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Title: Biology unit 1 notes
Description: this contains: Molecules, Cells, Physiology and Disease
Description: this contains: Molecules, Cells, Physiology and Disease
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Module 1 - Core Principles - page 1
AQA(B) AS Module 1
Contents
Specification
Biological Molecules
Cells
Physiology and Disease
Chemical bonds
Carbohydrates
Lipids
Proteins
Biochemical Tests
Enzymes
Eukaryotic Cells
Prokaryotic Cells
Cell Fractionation
Microscopy
The Cell Membrane
Movement across Cell Membranes
Exchange
Disease
Lifestyle and Disease
The Digestive System
Cholera
The Gas Exchange System
Lung Diseases
The Circulatory System
Heart Disease
The Immune System
Immunisation
Monoclonal Antibodies
2
4
5
7
9
15
16
22
27
29
30
34
36
42
43
45
47
51
53
57
61
65
67
76
77
These notes may be used freely by A level biology students and
teachers, and they may be copied and edited
...
I would be interested to hear of any comments and corrections
...
co
...
• Proteins have a variety of functions within all living
organisms
...
Condensation and the formation of peptide bonds
linking together amino acids to form polypeptides
...
• Monosaccharides are the basic molecular units
(monomers) of which carbohydrates are composed
...
Sucrose is a disaccharide formed by condensation of glucose and
fructose
...
• Glycerol and fatty acids combine by condensation
to produce triglycerides
...
In phospholipids,
one of the fatty acids of a triglyceride is substituted
by a phosphate group
...
Benedict’s
reagent for reducing sugars and non-reducing sugars
...
The emulsion test for
lipids
...
The lock and key and induced fit models of
enzyme action
...
Recognise its limitations
and be able to explain why the induced fit model provides a better explanation of specific enzyme properties
...
Description and explanation of the effec ts of temperature, competitive and non-competitive inhibitors, pH
and substrate concentration
...
Cell Biology
Cells
The appearance, ultrastructure and function of plasma
membrane; microvilli; nucleus; mitochondria; lysosomes; ribosomes; endoplasmic reticulum and Golgi
apparatus
...
HGS A-level notes
The structure of prokaryotic cells to include cell wall,
plasma membrane, capsule, circular DNA, flagella and
plasmid
...
Use the fluid mosaic model to explain appropriate properties of plasma membranes
...
• Osmosis is a special case of diffusion in which water
moves from a solution of higher water potential to
a solution of lower water potential through a partially permeable membrane
...
• The role of carrier proteins and the transfer of
energy in the active transport of substances against
a concentration gradient
...
The difference between magnification and resolution
...
Exchange
Diffusion is the passive movement of substances down
a concentration gradient
...
Disease
Disease may be caused by infectious pathogens or may
reflec t the effects of lifestyle
...
Disease can result from pathogenic microorganisms
penetrating any of an organism’s interfaces with the
environment
...
Pathogens cause disease
by damaging the cells of the host and by producing
toxins
...
Specific risk factors are associated with cancer and coronary heart
disease
...
Analyse and interpret data associated with specific
risk factors and the incidence of disease
...
Physiology and Disease
Digestive System
The gross structure of the human digestive system
limited to oesophagus, stomach, small and large intestines and rectum
...
The structure of an epithelial cell from the small intestine as seen with an optical microscope
...
Th e role of salivary and pancreatic amylases in the digestion of starch
and of maltase located in the intestinal epithelium
...
Absorption of the products of carbohydrate digestion
...
The role of microvilli
in increasing surface area
...
Cholera and Diarrhoea
The cholera bacterium as an example of a prokaryotic
organism
...
This results in severe diarrhoea
...
Discuss the applications and implications of science in developing improved oral rehydration solutions; and ethical issues associated with
trialling improved oral rehydration solutions on humans
...
The essential features of the alveolar
epithelium as a surface over which gas exchange takes
place
...
Pulmonary
ventilation as the product of tidal volume and ventilation rate
...
Lung Diseases
The course of infec tion, symptoms and transmission of
pulmonary tuberculosis
...
Explain the symptoms of diseases and conditions affecting the lungs in
terms of gas exchange and respiration
...
Analyse and interpret data
associated with specific risk factors and the incidence
of lung disease
...
The gross structure of
the human heart and its associated blood vessels in
relation to function
...
Roles of th e sinoatrial node (SAN), a trioventricular node (AVN) and bundle of His
...
Candidates should be able to
analyse and interpret data relating to pressure and
volume changes during the cardiac cycle
...
Investigate the effec t of a specific variable on human
heart rate or pulse rate
...
The link between atheroma and the
increased risk of aneurysm and thrombosis
...
Risk factors associated with coronary heart disease: diet, blood cholesterol, cigarette smoking and high blood pressure
...
Immune System
Mammalian blood possesses a number of defensive
functions
...
Definition of antigen and antibody
...
The essential difference between humoral and cellular
responses as shown by B cells and T cells
...
The effec ts of antigenic variabilty in the
influenza virus and other pathogens on immunity
...
The use of
monoclonal antibodies in enabling the targeting of specific substances and cells
...
Discuss ethical issues associated with the use of vaccines
and monoclonal antibodies
...
Discuss the ways in which society uses
scientific knowledge relating to vaccines and monoclonal antibodies to inform decision-making
...
At least 80% of the mass of
living organisms is water, and almost all the chemical reactions of life take place in aqueous solution
...
These macromolecules are
polymers, made up from specific monomers as shown in the table below
...
Group name
Elements
Monomers
Polymers
% dry mass of a cell
Carbohydrates
CHO
monosaccharides
polysaccharides
15
Lipids
Proteins
CHOP
CHONS
fatty acids + glycerol*
amino acids
triglycerides
polypeptides
10
50
Nucleic acids
CHONP
nucleotides
polynucleotides
18
* These are not monomers, but rather the components of triglycerides
...
We'll look at each of these groups in detail, except nucleic acids (DNA and RNA), which are studied in unit 2
...
Covalent bonds are strong
...
Because they are strong, covalent bonds cannot be broken
or made at the temperatures found in living cells
...
Covalent bonds
H
H
C
H
H
covalent
bonds
are represented by solid lines in chemical structures
...
They are formed between an atom
(usually hydrogen) with a slight positive charge (denoted δ+) and an atom
δ-
δ+
(usually oxygen or nitrogen) with a slight negative charge (denoted δ–)
...
Hydrogen bonds are represented by dotted
lines in chemical structures
...
The group includes
monomers, dimers and polymers, as shown in this diagram:
Carbohydrates
Sugars
Monosaccharides
(monomers)
Disaccharides
(dimers)
Polysaccharides
(polymers)
e
...
glucose, fructose,
galactose
e
...
sucrose,
maltose, lactose
e
...
starch,
cellulose, glycogen
Monosaccharides
These all have the formula (CH2 O)n, where n can be 3-7
...
Its structure is:
OH
H C H
C
H
O
O
H
H
C
OH
H
C
HO
C
H
HO
or more simply
C
OH
OH
OH
Glucose
Glucose forms a six-sided ring, although in three-dimensions it forms a structure that looks a bit
like a chair
...
There are many isomers of glucose, with the same chemical formula (C6 H12 O6 ), but different structural formulae
...
Threecarbon, or triose sugars (where n = 3, C3 H6 O3 ) are also found in respiration and photosynthesis
(see unit 4)
...
The reaction involves the formation of a molecule of water (H2 O):
O
HO
O
OH
HO
O
OH
O
H2O
O
HO
OH
glycosidic bond
This shows two glucose molecules joining together to form the disaccharide maltose
...
The reverse process, where a large molecule is broken into smaller ones by reacting with
water, is called a hydrolysis reaction
...
It is formed on di-
O
gestion of starch by amylase, because this enzyme breaks
starch down into two-glucose units
...
Sucrose (or cane sugar) is glucose–fructose
...
It is the common table sugar that you
Glucose
O
O
HO
Fructose
put in your tea
...
It is found only in
O
HO
mammalian milk, and is the main source of energy for infant
O
Galactose
Glucose
OH
mammals
...
It is a long chain of many glucose monomers joined together by glycosidic bonds:
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 7
Lipids
Lipids are a mixed group of hydrophobic compounds composed of the elements carbon, hydrogen,
oxygen and sometime phosphorus (CHOP)
...
Triglycerides
Triglycerides, or triacylglycerols, are made of glycerol and fatty acids
...
