Unit 5 Biology Scientific Article Pre-release material: JUNE 2023

Microbiota-gut-brain axis and the central nervous system

Teacher pack: Potential Questions and answers

Unit 5 is synoptic, so it is important that all aspects of the specification are understood.
In addition, there are several topics in the article that require revision of different aspects of the
specification. These are detailed below:

Areas of the specification covered in the article:

Unit 1:
 Polysaccharide structure: starch
 Hydrolysis of polysaccharides
 Transcription
 Translation

Unit 2:
 Eukaryotic and prokaryotic cells
 Bacterial culture technique
 Classification: Species, genus
 DNA methods used to classify organisms: DNA sequencing and DNA profiling
 Gene expression
 epigenetics
 Polysaccharide structure: cellulose
 Stem cells

Unit 4:

 Immunity: non-specific responses of the body to infection, including

Inflammation
 Roles of antigens and antibodies in the body’s immune response
 T cells in the host’s immune response
 Antibiotics
 DNA sequencing and DNA profiling techniques, including PCR

Unit 5:
 Homeostasis
 The nervous system
 Brain structure.
 The blood brain barrier
 Parkinson’s disease, depression
 Serotonin and serotonin reuptake inhibitors
 Control of heart rate
 FMRI
 Gene expression.
 Explanations of difficult sections and key words

Paragraph 1:
Mutually beneficial symbiotic state: any kind of relationship or interaction between two
dissimilar organisms, each of which may receive benefits from their partners that they did not
have while living alone.

Paragraph2:
Homeostasis: is the ability or tendency of the body or a cell to seek and maintain a condition of
equilibrium – a stable internal environment
Metabolic: chemical reactions that modify a molecule into another to maintain the living state of
a cell or an organism. It includes all the chemical reactions involved in modifying a molecule into
another.
Decomposing: the breakdown of organic substances by the action of microorganisms
Gut associated lymphoid tissue:. Found scattered throughout the small and large intestines.
Contains B and T lymphocytes.
Colonization: spreading of a species to a new area
Pathogen: Organisms that cause disease.
Metabolism: the sum of the chemical reactions in each cell of a living organism and that provide
energy for vital processes and for synthesizing new organic material.
Pathogenesis: the origination and development of a disease.
Species: a group of closely related organisms that are potentially capable of interbreeding to
produce fertile offspring

Paragraph 3:
High-throughput sequencing technology: Sequencing of large numbers of DNA molecules at
one time
Stool: Also called faeces is the solid waste left after food has been digested.

Paragraph 4:
Gastrointestinal tract: The organs that food and liquids travel through when they are
digested, absorbed and leave the body as faeces.
Flora: the microorganisms that exist on or within the body.
Microbiota gut-brain axis: network of connections involving multiple biological systems that
allows bidirectional communication between gut bacteria and the brain
Microecology: ecology of a microhabitat e.g. human gut microecology includes the microbes
in the gut (microbiota), their metabolic activity and the interactions between the microbiota,
the host and the environment.
Ecology: the study of the relationships of organisms to one another and to their physical
environment.
Neurological: associated with the brain, spine and nerves.

Paragraph 5:
Enteric nervous system: One of the main divisions of the autonomic nervous system. Consists
of a web of sensory neurones, motor neurones and relay neurones embedded in the walls of
the gastrointestinal tract. It controls the function of the gastrointestinal tract.
Vagus nerve: main nerve of the parasympathetic nervous system. Regulates digestion, heart
rate, breathing rate etc

Paragraph 6:
Motility: contraction of the muscles that mix and push the contents in the gastrointestinal
tract
Peripheral immune signals: chemicals released by immune cells including macrophages,
including the interleukins.
Anti-inflammatory response:
Sepsis: Sepsis is the body’s overwhelming and life-threatening response to infection that can
lead to tissue damage, organ failure, and death. In other words, it’s your body’s overactive
and toxic response to an infection.
Vagotomy: a surgical operation in which one or more branches of the vagus nerve are cut.

Paragraph 8:
Neurophysiological: the study of nervous system function

Paragraph 9:
Microbiota: the community of micro-organisms
Neurogenesis: the process by which new neurons are formed in the brain
Lateral ventricle: paired C-shaped structures comprising a body and atrium along with 3
projections into the frontal, temporal, and occipital lobes, termed “horns.”
Hippocampus: a complex brain structure embedded deep into temporal lobe. It has a major
role in learning and memory.
Epilepsy: a common condition that affects the brain and causes frequent seizures.
Alzheimer’s disease: The most common type of dementia. It involves parts of the brain that
control thought, memory, and language.

