big boy things

Question 1

explain how glucose is absorbed from intestinal lumen into portal vein

Answer 1

aim: transport glucose from intestinal lumen -> portal vein

1. primary active transport: The sodium-potassium pump maintains the electrochemical gradient of living cells by moving sodium out and potassium in of the cell

2. secondary active transport: SGLT1 symporter brings glucose into the enterocyte / intetinal epithelium cell. this is driven by Na+ and glucose transported (through 2ry AT) from the intestinal lumen into the intestinal epithelium.. (Na+ goes in and glucose goes along with it).

3. leads to high levels of glucose in intestinal epithelium. faciliated diffusion of glucose via Glut2 facilated diffusion transporter causes gluocse to move from intestinal epithelium into portal vein. (Glut 2 is only expressed on basal lateral membrane)

Question 2

what is / how does DNA mismatch repair occur?

Answer 2

this type of repair, repairs insertion or delation mutations that occurs during DNA replication and recombination:

1. DNA strand has an error
2. A nick (break) occurs in strand of DNA that has the error in.
3. This provides signals that direct mismatch proof reading proteins to DNA strand that has nick.
4. proteins scan the strand until the nick is found
5. proteins (MutS and MutL) remove the DNA strand from the error to the nick
6. DNA repair synthesis occurs to fill in corrected DNA into strand

Question 3

how does compaction of DNA occur?

Answer 3

1. compaction of histomes: (basic proteins that form subunit structures)

• 8 histomes form a nucleosome bead
• DNA wraps around histomes: 146 base pairs of DNA wraps around a histome

= v compact !

2. further compaction of histomes into chromatin
3. further folding of chromatin into chromosomes

Question 4

what is PCR used for?

how does PCR work?

Answer 4

PCR: amplifies a region of interest within the human genome, using a template DNA and specific primers

1. denaturation: heats DNA to over 90 degrees - opens DNA up
2. annealing: 54 degrees. primer is added. DNA binds to primers
3. extension: 72 degrees. add polymerase enzymes. builds DNA

repeat x lots

Question 5

what is sanger sequencing?

Answer 5

(golden standard for genetic testing)

(Sanger sequencing is the process of selective incorporation of chain-terminating dideoxynucleotides by DNA polymerase during in vitro DNA replication)

uses dideoxyribonucleic acids (ddNTP) to terminate polymerization reaction of DNA.

can find every single base pair in a sequence!

Question 6

Q what is next generation sequencing? what are the different types?

Answer 6

- whole genome sequencing

- whole exome sequencing - sequencing all exons in genome (~2% of genome). no info on mutations outside of exons.

RNA sequencing (RNAseq) - sequencing all expressed RNA and expression analysis. (RNA is direct result of exons to RNA, but also RNAseq gives info about which genes are expressed and if highly / lowly expressed).

Question 7

why is molecular diagnosis and targeted therapy good?

what can it be used for? (x4)

Answer 7

good: offers personalised approach to care. can tailor to specific genetic conditions of patient
- selection of embryos prior to implantation in IVF (carry out genetic testing on embryos and screen for mutations)
- personalised chemotherapy (take a biopsy of cancer and sequence DNA. if have specific changes to target molecules, can target those molecules with chemo. e.g. herceptin)
- gene therapy for genetic conditions (v experimental)

- pharmacogenomics

Question 8

describe 3 prenatal diagnoses that can be undertaken to test for aneuploidy

Answer 8

1. amniocentesis: genetic testing of amniotic fluid. using needle to extract transabdominal. 15-18 weeks of preg (risk to miscarriage: 1/100). ultrasound guidance used. t

2. chorionic villus sampling: genetic testing of tissue from placenta (choroinic villi), ultrasound guidance used transabdominal or transcervical. 12-14 weeks

3. non invasise technqiues: ultrasound imaging of back of neck of embryo at 11-14 weeks. if depth of fluid at back of neck is 3.5-4.4 mm = 70% chance of delivering baby with no major abnormalities.

Question 9

what is Xist?

Answer 9

• X-inactivation is assisted / coded by non coding RNA: XIST (X inactivion centre)
• Xist assocates closely with the X-chr from which it is expressed -> leads to chromatin changes and spatial reorganisation of chr. chr will condense into Bar > results in transcriptional inactivation in that chr.

