HUBS191

Lecture 1 – Introduction, the Human Tissue Act and Tissues

25/02/2019

Introduction

HUBS includes modules on the nervous system, musculo-skeletal system, endocrine system, immune
system and biostatistics

The HUBS lab is located in room G08 in the Microbiology building

Email is hubs@otago.ac.nz

Textbook is Martini (Visual anatomy and physiology) and is essential

Blackboard is once again essential

There is a FAQ section on the HUBS blackboard page

The “Lecture Outline” handout includes important points, and is expected reading prior to each
lecture.

Details on the ICL’s are on blackboard

Pre-read the required pages in the Laboratory manual prior to each lab. The laboratory manual will
be given to you in your first lab.

Learning modules are available on blackboard

4 learning modules; bones and mechanics, nerve and muscle, the endocrine system and immunology

Two progress tests in HUBS, the first worth 8% and the second worth 12%. These take place on the
30th of March and the 18th of May (at 10:30am) respectively.

Terms requirements are to attend all the labs.

For each system covered we will learn about the anatomy of the organ system (the structure, i.e
what/where), and physiology of the system (the function of the system, i.e the how of how it works),
and in addition the immunology of the body (how the body fights against disease).

Human tissue act

Bodies used are bequeathed to the university, not from criminals or unclaimed bodies.

People made the choice while alive and fully informed of what they were doing.

The Human Tissue Act requires that the donor and an immediate family member willingly and while
fully informed donate their bodies

Most bodies are held for around 18 months, however individual parts may be kept for longer periods
to teaching and research purposes.

Should do pre and post lecture readings (76 hours), lab preps (12 hours) and learning modules (20
hours, 4 hours each).
Tissues

There are 4 different types of tissue; Epithelial tissue, connective tissues, muscle tissue and nervous
tissues

Epithelial tissue covers exposed surfaces, lines internal passages and chambers such as veins and
organs, and forms secretory glands.

- This can be split into two groups. Epithelial tissues (allows movements) and glands
(endocrine and exocrine)
- Epithelial tissue provides physical protection, sensation, permeability and produces
secretions such as mucus and hormones

Connective tissue is what fills internal spaces, provides structure to the body, and stores energy, for
example fat.

- 3 different types of connective tissue; proper (eg. Fat), fluid (eg. Blood) and supporting (eg.
Cartilage and bone) tissues
- Connective tissue transports fluids, protects delicate organs, stores energy etc.
- The amount of collagen vs elastic fibers determines the nature of connective tissue. The
more collagen, the stiffer it is, the more elastic fibers, the “bendier” it is.
- Makes up about 45% of tissues

Muscle tissue contracts to produce movement and includes skeletal muscle, cardiac muscle and
smooth muscle.

- Makes up about 50% of all tissue in the body.

- Main muscle we will deal with in 191 is “skeletal” muscle
- These are the ones that are attached to bones, and is what allows us to move
- Cardiac muscles make up the heart, and is what causes it to contract (causing the heartbeat)
- Smooth muscle is what allows the gastrointestinal tract to contract among other things.

Nervous tissue conducts electrical information called impulses. This information flow occurs
throughout the entire body.

- It is the smallest system in the body, but is the control system of the body
- Includes the brain, cranial nerves, spine and sensory receptors
- Within the nervous system we have neurons, each of which has an “axon”
- Axons are what drives electrical communication.
- Glia exist too, and do more than just support neurons (i.e support nutrients and maintain
the environments of neurons)
Lecture 2 – Anatomical terminology
26/02/2019

Anatomical position

The anatomical position has the body placed upright, facing forwards, feet together and facing front,
and with the palms facing forwards.

The anatomical position does not change in terms of what the area is referred to, it stays the same
regardless of motion. So even if the palm faces the other way in reality, it is still referred to in the
same way as if it weren’t.

Terms of direction

Everything is in relation to another, eg. the knee in relation to the pelvis

Superior/inferior – refers to the whole body (but specifically the central area), with superior
referring to something close to the head and inferior further away from the ahead. i.e ribs are
inferior to the shoulder

Medial/lateral – relating to the middle of the body. Medial is close to the midline, lateral is
something further away from the midline. The sternum is medial, while the elbow is more lateral.

Proximal/distal – relating to things specifically in the limbs. Proximal is closest to the torso, while
distal is closer to the extremities. Eg. thighs are proximal while feet are distal.

Anterior/posterior – referring to the front and back of the body. Anterior is something that is closer
to the front, while posterior is closer to the back. Eg. nose is anterior, and the ear is posterior in
comparison. Ventral and Dorsal can also be used, however this is used in terms of animals instead. In
humans, as we are bipedal, the former is used instead.

Deep/superficial – relating to how deep within the body something is. Deep is further within, while
superficial is closer to the skin. So skin is superficial to muscle, while the bone is deep to muscle.

Terms of division

There are 3 different planes. These are imaginary sheets running through the body that serve to
divide it into different parts. These parts are:

- Sagittal – Divides the body into left and right portions.

- Coronal – Divides the body into front and back portions.
- Transverse – Divides the body into upper and lower portions.

These planes do not have to be directly central. They can be taken from any area. Eg. a transverse
scan at the top of the head.

Movement

Angular movements are movements that change the angle at the joint. There are several types:

- Flexion: Decreases the angle of the joint and brings the fleshy parts of limbs closer together.
For example lowering your chin, raising your leg in front of you of flexing your arm
- Extension: Increases the angle of the joint compared to flexion. Generally appears to involve
moving back to the mid point.
- Hyperextension: Further increase of the angle, moving even further back.
 - Dorsiflexion: Toes brought up towards face. Only used in terms of the ankle joint
- Plantarflexion: Toes pointing towards the ground. Again, only used in terms of the ankle
joint.

Walking involves a combination of the two. The gait starts off in dorsiflexion, with toes pointing
upwards before planting on the ground and changing to plantarflexion, with toes on the ground
pointing away from the face.

Movement is referred to in terms of planes as well, eg. arms moving front to back is movement in
the sagittal plane, away from side is in the coronal plane, and side to side is in the transverse plane

- Abduction: Movement at joint moves the limb away from the midline, eg. arm moving away
from side.
- Adduction: Movement at joint moves the limb towards the midline, eg. arm moving back
towards side.
- Circumduction: Combination of the 4 angular movements (flexion, extension, adduction and
abduction), for example moving the arm in a circle in front of you. This is not rotation.
- Rotation: Takes place around the long axis of a joint, for example the head rotating on top of
the spine. This involves bones moving around it in rotation, the angle does not rotate. The
shoulder and the hip can both rotate because the connecting bones have round heads.
o Lateral rotation: external
o Medial rotation: internal
- Pronation: movement of the palm to face the posterior
- Supination: movement of the pal to face the anterior, with forearm bones parallel (the
anatomical position is when we are in full supination).
- Inversion: sole of foot faces towards the midline, i.e towards the other foot.
- Eversion: sole of foot faces away from the midline, i.e away from the other foot.

Lecture 3 – Structure of the skeleton

27/02/2019

There are bones which are hard tissues, and other parts of the skeletal system such as cartilage
which are soft tissues.

Primary Functions

The skeleton provides support and form for the body.

It also facilitates movement by acting as levers for muscles to contract upon

It also provides protection for many internal organs.

Bones also provide storage for things like calcium which are vital for the human body to function.

Blood is also formed inside bones, within the marrow.

Structure of bones

There are two types of tissue:

- Compact bone. This is found within bones where there is a greater requirement for strength,
or which will undergo heavier loads.
 - Cancellous/spongy bone. This is found where shock absorption is required, such as the
joints.

At a microscopic level these two types of bone are made of the same material, they are merely
made up in different structures.

Bone classes

- Long bones. These are defined as being longer than they are wide, with extremities or
epiphyses that are wider and/or have different shapes. These have a shaft (diaphysis) and
they function as levers for movement. Long bones have a thicker section of compact bone
within the diaphysis, and sections of cancellous bone in the extremities.
- Short bones. These are roughly equal in width and length, and can take a variety of sizes.
These are found in areas which bear weight and undergo shock, and are mostly made up of
cancellous bone as a result.
- Flat bones. These bones are flat and thin. They provide protection, such as in the cranial
bones, or where muscle attachment is required, such as in the scapula. They are thin plates
of compact bone, with some cancellous bone within. In the cranium this spongey bone is
called diploe.
- Irregular bones. These have variable shape and function, such as in the vertebra in the spine.

Divisions of the skeleton

There are several divisions within the skeleton:

- Axial skeleton. These are the core of the body, upon which the rest of the body attaches and
moves around. It provides protection and support.
o Skull: This contains 3 regions. The cranium/cranial vault (the rounded part of the
skull), the facial bones (smaller bones on the anterior face of the skull, housing
sensory organs and opens for internal systems like the digestive and respiratory
systems), and the mandible (which allows for chewing, and is attached to the
temporomandibular joint, which attaches to the cranium).
o Vertebral column: This is the column of vertebrae stacked together to form the
spine. It has 4 regions. The cervical region (7 vertebrae, this makes up the neck and
is the most mobile region), the thoracic vertebra (12 vertebrae, main part of the
spine), and the lumbar region (5 vertebrae, the least mobile area, at the bottom).
These get bigger the further down the column they are. At the bottom are the
sacrum and coccyx, and are the vestiges of a tail.
o Rib cage: Formed up of the ribs and the sternum. This protects the heart and the
lungs, and is also known as the thoracic cage (because they articulate onto the
thoracic vertebrae). The ribs join the spine at the back and then cartilage which itself
joins the sternum on the front.
- Appendicular skeleton. These are the limbs, and include the humerus, radius, ulna, femur,
patella, tibia, fibula etc. Anatomically, the arm only comprises of the upper arm (the
humerus), and the leg the lower leg (tibia and fibula).
Human locomotion

Humans are unique in their bipedalism.

Animals which walk on 4 limbs are known as quadrupedal

Limbs are made up of a single proximal long bone and two distal long bones, and then the hands and
feet.

The tibia and fibula are unable to move like the bones in the upper limbs can, as they are required to
be stable as they hold up the rest of the body.

Limbs are attached via two girdles, the pectoral girdle and the pelvic girdle.

- The pectoral girdle is made up of the clavicle and the scapula. The clavicle allows us to move
our arms laterally. The scapula allows us to move up and down.
- The pelvic girdle is made up of two hip bones and the sacrum (axial). This helps with weight
transmission during locomotion. This varies between the genders. Female pelvic outlets are
more circular and open.

The humerus’ round head allows for rotation

The femur has a “neck” where it attaches to the pelvis, making it more stable due to greater
articulation. This makes it less vulnerable to injury, but less mobile.

The radius proximally has a round head, while the ulna has a round head distally. The ulna has a
hook on one end.

The tibia is a lot larger than the fibula, it is medial compared to the fibula being lateral. The fibula
acts as a strut, supporting the tibia.

The hand contains the carpal bones/tarsals (7), the metacarpals (5), and the phalanges (3).

Lecture 4 – Bone Tissue and Microscopic structure

04/03/2019

Bone grows. All bones started off as a cartilaginous model of what they would become, before
turning into bone proper about 6-8 weeks into development.

Once bone is fully developed it continues responding to external environment forces. For example,
with a lot of physical activity the point of attachment to muscles will start producing more bone to
make the point larger.

Bone is a connective tissue, found throughout our body. It is different from other connective tissues
in that it has an inorganic component to it. There are two extracellular components; organic and
inorganic. The inorganic aspect is what makes it different to other tissues.

The organic component makes of 33% of the extracellular matrix, and is made up of collagen (a
protein) which is embedded in ground substance (proteoglycans) which helps to resist tension.
Without these collagen fibers the bone becomes brittle and breaks easily.

Inorganic bone tissue makes up 67% of the matrix, and is called hydroxyapatite (mineral salts). This is
what gives bone its hardness, and helps it resist compression.
The extracellular matrix is produced and maintained by the cellular component of bone tissue. This
happens continually, with all bone tissue in the body turned over and replaced gradually over 7
years.

- Osteoblasts. Responsible for building the ECM (both organic and inorganic)
- Osteocytes. This are known as mature bone cells, as they are former osteoblasts which have
matured and turned into osteocytes after essentially building the ECM all around them,
trapping them. These monitor the bone and communicate with other osteocytes in order to
prompt bone turn over.
- Osteoclasts. These break down and destroy (resorb) the old parts of the ECM so that
turnover can occur.

Gross structure of bone

Two types of bone tissue, compact and cancellous. Made up of the same material, just arranged
differently

Compact bone.

- At the gross level it appears impenetrable, however it contains holes at a microscopic level
(foramina) to allow for blood vessels which maintain the osteocytes.
- At the microscopic level compacts bone is made up ofrf osteons, which are longitudinal
(lengthwise) units within compact bone.
o They maintain the osteocytes by supplying nutrients.
o They are formed by a series of tubes of ECM with collagen fiber called lamella, which
align to resist forces. They look like tree rings. At each level of the rings the collagen
fibers align in different directions, allowing them to resist tension.
o The central canal of each osteon contains blood vessels and nerves. This means that
bone tissue is highly enervated, which is why breaking bones hurt so much.
o Osteocytes are found in lacunae (singular lacuna), which are found interspersed in
the lamella.
o The channels in the bone tissue around the osteocytes which allow for
communication are called canaliculi.
- Periosteum (fibrous sheath, peri meaning round)) are found around the outside of the bone.
While it is firmly attached to the bones surface, it allows the penetration of blood vessels
into the bone in order to reach the osteons. This is where you find the osteoblasts.
- Underneath the periosteum is the subperiosteal surface.
- The endosteum is a membrane that lines the inside of the bone, and is where you find the
osteoclasts

Cancellous bone

- At the microscopic level this is much simpler than compact bone, because the osteoclasts
are fed directly from blood vessels.
- Made up of trabeculae (singular trabecula), which are struts of lamella bone
- The cavities are filled by marrow.
- Osteocytes are housed in lacunae on the surfaces of trabeculae.
- The organization of trabeculae is what allows bones to resist the shock of things like
movement.
- The more weight goes through an area, the greater the concentration of bone in that area.
- To break compact bone takes massive force.
Lecture 5 – Intro to Biostatistics
05/03/2019

Biostatistics in the health sciences is useful to understand things like the prevalence of disease, risk
factors for disease, and effectiveness of treatments.

Something about samples vs populations

Something about sampling. Collect representative sample, investigate sample and use to make an
inference about the population

Turn data into table and graphs. Or something, idk.

Poorly designed studies lead to poor results.

Larger samples limit the size of the distribution

Lecture 6 – More biostatistics

06/03/2019

Random sampling creates a more accurate conclusion by eliminating bias

There are two different types of error:

- Errors that make our answers more uncertain, i.e more variability
- Errors that move us away from the truth, i.e we get the wrong answer, often called bias.