Paragraph 10:
Cognition: the mental action or process of acquiring knowledge and understanding through
thought, experience, and the senses.

Paragraph 11:
Probiotics: Live microorganisms that are intended to have health benefits when consumed or
applied to the body. They can be found in yogurt and other fermented foods,
Fecal: the solid waste left after food has been digested.
Cognitive: relating to or involving the processes of thinking and reasoning
Supplementation: the act of adding something to improve or complete it.
Dysfunction: abnormality or impairment in the operation of a specified bodily organ or
system.
Chronic restraint stress: Chronic restraint stress is commonly used in both male and female
rodents. In this model, rodents are placed in a cylinder that prevents mobility for several
hours every day for at least two weeks (typically 14 to 30 days).This is a useful model for
exploring the molecular and physiological adaptations that occur when animals are exposed
to a regimen of chronic daily stress.
Fermented milk: Fermented milk is the collective name for products such as yoghurt, ymer,
kefir, cultured buttermilk, filmjölk (Scandinavian sour milk), cultured cream and koumiss (a
product based on mares' milk).
Equilibrium: balanced

Paragraph 12:
Schizophrenia: a serious mental illness that affects how a person thinks, feels, and behaves.
Neuropsychological: Neuropsychology is a branch of psychology concerned with how a
person's cognition and behavior are related to the brain and the rest of the nervous system.
Genome: A genome is the complete set of genetic information in an organism.
Mucosal: The moist, inner lining of some organs and body cavities (such as the nose, mouth,
lungs, and stomach). Glands in the mucosa make mucus (a thick, slippery fluid). Also called
mucous membrane.
Cytokines: Cytokines are tiny proteins that are secreted by both immune and non-immune
cells to communicate with one another.
Pro-inflammatory interleukin- 8: Interleukin-8 (IL-8) is a chemoattractant cytokine produced
by a variety of tissues and blood cells. Interleukin-8 attracts and activates neutrophils in
inflammatory regions.
IL-1: Interleukin-1 is made mainly by the macrophage, and helps lymphocytes fight
infections. Anti-inflammatory cytokines: are cytokines that play great roles in
counterbalancing the pro- inflammatory response in various infectious diseases. Major anti-
inflammatory interleukins include interleukin (IL)-1 receptor antagonist, IL-4, IL-6, IL-10, IL-13,
IL-1, IL-35 and transforming growth factor 
Serum: the fluid and solute component of blood which does not play a role in clotting.It may
be defined as blood plasma without the clotting factors, or as blood with all cells and clotting
factors removed.

Paragraph 13:
Neurotoxic: substances that alter the normal activity of the nervous system. These can
eventually disrupt or even kill neurones.
Genus: a principal taxonomic category that ranks above species and below family, and is
denoted by a capitalized Latin name, e.g. Leo.
Antigen: Any substance that induces the immune system to produce antibodies.
Host: a living organism that acts as a harbour for invading pathogenic organisms.
Molecular Induction: When genes are turned on during gene expression, it is called gene
induction, which is carried out by inducer or activator proteins.
Autoimmune disease: A condition in which the body's immune system mistakes its own
healthy tissues as foreign and attacks them.
Amygdala: a pair of small almond-shaped regions deep in the brain, which help regulate
emotion and encode memories
Frontal cortex: The frontal lobe is part of the brain's cerebral cortex. It consists of two paired
lobes: the left and right frontal cortex.
Antibodies: also known as immunoglobulins, are large, Y-shaped proteins used by the
immune system to identify and neutralize foreign objects such as pathogenic bacteria and
viruses. The antibody recognizes a unique molecule of the pathogen, called an antigen.
Paragraph 14:
Multiple sclerosis: is a presumed autoimmune inflammatory condition of the central nervous
system (CNS) resulting in areas of demyelination.
Chronic: is a health condition or disease that is persistent or otherwise long-lasting in its
effects or a disease that comes with time.
Demyelinating: the myelin sheath of neurons is damaged. This damage impairs the
conduction of signals in the affected nerves.
Etiology: the cause, set of causes, or manner of causation of a disease or condition.
Susceptibility: likely or liable to be influenced or harmed by a particular thing