(X chromosome inactivation (XCI) in females thus leads to similar transcription levels of X-chromosomal genes between males and females, who now both express genes from a single X chromosome. )

Question 10

what is the Barker hypothesis?

Answer 10

thrifty phenotype: if a baby in-utero is subject to poor nutrients (because of bad maternal diet), the epigenome is programmed to expect this environment post-natally. means there are developmental changes in cellular energy metabolism, such as: glucose handling, lipid metabolism and mt biogenesis. if exposed to nutrient poor environment postnally: means pre-disposed to have a survival offspring.

BUT

if born and given a nutrient rich environment -> get increased risk of susceptibility to metabolic disease, such as type 2 diabetes, obesity and CHD

Question 11

how does DNA methylation of cytosine occur?

Answer 11

• methyl groups can be added / removed from cytosine (the nucleotide base)
• methylation interferes with binding of transcriptional activators -> causes gene inactivation
• occurs when you get areas of DNA where cytosine and guanine are adjacent and repeated (CGCG / CpG islands). found in promoter regions.
• DNA methyltransferase (DNMT) is the enzyme
• methyl is added to cytosine to make 5-methylcytosine.

Question 12

describe how chromatin architecture is changed (a factor than influences epigenome mechanism)

Answer 12

chromatin architecture modifcations

• changes shape of histone / DNA complex

- ATP-depending remodelling:

• complex of proteins sits on the histone nucleosomes. uses ATP. alters:

1. the contact between DNA and histones,

2. the path of DNA wound around histones,

3. the structure of nucleosomes.

normally an immediate effect

Question 13

explain how histone modifications occurs (a factor than influences epigenome)

where do most modifications occur?

which enzymes used?

Answer 13

histone modifications

- post-translational modification of histone proteins: acetylation (acetyl functional group added), methylation M (addition of methyl group) , phosphorylation P, ubiquitylation (U)

• most of modifications are on lysine (K) and serine a.a. -> can make active genes by doing this. e.g. H3K4me3 (this is 3 methyl groups on K) OR make genes repressed (e.g. H3K27me3- adding 3 methyl groups to K)

can change histone modifcations using enzymes:

a) histone acetylase (HAT): opens DNA to make it accessible

b) Histone deactylase (HDAC) associated with closing DNA to make it inaccessible

Question 14

explain non-coding RNAs

(a factor than influences epigenome / regulates epigenome):

Answer 14

• non-coding RNA (ncRNA). functional, but not translated into proteins = called interfering RNA.
• this ncRNA interferes with gene expression at transcriptional and post-transcriptional level. combine to RNA and prevent it from being translated. (involved in splicing, editing and mRNA stability)

Question 15

how does protein targeting to ER occur?

Answer 15

• polypeptide chain will have an endoplasmic reticulum (ER) signal sequence on it
• the ER signal sequence interacts with signal recognition particle (SRP)
• the SRP binds to receptor (on a translocation channel) within the membrane of ER
• the SRP leaves complex
• the newly synthesised protein can translocate through the translocation channel.
• SRP is cleaved
• leaves the new folded protein in correct place

Question 16

describe how initiation of transcription works

Answer 16

• DNA unwinds close to a gene, RNA polymerase binds to a promoter sequence: how?:
• the promoter sequence acts as a template for the assembly of the multi component complex of proteins, called the pre-initiation complex, which brings pol II to gene
• once bound, the RNA polymerase II can then start trancribing the gene. (get transcription intition, elongation and termination)
• transcription always starts at ATG ​on Exon 1

Question 17

what are the two apoptopic pathways?

Answer 17

2 pathways:

extrinsic apoptopic pathway

• enviroment around the cell could cause cell death.

- tumour necrosis factor (TNF) binds to death receptor. activates caspases

intrinsic apoptopic pathway:

• targets the cell’s mitochondria -> activates caspases

Question 18

what are caspases? whats mechanism involved?

Answer 18

Initiator caspases

• pro-caspases get activated to active caspases (Caspase 2, 8 and 9)
• intiator caspases activate the executioner caspases

Executioner caspases

• again, activated from pro-caspase to activate caspase (Caspase 3, 6 and 9 -> effector caspases)

Cause:

nuclear fragmentation, cytoskeleton disruption, membrane alterations, organelle reduction

Question 19

what is role of ACh on:

a) skeletal muscle - how?
b) cardiac muscle - how?
c) acinar cells - how?

