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The Immune System
Topic 6.3 Defence Against Infectious Disease & 11.3 Antibody Production and Vaccination
PATHOGEN
 A pathogen is an organism or a virus that causes a disease in any other organism.
 Ie: Bacteria, fungi, viruses
 Exposure to the majority of pathogens does not result in a disease because
 We can prevent pathogens from entering our bodies
 We can develop an immunity to particular pathogens
 We can use chemicals (ie antibiotics) to defend ourselves.
VIRUSES
 Non cellular structures
 Contain DNA or RNA surrounded by a protein coat.
 Not considered to be a living cell because they cannot undergo
essential life process on their own (ie: replication or protein synthesis)
 (When a virus wants to replicate, it enters an (unwilling) “host” cell
and uses the host’s enzymes to replicate its DNA. It takes away
energy and resources from the host cell.)
 Viruses will have antigens on its protein coat/cell membrane.
 All viruses must find a type of cell in the body that matches their own
proteins in a complementary way so it can enter the cell (through endocytosis)
 This is why only certain body cells are damaged by certain viruses as is typically reflected
in the symptoms associated with the infection.
BACTERIA
 Prokaryotic cells, that can rapidly duplicate
 A colony of bacteria can obstruct regular function in the host organism
 Bacteria products can cause unpleasant side-affects to a host organism.
ANTIBIOTICS
 Antibiotics are chemicals that may be used to fight off bacterial infections.
 Antibiotics often work by disrupting the ability of the bacterium from replicating and/or
undergoing protein synthesis.
 (If they cannot undergo protein synthesis, they will lack the essential proteins for life –
and thus die)
 (If they cannot replicate, the colony will not be able to increase in number and
eventually the body’s immune system will be able to kill the remaining bacteria)
 Antibiotics do not disrupt cell function in your cells because bacteria cells are prokaryotic
and you are made of eukaryotic cells.
 Antibiotics are often derivatives of fungus such as penicillin (which comes from the fungi
Penicillium)
Why can’t antibiotics be used to kill viruses?
 Viruses don’t undergo replication or protein synthesis on their own so there is nothing to
disrupt.
Testing Penicillin (p307, 308)
 In 1928, Scottish scientist Alexander Flemming (accidently) discovered penicillin.
 In the 1930’s, scientists Howard Florey and Ernest Chain investigated the use of
penicillin.
 They first tested it on mice
 They next conducted human trials.
 The 1st human test subject was a 43 year old male with an acute, life-threatening
bacterial infection
 He was given penicillin for four days and his condition improved considerably.
 Unfortunately, supplies of penicillin ran out and he suffered a relapse and died from the
infection.
 Larger quantities of penicillin were produced and they tested it on 5 more patients with
acute infections.
 All were cured of their infection.
 Pharmaceutical companies in the US began producing penicillin in larger quantities
allowing for more extensive studies, confirming it’s use as a highly effective treatment
for previously incurable bacterial infections
 Florey and Chain’s test on the safety of penicillin would not be compliant with current
testing protocols.
 They tested the drug on human patients after a very brief period of animal testing –
there could have been severe side effects
 The samples they used were not pure and there could have been side effects from the
impurities.
 On the other hand, the subjects they used all had severe infections and were on their
death beds and were cured as a result of the experimental treatment.
Antibiotic Resistance
 Some strains of antibiotics have evolved genes giving them resistance to antibiotics and
some strains of bacteria have multiple resistance.
How to prevent antibiotic resistance
 Antibiotics should only be prescribed for serious bacterial infections.
 Patients must complete the prescribed course of antibiotics to eliminate infections
completely.
 High standards of hygiene require at medical facilities to prevent cross-infection.
 Farmers shouldn’t use antibiotics in animal feeds to stimulate growth
 Pharmaceutical companies need to develop new types of antibiotics (*no new types
have been introduced since 1980s)
How do we defend ourselves against pathogens?
1st Line of Defense
 The first line of defense against foreign invaders is mainly physical
 The skin and the mucous membranes defend against viral and bacterial invaders.
SKIN
 The skin provides a physical barrier
like a wall preventing pathogens
from getting in.
 The epidermal layer is constantly
being replaced as underlying
dermal cells die and are moved
upwards.
 The epidermal layer is mainly dead
cells and thus is a good barrier
because it is of no use to viruses.
 The sebaceous glands produce a
chemical called sebum
 The sebum provides moisture
 It is also an acidic secretions (pH 3-5) which inhibits the growth of microbes
MUCOUS MEMBRANES
 Weak points in our defense against foreign invaders are areas in which we are not
protected by skin.
 Mucous membranes secrete a mucus, which is a sticky solution of glycoproteins.
 Mucus may help in these areas by trapping micro-organisms and prevent further entry
Examples:
 In the trachea (which leads to the lungs), foreign particles are trapped in mucous or
filtered by tiny hair-like structures called cilia that sweep particles to the entrance where
coughs can expel them.
 In the stomach, corrosive acids and digestive enzymes destroy microbes that may be
found in food
 The head of the penis, and the inner layer of foreskin have mucous membranes.