Paragraph 15:
Intracranial: occurring within the cranium
Dopaminergic: releasing or involving dopamine as a neurotransmitter.
Permeability: The ease with which a molecule can pass through the cell membrane.
Endotoxin: a lipopolysaccharide contained within the cell wall of Gram-negative bacteria.
This molecule initiates a host inflammatory response to Gram-negative bacterial infection.
LPS: Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a
polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core,
and an inner core all joined by a covalent bond. LPS is the most abundant antigen on the cell
surface of most Gram-negative bacteria, contributing up to 80% of the outer membrane of E.
coli and Salmonella.
Substantia nigra: The substantia nigra (SN) is a basal ganglia structure located in the
midbrain that plays an important role in reward and movement. The substantia nigra is a
critical brain region for the production of dopamine.
Paragraph 16:
Degenerative: A disease in which the function or structure of the affected tissues or organs
changes for the worse over time
Recessive:
Chronically progressive: a disease or health condition that gets worse over time, resulting in
a general decline in health or function.
Pathological marker: a specific physical trait or measurable biologically produced change in
the body connected with health or disease conditions.
Extracellular: outside the cell.
Intracellular: Inside the cell.
Neurofibrillary tangles: abnormal accumulations of a protein called tau that collect inside
neurones.
Microglial: the most prominent immune cells of the central nervous system (CNS) and are the
first to respond when something goes wrong in the brain. The microglial population accounts
for approximately 10% of the cells in the whole brain

Paragraph 17:
BBB: blood brain barrier: a layer of specialized endothelial cells around the brain that
protects it—letting in only what is needed and keeping out what could be harmful. It crucially
maintains the right ionic balance within the brain and blocks substances that would disrupt
essential neural functions.
Integrity: The quality or state of the complete membrane in perfect condition
Induce: to bring about, produce, or cause
Intraperitoneal: Within the peritoneal cavity (the area that contains the abdominal organs).
Cognitive defects: Problems with a person's ability to think, learn, remember, use judgement,
and make decisions.
 Memory impairment: An impairment of memory as manifested by a reduced ability to
remember things such as dates and names, and increased forgetfulness.
Aggregation: The formation of large clusters of biomolecules.
Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins
that form blood clots are in plasma.
Pathophysiological: The disordered physiological processes associated with disease or
injury. A protein or  amyloid protein: Amyloid beta denotes peptides of 36–43 amino
acids that are the main component of the amyloid plaques found in the brains of people with
Alzheimer's disease.

Paragraph 18:
Serotonin: a chemical that carries messages between nerve cells in the brain and throughout
your body. Serotonin plays a key role in such body functions as mood, sleep, digestion,
nausea, wound healing, bone health and blood clotting.
Serotonin reuptake inhibitors: Selective serotonin reuptake inhibitors (SSRIs) are a widely
used type of antidepressant. When this transporter is blocked, serotonin accumulates in the
synaptic space, effectively keeping the serotonin signal “on,” which can help alleviate
symptoms of depression.
Amyloid plaques: abnormal levels of this naturally occurring protein clump together to form
plaques that collect between neurons and disrupt cell function.
BDNF: stands for Brain-Derived Neurotrophic Factor. BDNF is a protein found in the brain
and in the spinal cord. BDNF helps with the survival of neurons (nerve cells) and the
development of new ones. BDNF also helps neurons to make synapses.

Paragraph 19:
Ecological: relating to or concerned with the relation of living organisms to one another and
to their physical surroundings.

Potential questions and answers

1. Calculate the approximate number of cells present in the human body. Give your answer in
standard form (Paragraph 1) (2 marks)
100 million bacteria in the human gastrointestinal tract, which is 10-100 times the number of
cells in the human body.
100,000,000/10 = 10,000,000 = 1x 107
100,000,000/100 = 1000000 = 1 x 106
There are between 106-107 cells in the human body.

2. Explain what is meant by a ‘eukaryotic cell’ (Paragraph 1) (2 marks)

Eukaryotic cells have a nucleus and other organelles enclosed by a plasma membrane. They
contain a nucleolus, mitochondria, endoplasmic reticulum and the Golgi apparatus.