H
OH OH OH
Fatty acids are long molecules made of a
Carboxyl
acid group
Hydrocarbon chain (14-22 carbon atoms)
non-polar hydrocarbon chain with a polar
carboxyl acid group at one end
...
Because the length of the hy-
H
H
H
H
H
H
drocarbon chain can vary it is sometimes
called an R group, so the formula of a fatty
C
O
OH
or
CH 3 — (CH 2)n — COOH
or
R — COOH
acid can be written as R-COOH
...
They are used for
storage, insulation and protection in fatty tissue (or adipose tissue) found under the skin (subcutaneous) or surrounding organs
...
However, triglycerides can't be mobilised
quickly since they are so insoluble, so are no good for quick energy requirements
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 8
• If the fatty acid chains in a triglyceride have no C=C double bonds, then
they are called saturated fatty acids (i
...
saturated with hydrogen)
...
At room temperature they
H
H
H
H
C
C
C
C
H
H
H
H
saturated
are solids (fats), e
...
butter, lard
...
e
...
Fatty
H
H
H
H
acids with more than one double bond are called poly-unsaturated fatty
C
C
C
C
acids (PUFAs)
...
At room temperature they are liquids (oils), e
...
fish oil, vegetable oils
...
There may also be other groups attached to the phosphate
...
glycerol
H
H
fatty acid
fatty acid
R
R
O
C
O
C
C
O
O
C
C
O
hydrophobic
tails
phosphate
hydrophilic
head
H
O
OP
O
H
or
H
This mixture of properties is fundamental to biology, for
phospholipids are the main components of cell membranes
...
The hydrophilic heads facing the water and the hydrophobic tails
facing each other
...
This naturally-occurring structure is called a liposome, and is similar to a membrane surrounding a cell
...
They have an
astonishing range of different functions, as this list shows
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
Amino
hydrogen
acids are made of the five elements
C H O N S
...
The general amino
structure of an amino acid molecule is group
shown on the right
...
a hydrogen atom
2
...
an acidic carboxyl group (COOH or COO-)
4
...
Since each R group is slightly different, each amino acid has different properties, and this in turn means that proteins can have a
wide range of properties
...
You do not need to learn these, but it is
interesting to see the different structures, and you should be familiar with the amino acid names
...
There are 3-letter and 1-letter abbreviations
for each amino acid
...
The reaction involves the formation of a molecule of water in another condensation polymerisation reaction:
H
H
N
H
Cα C
R
O
H
H
N
OH
H
Cα C
R
O
H
H
N
OH
H
O
H
Cα C
N
R
H
Cα C
R
O
H2 O
OH
peptide bond
When two amino acids join together a dipeptide is formed
...
Many amino acids form a polypeptide
...
g
...
In a protein the polypeptide chain may be many hundreds of amino acids long
...
It takes place in ribosomes, and is special because it requires an RNA template
...
Protein synthesis is studied in detail in unit 5
...
To help to understand protein
structure, it is broken down into four levels:
1
...
However, the primary structure does determine the rest of the protein structure
...
Secondary Structure
This is the most basic level of protein folding, and consists of a few basic motifs that are found in almost all proteins
...
The two most common
secondary structure motifs are the α-helix and the β-sheet
...
The polypeptide chain is
wound round to form a helix
...
There are so
many hydrogen bonds that this is a very
stable and strong structure
...
H
H
Cα C N
Cα C N
O
O
O
O
O
H
The β-sheet
...
O
HGS A-level notes
C
C
Cα N C
O
O
Cα N
H
H
H
H
Cα C N
Cα C N
N
Cα C N
O
Cα C
O
O
Cα N
C O
O
O
parallel strands
...
Tertiary Structure
This is the compact globular structure formed by the
folding up of a whole polypeptide chain
...
For example the shape of the
active site in an enzyme is due to its tertiary structure
...
These bonds include weak hydrogen bonds and sulphur bridges - covalent S–S bonds between
two cysteine amino acids, which are much stronger
...
4
...
There are a huge variety
Haemoglobin consists of four chains arranged
in a tetrahedral (pyramid) structure
...
g
...
Collagen consists of three chains in
a triple helix structure
...
HGS A-level notes
Actin consists of hundreds of globular chains
arranged in a long double helix
...
In fact proteins fold into
all these structures at the same time, as they are synthesised
...
Globular Proteins
Fibrous (or Filamentous) Proteins
The vast majority of proteins are globular, i
...
Fibrous proteins are long and thin, like ropes
...
This They tend to have structural roles, such as colgroup includes enzymes, membrane proteins, lagen (bone), keratin (hair), tubulin (cytoskelereceptors and storage proteins
...
They are always combelow shows a typical globular enzyme mole- posed of many polypeptide chains
...
It has been drawn to highlight the different shows part of a molecule of collagen, which is
secondary structures
...
α helix
β sheet
A few proteins have both structures: for example the muscle protein myosin has a long fibrous tail
and a globular head, which acts as an enzyme (see unit 4)
...
The polypeptide chain just folds up into a random coil and the protein loses its function
...
Covalent bonds
are not broken under these conditions, so the primary structure is maintained (as are sulphur
bridges)
...
For each test take a
small sample of the substance to test, and shake it in water in a test tube
...
Many of these compounds are insoluble, but the tests work just as well on a fine
suspension
...
Starch (iodine test)
...
A
blue-black colour indicates the presence of starch as a starch-polyiodide complex is formed
...
Reducing Sugars (Benedict's test)
...
Add a few mL of
Benedict’s reagent (which is a copper (II) sulphate solution) to the sample
...
A coloured precipitate of copper (I) oxide indicates reducing sugar
...
The original pale blue colour means no
reducing sugar, a green precipitate means relatively little sugar; a brown or red precipitate
means progressively more sugar is present
...
Non-reducing Sugars (Benedict's test)
...
However, if it is first
hydrolysed to its constituent monosaccharides (glucose and fructose), it will then give a positive
Benedict's test
...
First test a sample for reducing sugars, to see if there
are any present before hydrolysis
...
Neutralise the solution by gently adding small amounts of solid sodium hydrogen carbonate until it stops fizzing,
then test as before for reducing sugars
...
Lipids (emulsion test)
...
This characteristic is used in the emulsion test
...
Decant the liquid into a
second test tube of water, leaving any undissolved substances behind
...
5
...
Add a few mL of biuret solution to the sample
...
The colour is due to a complex between nitrogen atoms in
the peptide chain and Cu2+ ions, so this is really a test for peptide bonds
...
There are about 40,000 different enzymes in human cells, each
controlling a different chemical reaction
...
They were discovered in fermenting yeast in 1900 by Buchner, and the
name enzyme means "in yeast"
...
How do enzymes work?
There are three ways of thinking about enzyme catalysis
...
1
...
The reaction
takes place in a small part of the enzyme called the active site, while the rest of the protein acts as
"scaffolding"
...
The amino acids around the active site bind to the
substrate molecule (usually by weak hydrogen and ionic bonds), so these amino acids make the
enzyme specific for one reaction only, as other molecules won't bind in the active site
...
This change distorts the substrate molecule in the active site, making it more likely to
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 17
change into the product
...
Alternatively if a bond is to be made
between two molecules, the two molecules can be held in exactly the right position and orientation and “pushed” together, making the bond more likely to form
...
Many enzymes also have small non-protein molecules called coenzymes at their active sites to help
bind to the substrate
...
2
...
) In an enzyme-catalysed reaction, the substrate first binds to the active site of the enzyme to
form an enzyme-substrate (ES) complex, then the substrate is converted into product while attached to the enzyme, and finally the product is released
...
The end result is the same (S
is taken, so that the S
P), but a different route
P reaction as such never takes place
...
3
...
We shall consider a reaction
where the product has a lower energy than the substrate, so the substrate naturally turns into product
(in other words the equilibrium lies in the direction
energy of molecules
The way enzymes work can also be shown by connormal
reaction
S
activation
energy
(EA)
ES
enzyme
catalysed
reaction
EP
of the product)
...
The larger the activation energy, the slower the reaction will be
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 18
because only a few substrate molecules will by chance have sufficient energy to overcome the activation energy barrier
...
Most physiological reactions have large activation energies, so they simply don't
happen on a useful time scale
...
For example for the breakdown of hydrogen peroxide (2H2O2
2H2O + O2):
• EA = 86 kJ mol -1 with no catalyst
• EA = 62 kJ mol -1 with an inorganic catalyst of iron filings
• EA = 1 kJ mol -1 in the presence of the enzyme peroxidase (catalase)
...
