Unit 6: Microbiology, Immunity and Forensics

6B - Immunity

• The state of being resistance to

i) injury
ii) invading pathogens
iii) foreign substances
• through defensive mechanisms in the body.

• The agents that can cause infectious diseases.

• include some parasites, protozoa, fungi, bacteria and virus.

• For a pathogen to cause disease it must enter the body of the host by the following ways,

• Pathogens that spread this way will require some part of the host, e.g. skin, body fluids, to
come into direct contact with a healthy individual.
• Pathogens that spread by this route can then pass through the mucous membranes and enter
the bloodstream, e.g.
▪ When shaking hands with another person who then puts their hand to their nose or
mouth. (e.g. ebola)
▪ During sexual transmission (e.g. HIV, syphilis)

• Inanimate objects can contain large numbers of pathogens that may be transferred between
hosts.
• An infected individual may touch or cough on an object which is later touched by a healthy
individual who transfers the pathogens to their mouth or nose by touching their face.
• Examples include bedding, towels, and surfaces.

• Droplets from the respiratory tract will be suspended in the air when an infected person
coughs, sneezes or talks.
• These droplets contain pathogens that can be inhaled by healthy people.

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 • The airways provide an entry point into the respiratory system of a new host and another
infection occurs, e.g. flu, measles, tuberculosis.

• Pathogens can enter through the digestive system when we ingest contaminated food or
drink.
• This is especially probable if food is undercooked, as heat destroys most of the pathogens.
• These pathogens can make their way through the lining of the gut and cause disease (e.g.
cholera, Salmonella poisoning)

• This typically occurs when a pathogen enters the body through broken skin, providing it with
a direct route into the bloodstream.
• Transmission could be through sexual contact, sharing needles during drug use, or bites or
scratches from infected animals.
• Examples include hepatitis B, HIV, tetanus, and rabies

• These are living organisms that carry pathogens and transmit them between hosts
• Insects, such as flies and mosquitoes, are common vectors for diseases like malaria and yellow
fever.

• 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.
• The cells of different organisms have differing genetically determined protein molecules on their
surface membrane that seem to be essential to cell recognition. Such proteins include
• All nucleated cells of the body possess unique and distinctive surface molecules that identify it as
self.
• These self-markers are called molecules (MHC class I) and
function as identification tags.
• The immune system will not normally react to cells bearing these genetically determined markers
(self-tolerance).
• However, non-self-glycoproteins act as antigens and are recognised by white blood cells (leucocytes)
during the specific immune responses.

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• Any substance that is recognized as foreign and can trigger an immune response is called an antigen
(non self).
• Antigens are often chemicals on the surface of a cell such as the proteins, glycoproteins or
carbohydrates or toxins made by bacteria or viruses.
• Self-antigens do not trigger an immune response.

• Antigens are recognized by lymphocytes which bind to and detect the characteristic shape of an
exposed portion (epitope).
• Lymphocytes produces which are specific to antigens.

• WBCs are the most important cellular component of immune system and immune responses.
• Leucocytes are much larger than erythrocytes, but they can squeeze through tiny blood vessels
because they can change their shape.
• There are around 4,000 -11,000 leucocytes per mm3 of blood and there are several different types.
• WBCs are formed in the bone marrow, although some mature in the thymus gland.
• Their main function is to defend the body against infection.
• They all contain a nucleus and have colourless cytoplasm, but some types contain granules that can
be stained.
• Some are involved in the non-specific responses of the body to infection. Others are involved in the
specific responses of the immune system.

• Granulocytes are usually involved in non-specific responses whereas agranulocytes are involved
mainly in specific immune response.

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 Neutrophils Multi-Lobed • These are the most common first responders to microbial
infection.
• They engulf and digest pathogens by phagocytosis.
• Up to 70% of all leucocytes are neutrophils.

Eosinophils Bi-Lobed • Parasitic infections and allergic reactions (inflammatory).

• They are stained red by eosin stain.

Basophils Bi/Tri-Lobed • They produce histamines involved in inflammation and allergic

reactions.

Kidney Shaped • The largest of the leucocytes.