3. Suggest what is meant by ‘a mutually beneficial symbiotic state’ (Paragraph 1) (1mark)

A close and prolonged relationship between organisms of different species, where both
species benefit from the relationship.
4. Suggest what is meant by ‘decomposing the complex polysaccharides in food’. (Paragraph 2)
(2 marks)
Bacteria in the gut are able to breakdown the complex polysaccharides in food that cannot
be digested by humans. These complex carbohydrates include cellulose, hemicellulose and
pectin, which are all components of plant cell walls. Cellulose is broken down by cellulases
into pyruvate and eventually into short chain fatty acids, mainly acetate and butyrate.

5. Suggest how gut microorganisms may ‘affect energy metabolism and mitochondrial function
of the host’ (Paragraph 2) (2 marks)

 High fibre diets lead to 400–600 mmol of short chain fatty acids (SCFA) in the gut per
day, which accounts for approximately 10% of human caloric requirements.
 The production of SCFA is due to microbes in the gut breaking down the cellulose in the
fibre.
 The most commonly produced SCFA is butyrate.
 Butyrate is taken into the epithelial cells lining the colon and transported to the
mitochondria, where it is oxidized into acetyl Coenzyme A.
 Acetyl Coenzyme A then enters the Krebs cycle, resulting in the generation of NADH.
 NADH then passes to the electron transport chain to generate ATP during oxidative
phosphorylation.
6. Define species (Paragraph 2) (2 marks)
A group of closely related organisms that are potentially capable of interbreeding to produce
fertile offspring.

7. Describe how a stool sample could be analysed using a bacteria culture technique (Paragraph
3) (4 marks)
 Prepare a suitable nutrient broth or nutrient agar; this must be autoclaved to sterilise it
so that unwanted bacteria do not grow on the medium.
 Aseptic technique must be followed at all times to keep everything sterile and
uncontaminated from other microorganisms.
 Take care to work near the Bunsen burner flame.
 Sterilise an inoculating loop by placing it into a Bunsen burner flame until it glows red
then leave to cool.
 Place the sterilised loop into the stool sample and then streak it across the surface of the
agar.
 Tape the agar plate closed, before labelling and inverting it before incubating at a
suitable temperature (in school this should be below 20 C, to prevent pathogenic
bacteria growing).
 After growth the plates must be sealed in a plastic bag and autoclaved before disposal.

8. Suggest what is meant by ‘traditional molecular biology technique’ (Paragraph 3) (3 marks)

The different gut microorganisms could be identified by analysing their DNA, by carrying out
DNA sequencing and DNA profiling.
 Purify the DNA from the microorganism.
 Amplify the DNA using the polymerase chain reaction (PCR)
 Cut the DNA into fragments using restriction endonucleases.
 Separate the fragments using gel electrophoresis.
 This gives a DNA profile which resembles a supermarket barcode.

9. Suggest what is meant by high-throughput sequencing technology (Paragraph 3) (2 marks)

 This is the sequencing of many DNA molecules in parallel.
 Analysed using bioinformatics.

10. What is meant by the enteric nervous system? (Paragraph 5) (2 marks)

 The enteric nervous system (ENS) is the largest component of the autonomic nervous
system.
 It is uniquely equipped with intrinsic microcircuits that enable it to orchestrate
gastrointestinal function independently of central nervous system (CNS) input.

11. Describe how the vagus nerve controls heart rate (Paragraph 6) (3 marks)
 The Vagus nerve is part of the parasympathetic nervous system.
 Action potentials from the cardiovascular control centre in the medulla pass along the
Vagus nerve into the Sino atrial node located in the right atrium.
 Decrease the wave of excitation across the SAN.
 Decrease heart rate.
12. Suggest what is meant by ‘trigger an anti-inflammatory response against the sepsis induced
by microorganisms’ (Paragraph 6) (3 marks)
 Microorganisms can release chemicals that can activate macrophages.
 The macrophages then release cytokines, which activate the afferent arm of the Vagus
nerve (containing the sensory neurones).
 Afferent Vagus nerve enters the medulla oblongata, then nerve impulses travel out
along the efferent Vagus nerve to the gut.
 The release of acetylcholine from the synapse reduces the release of cytokines (TNF, IL-
1β and IL-18) from the macrophages.
 This is called an anti-inflammatory response.