This optimum temperature is about 40°C for mammalian enzymes but there are enzymes that work best at very different temperatures, e
...
enzymes
rate of reaction
1
...
Up to the optimum temperature the rate increases geometrically with temperature (i
...
it's a
curve, not a straight line)
...
The rate is not zero at 0°C,
so enzymes still work in the fridge (and food still goes off), but they work slowly
...
This increase in rate with temperature would continue indefinitely except that the enzyme
molecule itself is affected by temperature
...
The substrate can no longer bind, and the reaction is no longer catalysed
...
So the optimum temperature of enzymes is usually about 40°C (and mammals and birds maintain their body temperature at around 40°C) because that is the temperature at which hydrogen bonds break
...
Enzymes have an optimum pH at which they work fastest
...
rate of reaction
2
...
For example carboxyl R-groups are uncharged
(COOH) in acid pH but negatively charged (COO–) in alkali pH
...
These changes can af3
fect the shape as well as the charge of the active site, so the substrate can no longer bind and
the reaction isn't catalysed
...
At very high enzyme concentration
the substrate concentration may become rate-limiting, so the rate
rate of reaction
3
...
Normally enzymes are present in cells in rather
enzyme concentration
low concentrations
...
As the substrate concentration
increases, the rate increases because more substrate molecules can
collide with enzyme molecules, so more reactions will take place
...
Substrate concentration
At higher concentrations the enzyme active sites become saturated
substrate concentration
with substrate, so there are few free enzyme molecules, so adding more substrate doesn't
make much difference (though it will increase the rate of E–S collisions)
...
They are found naturally, but are also used artificially as
drugs, pesticides and research tools
...
Inhibitors
while those that bind tightly and cannot be washed out are called
inhibitor concentration
irreversible inhibitors
...
It cule and does not fit into the active site
...
However, ing the shape of the whole enzyme, including
if the substrate concentration is increased high the active site, so that it can no longer bind subenough the substrate will out-compete the in- strate molecules
...
therefore simply reduce the amount of active
The sulphonamide anti-bacterial drugs are com- enzyme (just like decreasing the enzyme conpetitive inhibitors
...
Poisons like cyanide, heavy metal
ions and some insecticides are all noncompetitive inhibitors
...
rate experiment
in the presence and absence of the inhibitor
...
substrate concentration
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 21
Measuring the Rate of Enzyme Reactions
1
...
The signal should change with either substrate or
product concentration, and it should preferably be something that
can be measured continuously
...
If the reaction has none of these
properties, it can sometimes be linked to a second reaction that
does generate one of these changes
...
If you mix the substrate with enzyme and measure the signal, you
will obtain a time-course
...
In both
signal
concentration it will start high and decrease, while if the signal is
P
S
cases the time-course will be curved (actually an exponential
time
curve)
...
How do you obtain a rate from this time-course? One thing that
is not a good idea is to measure the time taken for the reaction,
for as the time-course shows it is very difficult to say when the
The rate is in fact the slope (or gradient) of the time-course, so
we can see that the rate (and slope) decreases as the reaction
signal
reaction actually ends: it just gradually approaches the end-point
...
The best measurement is the initial rate - that is the
initial slope of the time-course
...
(such as different temperatures or substrate concentrations) and
then plot a graph of rate vs
...
Each point on this second
graph is taken from a separate initial rate measurement (or better
still is an average of several initial rate measurements under the
same conditions)
...
rate of reaction
4
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 22
Cells
All living things are made of cells, and cells are the smallest units that can be alive
...
Prokaryotic cells are smaller and simpler than eukaryotic cells, and
do not have a nucleus
...
These show the individual organelles inside a cell
...
This is the solution within the cell membrane
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 23
• Nucleus
...
It is surrounded
by a nuclear envelope, which is a double membrane with
nuclear pores – large holes containing proteins that con-
nuclear
envelope
trol the exit of substances such as RNA and ribosomes
RER
nucleolus
from the nucleus
...
During cell division the chromatin be-
nucleoplasm
(containing
chromatin)
comes condensed into discrete observable chromosomes
...
• Mitochondrion (pl
...
This is a sausageshaped organelle (8 m long), and is where aerobic respi-
outer membrane
inner membrane
ration takes place in all eukaryotic cells
...
The space enclosed by the inner
ribosomes
membrane is called the mitochondrial matrix, and con-
DNA
tains small circular strands of DNA
...
• Chloroplast
...
Like mitochondria they are enclosed by a double
membrane, but chloroplasts also have a third membrane
called the thylakoid membrane
...
The space between the inner
granum
(thylakoid stack)
stalked particles
(ATP synthase)
starch grain
stroma
membrane and the thylakoid is called the stroma
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 24
• Ribosomes
...
They are composed of protein and RNA, and are manufactured in the nucleolus of
the nucleus
...
All eukaryotic ribosomes are of the
larger, "80S", type
...
This is a series of membrane
channels involved in synthesising and transporting materials
...
The ribosomes synthesise pro-
ribosomes
teins, which are processed in the RER (e
...
by enzymatically modifying the polypeptide chain, or adding carbohydrates), before being
exported from the cell via the Golgi Body
...
• Golgi Body (or Golgi Apparatus)
...
Its job
is to transport proteins from the RER to the cell membrane for export
...
• Vacuoles
...
Most cells can have small
vacuoles that are formed as required, but plant cells usually have one
very large permanent vacuole that fills most of the cell, so that the
cytoplasm (and everything else) forms a thin layer round the outside
...
Some unicellular protoctists have
feeding vacuoles for digesting food, or contractile vacuoles for expelling water
...
These are small membrane-bound vesicles formed from
the RER containing a cocktail of digestive enzymes
...
They can also fuse with a
feeding vacuole to digest its contents
...
This is a network of protein fibres extending
throughout all eukaryotic cells, used for support, transport and motilProtein
filaments
ity
...
The cytoskeleton is also responsible for cell movements such as: chromosome movement and cytoplasm cleavage in cell division, cytoplasmic
streaming in plant cells, cilia and flagella movements, cell crawling and
even muscle contraction in animals
...
This is a special pair of short cytoskeleton fibres involved
in cell division
...
• Undulipodium (Cilium or Flagellum)
...
It is an extension of the
cytoplasm, surrounded by the cell membrane, and is full of micro-
cilia
tubules and motor proteins so is capable of complex swimming
movements
...
g
...
g
...
• Microvilli
...
They are just visible under the light microscope as a
brush border
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 26
• Cell Membrane (or Plasma Membrane)
...
It separates the contents of the cell from the outside environment, and controls the entry and exit of materials
...
• Cell Wall
...
Cell walls consist of a network of fibres, which give strength but are freely permeable to solutes (unlike
membranes)
...
Plant cell walls
cell wall
cell membrane
are made mainly of cellulose, but can also contain hemicellulose, pec-
middle
lamella
plasmodesmata
tin, lignin and other polysaccharides
...
Fungal cell walls are made of chitin
...
All prokaryotes are bacteria
...
The main features of prokaryotic cells are:
• Cytoplasm
...
The smaller (70S) type, all free
cell wall
cell membrane
mesosome
plasmid
nucleoid
DNA
in the cytoplasm and never attached to membranes
...
flagellum
• Nuclear Zone (or Nucleoid)
...
It is not
surrounded by a nuclear membrane
...
Always circular (i
...
a closed loop),
and not associated with any proteins to form chromatin
...
• Plasmid
...
Used to exchange DNA
between bacterial cells, and also very useful for genetic engineering (see unit 4)
...
Made of phospholipids and proteins, like eukaryotic membranes
...
Made of murein (not cellulose), which is a glycoprotein (i
...
a protein/carbohydrate
complex, also called peptidoglycan)
...
A thick polysaccharide layer outside of the cell wall
...
In some species the capsules of many cells fuse together forming a mass of sticky
cells called a biofilm
...
• Flagellum
...
