Biosciences 1 combined

excitable cells

Cells capable of generating action potentials.

• e.g. neurons, skeletal muscle cells, cardiac muscle cells

action potential

Difference in electrical charge across plasma membrane

• is not static, must move, fastest process in cell

membrane potential

The voltage across a cell's plasma membrane.

• e.g.. movement of sodium ion out of cell: change in concentration gradient but also electrical gradient as now outside more positive

Resting Membrane Potential

In a resting neuron, -70mV

• more negative inside when excitable, inside temporarily become positive

AP generation

Induce pain signal: Voltage gated sodium channel opens up, allow extracellular sodium to move in quickly

• then all of a sudden, inside is more positive than before
• create action potential

Why does the resting membrane potential exist?

K+ constantly leaking out of cell The pump: if it keeps working, the inside would be more negative because of a net loss of positive ions

• however, at a certain point potassium ions will start to repel each other hence why at -70, the movement will stop

Two gates of voltage-gated Na+ channels

Activation gate (sliding doors) and inactivation gate (ball and chain).

When resting: ACTIVATION GATE is locked shut, doesn't matter if inactivation is open

Depolarisation: activation opens, Na+ in

• shortly after, inactivation gate slowly closes, putting time limit on Na+ entry

steps of action potential generation

1) depolarization to threshold (-55) -> point of no return 2) activation gates of sodium channels open- rapid depolarization (Na+ moves in, bc abundant outside) 3) inactivation gate CLOSES of sodium ion channels - activation of potassium ion channels 4) Repolarisation: voltage gated K+ opens, K+ rushes out, restores inside to -70mV

After repolaristion, which gradient is restored?

Only electrical state is restored, but concentration gradient not as Na+ is still high inside and K+ still high outside.

What restored the concentration gradient at end of action potential

Na/K pump, actively transports 3 Na+ out and 2K+ in using ATP back to baseline

myelinated vs unmyelinated fibres in dental pulp

Myelinated fibres your patient will be able to point directly to where the pain is coming from. With unmyelinated, they cannot as the message is slow and distorter

How does LA work?

Anesthetic drugs bind to the sodium channels, blocks it so no action potentials are generated.

Memory in Immunity

Once body has T/B cells that recognise antigen, they migrate to bone marrow and can be sedentary for decades

process of raising the alarm via antigen presenting cell

APC goes to lymph node: lymphocytes differentiate and proliferate in the node to see how to respond to particular antigen presented -> return to then focus on infection via blood (the T and B cells as they are lymphocytes)

T cells attack antigens

inside the cell

B cells attack antigens

outside the cell

Class 1 MHC

expressed by all nucleated cells in the body, but not as effect as class 2 intracellular

Class 2 MHC

on the surface of antigen-presenting cells (APCs), dendrites, b cells, and macrophages extracellular pathogen

(T- cell activation) exposure to iL-12 cytokine produces

Th1 (positive response, more inflammation)

(T-cell activation) Exposure to IL-4 cytokine from APC produces

Th2 (suppresses inflammation)

(T-cell activation) Exposure to IL-6, Il-23 from APC produces

Th17

B-cell receptors

recognise antigens in their native unprocessed forms (does not require peptide bound to MHC molecule)

Each B-cell decorated with IgM with unique specificity

One B cell that recognises sequence, will proliferate and make lots of antibodies

All B-cells that recognise the body;s cells are destoryed as we don't want autoimmunity

Physical

Epithelial surfaces: skin, mucous membranes Skin: 5.5 pH inhibits bacterial growth 1-3pH of Gastric acid: denatures proteins and kills most ingested microbes

Chemical

low pH or antimicrobial molecules:

• lysosome (found in sweat, urine) attacks non-specifc
• pepsin digests proteins, including microbial enzymes in the stomach
• igA antibodies in mucous membrane - unspecific antibodies

physiological

diarrhoea, vomiting, coughing, sneezing

Probiotic

harmless species, compete with more dangerous species for nutrients can block adhesion sites might be directly toxic to the antigen

TLRs (toll-like receptors)

Receptors on phagocytic cells recognize PAMPs (pathogen associated molecular pattern), non-self patterns like LPS in cell wall of bacteria, binds to it and stimulates an immune response. Second messengers: cytokine production, proinflammatory gene expression

Effects of activating TLRs

cytokine production → fever, inflammation chemokine production → cell recruitment/attractant activation of bacterial killing mechanisms activation of dendritic cells

defence in epithelia

tight junctions, adherens junctions, desmosoal junctions - creating seals/adhesion between cells - especially in statrified squamous

P. gingivalis

gram neg, anaerobic make proteins resembling cadherins/desmosome

via mimicry, replaces the cadherin family locations, toxin corrupts adhesion, allows access of bacteria into spaces between cells

Antigen presenting cells

dendritic cells, macrophages, B cells

• recognise and present pathogen to immune system in lymph nodes
• sedentary in epithelium
• changing phenotype from initially phagocytic to a presenting cell

Phagocytic cells

cells that engulf, ingest, and destroy foreign bodies or toxins without knowing identity

• macrophage and neutrophil oxygen dependent: engulfed and released as soluble debris oxygen independent: MHC 2 on surface

Acute Inflammation

local chemokine signalling:

• increase vascular permeability
• more WBCs moving into tissue area
• neutrophils early on
• later on macrophages
• phagocytosis occurs

Neutrophils

first on scene, kills bacteria, makes pus maturation of precursor cells in bone marrow contain granules rich in proteases generate free radical to kill phagocytised bacteria

Eosinophils

containing granules, protect against parasites

Monocytes

become macrophages in tissues, eat debris, kill bacteria, attack intracellular viruses

Lymphocytes

T, B, NK specific immunity tumour protection - flag cells for destruction

chemotaxis

Cell movement that occurs in response to chemical stimulus: fmlp and peptidoglycan produced by bacteria from existing, move towards this

Opsonization

coating antigen with antibody enhances phagocytosis - tagging it for destruction via igG

Complement System

proteins in the blood that help antibodies kill their target produced by the liver

Chemokines

Cytokines that attract immune cells to infected sites.

cell body (soma)

contains the nucleus and other parts of the cell needed to sustain its life

Axon

the neuron extension that passes messages through its branches to other neurons or to muscles or glands

Dendrites

Branchlike parts of a neuron that are specialized to receive information.

axon hillock

The conical region of a neuron's axon where it joins the cell body; typically the region where nerve signals is generated.

