Needed Flashcards
What makes up the university of Wisconsin solution
No sodium or chloride to prevent influx and swelling
extracellular impermeant solutes e.g. raffinose
Define tonicity
The strength of a solution that takes into account cell permeability
Define osmolarity
Osmolarity is a measure of the concentration of all solute particles in a solution
How much of fluids does interstitial fluid make up
36%
Give an example of a fibrotic disorder
Liver cirrhosis
Excessive production of fibrous connective tissue
Describe osteoarthritis
excessive loss of ECM so cushioning properties are lost
Cleavage of aggrecan by aggrecanase and metalloproteinase - loss to the synovial fluid
What is the function of aggrecan and how is structure related
Resistance of compressive forces
-ve charge helps retain water which is lost when compressed but then regained
Describe the structure of aggrecan
GAGs are highly sulphated and present in a no. of carboxyl groups -ve charge (sodium attracted) Feather like structure Chondroitin sulfate attachment largest Keratan sulfate attachment Hyaluronan binding region
Describe hyaline cartilage
Abundant type of cartilage found in many places
Cushions ends of long bones
Rich in Aggrecan
Describe decorin
Small proteoglycan
Binds to collagen, essential for fibre formation
Describe hyaluronan
Long repeated disaccharide with NO core protein
Unsulphated
Synthesised at the cell surface
Describe the structure of a GAG
1 of the 2 sugars is always amino sugar
sulphated or carboxylate -> highly -ve
Which property of GAGs contribute to function
Large volume to mass ratio and the hydrated gel can be very resistant to compression
What is a proteoglycan
GAGs are long, unbranched sugars of repeating disaccharides
What is the function of fibronectin
Regulating cell adhesion and migration in embryogenesis and tissue repair
wound healing
continuum with actin
Describe the structure of fibronectin
Multi-adhesive Large multi domain molecule open hairpin shape/horeshoe Collagen, integrin and heparin binding sites 50nm
What occurs in congenital muscular dystrophy
Absence of 𝛼2 in laminin 2 Symptoms evident from birth Hypotonia Weakness Deformities of joints
Give an example of a condition associated with laminins
Interacts with receptors such as integrins and dystroglycan
Self-associate with the basement membrane and other components (type IV collagen, proteoglycans)
Describe the structure of laminins
𝛼 chain, β chain, 𝛾 chain Very large (160-400 AA) and multi-adhesive
Describe the structure of multi-adhesive glycoproteins
Large and modular
Multifunctionality due to multiple binding sites for matrix components and receptors
Describe the structure of the basement membrane
Describe the structure of the basement membrane
Give an example of a disorder relating to the basement membrane
Alport syndrome
Mutations n gene for type IV collagen
Basal membrane is split and laminated - filtration issues and loss of kidney function
Describe elastin
Important for elasticity e.g. skin, blood vessels, lungs
Core of elastin and surface microfibrils rich in fibrillin
Interwoven with collagen to limit extent of stretching
Give an example of a disorder relating to elastin
Marfan’s
Elastic fibres cannot function due to mutations in fibrillar 1
Describe type IV collagen
network-forming collagen
Present in all basement membranes
assembles into a sheet-like network
Describe the biosynthesis of collagen
- Synthesis on the RER
- Ribosomes synthesise collagen polypeptides
- Hydroxylation with lysine and proline
- Glycosilation
- 3 chains form the helix
- Release from the cell via a vesicle
Describe the structure of collagen
3 𝛼 chains in a triple helix
Every 3rd amino acid is a glycine that occupies the interior as it is the only AA small enough
What is the function of the brainstem
Target source of all cranial nerves with numerous functions
Describe astrocytes
Most abundant in the CNS
Able to proliferate
Neuroglial
What are the functions of astrocytes
Structure
Cell repair
Immune cells
Neurotransmitter release and re-uptake
Describe an oligodendrocyte
Variable morphology and function
Numerous projections that form internodes of myelin
Myelinates axons
What is the function of Schwann cells
Produces myelin for peripheral nerves
What is the function of Microglial cells
Immune functions in the CNS
What is the function of ependymal cells and where is it found
Regulates the production and movement of cerebrospinal fluid. Found lining fluid filled ventricles
Describe the ultrastructure of skeletal muscle myofibres
Consists of myofibres (bundles) large and cyclindrical multinucleated packed with myofibrils sarcoplasmic reticulum - calcium stores T-tubules
Describe the structure of a sarcomere
Z-line - Lateral boundaries
Actin - Polymeric thin filament composed of two twisted 𝛼-helices - displays polarity
Myosin - Thick filaments with globular heads that interact with actin
Titin - Very large springy filaments anchoring myosin to the Z-line