 The vagina produces mucous and has an acidic environment too to protect itself.
 Lysozyme – an antimicrobial enzyme that is found in tears, saliva, mucous secretion,
perspiration will destroy bacterial cell wall killing the bacteria.
2nd Line of Defense
 Kicks in when the invader takes up residence with in the body.
 INFECTION: the successful invasion of a pathogen
 Leukocytes are used to fight off an infection
LEUKOCYTES
 are white blood cells (wbc)
 Found in blood stream but also in body tissues
 have a nucleus unlike rbc
 responsible for responding to foreign invaders and destroying them
 many different types
MACROPHAGE
 Is a type of wbc that ingests foreign invaders by phagocytosis
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(Because it undergoes phagocytosis, it is also referred to as a phagocyte)
All cells have proteins on their cell membranes called ANTIGENS
Antigens act as identity markers.
Macrophages recognize body cells of the host by its antigens
Foreign invaders will have different cell surface antigens which will cue macrophages to
get rid of them
Phagocytosis
 This is the process when wbc ingest invading
microbes and chemically destroy them with enzymes
 Macrophages –have pseudopods which are protrusions that will attach to the surface of
an invading microbe, engulf it and digest it with enzymes
 This is a non-specific immune response because the identity of the pathogen is not
determined (at this point)
ANTIBODY
 Also known as an immunoglobulin
 Soluble proteins that are produced by the immune
system as a response to the presence of an antigen
 Many different types
 Produced by different kinds of lymphocyte (each
lymphocyte will recognize a particular kind of antigen
and produce antibodies against that kind of antigen)
 Attach themselves to antigens of foreign invaders.
How does this help destroy pathogens?
 Neutralization of pathogens
 This will make the foreign invader useless because now
they cannot enter host cell (cannot “dock” on host cells
 Also can neutralize toxins produced by antibodies
 Opsonization - Antibodies target pathogens for
phagocytosis (by phagocytes)
 Agglutination
 The “clump” of pathogens cannot enter a host cell
 Easier target for lymphatic system to filter and phagocytes to ingest.
 Activation of Complement - Water and ions enter the cell causing the cell to lyse
HIV and the Immune System
 HIV: human immunodeficiency virus is a virus that infects the cells of the immune system
 It is a retrovirus: it contains RNA and when it enters a host cell it uses the enzyme
reverse transcriptase to make DNA from the RNA.
 It reduces the number of lymphocytes that are actively involved in the production of
antibodies
 Leads to less antibodies which means the individual will be more likely to develop a
disease.
 Hard to find a cure or a vaccine.
 HIV hides in its host cell for years
 Mutates relatively quickly – making it hard to vaccinate against and hard for body’s
immune system to recognize it.
 The rate of which HIV destroys lymphocytes can be slowed down with antiviral drugs
 HIV can lead to AIDS (acquired immune deficiency syndrome)
 In these cases, HIV has severely weakened the individual’s immune system and their
lymphocyte count is particularly low.
 These individuals are susceptible to illnesses that healthy individuals have no problem
fighting off such as the common cold
 HIV Transmission through: blood semen, vaginal secretions, breast milk
 Most common Transmission occurs via: unprotected sex; sharing of injection needles;
mother to child during birth or breastfeeding.
Blood Clotting
 When blood vessels get broken, blood is able to escape from the closed circulatory
system and pathogens have a way to enter the body.
 To prevent excessive blood loss and the entry of pathogens, a clot will form to seal the
damaged blood vessels.
 There are a few components in your blood that are important for blood clotting:
1) Prothrombin and Fibrinogen
 These are plasma proteins
 Always present in blood but inactive unless you start to bleed
2) Platelets
 Small, irregularly shaped blood cells made in bone marrow
 They start as large cells, and then break into many smaller fragments
 No nucleus
 Live only 8-10 days
Forming a Blood Clot
1) A cut occurs damaging a small blood vessel
2) Blood (including rbc, wbc, plasma proteins and platelets) will ooze out of the cut.
3) The damaged tissues will release chemicals that will cause platelets to adhere to each
other and the damaged area causing a plug.
4) The platelets and damaged tissue will release clotting factors which include the enzyme
thrombokinase.
5) Thrombokinase will catalyze the conversion of prothrombin (a plasma protein) into the
enzyme thrombin
6) Thrombin will catalyze the conversion of soluble fibrinogen (a plasma protein) into
insoluble fibrin
(FIBRIN: A fibrous protein which forms a mesh-like network to stabilize the platelet plug)
7) More cellular debris will become trapped in the fibrin mesh and a stable clot will form
preventing further blood loss or the entry of pathogens.
The Immune Response and Antibody Production
 When a pathogen enters your body, the immune system will try to get rid of it.
 The first type of leukocyte that will encounter a pathogen is usually a macrophage.
 The macrophage will ingest the pathogen through phagocytosis and partially digests it.