Can’t really avoid the first (taking a sample but measuring things imperfectly), but it’s very important
to avoid the second via random sampling.

Increasing the sample size doesn’t help avoid these errors.

Samples must match target population.

Use placebos to compare the change to non-change

Lecture 7 – Describing uncertainty in estimates

11/03/2019

Repeated sampling from the population is not possible

Our sample mean or proportion will be our best guess of the population mean or proportion

Similarly our sample SD is our best guess of the pop SD

The standard error can be estimated from the sample using the formula

SE=s ÷ √ n
Now that we have an estimate of the sampling uncertainty we can create a 95% confidence interval
around the sample mean to give an estimate of precision, which takes into account variability and
sample size.
The general formula to find the 95% is

Estimate ± 1.96 x SE
For means this becomes

standard deviation
mean ±1.96 x
√ sample ¿ ¿ ¿
Don’t round values.

Add to find the upper interval, subtract to find the lower interval

Lecture 8 – Bone growth and pathology; Joints – tissues and

structures
12/02/2019

Bone Growth

Bones begin as a cartilaginous model. The process by which this cartilage is turned into bone is called
ossification.

The primary centre of ossification is in the diaphysis (shaft) of the bone.

The secondary centres of ossification are in the epiphysis (extremities). These are responsible for the
creation of things like joints.

Growth plates (epiphyseal plates) are formed of cartilage, and are found between the diaphysis and
epiphysis areas of growth.

Growth in length occurs through growth plates. The cartilage is continuously destroyed and replaced
by bone, essentially pushing the growth plate higher/slower, increasing the length.

Growth in width (moulding) occurs via osteoblasts in the periosteum increasing width. Osteoclasts
from the endosteum mould the bone shape and form the medullary cavity.

When the bone stops growing, the growth plate is transformed totally into bone, and the epiphysis
and the diaphysis fuse together.

Bone pathology

Bone pathology is an imbalance of OC (osteoclast) or OB (osteoblast) activity. For example, in

osteoporosis the OC’s activity overtakes the OB’s, taking away bone fast than the OB’s can make it,
resulting in compact bone becoming thinner and porous. This can be caused by loss of estrogen
(through aging), lack of exercise, nutritional factors (lack of calcium).

Joints

Joints hold bones together. It’s where bones meet and join together. There are different
types/classes of joint, as they will involve different bone shapes and soft tissues.

They allow free movement or control of movement.

Soft tissues associated with joints have no inorganic components

Examples of this include

- Cartilage. Largely made up of collagen. Cells are called chondrocytes living in lacuna, and
nutrients are diffused through the matrix by joint loading rather than vascular, i.e through
usage.
o Hyaline (articular cartilage), appears where bones join together. Collagen fibres are
barely visible. It has a high water content within the matrix, which helps it resist
compression. Its main function is to provide a smooth, frictionless surface for bones
to move over one another. It degrades with age as water content is lost.
o Fibrocartilage. Collagen fibres form bundles throughout the matrix. The orientation
of the fibres aligns with stresses. Its function is to resist both compression and
tension, hence the higher concentration of collagen. An example of this are the
menisci in the knee joint (may be asked about this in the exam), which are concave
disks that deepen articulation at the knee joint. It can adapt its shape to stresses on
the joint vs movement, and distributes forces over a wider area.

Bony congruence is the amount of bone that creates an articulation. Less BC means there is more
soft tissue support, while more BC means that there is less support.

Structures associated with joints

Dense fibrous connective tissue (DFCT) is the tissue that makes up ligaments and tendons.

This is made up of collagen and fibroblasts, and its function is to resist tension. There is some
vascularity but it’s minimal compared to bone. This means that it can heal, but it takes a long time.

Ligaments connect bone to bone, and its function is to restrict movement away from itself. For
example lateral ligaments restrict adduction, and medial ligaments restrict abduction.

Tendons attach muscle to bone, and facilitates and controls movement through contraction.

Lecture 9 – Joint classifications; synovial joints

13/03/2019

Fibrous joints

Anchor bones together with very little movement.

Tissue is DFCT (dense fibrous connective tissue).

Is a ligament

Cartilaginous joints

Allows for some movement

Is made of fibrocartilage.

Has various structures with special functions, such as the interverbal disk and the pubic symphysis
(the joint between the anterior sections of the pelvic)
Synovial Joints

Free moving, making up most limb joints. The amount of and direction of movement is determined
by the structure of the joint.

Synovial joints are a complex association of tissues and structures. It facilitates free movement and
control of said movement.

The ends of bones determine the range of motion at a joint, for example the hip vs the knee; the hip
has a rounder head and therefore has a much move free range of movement.

Synovial joints are generally made up of:

- Bone ends.
- Articular (hyaline) cartilage. Covers bone ends where they articulate and move over each
other. The bone beneath it (subchondral bone) is smooth and matches the shape of the
cartilage.
- Joint capsule. Type of ligament which holds bones together. Is tight and thick where more
support is required, and loose where movement is allowed. Potential space or cavity, which
means there is potential for infection.
- Joint cavity. A dense fibrous connective tissue surrounding the joint.
- Synovial membrane. Lines the inner surface of the joint capsule. Secretes synovial fluid to
lubricate the joint.
- Ligaments.
o Capsular ligaments are thickenings of the capsule…. Two collateral ligaments, medial
and lateral. Medial restricts abduction, lateral restricts adduction.
o Intracapsular ligaments restrict movement between bones. These are the cruciate
ligaments. Come up from the tibia and insert into the femur. The ACL restricts
posterior displacement of the femur, and the PCL restricts anterior displacement of
the femur. They’re named for where they attach to the tibia, rather than where they
attach to the femur.
o Menisci. Improves congruence and helps stabilize the joint.

Synovial joints differ from fibrous and cartilaginous joints in that it has a slight gap between the
bones, which allows greater mobility but harms stability.

Synovial joints can move along one or more axis (coronal, sagittal and transverse)

- Uniaxial. Can moving along one axis, eg. elbow

- Biaxial. Can move along two axes, eg. wrist
- Multiaxial. Can move along many axes, eg. shoulder

The range of movement (ROM), the type and amount of movement determined by the structure of
the joint.

- Bone end shape

- Ligament location and length
- Body surface contact
7 types of synovial joint:

- Plane. This is multiaxial, and can slide and glide. It’s found on “blocky” shaped bones, or
bones which are relatively flat, such as intercarpal and intertarsal joints.
- Hinge. Uniaxial. Movements are only flexion and extension, such as ankles, elbows, and
interphalangeal joints.
- Pivot. Uniaxial. Movement is rotation, such as the radioulnar joints.
- Condylar. Biaxial, can do both flexion and extension. Can rotate when flexed, such as the
knee and the temporomandibular joint.
- Ellipsoid. Biaxial, can both flex and extend, do abduction, adduction and circumduction, but
cannot rotate, such as the wrist joint.
- Saddle. Biaxial, can flex and extend, do abduction, adduction and circumduction. Also has
slight obligatory rotation. Specific to the carpometacarpal joint (thumb)
- Ball and socket. Multiaxial, can do absolutely everything including rotation. Examples are the
shoulder and hip.

Lecture 10 [Start of Module 2] – Active cellular physiology

18/03/2019

Soft cells need to keep their shape too. The way they do this is down to water.

Concentration gradients are created via diffusion? Things move from areas of high concentration to
areas of low concentration

Osmotic pressure is also called tonicity, and keeps soft cells in their shape.

Interstitial fluid and intracellular fluid make up most of the water content of our body?

Solutes and ions are contained within the ICF (intracellular fluid) and ECF (extracellular fluid)

ICF and ECF are in balance, meaning they’re isotonic.

Dehydration causes the ECF to decrease in volume, making the solution hypertonic in comparison to
the ICF, meaning it has a greater concentration of solutes. This results in water moving from the ICF
to the ECF to try to recreate osmotic equilibrium.

If there’s more water in one than the other, it’s said to be hypotonic. For example if the ECF were
hypotonic to the ICF, water would flow from it to the ICF.

Too much water in the ECF will dilute Na+, which can lead to brain damage in hyponatremia.

Ions/Electrolytes

Ion absorption occurs through the epithelial lining of the small intestine and colon. Ion reserves are
primarily stores in the skeleton (eg. calcium).

Ions are found in the ICF and ECF, and also have concentration gradients.

Ions are important for excitable tissue.

- Neurons and muscle have excitable membrane potential

 - Epithelial cells also have membrane potential, but not excitable

Cellular membrane potential relies on K+ and Na+ separation.

Both cations and anions are present in and out of cells.

Lipid bilayers are insulators that prevent the free flow of cations and anions.

The distribution of ions creates electricity, called membrane potential.

ECF has high Na+ concentration and low K+ concentration

ICF has low Na+ concentration and high K+ concentration

This creates a charge difference between the two sides of the membrane, and is called the resting
membrane potential. In living cells it’s about -70mV, slightly negative inside.

Ions can only move across the membrane via ion channels or pores.

Sodium-potassium exchange pump maintains the gradient of the Na and K ions.

Depolarisation and hyperpolarization

The -70mV charge of the cell can be changed if the ion channels open. If for example sodium rushes
in the cell experiences depolarization, with the mV decreasing. This is then fixed by repolarization.
Vise versa with an inrush of potassium ions, with the cell becoming hyperpolarized, with the
membrane potential becoming more negative. Both of these events return when the chemical
stimulus is removed.

Lecture 11 – Skeletal muscle structure and function

19/03/2019

Smooth muscle mostly lines internal organs, and is not under voluntary control.

Cardiac muscle is found only in the heart, generating force to pump blood around the body, and is
not under voluntary control.

Skeletal muscle applies force to the bones to control posture and body movements. It is under
voluntary control and is also known as striated (striped) muscle or voluntary muscle. Its main job is
produce force.

It doesn’t only contract when producing force, force is also used to resist movement.

Muscles produce force by pulling. They cannot actively lengthen, and as such they cannot push.
However they can be lengthened passively by an external force

Other jobs muscle has:

- SM provides support and protection for internal organs.

- Provides voluntary control over major openings that allow passage of substances in or out of
the body
- Active muscles convert energy to heat which is used to maintain core temperature (eg.
shivering)
- Provides a major store for energy and protein.
Skeletal muscle has several major cell types:

- Skeletal muscle fibres are huge, multinucleate cells containing large amounts of protein
- Connective tissues surround the muscle fibres, and connect fibres to the bones
- Richly supplied with blood vessels and nerve fibers (which allow the brain to control them)

Working muscles produce a lot of waste products and CO2

Muscle fibers are gathered into bundles called fascicles

Fascicles in bundles are muscles

Muscles are each surrounded by connective tissue called epimysium.

Each fascicle is surrounded by perimysium.

Each of the fibres within the fascicle is surrounded by endomysium.

Each muscle fiber has a capillary and a nerve?

Myofibrils are the proteins that produce force.

Each myofibril is made up of a network of myofilaments.

The main proteins in this are actin (thin filaments) and myosin (thick filaments). These form
organized, repeated hexagonal arrays that give muscle its striated appearance.

Each thick filament is surrounded by 6 thin filaments.

The regular pattern is called a sarcomere.

During development of muscles, myoblasts fuse together to form large multinucleated cells enclosed
by a single common cell membrane. Each fibre has hundreds or thousands of nuclei, and are
generally 20-40 nanometres in diameter, but could be up to 10cm long.

Purple spots in muscle diagrams are nuclei.

Each nucleus controls a small amount of cytoplasm next to it.

These are called syncytial cells.

Each fibre is a cylinder of cytoplasm. The specific arrangement of proteins within the fibre gives it its
ability to respond to signals from the brain with the production of force.

The activity of the proteins are regulated. This is done by transverse tubules which penetrate the
membrane and connect with a network running through the muscle. Their job is to conduct
electrical signals (action potentials) deep into the core of the fibre.

Sarcoplasmic reticulum (SR) is an extensive membranous tubular network associated with the T
tubules at regular intervals. Its job is to hold calcium, and then to release it into the cytoplasm when
it receives an action potential.

Terminal cisternae of each SR associate with the T tubules to form a membrane triplet called a triad.

Triads are made up of two connections of cisternae and one T tubule.

Sarcomeric structures of the myofilaments arises due to the arrangement of contractile proteins.

Actin is a globular protein (G-actin), which when put together associate to form filamentous protein
strands called F-actin. It also contains tropomyosin, which attaches to the actin via binding at regular
intervals of another globular protein called troponin. This is what makes up the sarcomere.

It is interactions between the thick and thin filaments that cause force

Myosin has a long thin tail and a globular head.

Myosin spirals together with their tails towards the middle and heads pointing out towards the actin.

It’s formed by arrays of pairs of myosin molecules arranged with the tails pointing towards the M-
line (between two myosin strands) and forming a double headed structure.

ATP is used to change the position of the head.

Thick and thin filaments slide along each other. The thick filaments pull the heads of the thin
filaments towards the centre, producing force. This is called the sliding filament theory.

Neuromuscular junction

The primary motor cortex controls the muscles

Motor neurons are activated, becoming electively active, sending messages down the spinne to
motor neurons, which send nerve impulses down their nerve fibers to release a … in the muscle to
activate it

The synapse that receives the message is called the neuromuscular junction

It’s only ever excited.

Each muscle fiber only receives contact from one motor fibre, no matter how long.

One motor neuron contacts many muscle fibers, usually between 10-1000 depending on the size of
the muscle.

Together these are called a motor unit.

A muscle can be thought of as a collection of motor units, so that they all work together at the same
time.
Lecture 12 – Muscle structure and function 2
20/03/2019

- Know how action potentials arriving NMJ result in action potentials in the muscle fibre.
- Know how a muscle action potential leads to the development of tension within a muscle
fibre
- Learn the cross bridge cycle and understand excitation-contraction coupling
- Know how sarcomere length, rate of stimulation, and number of active fibres influences
muscle tension.

Muscle contractions are triggered by action potentials, which come from the brain

Action potentials in spinal cord motor neurons are conducted out of CNS along motor axons to
muscle fibres.

Points of apposition are called synapses. Synaptic transmission is transmission of the event from the
synapse to the attached cell

The electrical event in the nerve leads to the release of a chemical called acetyl choline. Thus NMJ is
a cholinergic synapse

When it binds to a receptor the receptor changes shape

Electrical signals are conducted away from the NMG down the fibre

Membrane around the fibre is sarcolemma

Now the muscle fibre is electrically active. Excitation reaches the triads, causing a change in a protein
which causes a channel to open, causing calcium ions to diffuse into the cytoplasm of the muscle
fibre from the SR.