13. Suggest what is meant by ‘’immune activation may be the pathway for transmitting microbial
actions to the CNS’ (Paragraph 7) (3 marks)
 Microbes produce chemicals that activate macrophages.
 Macrophages then produce cytokines, including interleukin1.
 Interleukin1 and the other cytokines can activate the Vagus nerve.
 Signals are then sent along the Vagus nerve into the brain.

14. Suggest what is meant by ‘T cell accumulation and transformation’ (Paragraph 7) (4 marks)
 Macrophages in the gut undergo phagocytosis of gut bacteria.
 Antigens from the bacteria, along with major histocompatibility complex (forming an
antigen-MHC complex) are then placed onto the outer membrane of the macrophage.
The macrophage is now an antigen presenting cell (APC).
 Immature T-cells migrate from the Thymus to the gut.
 The T-cells become activated by binding with the specific antigen on the antigen-MHC
complex on the APC, causing the T cell to divide to form a clone of cells.
 Many of these T-cells become active T-helper cells, which will bind to B-cells, release
cytokines which will cause them to release antibodies.
  The remaining T-cells become inactive T memory cells.

15. Suggest what is meant by ‘producing chemical substances that bind to receptors inside and
outside of the gut’ (Paragraph 8) (3 marks)
 Microorganisms produce chemicals that may act as neurotransmitters.
 These may bind to specific receptors on the post synaptic membrane of the Vagus nerve
and send action potentials into the brain, which will bring about physiological changes.
 In addition, microorganisms may produce chemicals that bind to receptors on the
epithelial cells lining the intestines, which may cause changes to the permeability of the
gut.
 This may then cause chemicals produced by microorganisms to leak out into the blood
and activate the lymphocytes and the immune system.

16. Suggest how ‘microbiota may affect the CNS by altering adult hippocampal neurogenesis’
(Paragraph 9) (4 marks)
 The hippocampus in the brain contains multipotent stem cells.
 These stem cells can differentiate into mature hippocampus cells in response to various
factors; including a healthy gut microbiota.
 This process is called hippocampal neurogenesis.
There are several theories as to how gut microbes can cause hippocampal neurogenesis.
a) The vagus nerve can be directly stimulated by chemicals released by the gut microbes.
This then causes the release of BDNF (brain derived neurotrophic factor) in the
hippocampus, which stimulates the growth of neurons.
b) Monocytes and T cells can become activated by microbial cell wall components, such as
lippopolysaccharide, and microbially-produced metabolites, such as short-chain fatty
acids and indoles, that have left the gut through the damaged intestinal epithelium. T
cells and monocytes can then travel to the brain, and produce cytokines, which can
cause hippocampal neurogenesis.

11 © Dr. Julie Mendis

17. Suggest how the ‘introduction of single, unique flora could lead to anxiety-like behaviour’
(Paragraph 10) (3 marks)
 Disturbance of the normal gut microbiota will cause the stimulation of macrophages.
 The macrophages will produce a cytokine called interleukin 1.
 On the vagal afferent nerve terminals are receptors for interleukin 1.
 The interleukin 1 will bind to the IL-1 receptors on the afferent neurones of the vagus
nerve and may cause an action potential to be fired off into the hypothalamus, activating
the hypothalamus-pituitary-adrenal axis.
 This causes the release of CRF (corticotrophin releasing factor) from the hypothalamus
which travels to the pituitary and causes the release of ACTH (adrenocorticotropic
hormone).
 ACTH then travels in the blood to the adrenal glands where it causes the release of
adrenaline and cortisol (a glucocorticoid).
 Adrenaline and cortisol are the stress hormones and will increase anxiety.

18. Suggest how a valid experiment was carried out to prove that probiotics affected brain
memory and processing of sensation (Paragraph 11) (4 marks)
 2 groups of females of the same age, same IQ and with no history of learning difficulties.
 10 females per group to increase reliability.
 fMRI carried out prior to being given the probiotics.
 Same tasks given to all the females e.g. matching cards; analyse the areas of the brain
which lit up whilst carrying out the task.
 1 group of females fed fermented milk containing probiotics (same volume and
manufacturer), the other group fed same volume of milk without probiotics.
 Wait for the same period of time after drinking the milk e.g. 1 hour, 2hours, 3 hours etc
 Carry out fMRI again carrying out the same tasks as undertaken previously.
 Compare the fMRI patterns between the females before and after drinking the
fermented milk.