Which ion triggers synaptic vesicles to discharge neurotransmitter into the synaptic cleft?

Calcium by entering the channel

Sympathetic chain runs where

beside the spine - chain of ganglia alongside spine

originated from T1-L2 (thoracolumbar)

Parasympathetic runs where

ganglia located near or within the target organs

originates from Cranial nerves 3, 7, 9 and 10

innervations of ANS

All tissues other than skeletal muscles

• smooth muscle, cardiac muscle, glands

Eyes: sympathetic and parasympathetic effect

S: widen pupils, flatten lens for far vision PS: Constrict pupils, thicken lens for near vision

salivary glands: sympathetic and parasympathetic effect

Increase secretion

Heart: sympathetic and parasympathetic effect

S: Increase heart rate and contractability PS: decrease heart and contractability

Blood vessels: sympathetic and parasympathetic effect

S: dilation PS: constriction

Lungs: sympathetic and parasympathetic effect

S: bronchial dilation, inhibit secretion PS: bronchial contract, stimulate secretion

Urinary tract: sympathetic and parasympathetic effect

S: contract sphincter (less pee) PS: relax sphincter (more pee)

neurotransmitters for sympathetic

Pre: acetylcholine to nicotinic acetylcholine receptor Post: noradrenaline (exception of sweat gland with acetylcholine to muscarinic receptor)

One Pre: releases adrenaline and little bit of noradrenaline

parasympathetic neurotransmitter

acetylcholine to muscarinic actetylcholine receptors

Why does local anaesthetic have adrenaline

Adrenaline is vasoconstrictor, ensures that anaesthetic is trapped locally

all adrenergic receptors are GPCRs

yes

Nucleus function

Control centre of the cell, contains DNA

Rough ER function

protein synthesis

Smooth ER function

lipid synthesis

Golgi apparatus function

modifies and packages proteins

Lysosomes function

Digestion and recycling, degrades viruses, bacteria and other waste

Mitochondria function

ATP production

Eukaryotic Evolution

Eukaryotes engulfed prokaryotes, e.g. example mitochondria, endosymbiotic relationship with cell

What is the structure of DNA?

DNA consists of two long chains of nucleotides twisted into a double helix.

What type of bonds join the chains of DNA?

Hydrogen bonds.

Which bases are complementary in DNA?

Adenine pairs with thymine (2 hydrogen bond), and cytosine pairs with guanine. (3 hydrogen bonds)

Reading Direction of dna

5' (free phosphate) to 3' (free hydroxyl)

RNA structure

single stranded

packing the genome

DNA wrapped around histones (protein) DNA + Histones = chromatin Chromatin further wound up and condensed into chromosome

mRNA

messenger RNA; type of RNA that carries instructions from DNA in the nucleus to the ribosome

• produced from transcription

Transcription

is the synthesize of RNA using information from the DNA.

Translation

RNA to protein

• occurs in ribosomes
• tRNA brings correct amino acid by reading codon, tRNA has anticodon to mRNA

small subunit of ribosome function

binds to mRNA, links codon in RNA with anti-codon in tRNA

large subunit of ribosome function

catalyses peptide bond formation

Codon

three-nucleotide sequence on mRNA - 1 amino acid

In transcription, what replaces T in DNA

Uracil

Which bond links amino acids together in a protein?

Peptide bond - joining amino and carboxyl group

Peptides

Chains of amino acids

Dipeptide

2 amino acids

Tripeptide

3 amino acids

Polypeptides

more than 10 amino acids

Proteins

more than 50 amino acids and one or more polypeptide chains

Reaction of amino acid joining together

condensation polymerisation, joined by peptide bonds

Which way do you read amino acid

From H3N+ to COO- N- to C- terminus

Central Dogma

DNA -> RNA -> Protein

What pairs with Adenine?

Thymine

What does Uracil replace?

Thymine in RNA

Types of point mutation

silent (doesn't change end), missense(produces different amino acid), nonsense (turns into stop)

Point mutation - only one letter replaced

frameshift mutation

mutation that involves the insertion or deletion of a nucleotide in the DNA sequence - shifts the reading pairs

sickle cell anemia casused by which point mutation

GAG to GTG

Primary structure of proteins

sequence of amino acids in a polypeptide chain

Secondary structure of proteins

alpha helix (spiral) and beta sheet (folding sheet arrangement) - local folding of polypeptide chain into repeating pattern

Tertiary structure of proteins

Three-dimensional structure of a peptide, gives the proteins its function

Quaternary structure of proteins

multiple polypeptide chains coming together as one functional unit. only in proteins made of more than one chain.

What happens when proteins denature

They lose shape and function.

• heat, UV, salts, acid/base Primary structure not changed but others are

Function of enzyme

speed up chemical reactions

Function of hormones

direct specific activities like regulation blood glucose levels

• Insulin