Phagocytes: Origin & Mode of Action

• Phagocytes are white blood cells that are produced

continuously in the bone marrow
• They are stored in the bone marrow before being distributed
around the body in the blood
• They are responsible for removing dead cells and invasive
microorganisms
• They carry out what is known as a non-specific immune
response
• There are two main types of phagocyte, each with a specific
mode of action. The two types are:
• Neutrophils
• Macrophages
• As both are phagocytes, both carry out phagocytosis (the
process of recognising and engulfing a pathogen) but the
process is slightly different for each type of phagocyte
• Neutrophils travel throughout the body and often
leave the blood by squeezing through capillary walls
to ‘patrol’ the body tissues
• During an infection, they are released in large
numbers from their stores
• However, they are short-lived cells
• Mode of action:
• Chemicals released by pathogens, as well as
chemicals released by the body cells under
attack (i.e. histamine), attract neutrophils to the
site where the pathogens are located (this
response to chemical stimuli is known
as chemotaxis)
• Neutrophils move towards pathogens (which may
be covered in antibodies)
• Mode of action:
• The antibodies are another trigger to stimulate neutrophils
to attack the pathogens (neutrophils have receptor
proteins on their surfaces that recognise antibody
molecules and attach to them)
• Once attached to a pathogen, the cell surface
membrane of a neutrophil extends out and around the
pathogen, engulfing it and trapping the pathogen within
a phagocytic vacuole
• This part of the process is known as endocytosis
• The neutrophil then secretes digestive enzymes into the
vacuole (the enzymes are released
from lysosomes which fuse with the phagocytic vacuole)
• These digestive enzymes destroy the pathogen
• After killing and digesting the pathogens, the neutrophils
die
• Pus is a sign of dead neutrophils
Neutrophil compared to eosinophil and basophil
The stages of
phagocytosis, as
carried out by a
neutrophil
• Macrophages are larger than neutrophils and are long-lived
cells
• Rather than remaining in the blood, they move into organs
including the lungs, liver, spleen, kidney and lymph nodes
• After being produced in the bone marrow, macrophages travel
in the blood as monocytes, which then develop into
macrophages once they leave the blood to settle in the various
organs
• Mode of action:
• Macrophages play a very important role in initiating an
immune response
• Although they still carry out phagocytosis in a similar way to
neutrophils, they do not destroy pathogens completely
• They cut the pathogens up so that they can display
the antigens of the pathogens on their surfaces (through a
structure called the major histocompatibility complex)
• These displayed antigens (the cell is now called an antigen-
presenting cell) can then be recognised by
lymphocytes (another type of white blood cell) for
destruction
• The vacuole formed around a bacterium once it has been engulfed by a
phagocyte is called a phagosome. A lysosome fuses with the membrane of the
phagosome (to form a phagolysosome) and releases lysozymes (digestive
enzymes) to digest the pathogen
Answer: D
• Lymphocytes are another type of white blood cell,
other than phagocytes
• They play an important part in the specific immune
response
• They are smaller than phagocytes
• They have a large nucleus that fills most of the cell
• They are produced in the bone marrow before birth
• There are two types of lymphocytes (with different
modes of action). The two types of lymphocytes are:
• B-lymphocytes (B cells)
• T-lymphocytes (T cells)
 How B cells and T cells got their names

Sir Hieronymus Fabricius, Bursa of Fabricius in a bird

Italian surgeon, 1533 – 1619,
founder of Bursa of Fabricius
in birds, later on become
important basis for research
about B cells
(chicken), where B cells were Prof. Dr. Max Dale Cooper,
first discovered and described, American professor in Emory
including maturation. In humans, University, 1933 – present,
B cells mature in bone marrow founder of B cells and T cells
 How B cells and T cells got their names