Ca ions trigger the contractile proteins from yesterday

Excitation-contraction coupling

At rest, Ca concentration is very low in the cytoplasm.

Myosin heads are extended (cocked), energized position. This happed by splitting ATP.

Arrival of Ca initiates contraction cycle.

Ca binds to subunits of troponin molecules. When this happens it changes its shape, rolling the
tropomyosin into a different position, away from the actin binding sites which they previously
covered

This allows the myosin to bind to the actin, forming cross bridges.

ADP and ATP then diffuses into the cytoplasm, causing the myosin head to flex and pull on the actin.
This is called the power stroke.

The ATP binding site is now vacant again, allowing ATP to once again bind and be hydrolyzed to ADP
(and inorganic phosphate), causing the myosin to lose its affinity for actin, and recock. This process
can continue, cocking and uncocking.

Power strokes cause the sarcomere to be pulled inwards, generating force.

Ca concentration drops because SR has a pump that uses ATP to pump Ca back in

Can be summarized as

1) Cross bridge formation

2) Power stroke
3) Cross bridge detachment
4) Reactivation of the myosin head

As long as binding sites on actin are exposed, this cycle will repeat

Need to regulate the amount of force used

Brief contraction from a single action potential is called a twitch

Prolonged AP’s fired in rapid sequence results in sustained release of Ca from SR, and all that ensues.
The contract from such activity is called a tetanus.

More cross bridges = more force

One determining factor of the number of cross bridges is the sarcomeres length

Length-tension curve is a relationship that plots the amount of force that a sarcomere can produce
vs the length of the sarcomere

As the sarcomere lengthens, overlap between actin and myosin is reduced, so number of cross
bridges is also reduced, and force produced falls

Force also decreases as myofilament overlap increases because the thin actin filaments overlap and
interfere with one another.

This means that each muscle has an optimal length where it will be strongest.

Tight angle=longest point?

The amount of force is also proportional to the frequency of its stimulation

If an action potential arrives before the previous reaches 0, it builds upon the previous one. This is
called summation.

Maximum release of Ca means that there is no loss of force between AP’s

Maximum is 80 AP’s per second?

Rate coding is the increase in force proportional to number of AP’s?

All of this is a function of how many motor neurons are activated. The process of activating more
motor units to make more force is called recruitment.

By activating different motor units in turn whole muscle tension can be maintained whilst allowing
individual units to “rest”

This asynchronous motor unit summation is under the control of the CNS. In such cases, the muscle
produces less than its maximal force, but it can stay active for longer.
Lecture 13 – Muscle form and actions at joints
25/03/2019

- Explain the relationship between the form and function of a muscle

- Describe how skeletal muscles can influence movements from a synovial joint.

Muscle form determines function. It depends on

- Length of muscle fibres

- Number of muscle fibres
- Arrangement of muscle fibres

Length

Sarcomeres can shorten to shorten up to 50% of the muscles resting length.

Large range of movement (ROM) is required – long muscle fibres are required for significant
shortening.

Number of fibres

The force created (tension) is directly proportional to cross sectional area (CSA).

So a greater number of fibres means greater CSA and therefore greater tension.

Arrangement of muscle fibres

- Fibres arranged vertically between muscle tendons are said to be parallel. This is the
simplest/most common arrangement. Only has one direction of movement
- Fibres oblique to muscle tendon are pennate, i.e at an angle. This allows more fibres in the
same space, which means there’s reduced shortening ability as the muscle is shorter, but
greater CSA.
- Can have different directions of pennate patterns in a muscle; so 2 pennate groups is
bipennate, more is multipennate

Anatomical levers

Bones act as levers

Joints are the pivot/fulcrum

Muscle contractions are a pull

Loads can be either external or internal, but is what is being moved

AF = applied force

Lever arrangement determines function.

- First class/primary lever = stabilize joint position, eg. head

- Second class/secondary lever = effective at overcoming loads, eg. the ankle joint undergoing
plantarflexion
- Third class = large range of movement and speed, this is most of what we cover in HUBS.
Examples are elbow or knee joints
Types of muscle action

These are the different types of movement muscles can cause?

- Concentric: shortening, eg. elbow flexing

- Isometric: staying the same length. Muscle is active, develops tension, but no change in joint
position or length. So both opposing muscles exert the same force
- Eccentric: lengthening. Muscle is active, develops tension. Change in joint position

Types of muscle role

- Agonist: Creates movement/change. Acts concentrically. Eg. biceps brachii when flexing
elbow
- Antagonist: Opposite of above. Acts eccentrically. On the opposite side of the joint, eg. the
triceps brachii when flexing
- Stabiliser: Active in order to hold a joint still, such as when you’re holding a heavy book.
- Neutraliser: stops anything happening. Eliminates an unwanted movement caused by
another muscle. For example, when bringing something like a glass up to your face the
biceps inserts into the radius, meaning it has a role in supinating the forearm. Other muscles
in the forearm hold the bicep in place in order to prevent it supinating

Anything medial to a joint produces adduction

Anterior = flexion

Lateral = abduction

Posterior = extension

Deltoid attaches proximally to the pectoral girdle, and distally to the middle of the shaft of the
humerus

A tuberosity is a structure on a bone where a tendon attaches to it, the tendon has to insert more
strongly into the bone, causing bone to grow around that region

Has triangular form.

- Flexion is caused by anteriorly crossing fibres

- Abduction caused by laterally crossing fibres
- Extension caused by posteriorly crossing fibres

Biceps brachii

Must say brachii for the top one, as there’s also biceps in the leg

Bi means two, ceps means head, so it’s a 2 headed muscle

Cross anteriorly over the shoulder causing flexion

Crosses anteriorly over the elbow, causing flexion of the elbow

Inserts in to radial tuberosity

When it contracts, when the radius is pronated it’ll flip the bone back over

So shoulder = flexion
Elbow = flexion

Radius = supination

Triceps brachii

3 heads

Long head crosses posteriorly over the shoulder joint, attaching to the scapula

All 3 heads attach to the posterior of the ulna, making it a powerful extensor of the elbow

Iliopsoas

Anterior surface of the hip

2 parts, made up of iliacus and psoas major

Psoas major crosses over the hipbone to attach to the femur

Is the anterior hip flexor

Gluteus maximus

Crosses posteriorly, concentric contraction causes powerful extension of hip joint

Attaches to femur

Quadriceps femoris

Causes knee to extend

4 muscles, rectus femoris, lateralis, intermedius, and medialis. Names are self explanatory

Rectus femoris is the only one that crosses both the hip and knee joints anteriorly, so can produce
both flexion of the hip and extension of the knee.

These 4 muscles cause powerful extension of the knee

Hamstrings

Causes hip extension

Causes knee flexion and rotation when flexed

Hamstrings attach to humerus tuberosity posteriorly

Crosses posteriorly over the knee

Biceps femoris has bulk of its medially and laterally?

Semi-membranosus is medial, and has an enveloping tendon that wraps over a large part of the
muscle

Semi-tendinosus is medial has tubular medial tendon

Google those last few locations

Tibialis anterior

Anterior of the tibia, attaches to the tibial tuberosity

Sends tendon into the medial surface of the foot

Causes dorsiflexion of the ankle, and inversion of the foot

Triceps surae

Made up of the gastrocnemius & soleus

Gastrocnemius is superficial, only one that crosses over the knee joint, allowing flexion of the knee.

Together they distally allow plantarflexion of the ankle (Achilles tendon)

Doesn’t interact with the other bones of the foot, so no role in inversion or eversion

Summary

- Skeletal muscle is designed to contract

- Arrangement of fibres influences function of muscle
- Muscle roles are varied
- Aspect of joint that muscle crosses influences movement

Lecture 14 – Complex movements (standing and gait)

26/03/2019

- Describe the anatomical fratures of the lower limb that allow us to stand with minimal
energy expenditure
- Define the phases of the gait cycle

Quadrupedal stand has a strong base of support, with limbs active at many point. However this
requires a lot of energy to put legs into flexion/extension.

Bipedal standing is done on a relatively small surface area, with the plantar surface of the feet. It’s
much more energy efficient due to the structures around the joints of the lower limb, such as the
large number of ligaments (very little energy expenditure associated with them compared to
muscle).

Gravity can act as either an agonist (forcing the body to fall to the ground) or an antagonist (any time
you perform an action to raise your body, eg. standing up, lifting something).

A stable upright stance requires anatomical solutions, balancing the body around the line of gravity.

Need to stabilize front, back, etc. of joints to hold them upright. The joint being in front of the line of
gravity gives it a tendency to try and tip the body backward.

Feet provide base of support, but aren’t large enough to be the only balance solution

Standing achieved with very little muscular effort; mostly at ankle joint.

Bipedal standing – hip

- Posterior to joint
- Joint pushed into extension
- When extended the ligaments around the hip are tight, locking it into place
Has a capsule of ligaments. Sheath of DFCT around the joint. Rather than thickenings just around
areas movement shouldn’t happen, the hip capsule is thick everywhere.

Each capsular ligament is named after the bones they attach to, i.e pubofemoral ligaments

Hip in flexion = lax anteriorly, taut posteriorly

Hip in extension = taut anteriorly, lax posteriorly

Knee

Anterior to joint

Joint pushed into extension

Extension = ligaments are tight, joint is locked

Low congruence

Behind line of gravity

Ankle

Anterior to joint

Fall into dorsiflexion

Not locked

Plantarflexors (eg. gastrocnemius) stabilize, consuming energy. Plantarflexors are antagonists to

gravity.

Line of gravity is quite far in front of joint, giving a tendency to fall forward

Bipedal walking

Gait is characteristic, basic pattern is the gait cycle. Dynamic, continuous pattern, both limbs doing
something at the same time

Two phases, (early) stance and (early) swing.

Includes heel-strike and toe-off phases.

Heel strike is when the heel hits the ground when moving forward, coincides with the stance phase

Toe-off is when the big toe of the foot leaves the ground and starts swinging forward.

- Hip is in flexion, knee is in extension, ankle is in dorsiflexion.

- Hip goes into extension, knee passively flexes (hamstrings), ankle in plantarflexion

Between each step there is dorsiflexion of the ankle to prevent dragging along the ground

Tibialis anterior also acts as an antagonist to gravity to prevent the foot slapping on the ground

Early stance

- Hip
o is in flexion but moving into extension
o Concentric activity of gluteus maximus/hamstrings and eccentric activity of iliopsoas
 - Knee
o In extension (locked for stability
o Isometric activity of quadriceps femoris and hamstrings/gastrocnemius
- Ankle
o In dorsiflexion but moving into plantarflexion

Mid stance

- Hip
o Moving into extension
o Concentric activity of gluteus maximus/hamstrings and eccentric activity of ilipsoas
- Knee
o Moving from extension to slight flexion. Preparing for toe off phase
o Concentric action of hamstrings and gastrocnemius
- Ankle
o Moving into plantarflexion
o Concentric action of triceps surae

Early swing

- Hip
o In extension, moving to flexion
o Concentric ilipsoas and eccenstric gluteus/hamstrings (to control rate of swing)
- Knee
o Flexion
o Concentric hamstrings and gastrocnemius
- Ankle
o Dorsiflexion to allow clearance of toes during swing
o Concentric action of tibialis anterior

Mid swing

Same as early swing

Late swing

- Hip
o In flexion
o Concentric iliopsoas of eccentric gluteus/hamstrings
- Knee
o Flexion but moving into extension to prepare for heel strike and knee locking
o Concentric quadriceps
- Ankle
o In dorsiflexion for stability
o Concentric tibialis anterior and isometric triceps surae to keep ankle stable

Good idea to make a table of these actions and the muscles associated with each phase, and why
they happen.
Lecture 15 – Cells and organization of the nervous system
27/03/2019

- Understand the basic organization of the nervous system

- Describe the general structure of a neuron and understand how this structure is functionally
related to directional flow of information and….

“Integrating and coordinating” in the nervous system

The nervous systems allow us to sense our environment and then respond to it, eg. sense that
you’re cold/thirsty and produces the response to get warmer/drink water.

Maintains homeostasis

Integration is the process of taking in information to determine whether or not something is

important, such as seeing food when hungry

Coordination results in things like craving for food, or if not needed thoughts of doing something
else

Finally the response, which is to either get food or not

Nervous system

Divided into two parts; the central nervous system (CNS) and the peripheral nervous system (PNS).

CNS is made up of the brain and spinal cord, both made up of neurons and glia.

PNS consists of peripheral neurons, which are composed of neurons and glia.

Neurons are specialized for specific tasks, and have many different shapes as a result.

Neurons have 2 general features:

- specialized for transmission of information

- 4 morphological types (shapes)

Glial cells have 3 general features

- Support for neurons

- 5 basic types (4 in CNS, 1 in PNS)
- Each type has a specific function

Neurons

Structural components:

- Dendrites (tentacle things on the outside). These receive input and send info to the cell body
- Cell body. These contains the nucleus and organelles, and stores information (sum input)
- Axon (long tail). These carry electrical impulses, and may or may not be myelinated
- Axon terminal(s). These are at the end of the axon, and release neurotransmitters.

The input zone is made up of dendrites and the cell body, and receives chemical signals from other
neurons

The summation zone (also called the axon hillock, as it’s where the axon begins) decides whether or
not to transmit signals further
Information then passes through the conduction zone (the axon), in the form of electrical signals

The output zone is made up of the axon terminals, and is in contact with input zone of other neurons
or effectors and release neurotransmitters (a chemical signal)

Morphological types of Neuron

- Multipolar. Multiple processes emanate from the cell body. Dendrites are attached to the
body.
- Bipolar. Two processes emanante from the same body, with the dendrites far away from the
body
- Unipolar. One process emanates from the cell body before splitting, before branching into
the dendrites and axon.
- Anaxonic (axonless). No distinct axon, all processes look alike.

Glia in the CNS

- Astrocytes (star shaped)

o Supply nutrients to neurons
o Ensheath blood capillaries
o Transmit information (not in the same way as other neurons, new research)
- Microglia
o Immune cells of the CNS
o Engulf microorganisms and debris, such as damaged cells, keeping the brain clean
and healthy
- Ependymal cells
o Line fluid filled spaces of brain and spinal cord
o Have cilia to circulate the CSF (cerebrospinal fluid) in a particular direction
- Oligodendrocytes (many processes emanating from cell)
o Support nerve fibres
o Ensheath them with myelin

Glia in the PNS

- Schwann cells
o Support peripheral nerve fibres
o Ensheath them with myelin, similar to ODC

Myelin Sheath

Cells situate themselves next to the axon and wrap their membranes around them

Essentially wrapped in fat, as the membranes are made of lipids

White cells appear so because most of them have been myelinated

Helps increase the velocity that nerves impulses can be transmitted

Nodes of Ranvier form gaps between myelin, which also helps increase conductivity

In the CNS

- Groups of cell bodies together are called the nucleus,

- Bundles of axons are called tracts
 - Groups of cell bodies in the cerebral cortex or spinal cord are called grey matter
- Groups of axons in the cerebral cortex or spinal cord are called white matter

In the PNS

- Groups of cell bodies are called a ganglion (pl=ganglia)

- Bundles of axons are called nerves

Communication between neurons occurs through a junction called a synapse.