12 © Dr. Julie Mendis

19. Explain why fMRI was used to test for changes in brain activity (Paragraph 11) (3 marks)
 fMRI or functional magnetic resonance imaging is used to scan for the brain in action.
 Areas of the brain which are more active light up on the image.
 fMRI scans show the location of oxygenated blood in the brain, therefore indicating
which brain regions are active at any one time.
 The scanner measures the ratio of oxygenated to deoxygenated haemoglobin
 Patients can be asked to carry out particular actions, answer questions, or think about
a specific topic while inside a scanner and the change in blood flow to regions of the
brain can be assessed.
 The region of the brain associated with the activity or thought will 'light up' in the
scanner

20. Suggest how ‘whole genome analysis’ could have been undertaken to ‘suggest that
immunity- related genes may be changed’ (Paragraph 12) (5 marks)
 Microarrays could be used to analyse the DNA from healthy brain cells and brain cells
from a schizophrenic patient.
 Use a microarray slide with cDNA probes for immunity-related genes e.g. Interleukin 1,
interleukin 8 etc
 Brain cells would be obtained from both healthy and schizophrenic patients postmortem.
 mRNA would be obtained from the cells.
 The mRNA would then be converted to cDNA using reverse transcriptase, using either a
green fluorescent label in healthy cells or a red label in diseased cells.
 The cDNA from both healthy and diseased patients would be hybridized with the
microarray slide.
 The slide would then be washed and scanned, before analysing.
 Red spot = upregulated gene
Green spot = down regulated gene
Yellow spot = equally expressed gene in both healthy and diseased samples.
Grey spot = not present in either sample

13 © Dr. Julie Mendis

21. Suggest how microorganisms and intestinal mucosal cells regulate pro-inflammatory and
anti- inflammatory cytokines (Paragraph 12) (3 marks)
 Microorganisms release chemicals that bind to receptors on the membrane of the
intestinal mucosal cell.
 This binding activates a transcription factor in the cytoplasm of the cell, which moves
into the nucleus and binds to RNA polymerase to form a transcription initiation complex.
 The transcription initiation complex then binds to a promoter next to the gene coding for
a cytokine.
 This switches on the gene and mRNA is made by transcription.
 The mRNA leaves the nucleus and travels to the ribosomes.
 The mRNA binds to the ribosome and translation occurs making a polypeptide chain of
the cytokine.
 The cytokine then leaves the cell, where it stimulates the immune cells.

22. Explain what is meant by ‘inflammatory markers are positively correlated with the clinical
symptoms of schizophrenia patients’ (Paragraph 12) (2 marks)
 A correlation is a relationship between two variables in which a change in one variable is
reflected by a change in the other variable.
 A positive correlation is when one variable increases the other variable also increases.
 In this case an increase in the symptoms of Schizophrenia increases the levels of the
inflammatory markers.

14 © Dr. Julie Mendis

23. Explain how ‘concentration of antibodies against Saccharomyces cerevisiae’ can be used as a
marker of gut inflammation (Paragraph 13) (3 marks)
 Saccharomyces cerevisiae is a fungus found in the gut.
 When the normal gut microbiota is disrupted then pathogenic microbes may produce
chemicals that affect the junctions between the intestinal epithelial cells, making the gut
wall ‘leaky’.
 This results in the presence of Saccharomyces in the blood.
 Macrophages in the gut undergo phagocytosis of the Saccharomyces.
 Antigens from the fungus, along with major histocompatibility complex (forming an
antigen-MHC complex) are then placed onto the outer membrane of the macrophage.
The macrophage is now an antigen presenting cell (APC).
 T-cells become activated by binding with the specific antigen on the antigen-MHC
complex on the APC, causing the T cell to divide to form a clone of cells.
 Many of these T-cells become active T-helper cells, which will bind to B-cells.
 The B-cells will have previously engulfed the Saccharomyces by endocytosis and will also
have attached the antigen-MHC complex on their surfaces, becoming APCs also.
 The T helper cells bind to the B-cells and release cytokines which will cause the B-cells to
divide and differentiate to become plasma cells releasing antibodies against the
Saccharomyces antigen.