T cells development in a mammal (human), at Prof. Dr. Max Dale Cooper,

the organ thymus American professor in Emory
University, 1933 – present,
founder of B cells and T cells
• B-lymphocytes (B cells) remain in the bone marrow until they are mature and then spread through
the body, concentrating in lymph nodes and the spleen
• Millions of types of B-lymphocyte cells are produced within us because as they mature, the
genes coding for antibodies are changed to code for different antibodies
• Once mature, each type of B-lymphocyte cell can only make one type of antibody molecule
• At this stage, the antibody molecules do not leave the B-lymphocyte cell but remain in the cell
surface membrane
• Part of each antibody molecule forms a glycoprotein receptor that can combine specifically
with one type of antigen
• If that antigen enters the body, B-lymphocyte cells with the correct cell surface receptors will be
able to recognise it and then divide by mitosis (clonal selection)
• During a primary immune response, B-lymphocytes divide repeatedly by mitosis (clonal expansion)
and differentiate into two main types of cell:
• Plasma cells
• Memory cells
• These two cell types each have a specific function
The maturation of B-
lymphocytes – by the time a
child is born, it will have
millions of different types of
B-lymphocytes, each with a
specific antibody receptor
• Immature T-lymphocytes leave the bone marrow to mature in the thymus
• Mature T-lymphocytes have specific cell surface receptors called T cell receptors
• These receptors have a similar structure to antibodies and are each specific to one
antigen
• T-lymphocytes are activated when they encounter (and bind to) their specific antigen
that is being presented by one of the host’s cells (host cells being the human’s own cells)
• This antigen-presenting host cell might be a macrophage or a body cell that has been
invaded by a pathogen and is displaying the antigen on its cell surface membrane
• These activated T-lymphocytes (those that have receptors specific to the
antigen) divide by mitosis to increase in number (similar to the clonal selection and
clonal expansion of B-lymphocytes) and differentiate into two main types of T cell:
• Helper T cells
• Killer T cells
• These two T cell types each have a specific function
The maturation of T-lymphocytes
Memory Cells & Long-Term Immunity
• During an immune response, B-lymphocytes form two types of cell: plasma
cells and memory cells
• Memory cells form the basis of immunological memory – the cells can last
for many years and often a lifetime
• There are two types of immune response:
• Primary immune response (responding to a newly encountered antigen)
• Secondary immune response (responding to a previously encountered
antigen)
Primary Immune Response
• When an antigen enters the body for the first time, the small numbers of B-lymphocytes with
receptors complementary to that antigen are stimulated to divide by mitosis
• This is known as clonal selection
• As these clones divide repeatedly by mitosis (the clonal expansion stage) the result is large
numbers of identical B-lymphocytes being produced over a few weeks
• Some of these B-lymphocytes become plasma cells that secrete lots of antibody molecules
(specific to the antigen) into the blood, lymph or linings of the lungs and the gut
• These plasma cells are short-lived (their numbers drop off after several weeks) but the
antibodies they have secreted stay in the blood for a longer time
• The other B-lymphocytes become memory cells that remain circulating in the blood for a
long time
• This response to a newly encountered pathogen is relatively slow
Secondary Immune Response
• If the same antigen is found in the body a second time, the memory cells
recognise the antigen, divide very quickly and differentiate into plasma cells
(to produce antibodies) and more memory cells
• This response is very quick, meaning that the infection can be destroyed and
removed before the pathogen population increases too much and
symptoms of the disease develop
• This response to a previously encountered pathogen is, relative to the primary
immune response, extremely fast
During a secondary immune response, memory cells that
remained in the blood divide very quickly into plasma cells (to
produce antibodies) and more memory cells
Secondary Immune Response
• T-lymphocytes also play a part in the secondary immune response
• They differentiate into memory cells, producing two main types:
• Memory helper T cells
• Memory killer T cells
• Just like the memory cells formed from B-lymphocytes, these memory T cells remain
in the body for a long time
• If the same antigen is found in the body a second time, these memory T cells
become active very quickly
An APC, such as a macrophage,
engulfs and digests a foreign
bacterium