 The macrophage will take the antigens of the pathogen and display on its own cell
membrane
 This is known as antigen presentation
 The macrophage will then go to the lymph nodes
 In the lymph node, the macrophage will present the antigens to various types of helperT cells (TH)
 Helper-T cells are a types of lymphocytes
 A helper-T cell with receptors on its membrane that are complementary to the antigen
will be selected. (They basically take an imprint of the antigen)
 These helper-T cells will undergo mitosis to make clones of itself.
 The helper-T cells will then go to a B lymphocyte (also called a B cell)
 B lymphocytes make antibodies
 The B cell will identify the blueprint of the antigen and make antibodies against the
antigen that can be released and attach to the antigens of the pathogen
 When a B cell is activated, it will also undergo mitosis to make clones of itself
 It will make plasma cells and memory cells
 Plasma cells (Plasma B cells):
 these cells will make antibodies immediately to fight off the current infection
 Memory Cell (Memory B Cells):
 These cells do not secrete antibodies during the 1st infection.
 They are long-lived cells which will remain circulating in the bloodstream
 If the individual becomes infected with the same pathogen, the memory B cells
will be ready to release antibodies against the pathogen
Note:
 When the macrophage displays the antigens on its cell membrane, the antigens are
attached to MHC proteins (major histocompatibility complex proteins)
 Helper T-cells will only respond to antigens attached to MHC proteins
 Cytotoxic T-cells or Killer T-Cells are another type of lymphocyte
 They recognize cells that have been invaded by pathogens and will destroy these
cells.
Immunity
 Immunity depends upon the persistence of memory cells or the presence of antibodies
for the antigens of the disease.
 Immunity develops when the immune system is challenged by a specific antigen and
produces antibodies and memory cells in response.
Vaccines
 Vaccines can trigger immunity
 The secondary response to an antigen is must faster than the first response
 Vaccinations deliberately expose an individual to a weakened/dead/similar pathogen
 In this way, the individual can create memory B cells against the antigens of the
pathogen and be prepared for an infection
 If the individual comes into contact with the pathogen after vaccination, they will have a
faster immune response and will likely avoid illness
 Eradication of some diseases (e.g. small pox – which was the first infections disease of
humans to have been eradicated by vaccination)
 Fewer people get the diseases (because already have the antibodies)
 Prevents disability and other effects of the pathogen
 Ex: polio can cause paralysis (no polio, no polio related paralysis)
 Herd immunity
 If many people in the population are vaccinated, the disease will not spread and
there will be a decreased chance that someone who did not get the vaccine will
contract it anyway
Monoclonal Antibody Production
 The primary immune response of an organism is called a polyclonal response.
 This is because the pathogen will have many type of antigens on its cells surface, not just
one.
 So several kinds of plasma B cells will go under clonal selection to produce several kinds
of antibodies
 After a polyclonal immune response, it is difficult to separate the different kinds of
antibodies
How are monoclonal antibodies obtained?
1. A mammal (i.e. a mouse) is injected with a
particular antigen
2. The mouse’s plasma B cells will produce
antibodies against the antigen
3. The plasma B cells are extracted and
fused with a B-cell tumour cell (a rapidly
dividing B-Cell) to create a hybrid called
“hybridoma cells”
4. Hybridoma cells grow in culture producing
identical antibodies that can be collected
 This technology can be used for: Blood
Type Tests, Pregnancy Tests, Tests for
diseases
Example: Pregnancy Tests
 The antibodies for HCG can be fixed to a testing strip and
attached to a dye.
 The test strip contains:
 (B) free moving antibodies for HCG which are
attached to a dye.
 (C) immobilized antibodies that will bind to HCG
 (D) immobilized antibodies that will bind to dye
bearing antibodies.
If a woman is pregnant:
 HCG in her urine attaches to the HCG antibodies (with dye) in
test strip.
 The complex of “HCG-antibodies-dye” attach at both C and D,
causing 2 lines to appear on the pregnancy test. (a positive result)
If the woman is not pregnant
 There will be no HCG in her urine.
 So nothing will attach to the antibodies (with the dye)
 The antibodies will not attach to point C, but will attach at point D, creating 1 line to
appear (a negative result)
Zoonosis
 Pathogens are usually specific to their hosts
 Humans are the only known organism susceptible to pathogens such as syphilis, polio,
and measles.
 A zoonosis is a pathogen which can cross a species barrier.
 Ex: west Nile virus, bird flu
 A major factor in the increased appearance of zoonotic disease is increased contact
between humans and animals (particularly livestock)
Histamines
 Some white blood cells release the molecule histamine in response to an infection.
 Histamine causes the dilation of small blood vessels in the infected area.
 This will increase the flow of fluid containing immune components to the area.
 It also causes the blood vessels to become leaky
 Histamine contributes to a number of symptoms of allergic reactions.
 Many cells have histamine receptors.
 Histamine plays a role in causing the symptoms of allergy in the nose (itching, fluid build
up, sneezing, mucous secretion, inflammation)
 Histamine also plays a role in the formation of allergic rashes
 Histamines can cause the dangerous swelling known as anaphylaxis
 Anti-histamines can lessen the effects of allergic responses.