Monocytes
• They can pass from the blood into the tissues to form cells
called macrophages.
• Macrophages also play an important part in the specific
immune system.
• They engulf pathogens by phagocytosis.
Lymphocytes Deep Staining, • Lymphocytes are small leucocytes with very large nuclei that
Eccentric are vitally important in the specific immune response of the
body.
• Include B cells, CD4+ helper T cells, and CD8+ cytotoxic T
cells.

• Immune responses in animals can be divided into two types:

1) Non-specific (Innate immunity)
2) Specific (Acquired/Adaptive immunity)

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• The ability to resist damage or diseases in the body through inherent body defences which offer
rapid responses against a broad range of pathogens and foreign substances.
• Non-specific responses to infection are initiated by body cells breaking down and releasing
chemicals, and by pathogens that have been labelled by the specific immune system.
• However, it lacks specific responses to specific invaders and its protective mechanisms functions the
same way regardless of the type of the invader.
• Provide but against foreign invasion.
• Found in both invertebrates and vertebrates.
• Innate defence mechanisms can be broadly divided into two types:
i) Barriers to entry (First line of defence)
ii) Internal nonspecific defences (Internal defences).

• External barriers discourage pathogens and foreign substances from penetrating the body.
• They act as physical and chemical barriers.
• So, they are considered as the first line of defence.
• External defences/barriers are found in,
a) the skin,
b) mucus membranes
c) secretions of various organs

• Skin is an impenetrable layer strengthened by , a fibrous structural protein.

• It forms a physical barrier between the many pathogens in the environment and the delicate,
blood-rich tissues beneath the skin.
• An oily substance produced by the skin, called , contains chemicals that inhibit the
growth of microorganisms.
• Sebum does not harm the natural skin flora which are adapted for survival on skin surface and
also play a role in preventing disease.
• competes successfully for a position on the skin and also, in some cases,
produce substances that inhibit the growth of other microorganisms.
• of epidermal cells helps remove microbes from the skin surface.
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 • The mucous membranes which line the body cavities provide a physical barrier to entrance
of many microbes (e.g., the linings of the respiratory tract, digestive tract, urinary tract and
reproductive tract).
• The mucous membranes produce which traps microbes and other particles.
• In the respiratory tract, ciliated epithelial cells sweep mucus and any entrapped material
upward.
• Coughing and sneezing speed up the mucus movement and its entrapped pathogens out of
the body preventing their entry to the lungs.
• Mucus contains , enzymes which can destroy microbial cell walls.
• These enzymes are particularly effective against Gram-positive bacteria.
• They destroy the cross-linkages in the peptidoglycans in the bacterial cell wall.
• Lysozymes are also present in tears, the secretions which keep eyes moist and protected from
the entry of pathogens.

• provide protection against irritants and microbes and provide continuous

washing action that helps to dilute microbes and prevent settling on the surface of eyes.
• washes microbes from the mouth surface and the flow of saliva reduces the
colonization of microbes in the mouth.
• which bathe various exposed epithelia provide a continual washing action
to dilute and inhibit colonization microbes such as bacteria and fungi.
• (an enzyme) present in tears, saliva, perspiration and mucous secretions can
destroy cell walls of some bacteria.
• which provides an acidic environment in the stomach can destroy many bacteria
and bacterial toxins ingested with food.
• Secretions of the and of the skin give acidity of the skin which helps
to prevent growth of bacteria.

• When the pathogens penetrate the external defensive barriers in the skin and mucus membranes in
the human body, they encounter a responses called internal defences.
• In innate immunity, internal defences consist of,
a) Phagocytic cells.
b) antimicrobial proteins
c) Inflammatory responses

• These are specialized cells that can ingest microbes, foreign particles and cell debris for intra cellular
digestion and destruction.
• Phagocytes use the receptor molecules to detect components of foreign agents and particles.
• Neutrophils and Macrophages are the two main types of phagocytic cells in humans.
▪
▪ Neutrophil can only ingest a few pathogens before it dies.
▪ These cells cannot renew their lysosomes and once the enzymes are used up, the cell
cannot destroy any more pathogens.
▪ While circulating in the blood, neutrophils are attracted first to the infected site by
signals from affected tissues.
▪ Then neutrophils can ingest and destroy infected pathogens.