Answer 19

• *skeletal muscle:**
• acetylcholine binds to skeletal muscle cell receptors called nicotinic acetylcholine receptors (nAChR)
• depolarisation occurs (action potential more likely to happen)
• contraction of skeletal muscle
• *cardiac muscle:**
• acetylcholine binds to acetylcholine receptor on heart muscle (called muscarinic receptor M2)
• muscarinic receptors are G protein coupled receptors that activate ionic channels via a second messenger cascade
• this causes hyperpolarisation and a decrease in cardiac activity
• *acinar cells:**
• acetylcholine binds to mAChr
• activates the secretion of digestive molecules

Question 20

whats the mechanism of calcium ions being used as an intracellular messenger?

Answer 20

• calcium ions are stored in the ER
• calcium enters cytoplasm via transmembrane calcium channels or via channels in the ER
• calcium ions can bind to proteins and trigger events within the cell
• after events occurred, calcium signals are deactivated by pumping ions back into ER or out of cell

Question 21

how are intracellular receptor proteins activated?

Answer 21

• hydrophobic signal molecules diffuse directly across plasma membrane and bind to intracellular receptor proteins
• e.g signal molecules include: steroid hormones, thyroid hormones, retinoids
• then, intracellular receptors bind to specific DNA sequences adjacent to the genes the ligand regulates

inactive receptor

• each receptor will bind to short DNA-binding domain
• a receptor protein in its inactive state is bound to its inhibitory proteins

active receptor

• ligand binds to receptor and causes the (ligand-binding domain of the receptor to clamp shut around the ligand) inhibitory protein to dissociate
• receptor is active

Question 22

what happens with cell signalling when have a stroke?

Answer 22

• dying cells release large amounts of neurotransmitter: glutamate
• glutamate is toxic at high concs

- excitoxicity -> glumatate spreads outside area of initial damage = braindamage

Question 23

give over view of cell signalling in normal cell - growth factor -> activate gene expression?

Answer 23

• growth factor binds to receptor. two receptors interact (dimerization)
• intracelllar side: phosphorylation of tyrosine
• siganlling proteins bind to P-tyrosine
• causes cascade of phosphorylation events
• activates two pathways: MAPK pathway and PI3 Kinase Pathway
• once pathways are activated, activate gene expression and transcription factors occur.

Question 24

explain the ras pathway and how mutation leads to kras cancer

Answer 24

• when ras switched on: (normally ras is switched on by binding to GTP) can switch on ERK and AKT pathways. (ras regulates the pathways by turning on / off the ERK and AKT pathways)

- mutated ras (kras): hydrolysis of bound GTP (first stage in pathway) occurs v slowly. GTP is bound to ras in unhydroloysed form - ras is permenantly switched on. continois proliferation and growth.

Question 25

explain how Bax, p53 and Rb normally work and how they work when mutated?

Answer 25

**Bax (pro-apoptotic protein)** - allows cancer cells to survive even when challenged with chemotheropeautic or DNA damaging compounts that normally triger cytotoxic response **p53** _normal function_ - transcription factor (activates transcription) - causes cells with mutations to undergo cycle arrest, allows DNA repair or entry to apopotic pathway - p53 activated by DNA damage, hypoxia or cell injury - p53 activation activates p21 -\> inhibits cyclin complexes (prevents cell leaving G1 / entering S-phase _mutated function_ - cell progresses with cell cycle with cell damage -\> cells accumulate mutations -\> cancer **mutated pRB (retinoblastoma):** - pRb prevents cell cycle progression past G1 phase by inhibiting expression of S-phase genes - mutation in Rb gene = retinoblastoma

Question 26

where would u find dense irregular connective tissue?

Answer 26

in **hollow organs** -\> esp. **submucosa** (layer beneath epi. lining of organ)

Question 27

explain the cancer stem cell model

Answer 27

1. normal progenitor cell -\> can develop into differentiated normal breast cells 2. within tumours / tissues that will become cancerous: abnormal progenitor cells exist. can self-renew. 3. abnormal progenitor cells acquire mutations and ability to proliferate become: mutated progenitor cell 4. mutated progenitor cell self renew and become: cancer stem cell. can also dedifferentiate 5. further mutations: some will become tumour cells, others remain as stem cells

Question 28

explain clonal evolutionary model

Answer 28

(overview: differentiated mammry cells gain mutations and undergo dedifferentiation process. (NOT PROGENITOR CELLS LIKE LAST H) - start off as differentiated stem cell and mutation occurs - after 1st mutation: no longer properly functioning mammary epi. cells. acquires characteristics of mutated stem cell - after 2nd mutation: forms a cancer cell - undergoes dedifferentiation: forms cancer stem cell - cancer stem cell becomes cancer cell or cancer stem cell

Question 29

how do u break down origins of tumour?