The motor is embedded in
the cell membrane and is driven by a H+ gradient across the membrane
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 28
Summary of the Differences Between Prokaryotic and Eukaryotic Cells
Prokaryotic Cells
Eukaryotic cells
small cells (< 5 m)
larger cells (> 10 m)
always unicellular
no nucleus
or any membrane-bound organelles
ribosomes are small (70S)
often multicellular
always have nucleus
and other membrane-bound organelles
DNA is linear and associated with proteins
to form chromatin
ribosomes are large (80S)
no cytoskeleton
motility by rigid rotating flagellum,
made of flagellin
cell division is by binary fission
always has a cytoskeleton
motility by flexible waving undulipodium,
made of tubulin
cell division is by mitosis or meiosis
reproduction is always asexual
reproduction is asexual or sexual
huge variety of metabolic pathways
common metabolic pathways
DNA is circular, without proteins
Endosymbiosis
Prokaryotic cells are far older and more diverse than eukaryotic cells
...
5 billion years, while eukaryotic cells arose only about 1 billion years
ago
...
This idea is
called endosymbiosis, and is supported by these observations:
• organelles contain circular DNA, like bacteria cells
...
• organelles have double membranes, as though a single-membrane cell had been engulfed and
surrounded by a larger cell
...
• organelles are very like some bacteria that are alive today
...
All the processes of cell metabolism (such as respiration or photosynthesis) have been studied in
this way
...
Cut tissue (eg liver, heart, leaf, etc) in ice-cold
isotonic buffer
...
2
...
3
...
This removes insoluble tissue (eg fat,
connective tissue, plant cell walls, etc)
...
4
...
This pellets nuclei, which can be
resuspended
5
...
This pellets mitochondria and chloroplasts,
which can be resuspended
6
...
This pellets ER, golgi and other membrane
fragments, which can be resuspended
7
...
This pellets ribososmes, which can be
resuspended
8
...
The vast majority of living organisms are too small to be seen in any detail with the human eye, and cells and their
organelles can only be seen with the aid of a microscope
...
Units of measurement
...
The magnification of a microscope simply indicates how much
bigger the image is that the original object
...
g
...
By
using more lenses microscopes can magnify by a larger amount, but this doesn't always mean that
more detail can be seen
...
Resolution is therefore a distance (usually in nm) and is calculated by the formula:
resolution =
0
...
a
...
a
...
5 to 1
...
So the resolution of a microscope is ultimately limited by the wavelength of
light (400-600nm for visible light)
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 31
Different kinds of Microscope
...
Light Microscope
...
Specimens are illuminated with light, which is focused using glass lenses and viewed using the
eye or photographic film
...
Many different stains are available that stain specific parts
of the cell such as DNA, lipids, cytoskeleton, etc
...
eye
eyepiece lens
objective lens
specimen
condenser lens
illuminator (lamp)
Light microscopy has a resolution of about 200 nm, which is good enough to see tissues and
cells, but not the details of cell organelles
...
For example fluorescence microscopy has a resolution of about 10 nm, while interference microscopy has a resolution of about 1 nm
...
Electron Microscope
...
This may seem strange, but electrons behave like waves and can
easily be produced (using a hot wire), focused (using electromagnets) and detected (using a
phosphor screen or photographic film)
...
The development of the electron microscope in the 1930s revolution-
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 32
ised biology, allowing organelles such as mitochondria, ER and membranes to be seen in detail for
the first time
...
• specimens must be very thin, so are embedded in plastic for support, so can't be manipulated
under the microscope
...
• specimens are usually transparent to electrons, so must be stained with an electron-dense
chemical (usually heavy metals like osmium, lead or gold)
...
e
...
There are two kinds of electron microscope
...
This is the most common form of
electron microscope and has the best resolution
...
This has
poorer resolution, but gives excellent 3-dimentional images of surfaces
...
There are two ways of doing this:
1
...
The formula for the magnification is:
magnification =
image length
I
, or
actual length
M A
For example if this drawing of an object is 40 mm long and the magnification
is
x 1000,
then
the
object's
actual
length
is:
I
40
=
= 0
...
Always convert your answer to approM 1000
x 1000
priate units, usually m for cells and organelles
...
For example if this
drawing of an object is 40 mm long and its actual length is 25 m, the
magnification of the drawing is:
I
40
=
= ×1600
...
025
image and actual length must be in the same units
...
g
...
1), which means that the drawing is smaller than the actual object
...
Using a Scale Bar
Sometimes the picture has a scale bar on it
...
The image size and bar length must be measured in the
bar length
same units (usually mm), and the actual size will come out in the same units as the bar scale
...
10
5µm
It's good to have a rough idea of the size of objects, to avoid silly mistakes
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 34
The Cell Membrane
The cell membrane (or plasma membrane) surrounds all living cells, and is the cell's most important organelle
...
The membranes that surround the nucleus and other
organelles are almost identical to the cell membrane
...
peripheral
protein on
outer surface
carbohydrate
attached to
protein
phospholipid
fatty acid chains
polar head
part of
cytoskeleton
peripheral
protein on
inner surface
integral protein
forming a channel
The phospholipids form a thin, flexible sheet, while the proteins "float" in the phospholipid sheet
like icebergs, and the carbohydrates extend out from the proteins
...
The phospholipids are arranged in a bilayer (i
...
a double layer), with their polar, hydrophilic
phosphate heads facing out towards water, and their non-polar, hydrophobic fatty acid tails facing
each other in the middle of the bilayer
...
Different kinds of membranes can contain phospholipids with different fatty acids, affecting the strength and flexibility of the membrane,
and animal cell membranes also contain cholesterol linking the fatty acids together and so stabilising and strengthening the membrane
...
They can slide around the
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 35
membrane very quickly and collide with each other, but can never flip from one side to the other
...
Proteins comprise about 50% of the mass of membranes, and are responsible for most of the membrane's
properties
...
Transport proteins must span the
membrane (more details below)
...
Receptor proteins must be on the outside surface of cell membranes and have a specific binding site where
hormone
receptor
binding
site
hormones or other chemicals can bind to form a hormone-receptor
complex (like an enzyme-substrate complex)
...
• Proteins can be enzymes
...
P
• Proteins can be antigens
...
• Proteins can be structural
...
They
are involved in maintaining the cell's shape, or in changing the cell's
shape for cell motility
...
Proteins with carbohydrates attached are called glycoproteins, while phospholipids with carbohydrates attached are
called glycolipids
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 36
Movement across Cell Membranes
...
Diffusion does not require any energy (other than the thermal energy of the
surroundings), so it is referred to as a passive process
...
This means that cell membranes can allow some substances through but not others
...
This is compartmentalisation is essential for life, as it
enables reactions to take place that would otherwise be impossible
...
Obviously materials need to be able to enter and leave cells, and there are four main methods by
which substances can move across a cell membrane:
1
...
Osmosis (Water Diffusion)
3
...
Active Transport
1
...
The only substances that can do this are lipid-soluble molecules such as steroids, or very small molecules, such
as H2O, O2 and CO2
...
Since lipid diffusion
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 37
is a passive process, no energy is involved and substances can only move down their concentration
gradient
...
2
...
It is in fact just normal lipid diffusion, but
since water is so important and so abundant in cells (its concentration is about 50 mol L-1), the
diffusion of water has its own name – osmosis
...
The more concentrated the solution, the more solute molecules there are in a
given volume, and the more water molecules are tied up in hydration shell, so the fewer free water molecules there are
...
water molecules
membrane
solute molecules
hydration
shell
net movement of water
Water Potential
...
Water potential (Ψ, the Greek letter psi, pronounced "sy") is
simply the effective concentration of free water
...
100% pure water has Ψ = 0, which is the
highest possible water potential, so all solutions have Ψ < 0, and you cannot get Ψ > 0
...
The water potential of the solution that surrounds a cell affects the state of
the cell, due to osmosis
...
g
...
g
...
Net diffusion of water into
cell, so cell swells a bit and
becomes turgid
...
Animal
cell
Plant
cell
These are problems that living cells face all the time
...
These cells constantly need to expel water using
contractile vacuoles to prevent swelling and lysis
...
These cells must actively pump ions into their cells to reduce their
water potential and so reduce water loss by osmosis
...
Plants take up water through their root hair cells by osmosis, and must actively pump ions
into their cells to keep them hypertonic compared to the soil
...
3
...
channel
protein
f li p
carrier
protein
or
Facilitated Diffusion is the diffusion of substances across a membrane through a trans-membrane
protein molecule
...
This is a passive
diffusion process, so no energy is involved and substances can only move down their concentration gradient
...
This allows charged
substances to diffuse across membranes
...
In this way cells can change their permeability
to certain ions
...
• Carrier Proteins have a binding site for a specific solute and constantly flip between two states
so that the site is alternately open to opposite sides of the membrane
...