It’s the space between two neurons where the neurotransmitters are released and then received by
dendrites.

As the electrical signal cannot be conducted through this space, it’s turned into a chemical signal in
the synapse, before being turned back into electrical signals by the next neuron.

The gap between the two cells where the synapse happens is called the synaptic cleft. The synapse is
the term for the transfer of information

The neuron transmitting the information before the synapse is called the pre-synaptic neuron, and
contains synaptic vesicles which release the chemical signal from the axon terminal

The second cell is called the post-synaptic neuron (after the synapse) and contains receptors for
neurotransmitters.

Flow of information occurs in both directions:

- Information going into the brain is called afferent (ascending)

- Information leaving the brain is called efferent (descending)

Lecture 16 – Nervous system…?

01/04/2019

Information received through receptors -> through spinal nerves to brain/spinal cord ->
integration/coordination -> back down spinal nerves to effectors -> action

Divided into sensory afferent and motor efferent.

Types of information transmitted:

- Somatic: stuff we’re away of and have control over, such as voluntary movement (somatic
efferent) and sensory information we’re aware of (eg. sigh, somatic afferent)
- Autonomic: Stuff we’re not aware of and have no control over, such as involuntary muscle
control (eg. heartbeat, autonomic efferent) and sensory information we don’t know about
(eg. blood pressure, autonomic afferent)

Somatic Division

Efferent (motor)

This is how the brain controls the muscles.

2 neurons that run between brain and the effectors throughout the body

- Upper motor neuron. Cell body in brain, axon in spinal cord, carries info out of the brain
before synapsing with…
- Lower motor neuron. Cell body in spinal cord, axon in spinal nerve, nerves go into the PNS

The effectors in this case are skeletal muscle fibres.

Axons are myelinated.

Gap between the neuron and the skeletal muscle is essentially the same as with neurons, but as it’s
not a neuron it’s called a neuromuscular junction. Neurotransmitter is Acetylcholine (Ach)

Autonomic division

Involuntary control

Two divisions:

- Sympathetic NS
- Parasympathetic NS

Collectively called the autonomic nervous system

3 neurons:

- Neuron 1
o Cell body in brain
o axon in brain or spinal cord
- Neuron 2
o Cell body in brain or spinal cord
o axon in PNS
o Myelinated
o Synapse in autonomic ganglion
o Pre-ganglionic neuron
o Neurotransmitter = Acetylcholine
- Neuron 3
o Cell body in PNS, autonomic ganglion
o Axon in PNS connecting to effectors
o Unmyelinated
o Synapse on effector organ
o Post-ganglionic neuron
o Neurotransmitter = Acetylcholine or norepinephrine (adrenaline).

Reminder: Ganglions are groups of cell bodies in the PNS

AP’s travel from 1 -> 2 -> 3, synapsing between each one

The effectors are

i) Smooth muscle
ii) Cardiac muscle
iii) Glands
iv) Adipose (fat) tissue
Very small axons allow high amounts of autonomic intervention in small tissues

Small diameter axons don’t need to be myelinated, no loss in transmission rate

Divided into two separate nervous systems:

- Sympathetic
o Prepares the body for stressful situations, eg. fight or flight
o Effects include increased heart rate, constricting blood vessels allowing higher blood
flow to muscles
o Lowered gastric motility
o Lowered salivation
o Increased pupil size
o Increased sweating
o Produces more norepinephrine at the effector synapse
o Has quite a short axon before reaching the autonomic ganglion?
- Parasympathetic
o Prepares the body for restful sympathetic, essentially the opposite to above
o Decreased heart rate
o Increased gastric motility
o Decreased pupil size
o Increased salivation
o Produces more acetylcholine at the effector synapse
o Has a very long axon, stretching throughout the PNS to the effectors?

Sympathetic

Axon of preganglionic neurons leave the CNS at thoracolumbar levels (spinal chord, thoracic?)

Axon extends a short distance

Synapse and cell body of post ganglionic neuron are in sympathetic ganglion

Sympathetic chain ganglia: 21-23 pairs, alongside vertebral column, place where the preganglionic
neurons have their bodies and synapse,

Parasympathetic

Axon of preganglionic neuron leaves CNS at cranial and sacral levels

Axon of preganglionic neurons is long af

Ganglion is close to the effectors

Lecture 17 – Action Potentials and Synaptic Transmission 1
02/04/2019

Action potentials are the basis of all neuronal communication

ECF = Na+ 142 mM, K+ 4mM

ICF = Na+ 12mM, k+ 150mM

Ions move through sodium/potassium leak channels

Membrane potential between the inside and outside of the cell that’s important for the excitability
of the cell

Membrane potential varies with de/hyperpolarization

Chemical stimulus opens sodium ion channels

Action potentials sent down the axons cause excitation

Voltage gated ion channels have the ability to regulate movement of ions across, by being either
open or closed.

They have an activation gate and an inactivation gate

These open and closed based on the membrane potential. For example, if the membrane potential
changes to -60mV the gates will both open to allow movement through

The inactivation gate shuts when the membrane potential grows positive (slide example is +30mV)

Might only be sodium gated channels that have 2 gates, potassium only has 1 on the slides

During the action potential:

- Voltage gated channels start off shut, with a few leak channels open.
- A local graded change in membrane potential occurs and is sufficient to depolarize the cell
and open voltage gated Na+ channels
- The membrane rapidly depolarizes, at which point the sodium channels close. At this point
the potassium channels open
- Membrane potential goes back down to below the original resting membrane potential (-
90mV) at which point the K+ channels close and the membrane repolarizes

Action potentials have both absolute and relative refractory periods

Refractory essentially means stubborn or resistant to a process or stimulus. In this case it’s a period
where another action potential cannot happen because the membrane resists it. This is called the
absolute refractory period.

The relative refractory period is a period where AP’s can happen, but it’s more difficult, and they
potentially have reduced effect?

ARP peaks when the Na+ channels close and the K+ channels open

RRP is when the voltage gated K+ channels begin closing

Axon hillock is the decision point. If the action potential can get over the “hump” the threshold
voltage will be exceeded and the AP will propagate down the axon (check this again).
As an AP develops at the initial segment, the membrane potential at a specific site depolarizes to
+30mV. Once the Na+ channels open that depolarization spreads to the next bit of membrane. As
the AP develops in this next section the previous section is in its refractory period, beginning
repolarization.

AP’s in our body move at roughly 70 metres per second

AP speed is sped up by myelination of the axons (small gaps in between them). They create an
effective connector between nodes, allowing it to skip areas called internodes (which are the
covered bits)?

Lecture 18 – Synaptic connections

Can think of brain like the London underground. Each node/station is somewhere where information
can be transferred

Chemical synapses are a gap between neurons where an action potential is transferred from one
neuron to either another neuron or a muscle cell

Gap in the synaptic cleft where this transformation takes place

Once an AP exceeds the axon hillock it continues down the axon

Different neurons all have the same zones

All end in the synaptic terminal

Chemically gated ion channels are present at the terminals

Acetyl choline opens the chemically gated ion channels by binding to the protein and causing a
conformational change. This allows membrane potentials to be changed

AP’s are what make the acetyl choline available

Regulatory neurons can influence the chain of synaptic transmissions

Calcium cations are important in nervous system health and function. 2-2.5mM in the ECM

Key components of chemical synapses:

- Postsynaptic neuron/muscle fibre. Receives the signal.

- Axon terminal on presynaptic side. Contains vesicles and mitochondria.
o Mitochondria facilitate the reformation of acetyl choline
- In between the two, in the synaptic cleft, is Acetyl choline E (AChE)

Events occurring during a cholinergic (involving choline) synapse:

- Action potential triggers voltage gated calcium channels to open

o Causes depolarization
- Calcium ions diffuse into the axon terminal and trigger synaptic vesicles to release ACh
o Vesicles fuse with the synaptic membrane, which causes the release of ACh
- Ach diffuses across the cleft, binding to Ach gated sodium ion channels and producing
depolarization of the opposite membrane
 o Depolarization of the presynaptic neuron is turned into depolarization of the
postsynaptic neuron
o Opening of the channels causes a graded/local depolarization, also called excitatory
post synaptic potential (EPSP)
- Depolarization ends as Ach is broken down into acetate and choline by AChE
o Once turned into these components they can no longer activate the channels. If
AChE isn’t there ACh concentration remains high which can lead to overactivation of
the synapse
- Axon terminal reabsorbs choline from the cleft and uses it to synthesis new ACh

While depolarization of a neuron could be due to an EPSP, likewise hyperpolarization can be caused
by IPSP’s, which is inhibitory polarization.

The further away from standard potential the membrane is the less likely an AP is to occur

EPSP’s and IPSP’s can summate; as one is positive and one is negative however they cancel each
other out if they happen at the same time, meaning there’s no change in the overall membrane
potential

The summation of the potentials is important for the action potential to happen, as they determine
whether the membrane potential exceeds threshold

Synaptic transmission at the NMJ is always excitatory and absolute, there’s no axon hillock of
EPSP/IPSP summation.

Two types of summation:

- Temporal summation: “In Time”. AP arrives at the synapse and depolarizes the membrane.
Not enough to get over the axon hillock. If a 2nd AP arrives before the 1st one fades however
they summate, which could be enough to take the AP above the threshold and pass the
hillock. The sum is greater than the parts
- Spatial summation: “In space”. This involves summating AP’s in different parts of the neuron
happening at the same time. 2 simultaneous AP’s arriving, summating, and exceeding the
threshold.

These often happen at the same time.

Lecture 19 – Human movement and Sensation

08/04/2019

Recap:

Somatic efferent neurons use acetylcholine as a neurotransmitter

Sympathetic chain ganglia contain cell bodies that utilize norepinephrine

If the craniosacral nervous system is activated you are relaxed.

Post-ganglionic parasympathetic neurons cell bodies are distant from the CNS.

External anatomy of the spinal cord

Starts at the foramen magnum (big hole at the base of skull)

Ends at the inferior border of the first lumbar vertebra (L1)

Surrounded by a (meningeal) sack filled with fluid that fits inside the spinal cavity

Spinal cavity runs through the middle of the vertebrae.

The end of the cord tapers into a cone called the conus medularis, which is a non-neural tissue that
connects to the filum terminale, which extends down to the end of the spinal cavity, anchoring it in
place and preventing it from moving around. Filum terminale is also non-neural tissue.

Spinal cord has 31 segments. At each level of the vertebrae spinal nerves come out on either side,
even past where the spinal cord itself ends.

There are 8 cervical vertebrae (despite only having 7 cervical vertebrae)

In the thoracic section the vertebrae and nerves get out of sy nc due to increasing bone side,
increasing the length of the nerves as they have to extend down the spine to exist the vertebrae.

This collection of spinal nerves clustered inferior to the spinal cord is called the cauda equina.

Sulcus means furrow

Fissure means a deep sulcus

Posterior = dorsal

Anterior = ventral

Furrow on the posterior side is called the posterior median sulcus.

On the opposite (anterior) side is called the anterior median fissure.

Central area (hole down the middle)

Grey matter in the middle

All the stuff around the grey matter is the white matter.

Collectively these make up the spinal cord, and the CNS

The spinal nerves therefore, as they branch off, are part of the PNS

Divided into dorsal and central halves:

- Dorsal grey horn (cell bodies)

- Lateral grey horn (cell bodies)
- Central grey horn (cell bodies)
- Dorsal white column (axons)
- Lateral white columns (axons)
- Ventral white column (axons)

On dorsal side the spinal nerves have the big bulge

PNS:

- Ventral nerve root (axons)

- Dorsal nerve root (axons)
- Bulge is called the dorsal root ganglion (cell bodies)
- Spinal nerve (the two nerve roots joined together)
Dorsal side of the spinal cord is concerned with sensory (afferent) information

Ventral side of the spinal cord is concerned with motor (efferent) information

Ventral roots are myelinated

Autonomic neurons are found in the lateral grey horn

Somatic motor neurons are found in the ventral/central horn

If there was damage to the ventral horn there would be paralysis of muscles below, as no commands
would be able to reach the muscles

Cell bodies of sensory neurons are in the dorsal root ganglion, and have their exit zone towards the
spinal cord side. Input zone receives information from the peripheries and sends it to the spinal cord

If the spinal cord was damaged at the input zone it could no longer receive information, resulting in
loss of sensation from the regions of the body supplied by that neuron.

So in summary:

- Dorsal nerve roots carry only afferent information

- Ventral nerve roots carry only efferent information
- Spinal nerves contain both afferent and efferent information

Spinal nerve splits:

- Dorsal ramus. This brings efferent information from the back region, and brings afferent
information back to the spine.
- Ventral ramus. This brings information to the ventral side of the body, and brings afferent
information back to the spine.
- Rami communicantes, which leads to the sympathetic ganglion, which itself leads into
sympathetic nerves.

Peripheral nerves

Individual axons may be either myelinated or not

Axons are covered with endoneurium

Endoneurium covered axons are bundled together to form a fascicle

Fascicles are covered with perineurium

Fascicles bundle together to form a nerve.

Nerves are covered by epineurium.

Lecture 20 – Meninges and Ventricular system
09/04/2019

The meninges are the protective covering surrounding the brain.

It has 3 layers:

- Dura mater
o Has two layers of its own, outer and inner. In certain places these layers can
separate to form venous sinuses. Inner layer can form Dural folds
o Outer most layer, dense and fibrous, very tough
- Arachnoid
o Is elevated above the surface of the brain by a bunch of “legs”.
o Does not extend into sulci (valleys)
o Contains subarachnoid space and arachnoid granulations
o Contains blood vessels in the subarachnoid space
- Pia mater (adheres closely to the brain)
o Transparent and delicate
o Blood vessels in the subarachnoid space sit on top
o Follows gyri and extends into sulci

Dural folds are formed from an inner layer of dura mater. They separate the major divisions
(hemispheres) of the brain, and provide stability of the brain within the cranium.