Answer 29

*In terms of the origin of the tumour, there are only 2 broad types you need to know:* _Epithelial tumours_ involves **stratified squamous, simple cuboidal and simple columnar.** - Stratified squamous e.g. skin, lining of respiratory tract, upper oesophagus, cervix - Cuboidal and columnar e.g. adrenal gland, sweat gland, pancreatic ducts, stomach, etc. – these are cells that secrete things _Mesenchymal_ is pretty much any other tissue type E.g. bone, cartilage, nervous tissue, etc.

Question 30

give quick overview of how mestasis occurs

Answer 30

1. vascularisation of tumour occurs 2. cells detach from primary tumour 3. BM is degraded :( and invasion into ECM occurs 4. Intravasation of nearby blood vessels (need to breach membrane of enterocytes to do this) 5. tumour cells circulate in vascualar system 6. some cells adhere to walls of blood vessels 7. Extravasation (leave blood vessels) to local tissues 8. secondary tumour

Question 31

what happens when change in temperature is activated? (input vs output?) which areas detect the change of temp from warm and cold? what does this cause to change?

Answer 31

Goes to control centre: brain - specifically the **hypothalamus:** Input: **- preoptic area (POA)** monitors core temperature: recieves input from **warm** receptors from skin and and internal receptors - **paraventricular (PVN) and dorsomedial hypothalamic (DMH) nuclei:** recieve input from **cold** receptors Integration and Output to Effectors: - Preoptic area (POA): **regulate blood vessels in skin** (vasoconstriction / dilation). stimulates **posterior pituitary: conserves water** - paraventricular (PVN) and dorsomedial hypothalamic (DMH) nuclei: r**egulates skeletal muscle (shivering).** brown fat stimulation (aka:) **non-shivering thermogenesis.**

Question 32

whats a tautomeric shift

Answer 32

tautomeric shift: - when a tautomer occurs in DNA replication, the imino or enol pairs with non-complementary base -\> base sub - BUT: after the first DNAreplication occurs, the BP that was a tautomer reverts back to its stable form. HOWEVER, the the other non-complementary BP stays! (the mutation) result: in 3x wild type, 1 mutant. transition mutation. means can go undetected as shape of protein doesnt really change

Question 33

explain the Donnan effect

Answer 33

sources of intracellular osmolality: 1. charged molecules and their counter ions 2. smaller metabolites and their counter ions 3. small inorganic ions -\> cause Donnan effect **Problem: all of the above attract counter ions, which could create a constant flow of water to counteract ion imbalance into the cell. cause cell repture?** solution: animal and bacteria cells actively pump out inorganic ions (esp K), so that cytoplasm contains a lower total conc of inorganic ions than the ECF.

Question 34

explain where the different exogenic and endogenic reactions occur in the coupled reaction of glucose breakdown and protein synthesis?

Answer 34

**Coupled reaction of glucose breakdown and protein synthesis** exergonic reaction: glucose breakdown -\> Co2 + h20 + heat endogonic reaction: ATP synthesis Exergonic reaction: ATP breakdown Endergonic reaction: protein synthesis GET NET EXERGENIC REACTION

Question 35

- where does glycolysis occur? - what is high level overview of reaction? a) what produced in aerobic b) what produced in anaerobic conditions?

Answer 35

glycolysis **location**: cytoplasm **conditons**: with / without oxygen high level overview of reaction: glucose (6C) --\> 2 molecules pyruvate (3C). uses 2ATP in reaction. BUT produces 4 ATPs overall. also produces 2 NADH2+ molecules. THEN: - if in aerobic conditions: pyruvate used to generate Acetyl CoA for **citric cycle** - if in anaerobic conditions: pyruvate used to generate Acetyl CoA for **lactic acid**

Question 36

how does krebs cycle occur? where? what does it produce?