An antigen from the bacterium

is presented on the cell surface
in conjunction with an MHC II
molecule

Lymphocytes interact with

antigen-embedded MHC II
molecules to mature into
functional immune cells

Antigen-presenting cell
• Immunological memory (made possible by memory cells) is the reason why
catching certain diseases twice is so unlikely. For example, there is only one
strain of the virus that causes measles, and each time someone is re-infected
with this virus, there is a very fast secondary immune response so they do not
develop symptoms and get ill
• However, some infections such as the common cold and influenza are
caused by viruses that are constantly developing into new strains. As each
strain has different antigens, the primary immune response (during which we
often become ill) must be carried out each time before immunity can be
achieved
Answer: C
Answer: B
Answer: A
Answer: C
Answer: B
Antibodies: Structure
• Antibodies are globular glycoproteins called immunoglobulins
• Antibodies usually have a quaternary structure (which is represented as Y-shaped),
with two ‘heavy’ (long) polypeptide chains bonded by disulfide bonds to two
‘light’ (short) polypeptide chains. Some antibodies have tertiary structure
• Each polypeptide chain has a constant region and variable region
• The constant regions do not vary within a class (isotype) of antibodies but do vary
between the classes. The constant region determines the mechanism used to
destroy the antigens
• There are 5 classes of mammalian antibodies each with different roles
• The amino acid sequence in the variable regions of the antibodies (the tips of the
“Y”) are different for each antibody. The variable region is where the antibody
attaches to the antigen to form an antigen-antibody complex
A model of the generalised
structure of an antibody
molecule

Bonds present:
- peptide bonds
- disulfide bonds
- hydrogen bonds
Antibodies: Structure
• At the end of the variable region is a site called the antigen-binding site. Each
antigen-binding site is generally composed of 110 to 130 amino acids and includes
both the ends of the light and heavy chains
• The antigen-binding sites vary greatly giving the antibody its specificity for binding
to antigens. The sites are specific to the epitope (the part of the antigen that binds to
the antibody)
• A pathogen (i.e. virus) may therefore present multiple antigens, thus, different
antibodies need to be produced
• The ‘hinge’ region (where the disulfide bonds join the heavy chains) gives flexibility
to the antibody molecule which allows the antigen-binding site to be placed at
different angles when binding to antigens
• This region is not present in all classes of antibodies
Antibodies: Function
• Antibodies are produced by B-lymphocytes
• Antibodies bind to specific antigens that trigger the specific immune response.
Every antigen has one antibody
• Antigens include pathogens and their toxins, pollen, blood cell surface molecules
and the surface proteins found on transplanted tissues
• Antibodies are divided into five major classes (isotypes), each with a different role
Antibodies: Function
• The function of antibodies differ:
• Antibodies can combine with viruses and toxins of pathogens (i.e.
bacteria) to block them from entering or damaging cells

• Antibodies can act as anti-toxins by binding to toxins produced by

pathogens (i.e. the bacteria that cause diphtheria and tetanus) which
neutralises them, making them harmless

• Antibodies can attach to bacteria, making them readily identifiable to

phagocytes, this is called opsonisation. Once identified, the phagocyte
has receptor proteins for the heavy polypeptide chains of the antibodies,
which enables phagocytosis to occur
The functions of antibodies vary according to which type of
antigen they act on
Antibodies: Function
• The function of antibodies differ:
• Antibodies can attach to the flagella of bacteria making them less active,
which makes it easier for phagocytes to do phagocytosis

• Antibodies act as agglutinins causing pathogens carrying antigen-

antibody complexes to clump together (agglutination). This reduces the
chance that the pathogens will spread through the body and makes it
possible for phagocytes to engulf a number of pathogens at one time

• Antibodies (together with other molecules) can create holes in the cell
walls of pathogens causing them to burst (lysis) when water is absorbed
by osmosis
• You must know that, each antibody will have a different variable
region with an antigen-binding site that matches one antigen or
toxin produced by a pathogen. The antigen-binding site (and
therefore the antibody) is specific to one antigen
The Hybridoma Method