There are 3 Dural folds

- Falx cerebri
o Separates the two cerebral hemispheres, i.e each half down the middle
o Medial plane
- Falx cerebelli
o Separates cerebellar hemispheres
o Medial plane
o Back of the brain
- Tentorium cerebelli
o Separates the cerebrum from the cerebellum
o Horizonal plane

Venous sinuses are located where the two layers of dura mater separate, and are a collection of
veins? Collects venous blood from the brain and old CSF

The subarachnoid space is found between the arachnoid and the pia mater. It’s filled with
cerebrospinal fluid (CSF) and contains blood vessels. The CSF forms a sort of “cushion” around the
brain.

Arachnoid granulations perforate the inner layer of dura mater, and transport “old” CSF from the
subarachnoid space into venous sinuses.

Meninges of the spinal cord are the same as the brain pretty much.
Ventricular system

4 features:

- Network of interconnected spaces (ventricles) within the brain

o 2 lateral ventricles, one in each cerebral hemisphere
o 3rd ventricle is located in the diencephalon (midline)
o Cerebral aqueduct connects the 3rd ventricle to the 4th and is located in the midbrain
o 4th ventricle is located at the end of the cerebellum
- Filled with CSF for protection
- Spaces lined with ependymal cells, with circulate the CSF using cilia
- CSF is produced by the choroid plexus.

Cerebrospinal fluid

Four features:

- Surrounds the CNS within the subarachnoid space

- Provides support and cushioning
- Transports nutrients and waste
- Produced by choroid plexus within all of the ventricles

Within the subarachnoid space it flows around the brain and spinal cord

It exits through arachnoid granulations into venous sinus

Lecture 21 – Integrating and coordinating roles of the nervous system

10/04/2019

Anatomy of the Brain

Lateral View

Cerebellum (thing at the back) is at posterior of the brain

Posterior is often a little bit pointier

Frontal lobe (beneath frontal bone)

- Motor control (posterior part of lobe)

- Language/personality (anterior part of lobe)

Parietal lobe (beneath parietal bone)

- Somatosensory (touch)

Occipital lobe (beneath occipital bone)

- Vision

Temporal lobe (beneath temporal bone)

- Memory
 - Hearing

Sulcus/sulci = furrows/valleys in the brain

- Central sulcus separates parietal and frontal lobes

- Parieto-occipital sulcus separates parietal and occipital lobes
- Lateral sulcus separates temporal lobe from the frontal and parietal lobes
- Transverse fissure separates cerebrum from cerebellum. Dural fold called the tentorium
cerebelli is in here.

Gyrus/gyri = hills/protrusions in the brain

Medial division

Cerebral cortex

Below that is the corpus callosum (white matter)

Inferior to that is the diencephalon, made up of the thalamus and hypothalamus.

Below that is the cerebellum

Anterior to that is a series of structures that collectively are called the brainstem

- Midbrain
o Associated with cerebral aqueduct
- Pons
- Medulla oblongata (or just medulla)
o Ends at the foramen magnum

Coronal Division

Grey matter lines the outside of the cerebral cortex

White matter on the inside

Collections of cell bodies (nuclei) around the centre of the brain, called deep nuclei.

Tract of white matter spanning the centre called corpus callosum. Axons cross through this in both
directions

Axons that extend out of the brain are said to “project”

Association tracts are axons on the same side of the cerebral cortex, which allows communication
between different lobes. Can be both short and long distance.

Cortical areas

Pre-central gyrus is on the anterior side of the central sulcus.

- Primary motor cortex

- Efferent, sends information away from the CNS
- Different regions of he cortex control specific areas of the body (moves up from toes
medially to things like swallowing most laterally)
- Has 2 neurons, lower and upper, collectively called the corticospinal pathway
- Damage results in muscle weakness and/or paralysis in the region of the body corresponding
to the location of damage.
Post-central gyrus is on the posterior side of the central sulcus.

- Primary somatosensory cortex.

- Receives information (afferent information)
- Specific regions of the somatosensory cortex receive sensory information from specific areas
of the body (pretty much the same way as motor cortex)
- 3 neurons between receptors and somatosensory neurons. Collectively called the
dorsal/posterior column pathway.
- Damage to somatosensory cortex means afferent information has no place to go, no
sensation from corresponding area of body.

Lecture 22 – Motor Control

15/04/2019

- Define reflex and voluntary movements

- Draw a functional diagram of the stretch reflex
- Describe the primary motor cortex
- Outline major steps in the voluntary control of movement
- Briefly describe the roles of the cerebellum in voluntary movement

Involuntary Movement

Spinal reflex arc: Stimulation of receptor -> activation of sensory neuron through the posterior root
ganglion -> Information processing in the CNS -> activation of a motor neuron -> response of a
peripheral effector

This is an organized neural circuit contained within the spinal cord. It is a reproducible, automatic
response to a particular stimulus.

Stretch Reflex

Muscle spindles are the primary sensory input

Withdrawal reflex

Pain stimulus is the primary sensory input. Interneuron in the spinal cord activates the flexor muscle
and an inhibitory neuron. But as muscles can’t be inhibited instead the inhibitory neuron turns off
the motor neurons to the antagonizing muscle causing it to relax.

Voluntary movement

Parts of the brain are always monitoring the situation of the body and environment

Most lateral parts of the motor cortex are more closely associated with very fine motor control

Brain regulates muscle tension primarily through motor unit recruitment

Motor control is related to number of motor units in an area. Lots of motor units in a small area
results in much finer muscle control.

Another method of regulation is stimulation frequency. The frequency of AP’s can help control how
much tension the muscle has by controlling individual fibres.
The Cerebellum

Preparing for movement

Coordinates muscles, guided by sensory feedback

Compares intended movement with actual result

Helps maintain posture and gaze

Helps learn and automate movements

Allows many neurons to be concentrated in a smaller space

Decision made in frontal lobe -> information moves to premotor cortex -> information moves to
cerebellum, which contains the information about the body and its environment, and helps organize
the desired movement

Stores “muscle memory”, optimizing behaviors and movements

Performing voluntary movement

Motor cortex sends an output to the lower motor neurons

Cerebellum compares sensory feedback about the actual movement to the intended movement, and
signals adjustments to the primary motor cortex. Maintains balance.

Cerebellar deficits can cause ataxia, a “drunken gait”

Remember brain controls motor neurons, which in turn controls muscles; brain does not directly
produce/inhibit movement of muscles

Voluntary motor control loop

Decide to do something in the prefrontal cortex -> info moves through premotor cortex, primary
cortex, and back and forth from the cerebellum to adjust movement -> motor neurons activated ->
movement produced

Key point = involuntary movement inhibits itself to the spinal cord, voluntary movement happens in
brain
Lecture 23 – Somatic sensation
16/04/2019

- Define somatic sensation and special senses

- Describe and give examples of four types of information about a stimulus encoded by
sensory systems
- Outline the representation of somatic sensory information in the brain
- Briefly explain the integration of sensory and motor control systems

Various forms of neurons:

- Anaxonic
- Bipolar
- Multipolar
o Motor neurons take roughly this form
- Unipolar
o Sensory neurons take roughly this form, such as the dorsal root ganglion

Sensory information comes through dendrites and pass through the initial segment

Types of input to the CNS

Two types of senses

Special senses:

- Vision
- Hearing
- Taste
- Smell (and pheromones)
- Vestibular (balance)

Somatic and visceral sensations

- Touch
- Pain
- Warm and cold
- Body position (proprioception)

There are two methods of sensation; direct (e.g. temperature sensation) and endocrine (hormonal,
intake)

Special senses have specialized receptor cells. These receptor cells are highly sensitive to a particular
kind of stimulus (modality).

Transduction is the conversion of energy (sensory stimulus) into action potentials.

4 types of information that describe a stimulus:

- Modality. This is the type of sensory receptor that’s been activated. Different receptors are
sensitive to different stimuli, so this allows the determination of the stimulus
- Intensity. This is the frequency of action potentials firing in afferent neurons
- Duration. This is the duration of AP’s being fired in afferent neurons. Receptors fire more
slowly when stimulus is constant/steady
 - Location. Where the receptors that have been activated are.

Dendrites wind around a collection of fine, contractile muscle fibres. Whenever the muscle changes
length it depolarizes and gets __ to threshold. Mechanotransduction?

Gamma motor neurons innervate each muscle spindle surrounding the neuron to ensure it retains
its ability to detect length changes

Modality depends on the shape of the endings?

Intensity has a threshold below which there’s no response in the afferent neuron. Larger stimulus
intensity results in larger receptor potentials, which can cause the first node of Ranvier to depolarize
and send action potentials into the CNS. Increasing the stimulus intensity increases AP frequency.

Sensory receptors are most sensitive to change; they show adaptation over time in response to
continuous stimulation, decreasing their output; e.g. anosmia

Fingerprints are a method of detecting surface texture due to increased surface area

A receptive field is a region of space in which a stimulus can lead to activity in a particular afferent
neuron. Small fields and dense innervation results in good discrimination (i.e. ability to feel and
separate different stimuli). Fields can overlap.

Modality is represented as a “labeled line” . AP’s travel along the labelled line. Think old phone
lines. Brain can interpret the place of origin and type of stimulus from this.

Sensation is the conscious identification of “what” and “where”. Makes up the primary region of the
cortex

Perception is meaningful interpretation of stimuli. This takes place in the association (secondary)
region of the cortex

Densely innervated areas of the body occupy large regions of the cortex. Left cortex represents right
body and right cortex represents left body.

Lecture 24 – Biostatistics

To find the difference in proportion subtract one percentage from the other.

Compare that difference to the sample differences

Lecture 25 – The Endocrine System; What are hormones?

29/04/2019

Comparison of neural and endocrine systems

Synaptic: AP’s in axons and neurotransmitters are released at synapse

- Targeting achieved by specific “wiring”

- Has the fastest transmission speed and good for brief responses
Endocrine (aka hormonal): hormones are released into blood

- Targets by the presence of specific receptors on target cells

- Comparatively slow, but good for creating long lasting actions and widespread (systemic)
responses

Endocrine cells (in endocrine glands) secrete hormones. The hormones then travel through the
blood to the target cell, where it has an effect on the cell and changes its function.

Major endocrine glands include the hypothalamus (connection between neural and hormonal
systems), pituitary gland, thyroid gland, adrenal glands, pancreas, pineal gland and parathyroid
glands.

Some organs have secondary endocrinal functions, covered in HUBS192

What are hormones?

There are several methods of hormonal communication

- Paracrine communication involves transmission through extracellular fluid through

paracrines. Primarily limited the local area where
- Autocrine involves affecting the same cell that secretes autocrines through the ECF.
- Endocrine involves hormones that moves from the cell, released into the ECF and is
transmitted through the blood stream, targeting cells primarily in distant tissues and organs.

Only need to consider signals in the bloodstream as hormones

Hormones can only affect cells with specific receptors for that hormone.

Each receptor is a protein, either in the target cells membrane or totally within the cell. This depends
on the type of hormone they respond to. If the hormone can freely diffuse through the membrane it
might be useful to have the receptor within the cell.

Surface receptors respond to water soluble hormones which cannot cross the cell membrane. These
are mostly peptides (which make up 75% of hormones) and some catecholamines. These are made
in advance and stored until they’re required to be released be exocytosis, and travel by diffusing in
the blood.

Lipid soluble hormones include steroids and thyroid hormones. These are made from cholesterol as
required, not stored like water soluble hormones, as they can diffuse through membranes. The
exception to this are thyroid hormones. These travel in the blood bound to a carrier protein as they
cannot dissolve in the blood. The receptors are located in the cytoplasm or nucleus.

Water soluble

1) Water soluble hormone binds to cell surface receptor

2) Hormone binding allows activation of associated G-protein
3) G-protein activates/inhibits adenylyl cyclase, or increases intracellular Ca2+
4) Second messenger production/reduction eg. cyclic AMP
5) Downstream proteins/pathways are activated or deactivated

This can take milliseconds to minutes to take effect

Lipid soluble

1) Hormone dissociates from carrier protein

2) Diffuses across cell membrane
3) Binds to intracellular receptor
4) Hormone receptor complex acts as a specific transcription factor, changing the production of
a particular protein
5) Target gene is activated.
6) New mRNA is generated
7) New protein is generated by translation of mRNA

Because this involves a change in protein development it takes a lot longer to cause an effect,
potentially hours or days

Control of hormone secretion

Amount of hormones in the blood depends on the balance of hormone secretion/removal from the
blood

Removal is controlled by enzymes in the blood or in target cells

Secretion is generally controlled by negative feedback loops; if a deviation occurs in the system and
is detected by a “receptor/sensor” and recognized by a control centre, a mechanism is activated to
bring the variable back to the previous point.

Having the wrong amount of a hormone can lead to endocrine disorders

Homeostasis

Homeostasis is the presence of a stable internal environment

Receptors detect change -> control center compares to set point -> effectors respond with various
effects, either localized of throughout the body

Different cells detect different changes, either positive or negative.

The Pancreas

Most of the pancreas is an exocrine gland, secreting digestive enzymes

1% of it however acts as an endocrine gland; beta cells which secrete insulin and alpha cells which
secrete glucagon

Need a certain level of glucose in the bloodstream for the brain to function as it’s the only fuel that
the brain uses

However as blood glucose changes throughout the day as we eat/don’t eat, we move between two
metabolic states; fed state and fasting state.

Fed state: cellular uptake of nutrients and synthesis of glycogen, protein and fat

Fasting state: mobilization of nutrients and breakdown of glycogen, protein and fat.

Above certain blood glucose level insulin is secreted, below glucagon is released
Insulin travels through the bloodstream to the target cells, stimulating muscle/adipose cells (causing
glucose uptake and storage as glycogen/fat) and liver cells (causing glucose output to stop and net
glucose uptake). This causes blood glucose to come back down to the normal range.

Glucagon is the same sort of negative feedback loop. Blood glucose concentration drops, glucagon is
released and targets the liver cells, causing breakdown of glycogen (glycogenolysis), glucose
synthesis (gluconeogenesis) and ketone synthesis (to free up glucose for the brain instead of being
used by other organs). This results in blood glucose level increasing to the normal level.