Important solutes like glucose and amino acids diffuse across membranes through specific carriers
...
This is called cotransport, and a common example is the sodium/glucose cotransporter found in
the small intestine (see next page)
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 40
4
...
protein
pump
change
shape
ATP
active
site
ADP + Pi
Active transport is the pumping of substances across a membrane by a trans-membrane protein
pump molecule, using energy
...
The proteins are
highly specific, so there is a different protein pump for each molecule to be transported
...
Active transport is
therefore not diffusion, but instead is an active process, and is the only transport mechanism that
can transport substances up their concentration gradient
...
This indirect active transport is called coupled active transport
...
Na/K
K+
Na+
glucose
Na+
Na/glucose
cotransporter
pump
2
1
ATP
ADP + Pi
Na+
3
Na+
1
...
This pump continually uses ATP to actively pump sodium ions out of the cell and potassium ions into the cell
...
2
...
But while the sodium
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 41
ions are diffusing down their concentration gradient, the glucose molecules can be carried up
their concentration gradient
...
The sodium ions are pumped out again by the Na/K pump, so they simply cycle in and out of
the cell
...
Effect of concentration difference on rate of transport
increases as its concentration gradient increases, but
whereas lipid diffusion shows a linear relationship, facilitated diffusion has a curved relationship with a maximum
rate
...
The rate of active transport has a
high rate even when there is no concentration difference
concentration difference
across the membrane
...
Summary of Membrane Transport
method
uses energy
uses proteins specific
controllable gradient
Lipid Diffusion
Osmosis
Facilitated Diffusion
Active Transport
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 42
Exchange
All organisms need to exchange substances such as food, waste, gases and heat with their surroundings
...
The rate at
which a substance can diffuse is given by Fick's law:
Rate of Diffusion ∝
surface area × concentration difference
distance
From Fick's law we can predict that, in order to support a fast rate of diffusion, exchange surfaces
must have:
• a large surface area
• a small distance between the source and the destination
• a mechanism to maintain a high concentration gradient across the gas exchange surface
...
system
large surface area
small distance
high concentration
gradient
Human small
intestine
7m long, folds, villi and microvilli give surface area of
2000m²
blood capillaries close
to surface of villus
stirred by peristalsis
and by microvilli
Human circulatory system
100m of capillaries with a surface area of 6000m²
capillary walls are only
one cell thick
constant blood flow
replenishes the blood
Human lungs
600 million alveoli with a total
area of 100m²
each alveolus is only
one cell thick
constant ventilation
replaces the air
For comparison, a tennis court has an area of about 260 m² and a football pitch has an area of
about 5000 m²
...
In the rest of this unit
we shall look at the digestive system; the gas exchange system and the circulatory system
...
Disease is a general term meaning a disorder of the
body
...
g
...
• Dietary Deficiency Diseases are caused by a lack of specific nutrients in the diet, e
...
kwashiorkor (protein), scurvy (vitamin C), rickets (vitamin D)
...
They include
skin cancer (caused by radiation), lung cancer (caused by smoking), asthma (caused by dust),
pulmonary fibrosis (caused by dust or pollution), and Creutzfeldt-Jakob disease (caused by prions)
...
They include alcoholism, emphysema, coronary heart disease, anorexia, drug addiction and even accidents
...
• Genetic Diseases are caused by genes inherited from parents
...
g
...
In fact all diseases are affected by genetics, but these “single gene disorders”
are governed entirely by the action of a single allele and are not influenced by any other factor
...
Infectious diseases are caused by a variety of pathogens, including viruses, bacteria, fungi and
protoctists
...
Some pathogens are more harmful than others; in other words they are have a greater pathogenicity or virulence
...
The pathogen must be transmitted to the human host
...
2
...
The human body is protected by a tough
layer of skin, but pathogens can enter via cuts in the skin (e
...
rabies, malaria); or the thinner interfaces, such as the digestive system (e
...
cholera, typhoid); gas exchange system (e
...
influenza,
tuberculosis) or reproductive system (e
...
AIDS)
...
The pathogen must evade the defences of the host
...
But it only takes a few pathogen cells resisting the defences to
multiply and cause a disease
...
The pathogen must harm the host
...
First, by reproducing inside host cells, using up cellular resources and preventing the cell from carrying out its
normal reactions
...
Second, by producing toxins – chemicals that interfere
with the body's reactions
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 45
Lifestyle and Disease
A person’s lifestyle affects their chances of suffering from any of the diseases listed on the previous
page, except the single gene disorders
...
Some of these factors have obvious association with disease (like smoking), while others are less obvious (like occupation), but all the factors have an associated risk
...
But smoking 20 cigarettes a day gives a high probability of developing lung cancer and emphysema, which are unpleasant and fatal conditions, so the risk of
smoking is high
...
e
...
For example smokers are 15 times more likely to develop lung cancer than non-smokers
...
e
...
A few examples are:
• For lung cancer the main risk factors are smoking and cleanliness of the environment
...
• For coronary heart disease the main risk factors are diet, age, genetics and exercise
...
• For AIDs the main risk factors are sexual habits, drug habits and genetics
...
g
...
But the others are lifestyle
factors and so within our power to change
...
Epidemiology is the study of the incidence, distribution and associations of diseases with a view to
identifying their causes and so effect their prevention
...
50
This scatter chart plots the incidence of lung cancer in a
40
30
sample of several thousand men against their annual in-
20
come
...
incidence of cancer per
100 000 men
This scatter chart plots the incidence of lung cancer
300
against number of cigarettes smoked
...
100
But this correlation is not evidence that smoking
causes lung cancer
...
To demonstrate a causal relationship we need to carry
Rate of DNA l igase
reaction (arbitrary units)
out controlled laboratory experiments
...
The re-
8
6
sults show that arsenic inhibits DNA ligase, and in cells
4
that would cause damage to DNA and cancer
...
incidence of cancer per
100 000 men
This scatter chart plots the incidence of lung cancer
80
against alcohol consumption
...
Instead, the correlation is indirect:
0
0
20
40
60
alcohol consumption (units per we ek)
HGS A-level notes
heavy drinkers tend also to be heavy smokers and the
smoking causes lung cancer
...
(Do not confuse egestion, which is the elimination of material from a body cavity, with excretion, which is the elimination of waste material
produced from within the body's cells
...
oesophagus
1
...
The teeth and
tongue physically break up the food into liver
stomach
small pieces with a larger surface area, and
pancreas
form it into a ball or bolus
...
The food bo-
colon
rectum
anus
lus is swallowed by an involuntary reflex action through the pharynx (the back of the
mouth)
...
2
...
This is a simple tube through the thorax, which connects the mouth to
the rest of the gut
...
The oesophagus is a soft tube that can be
closed, unlike the trachea, which is a hard tube, held open by rings of cartilage
...
These two
muscles therefore have opposite effects and so are antagonistic
...
This is a wave of circular
muscle contraction, which passes down the gut and is completely involuntary:
Food
circular muscle
circular muscle
contracted
relaxed
+
+
longitudinal muscle longitudinal muscle
relaxed
contracted
circular muscle
circular muscle
relaxed
contracted
+
+
longitudinal muscle longitudinal muscle
contracted
relaxed
3
...
This is an expandable bag where the food is stored for up to a few hours
...
This is gradually released in to the small intestine by a sphincter, a region of thick circular muscle that acts as a
valve
...
No other digestion takes place in the stomach
...
Small Intestine
...
Although this is
short, almost all the digestion takes place here, due to two secretions: pancreatic juice and bile
...
It
contains numerous amylase, protease and lipase enzymes
...
Bile doesn’t contain any
enzymes, but it does contain bile salts to aid lipid digestion, and the alkali sodium hydrogen carbonate to neutralise the stomach acid
...
5, so
the pancreatic enzymes can work at their optimum pH
...
This is the site of final digestion and absorption
...
It is over 6m long; the internal surface has large and
small folds (villi); and the epithelial cells lining the ileum have microvilli
...
Microvilli can only be seen
clearly with an electron microscope, and appear as a fuzzy brush border under the light
microscope
...
folds in ileum wall
villi
microvilli
1 m
500 m
epithelial cell
40 mm
•
There is a short diffusion distance
...
•
A high concentration gradient is maintained by mixing the fluids on either side of the exchange surface
...
The microvilli can also wave to stir the contents near the epithelial cells
...