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 ▪
▪ erived from monocytes, which are agranulocytes.
▪ They constitute about 4% of the WBC in the blood.
▪ migrate to the infected tissues and become , so there are
large numbers of macrophages in the tissues.
▪ Macrophages have an enormous capacity to ingest pathogens because, unlike
neutrophils, they can renew their lysosomes so they last much longer.
▪ They accumulate at the site of an infection to attack the invading pathogens.

• They are proteins present in the blood and interstitial fluids which function in innate defence by
attacking microbes directly or impeding their reproduction.

•
▪ Proteins secreted by virus-infected body cells that protect uninfected host cells from viral
infections by interfering with the viral replication.
▪ Once released by virus-infected cells, interferons diffuse to uninfected neighbouring cells
where they are stimulated to produce “anti-viral proteins” which inhibit viral replication.
▪ Some interferons activate macrophages which enhance the phagocytic activity.

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• An innate immune defence response in the body to tissue damage triggered by microbial infections
or injury of the tissues.
• Inflammation attempts to destroy the microbes at the site of the injury preventing the spread to
other tissues and promote tissue repair.
• Inflammatory response is brought about by various signalling molecules upon infection or injury.

• The process involves the following stages,

i) release of substances that promote increased permeability and dilation of blood vessels
▪ Mast cells and damaged white blood cells release histamines which cause the blood
vessels in the area, particularly the arterioles, to dilate causing local heat and
redness.
▪ Heat reduces the efficiency of reproduction of pathogens.
▪ Histamines also make the walls of the capillaries leaky so fluid, including plasma, white
blood cells and antibodies, is forced out of the capillaries causing swelling (oedema)
and often pain.
ii) enhance migration of phagocytes and destruction of invading pathogens.
▪ White blood cells engulf pathogens by phagocytosis, antibodies inactivate
pathogens, pain makes you take care of injured site.
iii) aid in tissue repair

• Signs and symptoms of inflammation

i) Redness – due to dilation of blood vessels
ii) Heat – due to high metabolism
iii) Swelling - due to leaking of tissue fluid into neighbouring tissues.
iv) Pain – due to the injury to neurons and microbial toxins.

• As a result of most inflammatory responses, may be accumulated.

• It is a fluid rich in dead phagocytes, dead pathogens, and cell debris from the damaged tissue.
• Minor injury or infection causes a localized inflammatory response.
• If the injury or infection is severe it may lead to a systemic response (throughout the body) leading
to fever.
• Elevated body temperature within limits may enhance the phagocytosis and accelerate tissue repair
by speeding up the chemical reactions.

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• Acquired immunity is the ability of the body to defend itself against invading foreign agents (e.g.
pathogens) through specific defence responses mediated by diverse T lymphocytes and B
lymphocytes.
• Acquired immunity shows,
1) for particular foreign molecules
2) of animal’s own molecules (self-molecules) from non-self-molecules
3) for most previously encountered pathogens such that the subsequent encounter
causes a stronger and more rapid response (immunological memory).
4) In the animal kingdom, acquired immunity is found .

• The cells that have developed the ability to carry out acquired immune responses if they are activated
against foreign agents are called T lymphocytes and B lymphocytes.
• In humans, both types of lymphocytes are originated from stem cells in the bone marrow.
• Some of the lymphocytes that migrate to thymus for maturation are called T lymphocytes (T cells).
• The lymphocytes that remain in the bone marrow for completion of development are called B
lymphocytes (B cells).
• Before leaving these lymphocytes to the secondary lymphatic tissues, their plasma membranes
acquire diverse specific protein receptors (antigen receptors) which have the ability to recognize
specific foreign invasions (There can be over 100,000 antigen receptors on the surface of a single B
lymphocyte or T lymphocyte).

• A substance that can stimulate an immune response through T lymphocytes and B lymphocytes and
to react with the specific cells or antibodies that resulted from the stimulated immune response.

1) Viral proteins
2) Bacterial toxins and chemical components of bacterial structures such as flagella and cell walls.
3) Structural components of incompatible blood cells.
4) Transplanted tissues.