If glucose concentration rises above normal levels it’s detected by beta cell receptors in pancreatic
islets

If glucose concentration drops below normal levels it’s detected by alpha cell receptors in pancreatic
islets

Problems with hormone signaling

Hyposecretion: too little

Hypersecretion: too much

Hyposensitive: little response

Hypersensitive: too much response

Autoimmunity: destruction of receptors

Genetic mutation can cause gain or loss of function

Lecture 26 – The Hypothalamus and Pituitary glands

30/04/2019

- State the major effects of the anterior and posterior pituitary hormones.
- Explain how the hypothalamus controls the release of hormones from the posterior pituitary
gland
- Explain how the hypothalamus controls the release of hormones from the anterior pituitary
gland.
- Describe the effects of growth hormone on human growth

Diabetes Mellitus

Two types of diabetes we’re concerned with:

- Type I
o Hyposecretion of insulin
o Caused by autoimmune disorder that destroys pancreatic cells
o This results in:
 glucosuria (glucose in urine)
 polyuria (large quantities of sweet urine)
 polydipsia (dehydration, thirstiness)
 Diabetic neuropathy (damaged neural tissue)
 Heart problems
 Diabetic retinopathy (blindness/eye damange)
 Disrupted blood flow
 o Treated by injections of insulin. Can’t be a tablet because it’s a peptide and would be
digested

Only need to remember at most two of the symptoms for exam questions

- Type II
o Hyposensitive to insulin.
o Cased by desensitization of insulin receptors, associated with obesity
o Results in the same symptoms as type I
o Treatment however involves changes in diet and exercise, though there are various
medications available to re-sensitize the receptors or produce more insulin

Hypothalamus and Pituitary Gland

Pituitary gland split into two parts:

- Posterior lobe: made of neural tissue

- Anterior pituitary

Secretions from both are controlled by the hypothalamus

Hormones released by the pituitary gland can affect other endocrine glands. Both parts have
distinctive mechanisms for hormone secretion.

Posterior pituitary lobe is attached to the hypothalamus by neurons. Its hormones are produced in
the hypothalamus and stored in the axon terminals in the pituitary. Hypothalamus uses neural
communication to release hormones into the blood.

Hormones released by the posterior lobe include:

- Antidiuretic hormones: stimulates the kidneys to reabsorb water

- Oxytocin: stimulates the contraction of uterine muscles during childbirth and stimulates milk
release in breastfeeding

Anterior lobe of the pituitary gland is connected to the hypothalamus by blood vessels.
Hypothalamus communicates with it via hormonal stimulation after receiving neural stimulus. It
secretes releasing hormones which bind to receptors on the membrane of specific cell types in the
anterior lobe, causing specific peptides to be secreted.

Hormones released by the anterior lobe include

- Prolactin: stimulates the mammary causing production of breast milk.

- Growth hormone: targets the liver gland and secretes IDF-1
- Thyroid stimulating hormone: targets the thyroid which secretes T3 and T4
- FSH & LH: stimulates the gonads which secretes estrogen and testosterone
- ACTH: stimulates the adrenal cortex which secretes cortisol

These hormones have significant effects across the whole body, and so much be tightly controlled.

Regulation of the anterior pituitary hormones is controlled by a negative feedback loop

Hypothalamus produces both releasing and controlling hormones. These control the release of the 6
anterior pituitary hormones

Growth Hormone
Growth hormone releasing hormone from the hypothalamus causes the release of growth hormone
from the anterior pituitary. This travels to the liver and causes the release of somatomedin C (IGF-1),
which promotes cell division, causing the growth of bones, muscle and other tissues.

This negatively impacts (in the loop) the pituitary by returning the to hypothalamus causing the
release of somatostatin neurons (growth hormone inhibiting hormone)

Growth hormone also uniquely has direct effects of things like muscle and fat as well, stimulating
protein synthesis and inhibiting cellular uptake of glucose in muscles, stimulating glucose synthesis
in the liver, and increasing triglyceride breakdown in adipose tissue.

Growth hormone secretions peak during the night

Excess secretion of growth hormone causes gigantism, increasing height, thickening of certain
tissues and continual growth throughout adult life.

Deficient secretion of growth hormone causes a particular type of dwarfism which results in them
being smaller across the board, unlike chondroplasia which causes abnormal long bone growth.

There are other hormones that are also important for normal human growth, including insulin,
thyroid hormones and sex hormones.

Lecture 27 – Adrenal Gland Hormones

1/05/2019

The adrenal glands are made up of two parts; the cortex and medulla. The cortex is yellow, while the
medulla is red or grey. These are made up of different tissues.

They’re located superior to each kidney.

Made up of two separate glands.

- The adrenal cortex is the outermost layer, and has 3 layers of its own
o Outermost layer secretes mineral corticoids like aldosterone (manages blood
sodium)
o Middle layer produces cortisol
o Inner layer produces androgens which have a minor reproductive role
- The adrenal medulla is made up of neural tissue, and is part of the sympathetic nervous
system. Contains sympathetic preganglionic neurons.
o Secretes mainly adrenaline

Cortisol is a steroid hormone, and therefore has to be produced from cholesterol as required.
Carried in blood bound to a carrier protein and binds to receptors inside the cell, increasing the
expression of certain genes and causing the production of proteins. As such this has quite a slow
response, as the proteins take a while to be produced in enough quantity to have an effect.

The hypothalamus secretes corticotropin releasing hormone (CRH), which causes the anterior
pituitary to secrete adrenocorticotropic hormone (ACTH). This travels through the blood before
reaching the adrenal cortex, causing it to create and secrete cortisol. The cortisol goes on to have
the following effects:

- Muscle: Increase in protein breakdown and decrease in glucose uptake, keeping the glucose
in the blood
 - Fat: Increased fat breakdown and decreased glucose uptake
- Liver: Increase in glucose synthesis (gluconeogenesis)
- Helps the body cope with stress
- Long term exposure can suppress the immune system
- Essential for maintaining normal blood pressure.

Cortisol secretion is controlled by negative feedback except during stress response.

Cortisol secretion peaks when you wake up. Variations in the sleep-wake cycle can cause issues with
cortisol release.

In response to stress, cortisol:

- Increases blood glucose levels

- Increased fat, protein and carb metabolism to maintain blood glucose
- helps immune system function
- Increases anti-inflammatory actions
- Increases blood pressure by increasing tone and contraction of blood vessels
- Can cause changes in the CNS

Addison’s Disease

Caused by damage to the adrenal cortex, so lowered secretion of both cortisol and aldosterone

Low cortisol levels leads to an increase in ACTH secretion, which is structurally similar to another
hormone that influences melanin production. Excess amounts of it can therefore change skin
pigmentation, lower blood pressure and make the affected individual weak due to “lack of fuel”.

Lowered sodium levels leads to higher blood potassium levels, which can affect cardiac function

Cushing’s Syndrome

Caused by hypersecretion of cortisol.

This causes breakdown of fats and proteins but no use of them, resulting in them ending up in areas
they wouldn’t normally be stored. In this case it can result in a “hump” high on the back and “moon
face” as the fat is deposited around the face.

Also results in high blood pressure and weakness due to muscle wasting resulting from the
breakdown of muscle tissue.

Adrenaline

The medulla is made up of the same type of tissue as sympathetic chain ganglions, and is therefore
also stimulated by signals coming from the hypothalamus.

Noradrenaline (norepinephrine) is secreted as part of the SNS’s response to stress.

Adrenaline/noradrenaline travels through the blood, and can stimulate cells already stimulated by
the nervous system, extending the effect

Released as part of the flight, fight or fright response

Adrenaline is a catecholamine, and is water soluble. As a result it diffuses through the blood and
binds to receptors on the surfaces of target cells. It then activated the G protein inside the cell,
which itself activates a second messenger pathway, which causes an amplification of the response
within the cell.

Stimulus is stress. The hypothalamus detects this, and sends neural signals down to the adrenal
medulla, causing it to secrete adrenaline, creating the following effects:

- Skeletal muscle and liver: Increased breakdown of glycogen to glucose

- Fat: Increased breakdown of fat to fatty acids
- Some systems are activated for physical activity, while some systems not essential for short
term survival are shut down

This results in more fuel being available to achieve what we want to do (fight or flight)

Posterior lobe of the pituitary glad is also activated as part of the stress response. This causes the
release of anti-diuretic hormone (ADH), which stimulates the kidneys and causes a lowering in water
excretion, and an increase in blood volume and pressure.

Overall stress response results in increase in blood glucose (via gluconeogenesis in liver and
glycogenolysis in liver and muscle), increased blood pressure/volume and heart rate.

High blood pressure means the force the heart has to exert increased. Long term high blood
pressure causes the heart to expand, however the valves don’t, which can result in problems.

Lecture 28 – Thyroid Gland; regulation of basal metabolic rate

6/05/2019

Thyroid gland

In the throat, just inferior to the larynx. On the anterior and lateral surfaces of the trachea.

Makes and secretes:

- Thyroid hormone: essential for optimal metabolic activity

- Calcitonin: involved in calcium homeostasis

The thyroid gland is made up of small spherical sacs called follicles. Each follicle is surrounded by
follicular cells and this is the site of thyroid hormone synthesis. Clear cells (C cells) lie in clusters
between the follicles and make calcitonin.

Thyroid hormone synthesis involves iodine entering the follicle cell from the blood and travelling
into the follicle cavity. The follicle cells release protein, thyroglobulin (TGB) into follicle. The iodine
reacts with tyrosine in the TGB molecules. Iodised TGB moves into the follicular cells. Thyroid
hormones detach from TGB as needed; T3 is the more active form, however T4 is the more plentiful
form. They travel bound to carrier proteins (thyroid-binding globulin, TGB) to target cells.

Thyroid hormone is made in advance and stored until required unlike other lipid soluble hormones,
but otherwise is the same; i.e. binds and changes genes to change proteins, can take 45 minutes –
days.

Hypothalamus secretes thyrotropin-releasing hormone (TRH), which causes the anterior pituitary to
secrete thyroid-stimulating hormone (TSH). This reaches the thyroid gland and causes it to release
thyroid hormones (T3 and T4). This causes:

- Increase in basal metabolic rate

 - Stimulates growth during fetus and early childhood stages
- Keeps the nervous system at the normal level of alertness and reflexes

The basal metabolic rate is the rate of energy expenditure of the body just by existing. This
decreases with age, and generally males have a higher basal metabolic rate than females.

Appropriate levels of thyroid hormone are required for:

- Growth
- Alertness
- Metabolism
o Increases body heat production by increasing oxygen consumption and ATP
hydrolysis
o Stimulates fatty acid oxidation
o Increases proteolysis, mostly from muscle
o Stimulates carb metabolism (usage of glucose), enhances insulin-dependent entry of
glucose into cells, and increases gluconeogenesis and glycogenolysis
o Note: does not increase blood glucose as the increase is mostly used by other
effects of the hormone

Infantile hypothyroidism

Hyposecretion of thyroid hormone in newborns

Leads to low metabolic rate, cold intolerance, retarded growth and inhibited brain development

Most commonly caused by a lack of iodine in the mothers diet, and therefore iodine
supplementation during pregnancy is recommended.

Grave’s Disease

Caused by hypersecretion of thyroid hormone

Results in high metabolic rate and therefore weight loss, as well as:

- Heat intolerance
- Increased heart rate
- Nervousness
- Hair loss
- Exophthalmos (protruding eyeballs)
- Thyroid swelling (growth at base of the neck)

Only need to really remember high metabolic rate and weight loss

Caused by an autoimmune disorder, which unusually causes an increase in hormone production

Calcium Concentration Regulation

Consume around 100mg of calcium per day

Some absorbed in the digestive tract, and some more is reabsorbed by the kidneys.

Resorption by osteoclasts if levels are too low, and deposition by osteoblasts if levels are too high

Input/output should be balanced.

Bones are the body’s major calcium storage side. Quick adjustments can be made between bone and
blood.

There are 3 hormones involved in calcium regulation:

- Parathyroid hormone (PTH)

- Calcitriol
- Calcitonin

The parathyroid glands are on the posterior surface of the thyroid gland. There are 4 of them. They
only secrete parathyroid hormone, which is essential for life.

Low blood calcium is detected by parathyroid glands, which then secrete PTH. This causes bone
breakdown and therefore release of calcium into the blood. It also causes an increase in calcium
reabsorption in the kidneys, which lowers the urinary excretion of calcium, and also causes release
of calcitriol (activated vitamin D) which causes an increase in calcium absorption from food in the
intestine. The overall effect of this is to bring the concentration of blood calcium up.

The other hormone involved in this pathway is calcitonin, which as previously mentioned is
produced in the C cells of the thyroid gland.

If there’s an increase in blood calcium the thyroid gland will secrete calcitonin, which decreases
bone breakdown, which reduces the release of calcium into the blood. The overall effect of this is to
lower the concentration of calcium in the blood.

Calcitonin is generally an extreme measure, day to day regulation is just done by changing the
amount of PTH released

This is not controlled by the hypothalamus.

Hypocalcemia

When blood calcium is too low. This can result in increased excitability of the nervous system,
leading to muscle tremors, spasms or cramps.

When extremely low can lead to paraesthesia (tingling/burning in hands) in hands and face, muscle
cramps, and in some cases the muscles of the larynx may contract tightly (laryngospasm), shutting
off air flow and causing suffocation.

Caused by vitamin D deficiency, diarrhea, thyroid tumors, underactive or removal of parathyroid

glands, or pregnancy (lactation).

Hypercalcemia

Too much blood calcium. Results in nerve and muscle cells being less responsive and excitable. Can
lead to depression of the nervous system, emotional disturbances, muscle weakness and sluggish
reflexes.

If calcium levels get too high it can lead to cardiac arrest.

This is caused by changes in the resting membrane potential, as the outside will now be more
positive, which causes the membrane to compensate by becoming more negative.
Lecture 29 – Homeostasis
7/05/2019

There’s a set point for any controlled variable we try and maintain, eg. temperature. This is the point
the body will try to return to if there is any disruption. The safe range around this point is the normal
range.

There is variation within the population of these set points. Each individuals normal range is more
narrow than the population range. Moving outside the individual’s normal range may lead to
symptoms of a disorder, even if those hormone levels are within the populations overall average
normal range.

Most individuals however will have a set point that is within the population reference range.

Other variables controlled by hormones (excluding those already discussed) include:

- Body water/osmolarity/composition (eg. levels of Na+)

- Blood pressure/volume
- Circadian rhythms
- Hunger
- Red blood cell count
- Factors relating to sexual maturity and reproductions

Negative feedback loops are the most common method of maintaining homeostasis

- Reducing change until the stimulus is removed

- Or directly inhibiting further release of hormones

There are however occasionally positive feedback loops, where there’s a point you’re trying to
reach, and amplification of the change until that point is reached.

Diabetes mellitus is diagnosed by checking the body’s respond to glucose, insulin levels and longer-
term exposure.

Stress

Not all stress is bad, because without enough stressors the immune system ends up being affected
by the lack of cortisol (among other things)

Things like exercise count as stress

Stress can improve and maintain reaction times

Long term stress can have negative effects, such as hair loss, insomnia, headaches, personality
changes and cardiovascular problems.

Hyperparathyroidism

Leads to excess PTH secretion, and is usually caused by a parathyroid tumor.