• Monoclonal antibodies are artificially produced antibodies produced from a

single B cell clone

• The hybridoma method is a method used to make monoclonal

antibodies (Mabs)

• The method enables large quantities of identical antibodies to be produced

The Hybridoma Method

• The hybridoma method solved the problem of having B cells that could
divide by mitosis but do not produce antibodies and plasma cells that could
produce antibodies but not divide

• This method was established in the 1970s

• Monoclonal antibodies bind antigens, in the same way naturally produced

antibodies do
The hybridoma method is used to produce monoclonal
antibodies
The Hybridoma Method

• They are produced by injecting mice with an antigen that stimulates the
production of antibody-producing plasma cells

• Isolated plasma cells from the mice are fused with immortal tumour cells,
which result in hybridoma cells

• These hybrid cells are grown in a selective growth medium and screened for
the production of the desired antibody
The Hybridoma Method

• They are then cultured to produce large numbers of monoclonal antibodies

• Monoclonal antibodies have multiple applications, including medical

diagnostics of treating diseases, food safety testing, pregnancy testing and
many more
• Remember, monoclonal antibodies are produced from a
hybridoma cell – a cell formed by the fusion of plasma cells and
tumour (cancer) cells, which divide continuously therefore
producing large quantities of a wanted antibody
Answer: D
Answer: C
Answer: C
Diagnostic Uses

• Monoclonal antibodies can be used diagnostically for:

• Pregnancy tests

• Diagnosing HIV

• Detecting the presence of pathogens such

as Streptococcus bacteria

• Distinguishing between Herpes I and Herpes II

Diagnostic Uses

• Monoclonal antibodies can be used diagnostically for:

• Blood typing before transfusions and tissue typing

before transplants

• Detecting the presence of antibiotics in milk

• Detecting cancer cells

Diagnostic Uses

• Monoclonal antibodies can also be used to locate the position of blood clots for
patients thought to have deep vein thrombosis. This occurs by:

• Injecting a mouse with human fibrin (the main protein found in blood clots)

• This activates the plasma cells to produce antibodies against fibrin

• These cells are collected from the mouse spleen

• The plasma cells are then fused with tumour cells forming hybridomas that
produce antifibrin antibodies
Diagnostic Uses

• Monoclonal antibodies can also be used to locate the position of blood clots for
patients thought to have deep vein thrombosis. This occurs by:

• To detect where the antibodies are binding to fibrin molecules, a radioactive

chemical (producing gamma radiation) is attached to the antibodies making
them radioactively labelled

• A gamma-ray camera is used to detect where these radioactively labelled

antibodies have attached to a fibrin molecule, hence indicating where blood
clots can be found
•
• Generally, monoclonal antibodies are used only once
Another example of
the diagnostic use of
monoclonal
antibodies – test for
HIV
Therapeutic Uses

• Therapeutically, monoclonal antibodies have multiple applications, including:

• Treatment for the rabies virus, (which can be potentially fatal), by injecting
purified antibodies

• The prevention of transplanted organ rejection, achieved by intervening with

the T cells involved in the rejection process
Therapeutic Uses

• Therapeutically, monoclonal antibodies have multiple applications, including:

• Autoimmune therapies for allergic asthma and rheumatoid arthritis; here

monoclonal antibodies are able to bind and deactivate factors involved in
the inflammatory response

• Treatment for diseases caused by the overproduction or inappropriate

production of B-cells (i.e. leukaemia, multiple sclerosis and myasthenia
gravis); the antibody (rituximab) binds to cell surface receptor proteins on B-
cells (not plasma cells) and causes the death of the cells
Therapeutic Uses

• Prevention of blood clotting following angioplasty procedures; here

monoclonal antibodies bind to receptors on the platelet surface thereby
inhibiting fibrinogen from binding and subsequent clotting from ensuing