Nebulin - Large filaments associated with actin
Tropomyosin - Elongated protein bound to actin
CapZ & Tropomodulin - associated with +ve & –ve ends of actin, respectively
Explain sliding filament theory
- Ca2+ release -> movement of troponin from tropomyosin
- Exposure of the myosin binding site on the actin chain
- Charged myosin heads bind to the exposed sites
- Binding + ADP discharge causes the myosin head to pivot (power stroke), pulling the actin filament towards the centre of the sarcomere
- ATP binding releases myosin head from the actin chain
ATP hydrolysis provides energy to recharge the myosin head
Explain the process of excitation in skeletal muscle
- Action potential propagates along the myofibre membrane (sarcolemma) 7 T-tubules
- Depolarisation activates dihydropyridine receptors (DHPR)
- Conformational change in DHPR
- Transmission to ryanodine receptors (RyR) on sarcoplasmic reticulum
- Opening of RyR & release of Ca2+ from intracellular stores
- Depolarisation -> increase in intracellular Ca2+
Describe excitation contraction coupling in cardiomyocytes
Same as skeletal muscle
depolarisation opens voltage-gated calcium channels
What effects does calcium have in cardiac muscle
Ca2+ induced Ca2+ release by binding to RyR on SR
Initiate contraction binding to troponin
Further depolarisation
Describe the structure of smooth muscle
in walls of hollow organs e.g. blood vessels and the GI tract
doesn’t have the regular arrangement of actin and myosin
Explain the process of excitation contraction coupling in smooth muscle
- Depolarisation activates voltage gated Ca2+ channels
- Ca2+-CaM complex activates myosin light chain kinase
- MLCK phosphorylates myosin light chains
- Cross -bridges form with actin filaments -> contraction
Describe signalling by membrane attached proteins and give an example
plasma membrane proteins on adjacent cells interacting
APCs presenting parts of the pathogen through MHC I
circulating T cells engage with MHC molecules through TCR
others: HIV GP120 glycoprotein
bacterial cell wall components
Describe ionotropic receptors
Ligand binding opens an ion permeable pore leading to a signal transduction event
- ligand binds to receptor
- change in conformation of channel
- pore opens
- movement of ions according to gradient
Give an example of ionotropic receptor action
nicotinic acetylcholine
Acetylcholine causing muscle contraction in skeletal muscle
GABAa (gamma amino butyric acid) causes a decreases in neuronal excitability in neurones
Describe G-protein coupled receptors
Ligand binds to activate an intracellular G-protein
1. 7-TM receptor + heterotrimeric G-protein are inactive
2. Ligand binds changing conformation of the receptor
3. G-protein binds to the receptor
4. GDP exchanged for GTP
5. G-protein dissociates into 2 active units (alpha & gamma+beta)
6. units bind
7. GTPase dephosphorylates GTP to GDP
8. alpha subunit dissociates and becomes active
Receptor is active as long as the ligand is bound
What are the 3 types of G-protein coupled receptors and what are their functions (+examples)
Gs - stimulates adenyl cyclase
ATP -> cyclic AMP -> Activated protein kinase A
e.g. beta adrenergic receptor to increase heart rate
Gi - inhibits adenylyl cyclase
reduces PKA levels
e.g. Muscarinic receptor to decrease heart rate
Gq - stimulates phospholipase C
PIP2 -> IP3 + DAG -> calcium release + PKA activation
e.g. angiotensin receptor to vasoconstrict
Describe enzyme-linked receptors
Ligand binds to cause clustering of receptors
- ligand binds
- receptors cluster to activate enzymes
- enzymes phosphorylate the receptor
- signal proteins bind to cytoplasmic domain
- recruit other signal proteins to generate the signal
Give an example of enzyme-linked receptors
insulin receptor (CD220) insulin causes glucose uptake
ErbB
Epidermal growth factor causing cell growth and proliferation
Guanylyl-cyclase
Atrial natriuretic peptide causes vasodilation to decrease blood pressure
Ser/Thr-kinase
Transforming growth factor beta causes apoptosis
Describe type 1 signal transduction
cytoplasmic
association with chaperone molecules (heat shock proteins)
1. hormone binds to receptor
2. HSP dissociates
3. 2 hormone-bound receptors -> homodimer
4. translocates -> nucleus + binds to DNA
Describe type 2 signal transduction
nuclear
- hormone ligand binds
- transcriptional regulation
Give an example of signal transduction
glucocorticoid
cortisol/corticosterone causes a decrease in immune response and an increase in gluconeogenesis
Thyroid hormone
T4 and T3 cause growth and development
Describe the Stratum corneum
corneocytes (flat with no nuclei)
Protective
Filagrin gene mutation leads to eczema
Describe Stratum Spinosum
prickle/spinous cells that produce keratin
Desmosomes
Describe Stratum Basale
Basal cells that connect to eh basement membrane
Keratinocytes found here
Give some other components of the epidermis
Melanocytes (production of melanin) Langerhans cells (antigen presenting) Merkel cels (sensation)