Bones become soft, deformed and fragile, while blood levels of calcium and phosphate ions increase.
This contributes the formation of kidney stones composed of calcium phosphate.
Goitre

Caused by a lack of iodine in the diet (iodine deficiency). This means the thyroid gland cannot make
thyroid hormones.

When TH levels are depleted, TRH and TSH secretion increases to stimulate the thyroid gland to
make more TH, however without the iodine this doesn’t help. Instead it causes the thyroid gland to
grow to absurd sizes without the negative feedback loop to stop it.

There are some situations in which changing the set point may be beneficial. For example if you
change altitude, changing the red blood cell density to change the oxygen carrying capacity may be
useful. Or during a fever the body increases its core body temperature in order to kill the bacteria.

Lecture 30 – The Immune System

08/05/2019

The immune system is composed or organs (eg. spleen), cells (eg. T cells) and molecules. (eg.
antibodies)

Helps keep us healthy against pathogenic microorganisms

When the immune system goes wrong it can result in inflammatory diseases such as arthritis,
allergies, or autoimmune diseases like lupus and diabetes

The immune system is able to distinguish between cancer and non-cancer cells

Pathogens = disease causing

Microbes can range in size from:

- Viruses: The smallest, only wants to reproduce via attaching to cells and using it to make
copies of itself, which can eventually kill the cell.
- Bacteria: prokaryotic, slightly larger than viruses, not necessarily bad
- Fungi: eg. athletes foot, typically occur in people with compromised immune systems
(immunocompromised)
- Protozoa: Much larger and more complex, e.g. malaria

Organs of the immune system

Primary organs are where white blood cells develop, such as the bone marrow and thymus

Secondary lymphoid tissues are where immune responses are initiated

Bone marrow is a source of stem cells, which can adapt and develop into immune cells

The thymus is a “school” for white blood cells called T cells, where they learn to recognize and
respond to pathogens, as well as to not react to the body’s cells. Only a small percentage (10%)
make it through the thymus.

The spleen and lymph nodes are the secondary lymphoid tissues. They’re located along lymphatic
vessels which filter lymph fluid from the blood and tissue. The lymph nodes are where immune
responses start, with cells coming together and start to respond by dividing.

The spleen is the site of immune responses for blood borne pathogens.
The immune system has 3 layers of defense:

- Chemical and physical barriers that prevent microbes from entering the body
- Innate arm of the immune response
- Adaptive arm of the immune response

Chemical/Physical barriers

Includes the skin. Thin layer at the top is the epidermis (dead cells), followed by the dermis. In
between are dendritic cells, which are the immune cells. Each day dead cells are shed and renewed,
so if pathogens attach to the epidermis they won’t be there for long.

The skin has chemical properties too:

- Makes antimicrobial peptides which form pores in microbial cell membranes, which kills
microbes
- Makes enzymes such as lysozyme, which breaks down bacterial cell walls
- Sebaceous gland produces sebum which has a low pH, which is inhibitory to microbial
growth and survival
- Sweat glands products hypertonic (highly salty) sweat, which again prevents microbial
growth.

Also has mucous membranes, which line the surfaces connected to the outside. Outer layer
(epithelium) is made up of constantly renewed, mucus producing goblet cells which cover
themselves in mucus.

Includes ocular, respiratory, oral, gastrointestinal and urogenital/rectal tracts.

The mucociliary escalator uses cilia to move mucus up to the pharynx, causing trapped microbes and
dust to be removed from the oral tract.

Chemical defenses of internal organs include:

- Stomach: low pH
- Gall bladder: bile
- Intestine: digestive enzymes
- Mucus
- Defensins
- Lysozymes (tears, urine)

Innate vs Adaptive arms

Innate defenses include the above surface barriers, as well as internal defenses such as:

- Phagocytes (“vacuum cleaners”)

- Natural killer cells
- Inflammation
- Antimicrobial proteins
- Fever

Adaptive defenses include humoral immunity (B cells) and cellular immunity (T cells)

The two arms do communicate

Innate immunity is:

 - Already in place
- Rapid (hours)
- Fixed
- Limited specificities
- Has no memory

Adaptive immunity is:

- Improves during the response

- Slow (days-weeks)
- Variable
- Highly specific
- Has long-term specific memory

Lecture 31 – Innate Immunity

13/05/2019

- List and describe the function of the immune cells in the blood
- Give examples of phagocytic cells
- Explain how innate cells recognise pathogens
- Explain how fever is induced

Remember phagocytic cells are the ones that like to eat things

Plasma makes up 55% of blood, formed elements make up the remaining 45%

Plasma contains a lot of proteins (such as antibodies/immunoglobulin), other solutes (nutrients,

waste products, immune chemical messengers) and water.

Antibodies produced by B cells, important for binding to pathogens

Formed elements are made up of platelets (clotting cells), white blood cells (leukocytes, contain
most innate/adaptive immune cells) and red blood cells.

Blood cells are formed in the bone marrow through hematopoiesis. Marrow can do this due to
containing stem cells.

3 blood cell lineages:

- Erythroid -> red blood cells (erythrocytes)

- Myeloid -> granulocytes (contain pre-formed messengers), monocytes, dendritic cells
(trigger adaptive immune responses?), platelets
- Lymphoid -> B and T lymphocytes (adaptive immune cells)

Neutrophils make up 75% of all leukocytes, and are highly phagocytic. Their concentration in the
blood increases during infection. Make “nets” of DNA, can release it and trap other cells? Make up
the majority of pus.

Granulocytes circulate in the blood and can move into tissue during inflammation. Mast cells line
mucosal surfaces, and are not found in the blood. They release granules that attract white blood
cells to areas of tissue damage.
Other examples of phagocytic cells include monocytes and macrophages. These are the same cell in
different areas. Monocytes are in the blood and are not very phagocytic. However when they enter
tissue (eg. spleen, liver) and become macrophages they become highly phagocytic.

Macrophages can become either resident (sessile) or move through tissues (migratory).

They have 3 important functions:

1) Phagocytosis
2) Release of chemical messengers
3) Show information about pathogenic microbes to T cells, linking the innate and adaptive
immune systems. This is done by breaking down the proteins within the pathogen (antigen?)
and display them on the surface of their cells for T cells to act on.

The best phagocytic cells are dendritic cells. These have many long arms which give them much
larger surface areas, allowing them to sample more of the environment.

They’re found in low numbers in blood and any tissue which comes in contact with the environment.
They’re the most important cell type in helping trigger adaptive immune responses.

Transport around the body

Cells in the immune system move around the body by being carried in the blood and in the lymph.

Cells can leave the blood and enter tissues, moving through them, with lymph collecting them into
lymphatic vessels, which themselves drain into lymph nodes.

How do immune systems recognize pathogens?

Bacteria are very different from one another, but they tend to have features/building blocks in
common. In the case of pathogens there are molecule patterns that are recognized by surface
receptors, such as:

Viruses:

- DNA/RNA surrounded by nuclear coat

- Maybe a viral envelope
- Common building blocks are their nucleic acids, dsRNA

Bacteria:

- Capsule, cell wall, cell membrane, and then the nucleic acid
- Common building blocks include
o Lipopolysaccharide (LPS)/endotoxins and lipoteichoic acid in the cell wall
o Flagellin in the flagella.
o Unmethylated CpG DNA

Toll like receptors on the surfaces of cell recognize these components and send a message to the
nucleus, changing the level of gene transcription (either upregulating or downregulating). For
example upregulation of immune messengers.
Fever

This is an abnormally high body temperature (>37C), and is a result of the body re-setting its
thermostat (hypothalamus). This is why you can feel cold with a fever.

It’s caused by pyrogens being release pyrogens (“fire generator”) being released by cells of the
immune system.

Phagocytes produce the chemical messenger and pyrogen interleukin-1 (IL-1) after ingesting
bacteria.

This is “turned off” when the phagocytes stop ingesting bacteria, decreasing their phagocytosis and
resulting in lowered IL-1 and therefore decrease in temperature.

This is done potentially because of bacteria having more difficulty developing at higher
temperatures, and also potentially also due to increased expression of genes that are able to exhibit
immune functions

Lecture 32 – Innate Immunity II

14/05/2019

- Describe the key components of the inflammatory response

- Describe the 5 stages of phagocytosis
- Explain the main features of the complement system

The inflammatory response

Two types, … and acute inflammation

Chemical signals from cells within the tissue tend to attract more cells to the site of injury or
infection, forming a sort of “trail” for phagocytic cells to follow. Neutrophils enter the blood from
the bone marrow and, when they come to a site with inflammation, cling to the capillary walls, and
begin rolling along it. They try and squeeze through out of the capillary to the site of inflammation.

The chemical signals dilate blood vessels and make capillaries leakier, to allow the phagocytic cells
easier access to the site of infection/injury site.

Phagocytosis

There are 5 stages of phagocytosis:

1) Bacteria adheres to the surface of the phagocytic cell

2) This forms a pseudopod, which eventually engulf the particles to form a phagosome
(vesicle).
3) A lysosome then fuses with the phagosome to form a phagolysosome
4) The toxic compounds and enzymes in the lysosome then destroy the bacteria
5) There will sometimes be exocytosis of the indigestible or residual material

The phagolysosome has its own toll like receptors that are able to recognize bacterial and viral
nucleic acids.

The lysosome is very acidic, allowing it to kill the bacteria. It can also produce reactive oxygen
(hydrogen peroxide) and reactive nitrogen intermediates (nitric oxide), which are toxic to some
bacteria.
There are also protease, lipase and nuclease enzymes which can affect certain bacteria?

The complement system

There are 9 major proteins/protein complexes (C1 through to C9) acting in sequence to clear
pathogens from blood and tissues. Together these make up the complement cascade.

These have 3 functions:

- Labelling pathogens (opsonization)

- Recruiting phagocytes (chemotaxis)
- Destroying pathogens (lysis) by making pores in the pathogen membrane causing everything
to leak out

When one complement protein is activated an inactive complement protein gets cleaved and
develops a couple of cleavage products. These can go on to cleave more inactive proteins and so on.

There’s 3 ways it can start:

- Classical pathway. Antibodies bind to a pathogen, which binds to an inactive compliment

protein to activate it and start the cascade.
- Alternative. Pathogen directly binds to a compliment protein itself, or a component of it
binds. This activates it and starts the cascade.
- Lectin. Carbohydrate component of microbes binds to the compliment, activating it and
starting the cascade.

All 3 pathways converge at C3 convertase (an enzyme process), after which the 3 functions are
possible; labelling (C3b, a cleavage product), destroying (C9) or recruiting (C3a and C5a).

Opsonization involves coating a microbe with antibodies and/or with complement fragment C3b.

For recruitment, mast cells are degranulated by C3a and C5a. This causes the release of preformed
vesicles from the mast cell into the tissue, which release lots of stuff including signals to phagocytic
cells.

Membrane attack complexes (MAC’s) are what cause lysis.

Lecture 33 – Linking innate and adaptive immunity
15/05/2019

- Know that adaptive immunity evolved in vertebrates

- Understand how antigen is sampled by immune cells and how it is presented on MHC
- Know the expression patterns of MHC-I and MHC-II on cells
- Understand the structure of MHC and its peptide-bonding groove

White blood cells also present in solid tissues like skin.

Leukocytes make up a very small percentage of the blood, but are the main cells involved in adaptive
immunity.

Act as sentries; dendritic cells, act as antigen presenting cells.

If bacteria enters the body, even if the immune system deals with it fragments are transported to
the nearest lymph node (?) and alert T cells.

T cells can become cytotoxic or help produce antibodies.

Antibodies are soluble proteins that latch onto and destroy microbes, and can change T cells into
cytotoxic cells which destroy the cells the viruses have infected. Can kill cancer cells too.

Dendritic cells

Initiators of the immune response.

Are present in most major organs, and are able to phagocytose antigen and process it down to
peptides. These are then presented on their surface. They migrate from organs to draining lymph
nodes.

Peptides alert the immune system that something’s wrong

MHC are the part of the cell that is used to display the peptides. The peptides are placed on their
grooves and displayed to T cells

CD4 T cells help B cells make antibody. CD8 T cells become cytotoxic and kill virus infected cells and
cancer cells

Antigen is anything that is recognized by the immune system. Bacteria/viruses could have thousands
of antigens.

Antigens aren’t necessarily harmful, it’s just anything from outside the body. Reaction to harmless
antigens cause things like allergies.

Auto-antigen; the immune system is normally tolerant of self-antigen, which is the body’s antigen.
Autoimmune disorders are caused by the recognition of self-antigen.

The purpose of antigen uptake is to clear pathogens and for presentation to T cells. Clearance is
mostly done by the innate system.

Evolved roughly 500 million years ago due to selection pressure from microbes.

All vertebrates have both the adaptive and innate systems; invertebrates (eg. insects, spiders,
jellyfish) have only innate immunity.
Two types of MHC:

MHC-I present on all nucleated cells, so basically everything except red blood cells. Presents
endogenous (intracellular) antigen. Takes care of viral infections. Widely distributed.

MHC-II is in addition to I. More restricted distribution, only present on antigen presenting cells,
which turn on T cells. Presents exogenous (extracellular) antigen.

Endogenous antigens

Occurs when a virus hijacks the host to make its own proteins. Many of those proteins will be
shuttled for destruction, broken up into peptides in the cytoplasm and loaded onto MHC-I in the
endoplasmic reticulum. MHC-1 molecules are then sent to the cell surface.

Exogenous antigens

Happens to anything that happens via phagocytosis. Antigenic proteins are in the phagolysosome,
and are broken down into peptides and loaded onto MHC-II molecules.

Cell mediated immunity mainly involves activated white blood cells killing infected cells.

Lecture 34 – T Cells
20/05/2019

APC = antigen presenting cells like dendritic cell

Antigens detected by receptors on the T cells

Two varieties of T cells

- CD8, responds to MHC-I

- CD4, responds to MHC-II and peptides

CD8 are the main ones which become cytotoxic and kill stuff.

CD4 help other cells, helping B cells make antibodies and helping CD8 cells become cytotoxic by
releasing “help” cytokines. One of the first cells to be activated during the response.

T cells are lymphocytes that arise in the bone marrow and develop in the thymus. They express T cell
receptor (TCR) with co-receptors (CD4/CD8 are the two classes of receptor). They recognize
MHC/peptide complexes.

Trained in the thymus. TCR gene rearrangement occurs during this phase.

Thymus is located between the lungs, superior to the heart.

Immature T cells in the bone marrow have TCR genes in a germline state. Bits of these are then lost,
DNA is rearranged and functional receptors are produced. Each T cell is uniquely different at one
end, which allows them to recognize specific peptides

Most unique types won’t be used, but are kept just in case. Activated as needed.

Rearrangement process is essentially random.