24. Define genus (Paragraph13) (1 mark)

A group of species that all share common characteristics.
A principal taxonomic category that ranks above species and below family, and is denoted by
a capitalized Latin name, e.g. Saccharomyces.

25. Suggest what is meant by ‘can cause the host to respond to its own tissues and cells’
(Paragraph 13) (2 marks)
 Every organism has unique molecules on the surface of its cells.
 The immune system has the capacity to distinguish between body cells ('self') and
foreign materials ('non-self')
 It will react to the presence of foreign materials with an immune response that
eliminates the intruding material from the body.
 Sometimes the antigens on the body cells may have a similar sequence to those from a
pathogen and so the immune system will respond against these body cells as non-self.
 This is the basis of autoimmune diseases.

26. What is meant by an autoimmune antibody? (Paragraph 13) (2 marks)

 Autoantibodies or autoimmune antibodies are antibodies (immune proteins) that

mistakenly target and react with a person’s own tissues or organs. One or more
autoantibodies may be produced when a person has an autoimmune disorder and their
immune system fails to distinguish between “self” and “non-self.”
 Usually the immune system is able to distinguish between foreign substances (“non-
self”) and the body’s own cells (“self”). It produces antibodies only when it perceives that
it has been exposed to a threat (“non-self”), such as bacteria or viruses.

15 © Dr. Julie Mendis

  However, when the immune system ceases to recognize one or more of the body’s
normal constituents as “self,” it may produce autoantibodies that react with its own
cells, tissues, and/or organs.
 This may cause inflammation, damage, and/or dysfunction of organs or systems, leading
to signs and symptoms of autoimmune disorders.

27. Explain what is meant by ‘demyelinating disease’ (Paragraph 14) (1 mark)

 A demyelinating disease is any condition that causes damage to the myelin sheath that
surrounds the neurones.
 This results in a decrease in saltatory conduction, so decreasing the rate of action
potential propagation.
 Multiple sclerosis is an example of a demyelinating disease.

28. Explain what is meant by ‘dopaminergic neurons’ (Paragraph 15) (1 mark)

 Dopaminergic neurons are any neurones in the brain or other parts of the central
nervous system for which dopamine serves as the principal neurotransmitter.

29. Explain the link between the ‘death of dopaminergic neurons’ and the development of
Parkinson’s disease. (Paragraph 15) (3 marks).
 Parkinson’s Disease is a progressive disorder that develops due to the degeneration of
nerve cells in the brain that control movement. Normally, dopamine and other
neurotransmitters work together to help coordinate movement. But without sufficient
dopamine, this is not possible.
 The condition occurs due to damage or death of neurons, in an area of the brain called
the Substantia Nigra. This part of the brain plays a critical role in controlling movement.
 Neurons in the substantia nigra are dopaminergic. This means they are responsible for
producing dopamine. If they are unable to produce dopamine, a person will likely begin
to experience movement-related problems, such as tremors, rigidity, slowness of
movement, and poor balance, which are all symptoms of Parkinson’s disease.
 Dopamine is an important neurotransmitter that plays a critical role in a number of
bodily functions, such as movement and coordination. As such, at low levels can cause
problems with movement.
 Dopamine is the chemical messenger that transmits signals between the substantia
nigra and the corpus striatum. Researchers may refer to this as the nigrostriatal
pathway. Both the substantia nigra and corpus striatum form part of the Basal ganglia,
which is a group of structures in the brain that help facilitate movement.
 Low levels of dopamine may disrupt the nigrostriatal pathway and cause abnormal
nerve firing patterns, which can result in movement problems. Evidence suggests that
most people with PD lose 60-80% or more of dopamine-producing cells in the substantia
nigra by the time they present symptoms.

30. Explain what is meant by an endotoxin (Paragraph 15) (2 marks)

 Endotoxins are lipopolysaccharides that are an integral part of the cell wall of Gram-
negative bacteria.
 The lipid part of the lipopolysaccharide acts as the toxin and the polysaccharide
stimulates the immune response.