• Antigens are usually large foreign molecules such as proteins and polysaccharides.
• In general, not the entire antigen, but certain parts of a large antigen molecule act as the triggers
for the acquired immune responses.
• The small accessible portion of the antigen that binds to a specific antigen receptor of a T lymphocyte
or B lymphocyte is called an (for exp a group of amino acids in a large protein). Can serve
as an epitope.
• Usually, a single antigen has several epitopes each can bind with a specific antigenic receptor of the
single T or B lymphocyte.

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• In acquired immunity, two types of immune responses are mediated by T lymphocytes and B
lymphocytes.
• They are,
1) Humoral immune responses (Antibody mediated immune response).
2) Cell mediated immune responses.

• Both immune responses are triggered by antigens.

• .

• Humoral immune response is a type of acquired immunity in which specifically

attach to a particular antigen undergo proliferation and eventually differentiate into
“Plasma cells” that secrete circulating antibodies that can neutralize and inactivate the specific toxins
and pathogens in the blood and lymph.
• In addition, “Memory B cells” are formed that can cause stronger and more rapid response at
subsequent encounter of the same antigen.
• Humoral immune response works against and
.
• The humoral response results in the , which are not attached to cells but
are carried around the body in the blood and tissue fluid.
• B cells produce the antibodies, but T cells are first involved in activating the B cells.
• The humoral response consists of two main stages:
I. T helper activation stage
II. Effector stage

• When a pathogen enters the body. chemicals are

produced that attract the phagocytes, including
macrophages and neutrophils.
• Neutrophils engulf bacteria and destroy them in
about 10 minutes.
• Macrophages take longer as they prepare the
way for the specific immune system.
• The macrophage separates the antigens from the
digested pathogen and combines them with the
major histocompatibility complex.
• The complexes move to the surface of the
macrophage cell outer membrane.
• A macrophage with these antigen-MHC protein
complexes displayed on its cell surface is known
as an
• The next step involves T helper cells, which have
receptors on the outer membrane that bind to the
specific antigen of the on
the APC.
• The binding of the T cell with the APC triggers the
T cell to reproduce and form a .

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• Most of these cloned cells become , which are used in the rest of the immune
system.
• The rest of the cloned cells form , which remain in the body; they rapidly
become active if the same antigen is encountered again.

• Some of the millions of different B

cells have immunoglobulins on their
surfaces.
• These immunoglobulins are specific
for the antigen presented by the
pathogen and will bind to it.
• The B cell then engulfs the whole
pathogen by endocytosis.
• The vesicle formed combines with a
lysosome and enzymes break down
the pathogen to leave fragments of
processed antigen.
• These fragments become attached
to MHC proteins within the cell, and
the antigen—MHC complex is then
transported to the cell surface
membrane where the antigen is
displayed.
• A T helper cell from the active clone
produced in the T helper activation
stage recognizes the specific antigen
displayed on the MHC complex on
the B cell and binds to it. 'This
triggers the release of cytokines from
the T helper cell.
• These cytokines stimulate the B cells
to divide and form clones of identical
cells.
• This is known as clonal selection.
• New clones of B effector and B
memory cells are produced.
• The B effector cells differentiate to
form plasma cell clones.
• The plasma cell clones produce large
amounts of antibodies that are
identical to the immunoglobulin of the original parent B cell.

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• Antibodies are also called as .
• Antibodies has the same Y shaped structure as B lymphocyte antigen receptors but are secreted
than membrane bound.
• Antibodies are proteins secreted by plasma cells (differentiated B lymphocytes) in response to
specific antigens; the antibody binds with that antigen to neutralize, inhibit, or destroy it.

• Antibodies can neutralize and inactivate the specific toxins and pathogens in the body fluids.
• The antibodies but can interfere with activity of the pathogen or
mark the pathogen for inactivation and destruction.
• Antibody-antigen complexes can activate complement system and phagocytosis to destroy the
pathogen.

• The ability of most pathogens to invade the host cells is dramatically reduced when they are
combined with antibodies.
• Plasma cells live for only a few days. but as they can produce up to 2000 antibody molecules per
second this is long enough to be effective.