• Targeted treatment of breast cancer; Herceptin (trastuzumab) is a

monoclonal antibody used to treat breast cancer, it recognises receptor
proteins on the surface of cancer cells and binds to them allowing the
immune system to identify and destroy them
Therapeutic Uses

• Treatment of melanoma (a type of skin cancer); the antibody (ipilimumab)

binds to a protein produced by T-cells (whose role is to reduce the immune
response) which results in the immune system remain active against the
cancer cells
• Using monoclonal antibodies as a treatment requires multiple administrations
and this can cause problems

• Initially, the monoclonal antibodies were produced by mice, rabbits or other

laboratory animals (as these were easier to produce), however this triggered
an immune response when they were introduced to humans
• Scientists have largely overcome this by:
• Genetically modifying the antibody polypeptide chains so that the amino
acid sequences are now human, not mouse or rabbit sequences
• Altering the type and position of the sugar groups (antibodies are
glycoproteins) attached to the heavy polypeptide chains to reflect those
found on human antibodies
• Know specific examples of
how monoclonal antibodies
can be used as a diagnostic
tool and for treatment. You
can use a well-annotated
diagram to explain how
monoclonal antibodies can
be used as a diagnostic tool
Active Immunity

• Active immunity is acquired when an antigen enters the body, triggering a specific
immune response (antibodies are produced)

• Active immunity is naturally acquired through exposure to microbes or artificially

acquired through vaccinations

• The body produces memory cells, along with plasma cells, in both types of active
immunity giving the person long-term immunity
Active Immunity

• In active immunity, during the primary response to a pathogen (natural) or to a

vaccination (passive), the antibody concentration in the blood takes one to two
weeks to increase

• If the body is invaded by the same pathogen again or by the pathogen that the
person was vaccinated against then, during the secondary response, the antibody
concentration in the blood takes a much shorter period of time to increase and
is higher than after the vaccination or first infection
The primary and secondary response to
the same antigen
Passive Immunity

• Passive immunity is acquired without an immune response. Antibodies are not produced by the
infected person

• As the person’s immune system has not been activated, then there are no memory cells that can
produce antibodies in a secondary response. If a person is reinfected, they would need another
infusion of antibodies

• Depending on the disease a person is infected with (i.e. tetanus), they may not have time to
actively acquire the immunity, that is, there is no time for active immunity. So passive immunity
occurs either artificially or naturally
Passive Immunity

• Artificial passive immunity occurs when people are given an injection/transfusion of the
antibodies. In the case of tetanus, this is an antitoxin. The antibodies were collected from people
whose immune system had been triggered by a vaccination to produce tetanus antibodies

• Natural passive immunity occurs when:

• Foetuses receive antibodies across the placenta from their mothers

• Babies receive the initial breast milk from mothers (the colostrum) which delivers a certain
isotype of antibody (IgA)
Comparing Active & Passive Immunity
• Active immunity is when the
body produces the antibodies
whereas in passive immunity
the body is given the
antibodies
• A vaccine is a suspension of antigens that are intentionally put into the body
to induce artificial active immunity. A specific immune response
where antibodies are released by plasma cells will occur

• There are two main types of vaccines:

• Live attenuated
• Inactivated

• Vaccines are administered either by injection or orally (by mouth). When a

person is given a vaccine, they have been given a vaccination
• The vaccinations given by injection can be into a vein or muscle

• Vaccinations produce long-term immunity as they cause memory cells to be

created. The immune system remembers the antigen when reencountered
and produces antibodies to it, in what is a faster, stronger secondary
response
• Vaccines can be:

• Highly effective with one vaccination giving a

lifetime’s protection (although less effective ones
will require booster/subsequent injections)

• Generally harmless as they do not cause the

disease they protect against because the
pathogen is killed by the primary immune response
• Unfortunately, there can be problems with vaccines:

• People can have a poor response (i.e. they are

malnourished and cannot produce the antibodies
– proteins or their immune system may be
defective)