The layer of cells that line the ileum are called the epithelium, and the epithelial cells are highly
specialised for their role
...
5
...
The large intestine comprises the caecum, appendix, colon and rectum
...
Faeces is made up of plant fibre (cellulose mainly), cholesterol, bile, mucus, mucosa cells (250 g
of cells are lost each day), bacteria and water, and is released by the anal sphincter
...
Digestion of carbohydrates
By far the most abundant carbohydrate in the human diet is starch (in bread, potatoes, cereal, rice,
pasta, biscuits, cake, etc), but there may also be a lot of sugar (mainly sucrose) and some glycogen
(in meat)
...
Salivary amylase starts the digestion of starch in the mouth
...
2
...
Amylase digests starch
molecules from the ends of the chains in two-glucose units, forming the disaccharide maltose
...
3
...
This includes maltose from starch digestion as well as any sucrose and lactose in the diet
...
Absorption of Monosaccharides
The monsaccharides (glucose, fructose and galactose) are absorbed by coupled active transport
into the epithelial cells of the ileum, as shown in this diagram:
lumen
of gut
Na+
2
1
+
Na
epilthelium
3
tissue
fluid
blood
capillary
K+
5
+
Na
4
1
...
2
...
3
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 51
4
...
5
...
the epithelial cell
Active transport requires energy in the form of ATP, but it allows very rapid absorption, even up a
concentration gradient
...
Lactose Intolerance
Some people can’t eat food containing milk because it makes them ill, with symptoms including
flatulence and explosive diarrhoea
...
Since lactose can’t be absorbed it passes through to the large intestine, where
it is fermented by the bacteria in the colon, who produce acids and gases like methane and carbon
dioxide
...
In fact most humans (and all other adult mammals) are lactose intolerant, and this is the “normal”
state
...
Baby mammals all make lactase in order to digest the lactose in milk, but
when they are weaned (eat solid food) they stop drinking milk and the gene for lactase production
is switched off
...
These humans generally have a mutation that causes lactase to be produced throughout life, so
these people are lactose tolerant and can drink milk without any ill effects
...
V
...
The symptoms of cholera include
stomach cramps, vomiting, fever and severe diarrhoea
...
There were several serious
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 52
outbreaks of cholera in the UK in the 19th century and cholera remains a major killer of small children in developing countries (several million deaths each year)
...
1
...
CT enters the epithelial
lumen
How V
...
2
...
epilthelium
cells and activates a chloride ion channel in the cell memH2 O
Cl -
1
4
3
...
4
...
Treatment for Diarrhoea
The treatment for diarrhoea was revolutionised in the 1960s, with the development of oral rehydration therapy (ORT)
...
ORT makes use of the sodium/glucose cotransporter protein that normally absorbs glucose
into the ileum epithelial cells
...
lumen
1
...
ORS
contain equimolar concentrations of glucose and salt
...
The transporter protein carries the Na+ and glucose into
epilthelium
Transport only works if both molecules are present,
1
H2O
+
Na
Na+
low Ψ
2
4
3
the cell, down their concentration gradients
...
This lowers the water potential inside the epithelial cells
...
So water diffuses from the lumen into the epithelial cells by osmosis, rehydrating cells and re-
ducing diarrhoea
...
The actual gas exchange
surface is on the alveoli inside the lungs
...
Although each alveolus is tiny, an average adult has about 600 million alveoli, giving a total surface area of about 100m², so the area is huge
...
The walls of the alveoli are composed
of a single layer of flattened epithelial cells, as are the walls of the capillaries, so gases need to
diffuse through just two thin cells
...
The
steep concentration gradient across the gas exchange surface is maintained in two ways: by
blood flow on one side and ventilation on the other side
...
Water inevitably diffuses down its concentration gradient from the tissue fluid and alveoli
cells into the air in the alveoli, so the air in the alveoli is constantly moist
...
However, by having the gas exchange surface deep inside the body at the end of long
narrow bronchioles, the water loss is minimised
...
The epithelial cells secrete a soapy surfactant to reduce the surface tension of the water (due to
hydrogen bonds) and make it less "sticky"
...
Some of the epithelial cells of the bronchioles secrete mucus, which traps bacteria and other microscopic particles that enter the lungs
...
Phagocyte cells migrate from the blood capillaries to the alveolar air space to
kill any bacteria that have not been trapped by the mucus
...
Lungs are not muscular and cannot ventilate themselves, but instead the whole thorax moves and
changes size, due to the action of two sets of muscles: the intercostal muscles and the diaphragm
...
The
outer membrane is attached to the thorax and the inner membrane is attached to the lungs
...
The alveoli are elastic and collapse if not held stretched by the thorax
...
Ventilation in humans is tidal, which
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 55
means the air flows in and out by the same route
...
These volume and pressure changes are shown in this graph:
Inspiration
Rest
Volume
of lungs
Expiration
Pressure
in alveoli
above
atmospheric
pressure
atmospheric pressure
below
atmospheric
pressure
0
Inspiration
1
2
Time (s)
3
4
1
...
2
...
3
...
4
...
Normal
expiration
1
...
2
...
3
...
4
...
Forced
expiration
1
...
The internal intercostal muscles contract, pulling the ribs downward
3
...
Very soon after
birth the baby takes its first breath by contracting its diaphragm with a force 20 times usual
...
The alveoli then remain stretched throughout life
...
The product of
these two is called the Pulmonary Ventilation – the volume air ventilating the lungs each minute:
ventilation
rate
pulmonary
ventilation
tidal
= ventilation x volume
rate
tidal
volume
-1
pulmonary
ventilation
-1
(breaths min ) (cm³ breath )
-1
(cm³ min )
at rest
12
500
6 000
at exercise
18
1000
18 000
When the body exercises the ventilation rate and depth increases so that
• Oxygen can diffuse from the air to the blood faster
• Carbon dioxide can diffuse from the blood to the air faster
These changes allow aerobic respiration in muscle cells to continue for longer
...
The large volumes of air passing through the lungs may carry infectious pathogens or
other microscopic particles that cause disease
...
Pulmonary Tuberculosis
Pulmonary Tuberculosis (or TB) is an infectious disease caused by the bacterium Mycobacterium
tuberculosis
...
5 million deaths in 2006
...
TB is transmitted by aerosol droplets from coughs and sneezes of infected persons
...
• The bacterial cells are breathed in and invade the
epithelial cells of the alveoli and bronchioles
...
• The tubercles stimulate an inflammatory response by
the white blood cells of the immune system, resulting
scar tissue that can be seen in a chest X-ray
...
• This destroys the alveoli, so making gas exchange diffi-
tubercle
cult and causing the persistent cough
...
This causes
weakness as the body wastes away and the bacteria appear to “consume” the body – hence the old name for
TB: consumption
...
This decline is due to a combination of reasons:
• Improved housing and hygiene
...
• Improved diet
...
• Pasteurisation of milk and improved animal husbandry
...
• Antibiotics
...
The most effective antibiotic
was streptomycin, but now some M
...
• Vaccination
...
This vaccine is named after the two
Frenchmen (Calmette and Guerin) who developed it at the Pasteur Institute in Paris in 1921
...
bovis, a similar bacterium that causes TB
in cattle
...
Asthma
Asthma is an allergic response that causes difficulty breathing, wheezing, tight chest and coughing
...
Asthma is not an infectious disease, but is caused by physical factors called allergens in the environment
...
Other factors that
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 59
can contribute to asthma include polluting gases like sulphur dioxide, exercise, cold weather, infection and stress
...
White blood cells called
mast cells release histamines, which cause the
smooth circular muses of the bronchioles to contract, narrowing the airways - bronchoconstriction
...
• The constricted bronchioles slows ventilation, thus
reducing gas exchange in the alveoli and cellular
respiration throughout the body
...
Asthma can be treated by inhaling drugs that relax the smooth muscles and by anti-inflammatory
drugs
...
The particles stimulate an inflammatory response in the lungs, which results in the
growth of fibrous scar tissue around the alveoli
...
There are hundreds of different
causes of pulmonary fibrosis, and since these are usually found in work-place environments, pulmonary fibrosis is known as an occupational disease
...
It caused almost exclusively by smoking and 20% of all smokers suffer from emphysema; 10% of absence from work in the UK is due to emphysema and it kills 20 000 per year in
the UK
...
These protease enzymes digest the proteins forming the elastic tissue in the epithelial cells
of the alveoli, so the alveoli can’t expand and recoil, making ventilation difficult
...