Answer 36

location: **matrix of mitochondria** - Acetyl-CoA (from glycolysis) used, extracts electrons for use in electron transport - **Electrons given** off are harnessed by electron carrier molecules - produces: **Co2**, 3NADH, 1 FADH2, 1GTP. feeds into oxidative phosphorylation pathway - role in producing energy even in cells performing fermentation

Question 37

how does ETC occur?

Answer 37

**- location: mitochondrial membrane** - 4 protein complexes (I to IV): electrons are passed from one complex to next, causes electrons to be released - as electrons are released to acceptors from donors (e.g. NADH), H ions pumped out of the matrix into intramembrane space - Proton motive force established and electrons flow down electrochem gradient through ATP synthase channel

Question 38

Q cholera toxin: - produced by? - what does it do in the body? - does it induce ^?

Answer 38

Cholera toxin produced by: ***Vibrio cholerae*** effect: **speeds up normal excreotry process in gut epithelium**: massive fluid loss. diarrhoea _induces diarrhoea by:_ - A-B toxin - A part activates cell's G-protein, modifies G-protein and keeps it in active state - causes more and more production of adenylate cyclase: causes more cAMP - this stimulates CFTR channel to have more Cl- leave cell: imbalance of electrolytes - water follows Cl- and electrolytes - causes severe diaarhea - treatment: fluodsa and electroyltes

Question 39

name 3 A-B toxins, what they cause and by which bacteria

Answer 39

**- Dipertheria**: toxin inhibits protein synthesis in heart muscle and and other cells. produced by Corynebacterium diptheriaie **- Tetanus:** toxin affects neuromuscular junctions - blocks release of NT (GABA and glycine) in CNS. causes irreversible contraction of muscle and spastic paraylsis. Clostridium tetani - **Botulism**: toxin affects neuromuscular junctions - prevents release of excitatory NM (acetyl choline): lack of stimulus to muscle and flaccid paralysis. Clostridium botulinum

Question 40

## Footnote which drugs target bacterial cell walls? how work? explain how pencillin works explain how glycopeptide antibiotics work explain how polymyxins work

Answer 40

* *beta-lactam antiobiotics: inhibit cell wall synthesis** work: inhibit step in synthesis of peptidoglycan (most contain a B-lactam ring). causes cells to osmotically lyse. e.g: **pencillin**: bacterial cell wall grows: get cross links between cell wall by pentaglycine (using enyzme transpeptidase) penecillin acts as a mimic: as a substrate for transpeptidase. blocks it working * *glycopeptide antibiotics:** - too big to get through cell wall - block D-ala residues (D-ala form the cell wall cross links) from forming cross links by forming H-bonds between the D-ala - used on gram-positive bacteria * *polymyxins**: - bind to charge structures of cell walls on gram negative bacteria - changes the charge - this destabilises cell wall - rupture

Answer 41

- bacterial plasmid makes a **toxin** and an antidote - **antitoxin** - antitoxin **degraded** by intracellular enzymes - toxin is **not degradeed** - if daughter cell does not inherit the plasmid - cant synthesie the antitoxin = death - ensures that daughter cells carry the plasmid plasmid addiction systems are now on the same plasmids as the resistance genes

Question 42

explain what absolute v relative refractory periods are

Answer 42

_refractory periods: period time where cell membrane is resetting itself._ * *absolute refractory period:** - the period of time during which a second action potential absolutely cannot be initiated. - occurs due to inactivation of Na channels * *relative refractory period:** - period after firing of nerve when _partial repolirasation has occurred a greater than normal stimulis / depolarisation can stimulate a second response_ - peak of AP will be lower (but still goes over threshold) - recovering Na channels and open K channels

Question 43

how does chemical synapse work?

Answer 43

- AP passes down axon: depolarisation of presynaptic terminal. **- Ca2+ voltage gated channels open** - increase in cellular Ca2+ is the **trigger** to release **synaptic** **vesicles** - Synaptic vesicle bind to membrane and release **neurotransmitter across synaptic cleft** - NT binds to **ionotropic or metabotropic receptors = docking.** help from **SNARE complex** (change from closed to open channels) - change in membrane potental (hyper or dep) of post synatpic terminal ONLY ONE DIRECTION

Question 44

what makes it easier for Ca2+ to diffuse across into presynaptic cleft?