Describe the basement membrane in the skin
Highly specialised region where epidermis meets dermis
via hemidesmosomes, anchoring plaques and proteins
Blisters are common e.g. epidermolysis bullosa
Describe the structure of the basement membrane in skin
hemidesmosomes
tonofilaments
demo-epidermal junctions
anchoring fibrils
Describe the dermis
supportive connective tissues - collagen, elastin, GAG
Thickness varies between 0.1mm and 3mm
contains fibroblasts that synthesises collagen, elastin and GAG
Dendritic cells found here
Describe the subcutaneous layer
Connective tissue and fat
What are the two types of sweat glands found in skin
Apocrine - only located in the axillary and groins that produce discus sweat - subject to bacteria and therefore produce odour
Eccrine
What are the components of the dermo-epidermal junction
Lamina lucida Lamina densa Anchoring fibrils Hemidesmosomes Anchoring filaments
Explain the role of melanocytes and their development
Dendritic cells in Stratum Basale
Produces melanin pigment in the melanosome, which is then packed into granules that are transferred to adjacent keratinocytes via phagocytosis
Granules form a protective cap around the nuclei to protect DNA from UV (which stimulates melanin production)
Variation in pigmentation is from no. and size of melanosomes
Describe anagen in hair growth
growth phase (85% cells)
Energy intensive + highly vascularised
Most metabolically active
Rate depends on body site
Describe catagen in hair growth
Cell devision slows and stops
End of shaft keratinises to form a club shape
Dermal papillae and club moves to the base of muscle insertion
Describe telogen in hair growth
Hair is shed actively
Next anagen phase begins
Club hair takes 4-6 weeks
Give the actions of antibody-antigen
Neutralisation Agglutination Opsonisation Complement activation Bound by cells expressing Fc receptors (innate immunity: phagocytes, NK cells)
Describe IgG
gamma heavy Most abundant Has 4 subclasses Actively transported across the placenta Major activator of the classical complement pathway (1&3) Blood and extracellular fluid
Describe IgA
alpha heavy 2nd most abundant 2 subclasses Occurs as a monomer or dimer secretory Protects mucosal surfaces from pathogens Across epithelia
Describe IgM
Micro heavy First Ig synthesised after exposure Multiple low affinity binding sites Large pentamer Agglutination and complement activation Blood
Describe IgE
E heavy Allergic reactions Parasitic infections Binds to mast cell receptors and basophils to release histamine Very low levels
Describe IgD
Delta heavy
Expressed in B cell development and activation
very low levels
Give examples of antibody-cross reactivity
Vaccination with cowpox induces antibodies which are able to recognise smallpox
ABO blood group antigens
Antibodies made against Microbial antigens on common intestinal bacteria may cross-react with carbs on RBC
What are hyper variable regions
there are 3 in antibodies: CDR 1,2,3)
CDS = complement determining regions that acts as binding sites for antigens
What are the secondary effector functions of immunoglobulins after binding
Complement activation
Opsonisation (promotion of phagocytosis)
Cell activation via antibody-binding receptors (Fc receptors)
Describe natural killer cells
10% of blood
Infected cell lysis, secretion of interferon gamma, activating and inhibitory receptors (NO antigen receptor), binds to opsonised cells
Large granulated lymphocytes (cytotoxic)
Bind to opsonised cells
Cancer and viral infections
Describe dendritic cells
APC and cytokine secretion
migration to lymph node
network site of infection
adaptive
Describe mast cells
Phagocytosis, granule release (pro-inflammation), histamine and leukotrienes
Mucosal in the lung or connective tissue in the skin
Activation by complement products (anaphylatoxins)
vasodilation (red skin) and increased vascular permeability (inflammation)
Describe monocytes
phagocytosis , killing, cytokine release, APC
less abundant
dispersed in tissue
Signal infection to soluble mediators
Become macrophages when the leave the blood
Describe basophils
Granule release
Acts as an APC for type 2 immunity
Describe eosinophils
phagocytosis and granule release
Defence against parasites
Helps B cells in GALT (IgA production)
What are NETs
neutrophil extracellular traps
Release of granules and chromatin to form extracellular fibres
Describe a neutrophil
Phagocytosis 40-75% of leukocytes short-lived circulates the blood First cells recruited
Describe the process of extravasion
- Naive T cells rolls along the endothelium
- They bind to proteins and carbs along the epithelium
- HEV has chemokine bound to the cell surface
- Lymphocytes have receptors for this and binds to the receptor
- Lymphocytes deliver a signal to the T cell, changing the structure of integrin
- Integrin becomes high affinity binding and binds to the epithelium to stop movement
- Transport through epithelium