These all reduce the rate of gas exchange, so reducing cellular respiration and
making any muscular activity very difficult
...
Breathing pure oxygen compensates for the poor efficiency of gas exchange, so allowing more respiration
...
Disease
TB
Cause
bacterial
infection
Symptoms
chest pain, coughing
blood, fever, death
Asthma
allergens
temporary breathing
difficulties; wheezing
breathing difficulty
Pulmonary dust
fibrosis
emphysema smoking
HGS A-level notes
permanent breathing
difficulty
Effects
bacteria form tubercles
in lungs then reproduce
and consume tissues
...
coal dust, silica dust,
mould spores
...
Veins carry blood into the atria and arteries carry blood away from the ventricles
...
The left valve has two
flaps and is called the bicuspid (or mitral) valve, while the right valve has 3 flaps and is called the
tricuspid valve
...
There are
also two semi-lunar valves in the arteries (the only examples of valves in arteries) called the pulmonary and aortic valves
...
The walls of
the right ventricle are 3 times thinner than on the left and it produces less force and pressure in
the blood
...
The internal volume of the left and right ventricles is the same
...
When myocytes receive
an electrical impulse they contract together, causing a heartbeat
...
These arise from the aorta as it leaves the heart
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 62
The Cardiac Cycle
When the cardiac muscle contracts the volume in the chamber decreases, so the pressure in the
chamber increases, so the blood is forced out
...
It does
this continuously for up to 100 years
...
Contractions
are initiated within the heart by the sino-atrial
node (SAN, or pacemaker) in the right
sino-atrial node (SAN)
atrio-ventricular node (AVN)
atrium
...
There is a complicated sequence of events at each heartbeat called the cardiac cycle
...
Atrial Systole
...
The ventricles are electrically insulated
from the atria, so they do not contract at this time
...
2
...
The electrical impulse passes to the ventricles via the atrioventricular
node (AVN), the bundle of His and the Purkinje fibres
...
1s
...
The blood can't go into the atria because of the
atrioventricular valves, which are forced shut with a "lub" sound
...
Diastole
...
The semilunar valves
in the arteries close as the arterial blood pushes against them, making a "dup" sound
...
The pressure changes show most
clearly what is happening in each chamber
...
So during atrial systole the atria
contract, making the atrium pressure higher than the ventricle pressure, so blood flows from the
atrium to the ventricle
...
The valves are largely passive: they are opened by
blood flowing through them the right way and are forced closes when blood tries to flow through
them the wrong way
...
Atrial Systole
Diastole
ventricles contract
blood enters arteries
atria and ventricals both relax
blood enters atria and ventricles
Events
Ventricular Systole
atria contract
blood enters ventricles
Name
semilunar
valves open
0
0
...
2
semilunar
valves close
0
...
4
0
...
6
0
...
8
0
...
8
Pressure (kPa)
20
i n arter y
15
in artery
10
5
0
in atriu m
in ventricl e
in atriu m
in ventricle
atrioventricular
valves open
atrioventricular
valves close
PCG
"dup"
"lub"
ECG
Time (s) 0
HGS A-level notes
0
...
2
0
...
4
0
...
6
NCM/9/08
Module 1 - Core Principles - page 64
This diagram just shows one side of the heart
...
The PCG (or phonocardiogram) is a recording of the sounds the heart makes
...
The first sound (lub) is due to the
atrioventricular valves closing and the second (dup) is due to the semi-lunar valves closing
...
There are
characteristic waves of electrical activity marking each phase of the cardiac cycle
...
The heart rate can be calculated from this chart by measuring the time taken for one cycle and
using the formula:
heart rate (beats per minute) =
60
cycle time (s)
Cardiac Output
The rate at which the heart beats and the volume of blood pumped at each beat (the stroke volume) can both be controlled
...
There
are several benefits from this:
• to get oxygen to the muscles faster
• to get glucose to the muscles faster
• to get carbon dioxide away from the muscles faster
• to get lactate away from the muscles faster
• to get heat away from the muscles faster
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 65
Coronary Heart Disease
Coronary heart disease (CHD) is caused by a blockage in
the coronary blood system
...
Cardiac muscle works constantly throughout life and
is incapable of anaerobic respiration, so it has a great de-
coronary
arteries
mand for oxygen and glucose
...
A blockage in a coronary artery can restrict
the supply of oxygen to the cardiac cells, killing them and causing a heart attack
...
Cholesterol and other insoluble lipids collect on the inside of a coronary artery
...
clean
artery
2
...
3
...
If the wall is particularly weak the aneurism may burst caus-
Fatty
deposits
inside
artery
(atheroma)
ing blood loss and probable death
...
The plaque can also encourage the formation of a blood clot called a thrombus
...
The clot grows until it completely blocks the artery, forming a coronary thrombosis
...
Any cardiac cells “downstream” of the thrombosis will be starved of oxygen, cannot respire
and so die
...
The severity of the heart attack depends on how far along the coronary artery the thrombosis is
...
The five stages in a heart attack are summarised in this diagram
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 66
1
Atheroma
(fat deposits)
2
Plaque
(hardened atheroma)
4
3
Coronary Thrombosis
(blockage due to blood clot)
Aneurism
(swelling due to weak wall)
5
Myocardial Infarction
(death of cardiac cells)
Risk Factors for Coronary Heart Disease
There are a number of risk factors that are associated with coronary heart disease
...
Some of the main factors are:
• Blood Cholesterol
...
Cholesterol is carried in large complexes with proteins, called lipoproteins
...
• Blood Pressure
...
Stress, diet and lack of exercise can all increase blood pressure
...
Both blood pressure and fat metabolism are affected by genes, so genes undoubtedly
affect the chance of a coronary thrombosis
...
• Diet
...
High levels of salt increase blood pressure and so increase
the risk of aneurism
...
• Smoking
...
The carbon monoxide and nicotine in cigarette smoke both cause an
increase in blood pressure
...
It consists mainly of the white
blood cells, but parts of the immune system are spread all over the body
...
These
transport pathogens and leukocytes all
over the body
...
These contain mil-
lymph nodes
in neck
lions of phagocyte and lymphocyte cells,
which identify and remove pathogens from lymph nodes
in armpits
lymph
...
This contains millions of
spleen
phagocyte and lymphocyte cells, which
identify and remove pathogens from
blood
...
This is where blood stem
cells are differentiated into T-lymphocytes
...
These stem cells differentiate to
form dozens of different kinds of leukocytes, which fall into four categories:
White Blood cells
(Leukocytes)
Phagocytes
Granulocytes
T Lymphocytes
B Lymphocytes
for
phagocytosis
for
inflamation
for
cell-mediated
immunity
for
antibody-mediated
immunity
Macrophages
Neutrophils
Monocytes
Mast cells
Eosinophils
Basophils
Helper T-cells
Cytoxic T-cells
Memory T-cells
Plasma B-cells
Memory B-cells
Non-Specific Immune System
HGS A-level notes
Specific Immune System
NCM/9/08
Module 1 - Core Principles - page 68
The Three Lines of Defence
Humans have three lines of defence against invading pathogens:
1
...
The non-specific immune system – phagocytes quickly destroy microbes that pass the first line
of defence
3
...
The First Line of Defence – Barriers
The body has many mechanism to try to stop microbes entering the body, particularly the bloodstream
...
The
outer layer, the epidermis, is 20-30 cells thick (about as thick as a sheet of paper) and its cells
are toughened by the protein keratin
...
• The digestive tract is a potential entry route for pathogens, but it is protected by concentrated
acid in the stomach, which denatures microbial enzymes and cell surface proteins, as well as
protease enzymes
...
• The respiratory tract is another potential entry route, but it is protected by sticky mucus secreted by glands in the bronchi and bronchioles, which traps microbes and other particles in inhaled air before they can reach the delicate alveoli
...
• The human body is home to billions of bacterial cells called variously the natural microbiota, the
normal flora, the commensal flora (because they have a non-harmful or commensal relationship
with their host) or even the "friendly bacteria"
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 69
The Second Line of Defence – The Non-Specific Immune System
The phagocytes and the granulocytes form the non-specific immune system, a host of quick, nonspecific methods of killing microbes that have passed the first line of defence and entered the
body
...
Phagocytes are large, irregularly-shaped leukocyte cells that remove
bacteria, viruses, cellular debris and dust phagosome
particles
...