Answer 44

calcium concentration outside of cell is **10 000x time higher than inside** - large inward concentration and electrical gradient allows free calcium to pass into cell

Question 45

explain ion trapping of aspirin in stomach

Answer 45

**aspirin: R-COOH. exists in equilibrium of R-COOH (protonated) to R-COO- H+ (un protonated)** - when take aspirin orally: goes into stomach - **stomach has low pH,** more free H+ ions in solution : pushes aspirin equation to **R-COOH** (_uncharged aspirin, fat soluble, protonated form)_ = absorbed across stomach mucosa - then moves to blood plasma: pH 7. - moves to **R-COO- + H+** (_ionic aspirin, hydrophilic - water soluble_) = trapped in blood plasma (where want to be trapped) cant return to stomach. THEREFORE - NEED TO BE ABSORBED IN THE STOMACH BECAUSE V LITTLE WOULD BE STORED IN AN ALKALI SOLUTION - this process = ion trapping

Question 46

what happens in the kidney when you have a tricyclin antidepressant (TCA) overdose?

Answer 46

- pKa = 9.5 (weak base) - in the body TCA causes metabolic acidosis - in blood: sodium bicarbonate dissociates TCA = charged R-NH2 form: lipid soluble - once in acidic urine: reforms R-NH3 form: water soluble - excreted

Question 47

how can prodrug use its environment to stop growth of a tumour cell? (e.g. using EGFR)

Answer 47

due to different environments: - Epidermal Growth Factor Receptor (EGFR) is an oncogene - drug is attached to cobolt: in normal o2 conditions = inactive - drug moves into hypoxic tissue (the tumour): activated: - hypoxic env means cobolt3+ --\> cobolt 2+ - this releases the inhibitor of EGFR to bind to EGFR = switched off / inhbited

Question 48

what are the two types of drug metabolism?

Answer 48

* *phase 1- biotransformation:** **drug becomes smaller and more water soluble so the kidney can remove it** - _a polar group is introduced or unmasked_ (this is the biotransformation) to the drug - biotransformation occurs by: _oxidation (majority), hydrolysis or reduction_ - some metabolites after this: water soluble enough to be excreted straight away (via kidneys) = metabolite A - other drugs may need additional step to make more water soluble / polar -\> go to phase 2 * *phase 2: synthesis** (stick a group onto drug to make it more soluble) - conjugation - e.g. liverr takes big chem (e.g. glucose) adds it onto drug - is able to be excreted

Question 49

describe the differnt pathways of synapses for parasympathetic and sympathetic: a) general b) adrenal gland c) kidney d) sweat gland

Answer 49

**parasympathetic:** - long preganglionic neurons -\> synapse = Ach and nicotinic Ach receptor --\> short postganglionic neuron: synapse is between Ach and muscarinic receptor at target organ **sympathetic:** most = a a) short pre ganglionic neuron -\> sympathetic ganglion: **Ach and nicotinic Ach synapse** --\> long post-ganglionic neuron to target organ: **synpase is between norepinephrine / noadrenaline NT and a or b adrenoreceptor** b) straight to adrenal gland: **synapse = Ach N: release of noreinephrine release or epinephrine** c) sweat glands: short preganglionic neurons -\> synapse **= Ach and nicotinic Ach receptor -**-\> long postganglionic neuron: synapse is between **Ach and muscarinic receptor at target organ** d) kidney: short preganglionic neurons -\> synapse **= Ach and nicotinic Ach receptor -**-\> long post ganglionic neuron -\> **synapse between dopamine and dopamine receptors**

Question 50

how does cell migration in the ECM occur?

Answer 50

1. **Polymerization of actin filaments** at leading edge gives a protrusive force **_EXTENSION_** 2. **New adhesions** are rapidly **linked** to network of **actin** **filaments. _ADHESION_** 3. Combined activity of retrograde actin movement & contractile forces produced by stress fibers generates tension to pull cell body forward. **_TRANSLOCATION_** 4. Forces produced by **contractile network** combined with actin filament & disassembly help to retract the trailing cell edge. **_DE-ADHESION_** **eat all the dick**

Question 51

what is Leukocyte extravasation and what are the five steps of the mechanism?

Answer 51

= is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection Five steps: (1) **rolling** and (2) **adhesion** to the **endothelium**, (3) passage **through the endothelial layer** (4) **remaining** in the **venular** wall, and (5) **passage through** the basement membrane.