Download The Immune System - Labs - Department of Plant Biology, Cornell

Clicker Question
Which of the following process(es) that
occur(s) at a synapse could be targeted
by a drug designed to treat mental
illness?
A) Secretion of the neurotransmitter
B) Binding of the neurotransmitter to a
receptor
C) Degradation of the neurotransmitter
D) Re-uptake of the neurotransmitter
E) All of the above and more
Where are we?
• Last time I discussed…
– that before the introduction of psychopharmacology, mentally
ill patients were treated barbarically.
– the brain is a trillion cauldrons of chemical activity in which
neurotransmitters in the synapses regulate the transmission
of electrical signals.
– how psychopharmacological drugs influence the concentration
of neurotransmitters in the synapses.
– that while we understand a lot about the physico-chemical
processes that take place in the brain, we still do not
understand the mechanism of normal and abnormal thinking
and the way the psychopharmacological drugs work.
• This time I will discuss…
– immunity—how the body protects itself from invaders.
– the innate immune system.
– the acquired immune system that, like the nervous system,
can learn, remember and recognize self from non-self.
The human body is capable of resisting
many harmful disease-causing agents
in the course of everyday life.
• Not everyone in a family,
•
dorm, sorority, fraternity
or classroom is equally
resistant to disease.
Luckily, immunity (from
the Latin word immunis
meaning “free of”) against
disease can be conferred
to sensitive people though
vaccinations.
The Ancients Realized that Survivors of a Disease
were often Immune to Getting that Disease Again
• In 429 BC, Thucydides noticed
that smallpox survivors did not
get re-infected.
• In the 10th century, also
realizing that survivors of small
pox were immune to the
disease, Chinese doctors put the
fluid from small pox pocks into
the noses of susceptible people
to protect them from small pox.
Puritans Learned that Africans also Inoculated
People to Make them Immune to Small Pox
• In 1706, the Puritan minister,
•
Reverend Cotton Mather,
learned from a slave named
Onesimus, that he had been
inoculated with small pox as a
child in Africa as a protective
measure.
Courageously going against the
Church and State, in 1721, during
the small pox epidemic in Boston,
Cotton Mather and Dr. Zabdiel
Boylston inoculated the people.
• Lady Mary Wortley
•
•
Montagu (1721), the wife
of the British Ambassador
to Turkey, brought back
to England a method of
preventing the deadly
small pox disease.
Physicians would take a
small amount of pus from
the pocks of a person with
a mild case of small pox
and rub it in to a scratch
in the arm of a healthy
person.
Unfortunately, the healthy
patient often contracted a
full blown case of small
pox and died.
Edward Jenner
Jenner (1798) and many
milkmaids he treated noticed that
people who got cow pox
(variolae vaccinia) were
immune to the deadly small pox.
One day, when Sarah Nelmes
came to him with cow pox, he
decided to see if inoculating
someone with cow pox would
prevent them from getting small
pox. He took pus from Sarah
Nelmes’ pocks and rubbed it into
scratches in James Phipps’ arm.
The 8 year old son of the
gardener developed cow pox.
Once he was over the cow pox,
Jenner exposed him repeatedly to
small pox, but he had become
immune to the small pox virus.
A Profile in Courage: Edward Jenner
• Jenner reported his results to
the Royal Society; however,
Sir Joseph Banks, the president
of the Royal Society suggested
that he should not risk his
reputation by presenting
something "so at variance
with established
knowledge".
• Thankfully Jenner used his
meager savings to publish his
work privately and within a few
years vaccinations for small pox
became common practice.
Cholera: A Bacterial Infection
• Cholera is transmitted from
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•
•
person to person by the fecaloral route resulting from
drinking water contaminated
with feces that contain the
bacterium, Vibrio cholerae.
Vibrio secretes a toxin into the
intestine that results in massive
diarrhea followed by
dehydration.
If the patient is not rehydrated
orally or and/or intravenously
within hours of being infected,
death can result.
Cholera can also be prevented
by a vaccine.
Louis Pasteur Had a Prepared Mind
• Louis Pasteur (1880) reasoned
•
that if a vaccine could be found for
small pox, then a vaccine could be
found for all diseases. Pasteur
found a vaccine against chicken
cholera by chance.
One of his colleagues had
inoculated chickens with chicken
cholera bacilli from an old culture
and the chickens did not get sick.
Even when he exposed these
chickens to fresh chicken cholera
bacilli that would kill other
chickens, the chickens who were
exposed to the old strain first still
did not get sick.