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• They have extensive endoplasmic reticulum and many ribosomes, which are adaptations for
producing large quantities of protein antibodies.
• The antibodies remain in the blood for varying lengths of time.
• The memory cells may stay in the blood for years or even for a lifetime.

• Sometimes, the pathogen infects the host cell which makes the humoral immune response less
effective.
• T lymphocytes respond to cells that have been changed in some way.
• Examples include,
• Cells infected by a virus,
• Cells changed by mutation to form cancer cells,
• Cells of a transplanted organ.
• After a body cell has been infected with a
bacterium or virus, the pathogen is
digested and the surface antigens become
bound to an MHC in a process similar to
that seen in macrophages.
• Consequently, the body cell effectively
becomes an APC even though, it is still
infected by the pathogen.
• T killer cells present in the blood have a
wide range of complementary receptor
proteins on the surface of their cell surface
membrane.
• T killer cells bind to the matching antigen
MHC complex on the surface of the
infected body cell.
• The T cells are then exposed to cytokines
from an active T helper cell and
experience a rapid series of cell divisions.
• These cell divisions produce a clone of
identical active T killer cells which can all
bind to infected body cells.
• The T killer cells release enzymes
(granzymes) that forms pores (small holes)
in the membrane of the infected cells
allowing the free entry of water and ions,
so the cells swell and rupture.
• Any pathogens that are released
undamaged are labelled with antibodies
produced by the plasma cells, and then
destroyed by the T killer cells.
• T killer memory cells are also produced.

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• It occurs as a result of primary contact with
an antigen.
• Antibody level reaches peak in 7 to 10 days.
• Prolonged period is required to establish
immunity.
• There is rapid decline in antibody level.
• It appears mainly in the lymph nodes and
spleen.
• It occurs as a result of second and
subsequent contacts with the same antigen.
• Antibody level reaches peak in 3 to 5 days.
• It establishes immunity in a short time.
• Antibody level remains high for longer
period
• It appears mainly in the bone marrow,
followed by the spleen and lymph nodes.
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• The primary immune response involves the production of antibodies by the plasma cells (produced
from the B effector cells) and the activation of T killer cells.
• Although it is extremely effective the only drawback is, it can take days or even weeks for the primary
immune
response to become completely active against a particular pathogen.
• This is why we develop the symptoms of disease; we feel ill when pathogens are reproducing freely
inside our bodies, before the immune system has become fully operational against the pathogen
concerned.

• Unlike other cells B and T memory cells are very long-lived.

• They can remain in the body for years, and they are important in producing a rapid response to a
second invasion by the same pathogen.
• When the same pathogens encounter for the second time, B memory cells recognise the antigens
on the surface and help to produce the antibodies against it so rapidly that the pathogen does not
have time to reproduce sufficiently and is destroyed before the symptoms of the disease develop.

• Immunity can be described as either active or passive, depending on how it is acquired:

• Both active and passive immunity can be induced by either natural or artificial mechanisms

• Active immunity involves the production of antibodies due to the exposure to the Antigens by the
body itself and the subsequent development of memory cells.
• Active immunity will result in long-term immunity but passive immunity will not (due to the presence
or absence of memory cells)
• Natural – Producing antibodies in response to exposure to a pathogenic infection (i.e. challenge and
response)
• Artificial – Producing antibodies in response to the controlled exposure to an attenuated pathogen
(i.e. vaccination)

• Passive immunity results from the acquisition of antibodies from another source and hence memory cells are
not developed
• Natural – Receiving antibodies from another organism (e.g. to the foetus via the colostrum or a newborn via
breast milk)
• Artificial – Receiving manufactured antibodies via external delivery (e.g blood transfusions of monoclonal
antibodies)

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• There are many diseases for which the pathogen survives in soil, water or animal hosts.
• For such diseases, there is always a very large reservoir of potential infection so eradication is not
realistically possible.
• The aims of immunisation are, therefore, elimination and control.