16 © Dr. Julie Mendis

31. Suggest the potential link between increased gut permeability, LPS, the immune system and
Parkinson’s disease (Paragraph 15) (4 marks)
 Parkinson’s disease sufferers may have an altered microbiota in their gut.
 This may lead to a reduction in the symbiotic microbes, which may be involved in mucus
production and prevention of gut permeability.
 The gut becomes more permeable and LPS an endotoxin leaves the gut and enters the
blood.
 The LPS then attaches to a receptor on a macrophage.
 This binding activates a transcription factor called NF-kB, which enters the nucleus.
 This binds to the promoter of several cytokine genes, switching them on
 Transcription occurs and mRNA for these cytokines is synthesised.
 The mRNA leaves the nucleus and travels to the ribosomes, where it binds, and
translation occurs.
 The cytokines are made and leave the macrophage.
 The cytokines then activate other cells in the immune system.
 This can result in degeneration of the cells in the Substantia nigra, resulting in decreased
dopamine production and the onset of Parkinson’s disease.

32. Suggest the significance of the ‘LPS synthesis gene was significantly higher in PD patients
than in normal controls’ (Paragraph 15) (2 marks)

 The rfa gene cluster, which contains many of the genes for LPS core synthesis, includes
at least 17 genes.
 This was significantly higher in the stool samples from PD patients.

17 © Dr. Julie Mendis

  This suggests that more LPS was being synthesized in the bacteria in the stool samples
from PD patients.
 More LPS would then cause the changes seen in question 30.

33. Suggest what is meant by ‘the number and maturation of microglial cells in sterile mice is
abnormal, resulting in damage to the immune system’ (Paragraph 16) (3 marks)
 Sterile mice have been raised in sterile conditions, with no exposure to microbes.
 They have no gut microbiota.
 The normal gut microbiota produce chemicals, including short chain fatty acids that can
activate the immune cells including the macrophages and lymphocytes to produce
cytokines which can mature microglial cells.
 If these microbes are not present, then maturation of the microglial cells will not occur
resulting in dysfunction of the nervous system.

34. Suggest what is meant by ‘the inflammation caused by the changes in gut microorganisms
will lead to changes in BBB, which in turn affects brain function’ (Paragraph 17) (3 marks)
 When the normal gut microbiota is altered, pathogenic microorganisms can produce
chemicals including LPS and amyloids.
 LPS and amyloids then enter the bloodstream and activate the macrophages and
lymphocytes to produce cytokines.
 LPS can damage the blood brain barrier.
 This causes the buildup of amyloid in the brain, which results in A  protein accumulating
in the hippocampus.
 The hippocampus has a role in learning and memory.
 Build-up of A protein forms plaques in the hippocampus which disrupts learning and
memory.

35. Explain how serotonin is ‘important for cognitive function’ (Paragraph 18) (2 marks)
 Gut bacteria synthesize serotonin.
 They synthesize approximately 95% of the body’s supply of serotonin.
 Serotonin is synthesized from tryptophan.
 Serotonin is a neurotransmitter, that binds to stereospecific receptors on the vagus
nerve.
 This binding will open Na+ gates, and Na+ ions will enter the vagus nerve by facilitated
diffusion.
 If enough Na+ ions enter then an excitatory post synaptic potential (EPSP) is generated
which if high enough will reach threshold level and fire off an action potential into the
hippocampus of the brain.

36. Suggest how the ‘use of serotonin reuptake inhibitors can reduce A protein levels in the
brain’ (Paragraph 18) (3 marks)
 Serotonin reuptake inhibitors prevent the reuptake of serotonin back into the pre-synaptic
neurone.
 This keeps serotonin in the synapse, increasing the levels of serotonin and prolonging its
effects.
 This reduces the formation of A in the brain, decreasing the risk of Alzheimer’s disease.

18 © Dr. Julie Mendis

  This suggests that serotonin may have a role in reducing the risk of Alzheimer’s Disease.

37. Suggest how the lack of a gut microbiota can lead to a decreased cognitive function (Paragraph
18) (3 marks)
 Sterile mice do not have gut microbiota.
 This means that there are no microbes to produce chemicals to activate the vagus nerve
directly from the gut.
 This means that brain derived neurotrophic factor (BDNF) is not produced.
 Brain-derived neurotrophic factor (BDNF) is one of the neurotrophic factors that support
differentiation, maturation, and survival of neurons in the nervous system.
 If the levels of BDNF are decreased, then there will be decreased cognitive function;
resulting in many neurodegenerative diseases such as Parkinson's disease and
Alzheimer’s Disease.

19 © Dr. Julie Mendis