CD4 and CD8 molecules are closely associated on their membranes with the TCR’s

They act as docking molecules essentially, allowing the TCR’s to attach to their corresponding thing.
T cells that have not been activated by MHC/peptides are called naïve.

Activated T cells are known as effector T cells.

CD8 T cells develop into cytotoxic T lymphocytes (CTL) which kill stuff with their enzymes.

Cytokines produced by CD4 cells are what help CD8 become cytotoxic. CD4 needs to be activated by
dendritic cells in order to produce the cytokines.

Most cells are able to present using MHC-I, and the CTL can then go kill cells which display stuff that
way.

Apoptosis = cell death

When a cell dies all the proteins are degraded, DNA/RNA etc. is all destroyed. Uses its own energy to
destroy itself.

Can’t blow up the cell because then the virus would go everywhere. Very controlled destruction in
order to avoid this.

When T cells are stimulated it involves a lot of cell division. When effector cells are formed it also
results in the formation of memory T cells. Memory CD4 and CD8 T cells reside in the body for long
periods of time, and come become effector cells much quicker than naïve T cells. This results in a
much faster/more vigorous response if the same infection ever shows up again.

When memory cells are formed, and there’s a second response the supply of memory cells isn’t
depleted; more memory cells will always be created to replace those which are lost.

The HIV virus attached to CD4 cells via the CD4 molecules on their membranes, leading to their
depletion. When they go below a certain threshold the immune system stops functioning.

Viral antigens are mostly presented on MHC-I but can also be presented on MHC-II by APC’s

Lecture 35 – B cells and antibodies

21/05/2019

B cells are what make antibody (or rather differentiate into cells that produce antibody)

B cells only make antibody if they’re assisted by helper cells

Recognises native antigen

B cells are lymphocytes that are created and fully mature within the bone marrow. They express
unique antigen receptors (BCR or secreted antibody).

Plasma cells are activated B cells that secrete antibody.

Memory B cells are produced when they’re activated

Antibodies are in the B cell membrane. They have two identical

heavy chains, and two identical light chains.

When secreted into the blood it’s always essentially the same
structure.
Every B cell is covered in around 100,000 BCR’s (mostly IgM and IgD antibodies)

BCR binds antigen and activates the B cell.

Antibody kills stuff in the following ways:

- Neutralization. Binds to and stops viruses/toxins from attaching to cells and infecting them.
- Opsonisation. Binds to microbes and makes them “tastier” for phagocytes by making it
easier for them to bind to specific antibody receptors on the phagocytes.
- Activates the complement system? Allows formation of membrane attack complexes

Types of antibody

IgG (monomer). Called constant because it doesn’t generate diversity at the antigen binding site?
Most abundant Ig class in the blood. Opsonises/neutralizes. Only Ig class that crosses placenta
providing passive immunity for the unborn child. Targets viruses/bacteria.

IgA (dimer). Important for protecting mucosal surfaces, and is secreted in high amounts in the
mucosa such as tears, saliva, mucus and break milk. Especially important for the gut. Confers passive
immunity on nursing infants. Targets viruses/bacteria.

IgM (pentamer). Typically produced in primary immune responses, early in the response. Pentameric
(5 arms) with the same “arms” as IgB. Expressed on naïve B cells, but not pentamerically. Doesn’t
bind that strongly to antigen, but very effective in activating complements. Targets extracellular
bacteria, and acts as antigen receptors when in monomeric form on the naïve B cell.

IgE (monomer). Low concentration in the blood. Activates mast cells to expel multicellular parasites.
Also causes allergic reactions?

IgD (monomer). Don’t know what it does but is expressed on naïve B cells. Works as an antigen
receptor but specific function is unknown.

Summary: B cells recognize native antigens via their BCR, providing them with signals to secrete
antibody. Cytokine help from T cells is required to produce antigen.

Stimulation of B cells by antigen + T cell leads to formation of plasma cells. In addition some turn into
memory cells

Memory B cells express antibody as BCR but do not secrete it. Like memory T cells they respond
rapidly to antigen encounter. This is what causes vaccinations to work.

The primary immune response to antigen A is small and occurs after a small delay. The secondary
immune response to antigen A is faster and larger

Primary immune response is characterized by production of IgM, which is the complement one.

The secondary (memory) immune response has more IgG produced and has a larger response. Takes
2-3 days to develop.
Lecture 36 – Immunodeficiency/autoimmune
22/05/2019

Severe combined immunodeficiency (SCID) is a genetic disorder that occurs when a child is totally
unable to produce T and B cells. This is even more serious than HIV/AIDS as it destroys both adaptive
cells.

This leaves the children totally at the mercy of bacteria/viruses. Have to rely totally on innate
immune response. Have to be totally isolated as a result.

Immune privileged sites are parts of the body where there are no elements of the immune system.
These places include:

- … vesicles of the testes, as sperm cells are counted as antigens and would therefore be
destroyed
- Eyes, as stuff like inflammation would cause you to go blind. This means that corneal
implants are never subject to potential problems

Don’t actually really need to know this for exam

Peripheral tolerance is a backup mechanism

Rheumatoid arthritis

Autoimmune disorder that primarily affects synovial joints. B/T cells attack own tissue

Happens with age, often in combination with injury

Caused by cells not properly screened by the thalamus accidentally being released

Results in inflammation and tissue injury.

Allergies

Reactions to things which are not specifically needed to be defended against

Caused by the body thinking these foreign substances are microbes and defending against them.

Peanut allergies can be deadly. Can also dissipate with age (interest only?)

Steps of allergy:

- Ingestion of peanut
- Bits get picked up by dendritic cells which present them to lymphoid cells
- Causes production of IgE
- IgE targets mast cells
- Any further peanut bits will then land on IgE, at which point it panics and makes the mast
cell explode (degranulate), releasing histomines, cytokines and prostaglandins
- These are extremely potent molecules, which cause inflammation.
- This can result in suffocation as IgE in the throat is triggered

Treated with epinephrine, which blocks the swelling, but must be done quickly.

Allergies are Type I hypersensitivity.

There are 4 types in total, but we only need to know I.

So just to repeat more generally:

1) First exposure to allergen

2) Antigen activation of B cells which make IgE secreting plasma cells
3) These IgE then diffuse into the blood and attach to mast cells
4) They coat the surfaces of mast cells
5) Second exposure to the allergen, attaches to the IgE
6) Activation of mast cells and degranulation.

Most important antigen = IgE

Most important mediator = histomine

Lecture 37 – Immune response to bacteria

27/05/2019

Innate immune response is particularly effective against bacteria (adaptive is important long term
too obviously)

Remember innate is fast, non-specific and has no memory

Innate response is good at preventing initial stages of pathogenesis (adherence, invasion etc.)

Epidermis shedding helps prevent adhesion/invasion

Sebum traps and inhibits the growth of bacteria

Airways are covered with cilia, which beat in a regulated fashion to move trapped bacteria up to the
throat where they are swallowed.

The gut has a constant flow of fluids across its surface (as well as acid, enzymes, bile), which
dislodges bacteria

Enzymes/bile break down cell walls, and bile also inhibits adhesion

Antimicrobial peptides (AMPs)

Skin, respiratory tract and gut all produce AMPs

Eg. defensins. Secreted from skin. Has a charge on the peptide, which interact with the membrane of
the bacteria, disrupting it an causing it to break.

Lysozymes are another example, produced in the skin and airways. They also attack the cell walls,
but in this case they attack the peptidoglycan cell wall instead, breaking the NAM and NAG apart.
Especially important for the innate response to gram positive bacteria.

Diapedeses = the way neutrophils slip through capillary walls to points of damage/infection

Higher temperature results in faster phagocytosis

Cytokines also help stimulate phagocytosis

However the best way of getting phagocytosis moving is the complement system
Important parts of the complement system to know

Complement proteins just float around blood in inactive form

Pathways are alternative, classical and lectin

Alternative is when the microbe has parts that the complement system recognize

Classical is when antibodies connected to a microbe stimulate the complement protein

The lectin pathway is similar to alternative in that they both look for basic patterns, however lectin is
specifically looking for mannose, which is a sugar not found in humans but is on certain pathogens.

C3 molecules are turned into C3b, and when little bits are chopped off to form C3a it causes
inflammation. These are the chemical signallers

The larger C3a adhere to microbes, signaling the phagocytes to come and eat it (opsonization).
Opsonized bacteria are phagocytized much faster

Lysis is when MAC complexes (big hole) is punched through the bacteria, killing it.

Increased inflammation causes more phagocytes to come to the area.

Complement system is an example of the two immune arms working together

The classical pathway requires antibodies to be activated, and therefore is cannot be considered
solely as part of the immune response, as antibodies are part of the adaptive immune response.

Lecture 38 – Immune response to viruses

28/05/2019

- Understand how the innate immunity protects our body from viral infection and disease
- Know how adaptive immune response destroys viruses (using cellular and humoral means)
- Understand the basic components of a vaccine and how these work to prime the adaptive
immune response.

Largely involves the adaptive immune system

Problem with adaptive is that it’s very slow, however makes up for it by being highly specific and
having memory.

Greatly reduces replication of viruses within host tissues, as well as being much better than the
innate response at preventing all the other stages of pathogenesis.

Viruses are intracellular organisms; they spend most of their life cycle within cells.

2 stages, hidden (while they’re in the cell) and open (when they’re released from the dead cell)

The adaptive response is able to deal with viruses hidden within cells.

When entering the body viruses are recognized by antigen recognizing cells, most importantly the
dendritic cells.
Once the dendritic cell captures a virus, the following happens:

- Virus is phagocytized by the dendritic cell

- Phagolysosome digests the virus
- Bits of the virus (capsid proteins) are missed out in digestion, “falling out” of the
phagolysosome into the cytoplasm of the dendritic cell
- These capsid proteins are picked up by MHC-1 proteins
- Cell recognises that these are not supposed to be there, and presents the MHC-I on the
surface of the cell along with the capsid protein.
- Inside the phagolysosome the dendritic cell modifies the viral proteins (endogenously
processed antigens/antigens). These bind to MHC-II proteins which are then presented on
the surface of the dendritic cell
- Dendritic cells are special in that they have MHC-II proteins (these only deal with
endogenously processed proteins)
- At this point the activated dendritic cell enters the blood stream and travels to the nearest
lymph node
- Particularly happy to interact with T cells. The dendritic cell moves around checking the T
cells until it finds one with a matching receptor (TCR) to the antigen. This is why it takes so
long for the adaptive system to take effect
- At this point this T cell starts replicating

- Similar happens with B cells. These don’t have TCR, instead BCR. These are a type of
antibody which are good at picking up the capsid proteins floating around the blood having
been missed by the DC’s. These also end up in the lymph nodes, at which point they
eventually match with a B cell, which then starts replicating.

T cells are very good at dealing with intracellular pathogens.

3 types of T cell that expand

- CD8, cytotoxic T cell.

- CD4, helper T cell. Important for making sure the immune system work (study up on this)
- Memory T cells. Inactive T cell of the same specificity as the CD8, lay dormant until needed.

T cells kill intracellular viruses after activation in the following process:

- CD8 is specific to MHC-1. The CD8 TCR is specific to the capsid protein displayed on the
MHC-I on the outside of the infected cell
- The CD8 binds to the MHC-I
- CD4 binds to the MHC-II, and is stimulated as a result (CD4 only stimulated by MHC-II). This
causes it to release its cytokines, which makes the CD8 highly stimulated.
- Once highly stimulated and attached to a cell, CD8 released a package of granzyme and
perforin.
- Perforin smashes holes through our own cells and releases granzyme into the infected cell
and oxidises it, killing the cell and any viruses inside

To kill any extracellular viruses the CD8 is useless. This is where B cells come in

They don’t need MHC-II to be activated

B cells, once mature, make antibodies.

Memory B cells exist too.

B cells, once the unprocessed antigen is bound, become mature B cells

At this point the mature B cell is stimulated by CD4 releasing cytokines. This causes them to become
plasma cells.

Basically:

1) Antigens in blood bind to B cells, causing them to expand into memory B cells and mature B
cells
2) Mature B cells are stimulated by cytokines from CD4 (which itself needs to be stimulated by
MHC-II to do so). This causes them to become plasma cells.

Plasma cells produce a fuck tonne of antibody

Different types of antibody

- First one usually produced is IgM. Produced at first response to antigen, can act as a BCR
- IgG is most important, is the workhorse. Very small, can pass through placenta to give fetus’
immunity. Generally popped out a bit after IgM.
- IgE is the antibody of allergies, found on mast cells. Causes type one hypersensitivity
- IgA is important for young babies, included in breast milk and gives babies immunity.
Characterized by a J protein which allows it to be excreted on mucous membranes.
- IgD is the best example of a B cell receptor.

IgM and IgG are the most important ones to know about, and IgE and IgA to a lesser extent.

Antibodies are the things that destroy extracellular viruses.

They attach to viruses and neutralize them. Once stuck to viruses they also act to opsonize them,
making them more attractive to phagocytes. They also activate the classical pathway of the
complement system.

Important to remember that when first exposed to pathogen, small amount of IgM is released, and
then a large amount of IgG on second exposure.

This second exposure is important for vaccines.

Vaccines have 2 components:

- Antigen: the molecule that the immune system recognises, heat treated to kill it and
attenuated.
- Adjuvant: helps enhance the immune system against the antigen

Enables us to attenuate viruses by passage through human cells, passing it through cells (causing it
to mutate) until it’s no longer very good at causing disease in us, and then inject it into a human. It
can no longer cause disease, but it still causes the adaptive immune system to create memory T and
B cells which can destroy it. At this point, on second exposure it’s much faster as there’s heaps of
memory cells, which can produce heaps of IgG to take out the virus.

So combined adaptive and innate:

Bacteria pushed into a wound by, eg. a nail. Once cells are damaged causes inflammatory chemicals
and chemokines to be released, causing recruitment of neutrophils, inflammation and fever. The
neutrophils go around eating bacteria. Fever increases the rate of phagocytosis. Floating around the
region of injury are inactive complement proteins. These are then activated by one of the bacteria,
causing the alternative pathway to be activated and causing complement opsonisation. Crumbs from
complement proteins increase inflammation and more recruitment of neutrophils. Complement
proteins can also create the MAC’s to kill bacteria.

Bacterial proteins end up on B cells, which undergo clonal expansion and mature the B cells. DC’s eat
bacteria and present on MHC-II, which stimulate CD4 cells, which produce cytokines to stimulate the
B cells to become plasma cells. The plasma cell releases antibodies, which attach to bacteria and
opsonize them, causing them to be phagocytised. Also stick them together in clumps and neutralize
them. Antibodies also bind to bacteria and activate the classical pathway of complement activation.