• A live pathogen may be transmitted (e.g. through

faeces) to others in the population (ideally enough
number of people are vaccinated at the same
time to give herd immunity)
• Unfortunately, there can be problems with vaccines:

• Antigenic variation – the variation (due to major changes) in the antigens

of pathogens causes the vaccines to not trigger an immune response or
diseases caused by eukaryotes (i.e. malaria) have too many antigens on
their cell surface membranes making it difficult to produce vaccines that
would prompt the immune system quickly enough

• Antigenic concealment – this occurs when the pathogen ‘hides’ from the
immune system by living inside cells or when the pathogen coats their
bodies in host proteins or by parasitising immune cells such as
macrophages and T cells (i.e. HIV) or by remaining in parts of the body
that are difficult for vaccines to reach (i.e. Vibrio cholerae – cholera,
remains in the small intestine)
• The principles underpinning vaccinations were discovered by Edward Jenner
in the 1700s when he developed the first smallpox vaccine
• Live attenuated vaccines contain whole
pathogens (i.e. bacteria and viruses) that
have been ‘weakened’

• These weakened pathogens multiply slowly

allowing for the body to recognise the
antigens and trigger the primary immune
response (plasma cells to produce
antibodies)

• These vaccines tend to produce a stronger

and longer-lasting immune response
• They can be unsuitable for people with weak
immune systems as the pathogen may divide
before sufficient antibodies can be produced

• An example of this type of vaccine is the

MMR (Measles, Mumps and Rubella)
• Inactivated vaccines contain whole pathogens that have been
killed (‘whole killed’) or small parts (‘subunit’) of the pathogens (i.e.
proteins or sugars or harmless forms of the toxins – toxoids)

• As inactivated vaccines do not contain living pathogens, they

cannot cause diseases, even for those with weak immune systems

• However, these vaccines do not trigger a strong or long-lasting

immune response like the live attenuated vaccines. Repeated doses
and/or booster doses are often required
• Some people may have allergic reactions or local reactions (i.e.
sore arm) to inactivated vaccines as adjuvants (i.e. aluminium salts)
may be conjugated (joined) to the subunit of the pathogen to
strengthen and lengthen the immune response

• An example of a whole killed vaccine is polio vaccine

• An example of a toxoid subunit vaccine (where inactivated versions

of the toxins produced by pathogens are used) is diphtheria
• Remember, vaccines trigger the
primary immune response (T helper
cells trigger B plasma cells to secrete
specific antibodies) which leads to the
production of memory cells which will
give a faster and greater (higher
concentration of antibodies) during the
secondary response
Answer: A
Answer: D
Answer: D
Answer: C
Answer: D
Answer: B
• Eradicating disease presents a challenge

• On one hand some pathogens are simply complicated and

present with disease processes that are not straightforward and
so a successful vaccine has not been developed

• On the other hand, diseases that could be eradicated where a

vaccine does exist, have not been eliminated because too few
in the community have been vaccinated
• It has also been difficult to eradicate other infectious diseases due
to:

• Unstable political situations in areas such as Africa, Latin America

and parts of Asia, perhaps resulting in civil unrest or wars

• Lack of public health facilities (poor infrastructure, few trained

personnel, limited financial resources)
• The eradication of Smallpox is a success story, but its success had specific reasons that
cannot be universally replicated in the struggle to eliminate disease

• Smallpox is a highly contagious disease caused by a virus that exists in two forms: Variola
minor and Variola major, the latter being the worst of the two, with a death rate of 12 to 30%

• Smallpox was transmitted by direct contact and caused red spots (which filled with pus) to
cover the body. People who recovered were disfigured as a result of scabs that formed from
these spots. It also affected the eyes resulting in permanent blindness for many who
recovered
• The WHO began an eradication programme against Smallpox in 1967, stating their intention
to eradicate the virus within ten years. The WHO did not declare smallpox eradicated until
1980

• The programme focused on:

• Vaccination – the aim was to vaccinate more than 80% of populations at risk and if a
case of smallpox was reported ring vaccination would occur (where everyone in the
household with the reported case, the surrounding 30 households, relatives and anyone
else who had contact would get vaccinated)

• Surveillance
• Its success was attributed to:

• The virus being stable – it did not mutate therefore its surface antigens did not
change, therefore the same vaccine could be used worldwide which made it
cheap to produce the vaccine

• The vaccine was a ‘live attenuated’ one, being produced from a harmless strain
of a similar virus

• The vaccine could be transported without becoming unviable, as it could be

freeze-dried and kept at high temperatures for up to 6 months, thus it was suitable
for the tropics
• Its success was attributed to:

• The symptoms made it easy to identify infected people (surveillance was

possible)

• Humans being the only reservoirs of infection and there were no carriers making
it easier to break the transmission pathway

• The consistency of the effort, vaccination, surveillance and containment of all

outbreaks on a global scale
• Malaria has proven to be very difficult to eradicate – this is because
the Plasmodium parasite that causes it, has a complex life cycle and produces a
multitude of genetic variants

• Vaccine attempts so far have had limited effectiveness as exposure to the parasite
does not trigger a strong immune response (or it is even thought the parasite has the
ability to interfere with the immune system) and long-term protection has not been
possible
• The vaccine being trialled currently also requires multiple doses (up to four), is
applicable only to the Plasmodium parasite found in Africa and appears to be most
effective on children that have reached their fifth month

• Also, as with all vaccine programs, the financial costs are high and this can impede
progress
• Measles does actually fit the profile of a disease that, in theory, should have already been eradicated:

• There is only one strain

• Humans are the only reservoirs

• Effective diagnostics exist (it can be detected easily)

• A successful vaccine exists, it has been implemented into the standard vaccine schedules given to
children internationally and yet an estimated 160,000 children die of measles annually
• Unfortunately, although it is a preventable disease, it is still endemic in parts of the world and this is
attributed to:

• Poor vaccination uptake – it is thought that 93 – 95% of the population need to be vaccinated for
herd immunity to be achieved (that is, to prevent transmission in a population)

• Some children having a poor response to the vaccine and requiring several boosters

• Large cities with high birth rates and a shifting population making it hard to isolate and trace
contacts of cases of measles

• Measles being highly communicable (infectious) with an R rate (reproduction rate of measles virus)
of 12-18 (so for every individual infected between 12 and 18, further individuals will become
infected)

• Travellers reintroducing the measles virus to areas where it was previously deemed eliminated
• Cholera is caused by infection with a bacterium called Vibrio
cholerae caused by eating or drinking contaminated water (in areas where
there is poor hygiene and inadequate sanitation)
• Vaccination programmes have not eradicated cholera because:

• The vaccine only affords protection that is 50-60% effective, which decreases to
less than 50% two years later

• There are many different strains of cholerae making it difficult to produce an

effective vaccine

• If a cholera outbreak has started, the 2-dose regimen (which are given a week
apart and require a buffer solution) and the time required to reach protective
efficacy is too great (about three weeks)

• The vaccine’s high cost

• The BCG vaccine (BCG stands for 'Bacillus
Calmette-Guérin', and is named after the
two French scientists who developed the
first tuberculosis vaccine – Albert Calmette
and Camille Guérin)

• BCG is not very effective (the immune

response they trigger occurs too slowly)
and it is very variable amongst
populations; in those with latent (dormant)
TB infections the vaccine does not prevent
TB from developing
• Latent TB is challenging to treat and can
become active TB at any time

• The BCG vaccine effectiveness decreases

unless the person is exposed to TB
• Remember, for a disease to be eradicated by a vaccine, the pathogen
should not:
• Mutate
• Have a life cycle that includes other organisms
• Have symptoms that make it hard to diagnose or trace
Answer: B
Answer: B
Answer: B
Answer: C
Answer: A
Answer: B