• is the situation in which the disease disappears in defined areas but the pathogen
remains in animals, the environment or in mild infections which are not recognised. In this case,
immunisation must continue even when no clinical cases are observed.
• For example, the vaccination programme against polio has not eradicated the disease, even
in countries where the number of people who are vaccinated is high. A live vaccine is used,
so very occasionally an infant or an unvaccinated carer develops the disease. In spite of this,
polio remains endemic only in Afghanistan, Nigeria and Pakistan.
• A disease that is controlled still occurs, but not frequently enough to be a significant health problem.
For some serious infectious diseases such as malaria, the rapid evolution of the pathogen makes it
very difficult to develop a vaccine because the surface antigens are always changing, but some
progress is being made.

• Herd immunity occurs when a significant proportion of the population is vaccinated against a disease.
• Which makes it very difficult for the disease to continue affecting a population, as the pathogen
cannot survive without hosts to infect, and very few people are vulnerable to it.
• Herd immunity can effectively stop the spread of a disease through a community.
• It is important that everyone who can be vaccinated is vaccinated.
• This protects those individuals against the disease, and also protects people who cannot be or have
not been vaccinated.
• These include very young babies, very old people, people with compromised immune
systems and people who are very ill with other diseases. Because everyone else is vaccinated,
the people who cannot be vaccinated will probably never encounter the pathogen.
• The percentage of the population that needs to be vaccinated to give herd immunity varies from
one disease to another.
• It depends on factors such as,
• how the disease is spread
• how infectious it is.

• To give herd immunity against whooping cough (pertussis), 92-94% of the population need to be
vaccinated. For measles, it is 83-94%. For polio only 80-86% of the population need to be vaccinated
against the disease to protect everyone.
• Some diseases are so serious that in many countries, including the Republic of Maldives, the UAE
and the UK, all young children are offered vaccines against them which gives herd immunity to the
whole population. These diseases include diphtheria, tetanus, polio, whooping cough, TB and
measles. Thousands of people were killed and disabled by these diseases every year before the
arrival of vaccines and better living conditions for all.
• In other cases, only vulnerable people are vaccinated as a general rule, with mass vaccination to
provide herd immunity only introduced when there is a serious outbreak of disease (e.g. certain
strains of flu).

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• Mast cells and damaged white blood cells release chemicals known as histamines which cause the
blood vessels in the area, particularly the arterioles, to dilate causing local heat and redness.
• Heat reduces the efficiency of reproduction of pathogens.
• Histamines also make the walls of the capillaries leaky so fluid, including plasma, white blood cells
and antibodies, is forced out of the capillaries causing swelling (oedema) and often pain.
• White blood cells engulf pathogens by phagocytosis, antibodies inactivate pathogens, pain makes
you take care of injured site.

• Because they simply react to non-self- the response is not specific to a particular pathogen.

• A raised temperature can help the body combat infection by lowering the reproduction rate of the
pathogens, and the immune system works better at higher temperatures and so will be more
successful at combating the infection.
• If body temperature rises above 40°C the denaturation of some enzymes may occur causing
permanent tissue damage. If the temperature is not lowered fairly quickly, death may result.

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• The immune system responds to foreign antigens on the surface of pathogens. The cells of the body
have antigens which the immune system recognises as ‘self’ and so does not attack them.

• An antibody is a special glycoprotein known as an immunoglobulin, released into the circulation by

B cells.
• The antibody binds to a specific antigen on the pathogen that has triggered the immune system, so
it is destroyed in one of several ways.
• The plasma cells that make antibodies only last a few days, but can produce up to 2000 antibody
molecules per second while they are alive.
• Antibodies remain in the blood for varying lengths of time and the memory cells may stay in the
blood for years or even life.
• Antibodies work in several ways to greatly reduce the ability of most pathogens to bind to their host
cells:
o When antibodies bind to the antigens on pathogens, the microorganisms agglutinate or
clump together, preventing them spreading through the body and making it easier for them
to be engulfed by phagocytes.
o The antibody acts as an opsonin, a chemical which makes an antigen or pathogen more easily
recognisable by phagocytes.
o Antibodies neutralise the effects of bacterial toxins by binding to them.

• B cells have receptor proteins which recognise the antigens on the surface of invading pathogens.
They give rise to clones of cells which produce antibodies to a specific pathogen.
• T cells come in two types.
o T helper cells produce chemicals which stimulate the production of antibodies.
o T killer cells produce chemicals which destroy pathogens.

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