom fish; grazer (cow); wild migrators vs domestic birds; halibut vs tuna;
--Humans: limb muscles are mixtures of all 3 types, but vary by athletic
styles/training
USAGE and CHANGES: what happens during various types of training to
fibers size, types; some possible controls (myostatin vs testosterone, IGF,
somatomedins for size; PPAR-delta…speed/energy source)
G. MECHANICS: from LAB! 1. tendons, ligaments as springs; 2. How
antagonistic muscles work, and 3. LEVERAGE for speed or force
II. CARDIAC MUSCLE--has sarcomeres, but not multinucleated; has gap
junctions
III. SMOOTH MUSCLE: no sarcomeres; meshlike, alternating actin/myosin
filaments for churning/squeezing etc. CATCH muscle of scallop as example of use
FROM LABS
NERVES
II: reinforce lecture on reflex
vs.higher
pathways, major brain regions & functions; how cocaine might alter synaptic
"shut-off" system; how overstimulated neurons respond to this.
SENSES:
reinforce
lecture: sensory "adaptation"; types of skin sensors; semicircular
canals; how eyes work (blind spot); retinal bleaching; & evolutionary flaws
in vertebrate eyes vs cephalopod eyes. What synaesthesia reveals.
INSULIN-GLUCAGON: reinforce lecture on
pancreas feedback and diabetes; know also GLYCEMIC Index concept.
MUSCLES: How nerves control twitch and tetanus; what happens in
fatigue; how neurons and motor units make graded contractions; how antagonistic
muscles work; how Muscle-Bone LEVERS can amplify speed, or force, but not both; basic skeletal, cardiac, smooth
differences
FROM
HANDOUTS: READINGS TO PAY
ATTENTION TO!
Lecture
#11:
"Exploring the Brain": how do fMRI and TMS work, and how are they
used?
ii) "Brain Imaging.." what is the anti-terrorism proposal? iii)
"Neuroethics Needed" what is NEUROETHICS and its concerns? iv)
"Brain Reader.." why does this raise neuroethic concerns?; v)
"An Evolutionary Squeeze.." what is the proposed limit to our brain
size?
Lecture #12: i) "FOOD
for Thought" how might cooking have boosted human brain evolution?
Lecture #13:
i) ) "Anatomy of Anxiety" role of the amygdala!!! ii) "Brain
Storm"--how do teenage brains differ from adult brains, and what behaviors
might result? iii) "..Our Messy Reptilian Brains" cause what kinds of
problems? iv) "Conditioned Fear" says what about the roots and
control of racism?
Lecture #14: i) "Rose-scented Sleep" --what improves memory
here? ii) "PRIONS.." might be beneficial how?
iii) MACOMB DAILY article: says what about racism?
Lecture #15: i)&ii) BEHAVIOR and Anthropology articles: how might a
mental "disorder" be an evolutionary adaptation? iii) "How our
brains..MADNESS" what does anandamide do? iv) "Expression of
Endorphin.." what is proposed about human evolution? v) "Natural Born
Addicts" differ how? vi) "Humanity…WIRING" what are spindle
cells
and their possible role? vii) "BORN to be WILD" says what about brain
maturation and implications? Viii) "NUNS..Brain Scanner" says what
about brain wiring for religious experiences? ix) "Long
unappreciated.." -- what are some recent findings about GLIAL cells?
Lecture #16: i) "SENSES SPECIAL" -- why is the
"five-senses" concept flawed?
Lecture #17: i) "Look and Listen" --what does this reveal
about limited brain power? ii) "Music Lovers…": what did we
inherit from fish in terms of MUSIC? iii) "HEAR how they RUN" says
what about the semicircular canals and evolution? iv) "Math Clears
Up.." what about the spiral shape? v) "Making Sense" what is the
proposed role of Proprioception in humans? vi) "Tongue Sensors..Fat"
what was found about FAT taste?
Lecture #18:
i) "Don't Care for BROCCOLI?"--what is the evolutionary selection for
a bitter gene to hate broccoli? ii) "LOOK MUM.." how is capsaicin
being used here? iii) "MYOPIA Clarified"--how did this spread in
humans?
Lecture #19:
i) "COLD COMFORT" makes use of TRP-M8 channel how? ii)
ELECTROSENSORS: how do these shark sensors work? Iii) "For my Next
Trick.." shows what about rattlesnake thermosensing?
Lecture #20: i) "Body Clock..Prowess" says what about
athletics? ii) "Slumber gene.." involves adenosine how?
iii) "PLASTIC CHEMICALS.." in what affect our hormones how? iv)
"Why We SLEEP" says what?
Lecture #21:
i) IN DIABETES.." what are some recent complexities discovered? Ii)
"The origins of Immunity" shows what? iii) SICK-Making
BUgs..Deep" says what about VENTS? Iv) "Genes won't CLOCK" says
what about clocks and genes? V) "BRAIN's Support Cells" says what
about MICROGLIA? Vi) "Jawless Fish" says what?
Lecture #22: i) "Your Bodies..Bacteria"--where are helpful bacteria
found? Ii) "Homegrown Defender" what is this bladder protein? Iii)
"Mast Cells Defang.." What new role for mast cells was found? iv)
"A SPOONFUL.." how might this help against HIV? V)
"FEVER.." helps how? vi) "NO PAIN, NO GAIN" says what about
anti-inflammatory drugs?
Lecture #23:
i) "AN Immune..so Versatile.." what is the tradeoff with CANCER
proposed? Ii) "Distraction Tactic.." helps allergies how? iii) "Idle Hands"--what is the
HYGEINE Hypothesis? Iv) "The INNER STRENGTH.." how do males and females
compare? V) IOMAI--know their method!
Lecture #24: i) What superbugs are emerging and why? ii) " UNDER
STRESS" and "BOUTS OF TERROR": how is immunity HELPED? iii)
"Survival of the SICKEST" says what about some common human diseases?
Lecture #25:
i) HYENA article says what about human
evolution? ii) MR. UNIVERSE JR: what is myostatin? iii) "SUPERHUMAN.." what are some key
genetic features of champion sprinters and marathoners? iv) " MARATHON MICE -- what is PPAR-delta and its effects
here? v) "Scientists take.." what did they do with dark vs light
meat?..