The phagosome then fuses
with lysosomes - small vesicle containing lysozymes, which are released into the phagosome, killing and digesting the microbe
...
• Complement System
...
They
are also involved in activating other parts of the immune system
...
This is a localised response to an injury or infection
...
The dead pathogens and phagocytes, together with excess tissue fluid, are release as
pus
...
• Fever
...
These stimulate the hypothalamus of the brain to increase the
body's temperature from 37°C up to 39°C
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 70
The Third Line of Defence – The Specific Immune System
The lymphocytes form the specific immune system, which is a more complex and sophisticated
collection of reactions that not only kill invading pathogens, but also remember the pathogen's features so that it can be killed quickly on subsequent infections
...
The key difference of the specific immune system is that it is capable of recognising foreign cells as distinct from its own cells, an ability called self/nonself recognition
...
An antigen is a large molecule (protein, glycoprotein, lipoprotein or polysaccharide) on the outer
surface of a cell
...
The
capsid proteins of viruses and even individual protein molecules (such as toxins) can also be
classed as antigens
...
Antigens
are genetically controlled, so close relative have more similar antigens than unrelated individuals
...
There are two kinds of lymphocyte – B-lymphocytes (or just B-cells) and T-lymphocytes (or just
T-cells)
...
An antibody (also called an immunoglobulin) is a protein molecule that
can bind specifically to an antigen
...
The stem of the Y is called the constant region because in all immunoglobulins
it has the same amino acid sequence, and therefore same structure
...
These variable regions are where
the antigens bind to form a highly specific antigen-antibody complex, much like an enzymesubstrate complex
...
Every human has around
108 different types of B cell, each making antibodies with
membrane-bound
antibodies
slightly different variable regions
...
T-cells have receptor molecules on their surfaces which
are very similar, but not identical, to antibodies
...
Each T-cell has around 105 re8
ceptor proteins, and again there are about 10 different
antigen
membrane
receptors
types of T-cell, each with slightly different receptor
molecules, so they can also specifically bind to any conceivable antigen
...
The B and T cells are exposed to so many "self" antigens on every normal cell they come across,
that they quickly "learn" to recognise them very early in life
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 72
The actions of the specific immune system are summarised in this diagram:
virus
bacterium
toxin
phagocyte
viral-infected cell transplant organ tumour cells
1 Antigen Presentation
T
-Cells
B-Cells
chemical
signaling
2
CytoxicT
-cells
Memory
T
-cells
cloning
Clonal Selection
cloning
Helper
T-cells
3 Cell-mediated immunity
Plasma Cells
Memory
B-cells
4 Antibody-mediated immunity
1
...
The antigens
can be from a variety of sources:
• a virus capsid protein or envelope protein
• on the surface of a bacterial cell
• on a cell infected with a virus so that it has
viral proteins on its surface
• a toxin released from a bacterium
• on the surface of cells of a transplant
• on a phagocyte that has ingested a pathogen
• on a cancerous cell
Macrophages are the most important antigen-presenting cells because they are the most numerous
...
If the antigens are not recognised as self antigens, then the macrophage ingests the antigen and its cell by phagocytosis
...
This amplifies the number of antigens
...
2
...
Whenever a particular
antigen enters the body it comes into contact with all the various cells in the blood and lymph, including the lymphocytes
...
It's a bit like Prince Charming trying to fit the glass
slipper (the antigen) onto all the girls in the kingdom (the different lymphocytes) until eventually
he finds Cinderella, who is an exact fit
...
This is called clonal selection, because only the selected cell is cloned
...
3
...
• Cytoxic T-cells (or killer T-cells) bind to antigens on infecting cells and kill the cells by releasing
perforin proteins
...
• Helper T-cells bind to antigens on infecting cells and secrete chemicals called cytokines
...
The AIDS virus HIV destroys these helper T-cells, and the immune system doesn't work nearly as well without them
...
This means that the
same antigen will be identified much more quickly in a subsequent infection, when the memory
T-cells will quickly divide to form cytoxic T-cells and helper T-cells
...
B-Cells and Antibody-Mediated Immunity (or humoral immunity)
The B-lymphocytes also differentiate into cells with different functions
...
These antibodies are carried around the blood,
lymph and tissue fluid binding to any antigens they come into contact with and forming antibodyantigen complexes
...
So during the immune response to an infection there is
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 74
an enormous number of antibodies in the body and it is highly likely that every antigen will be
targeted by one
...
By binding to antigens on viruses and bacteria they prevent the viruses or bacteria attaching
to cells and so infecting them
...
By binding to free toxin proteins they change the shape of the active region so that these
proteins can no longer take part in the reactions that caused disease
...
By linking antigens together
...
This
process, called agglutination, immobilises viruses and cells, and precipitates soluble toxins so
that they can easily be destroyed by phagocytes or cytoxic T-cells
...
• Memory B cells continue to secrete antibodies in small quantities for many decades, and can
multiply rapidly to produce an instant supply of plasma cells if the same pathogen invades again
...
Furthermore the clone army tends to be fairly small
...
It is during this
period that the symptoms of the disease are shown, partly due to toxins and cell death due to the
pathogen, and partly due to the immune response itself (e
...
fever, inflammation)
...
This
means that after a subsequent infection by the same antigen the clonal selection stage can be bypassed and the specific immune response is much faster and much greater (i
...
more clone B and T
lymphocytes and antibodies are produced)
...
In other
words the individual is immune to that disease
...
Concentration of
antibody in blood
secondary
response
primary
response
antibody concentration
required for immunity
0
First
infection
10
20
30
40
Delay of
years
0
10
20
30
Time after
40 infection (days)
Second
infection
Antigenic Variability
This immunity works well for many diseases, such as chicken pox, measles or mumps
...
However it appears that you can keep on catching some diseases, such as the common
cold and the flu
...
This is referred to as antigenic variability,
and it is caused by mistakes in DNA or RNA replication (mutations) due to poor polymerase enzymes
...
With some diseases the pathogen is so active and the toxins so effective that the first infection causes a disease that is fatal (e
...
cholera, smallpox, diphtheria, AIDS)
...
The trick is to inject with an antigen that will promote the primary immune response, but has been modified so that it is nonvirulent (or non-pathogenic), i
...
will not cause the disease
...
This technique is called vaccination and is commonly used to provide artificial
immunity to a number of potentially-fatal diseases
...
Passive Immunity
Injecting antigens to promote an immune response is called active immunity, but it is also possible
to inject antibodies against certain pathogens into the blood
...
The antibodies in it assist the body's normal immune response and help it deal with serious diseases
...
Passive immunisation is not very
common, but can be used for rabies, tetanus, measles and hepatitis B, and is being tried to combat
AIDS
...
Antibodies
can pass across the placenta to the foetus and are also found in colostrum, the milk produced in
the first few days after birth
...
This passive immunity helps the new-born baby
survive in a world full of pathogens, and is one reason why breast feeding is so important
...
Active Immunity
(antigens received)
Passive Immunity
(antibodies received)
Natural
Achieved through the passing of antibodAchieved through the primary immune
ies from mother to child through the
response following an infection
placenta and milk
...
(antiserum)
...
[In vivo means “in life”, i
...
in a
living organism; and in vitro means “in glass”, i
...
in a test tube
...
So in 1975 Kohler and Milstein found a way to make pure monoclonal antibody proteins in the lab
...
Inject a mouse with the antigen proteins that you want antibodies for
...
The mouse will show a primary immune response and make a clone army of B lymphocytes with antibodies specific for that antigen
...
After a few days, kill the mouse and extract B lymphocyte cells from its spleen
...
HGS A-level notes
NCM/9/08
Module 1 - Core Principles - page 78
3
...
4
...
The fused, or hybrid, cells are called hybridoma cells
...
5
...
The cells multiply in their wells and secrete antibodies – a different antibody in each well
...
Each well is then screened for production of the antibody required
...
The B cells from that well are then grown in a culture flask, where they multiply by mitosis,
making millions of identical cloned cells, each secreting identical antibodies – monoclonal antibodies
...
g
...
g
...
The antibody/toxin complex can then be injected into a
cancer patient and the antibody will ensure that the agent is carried only to cancer cells and
nowhere else
...
• Antibodies can be used directly in passive immunity to help the body's normal immune response to a serious infection
Title: Biology unit 1 notes
Description: this contains: Molecules, Cells, Physiology and Disease
Description: this contains: Molecules, Cells, Physiology and Disease