Louis Pasteur Had a Prepared Mind
• Pasteur reasoned that
•
the potency to cause
cholera in chickens had
attenuated in the old
culture.
He guessed that the
chickens used the
weaker germs to form
a defense against the
more powerful germs
•
in the fresher culture.
Pasteur pioneered the use
of attenuated bacilli for
vaccinations, a word he
coined in honor of Jenner.
Anthrax
• Anthrax is often a fatal disease characterized by
•
hemorrhaging and tissue decay.
It is caused by a toxin produced by Bacillus
anthracis, which can enter the body through the
lungs, skin or intestines.
Louis Pasteur and Anthrax
• Pasteur (1881) aged cultures of
anthrax to weaken them and
used the weakened germs to
make a vaccine.
• The idea that germs could
make an animal healthier
•
•
seemed unbelievable and
Rossignol, the editor of The
Veterinary Press, challenged
Pasteur to a public test.
Pasteur inoculated twenty five
sheep with his vaccine while
twenty-five were not.
Subsequently, all fifty were
injected with anthrax. Those
injected with the vaccine lived
while those that were not
inoculated died within two days.
Rabies
• Rabies is a fatal disease characterized by the
•
•
inflammation of the brain.
Rabies is caused by the rabies virus, which is found in
the saliva of an infected animal.
Rabies is often transmitted by a bite.
Louis Pasteur, Joseph Meister, Human
Experimentation and Rabies
• Pasteur injected healthy dogs with aged
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rabies germs (viruses) from the spinal
cord of rabid rabbits. The vaccinated
dogs became immune to rabies.
A 9 year old boy named Joseph
Meister was bit by a rabid dog. Since
the boy would have died had he been
left untreated, Pasteur (1885)
reluctantly took the risk on treating
Joseph Meister with the vaccine that
had only been tested on dogs.
Happily, the vaccine worked and the
boy survived to become the caretaker
of the Pasteur Institute.
Pasteur’s Father and Mother Painted by
Louis Pasteur, Himself
The Wisdom of the Body in the Fight
Against Infectious Diseases
The body protects itself from infectious microbes in
two ways:
– Innate Immunity (skin, phagocytes, interferon)
– Acquired Immunity (B and T lymphocytes)
The Body’s First Line of Defense:
Innate Immunity
• Skin and the mucosa lining the digestive and urogenital
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•
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tracts are physical barriers to disease, although a tiny cut
will allow pathogens to enter the body.
Sweat, saliva and tears contain lysozyme, an enzyme
that degrades the cell wall of gram positive bacteria. This
causes the bacteria to lyse. Lysozyme was discovered by
Alexander Fleming in 1922.
The respiratory tract is guarded by the hairs in the nostrils
as well as the mucus that traps microbes and cilia that
sweep the mucus out of the respiratory system and down
the esophagus.
The hydrochloric acid produced by the parietal cells in the
stomach kills microbes (with the exception of Helicobacter)
that come from the respiratory system or enter the body
along with food.
The Inflammatory Response:
Phagocytes and Pus
• Microbes that breach the first line
•
of defense are accosted by the
white blood cells which are
found in the blood, the interstitial
fluid, and the lymph.
The white blood cells that
engulf microbes by
phagocytosis are known as
phagocytes. The neutrophils,
which are a kind of phagocyte
that most rapidly fights
infections, make up most of the
pus that occurs with an infection.
nobelprize.org/educational_games
Ilya Mechnikov
In 1882, Ilya Mechnikov was
studying the larvae of starfish.
He noticed that when he
inserted a splinter into the
larva, strange cells gathered at
the point of insertion. The cells
surrounded the splinter, eating
any foreign substances that
entered through the ruptured
skin. Mechnikov named these
new cells phagocytes from
the Greek words “eating cells.”
Splinters
“Sharp splinters were
introduced into the bodies of
these Bipinnaria and the next
day I could see a mass of
moving cells surrounding the
foreign bodies to form a thick
cushion layer. The analogy
between this phenomenon and
what happens when a man has
a splinter that causes
inflammation and suppuration
is extraordinary.”
Disease: A Fight Between Microbes
and Phagocytes
• This observation led
Mechnikov to propose that in
humans, phagocytes move to
the wound and engulf the
bacteria.
• “…disease would be a fight
between the morbid agent,
the microbe from outside,
and the mobile cells of the
organism itself. Cure would
come from the victory of the
cells and immunity would be
the sign of their acting
sufficiently to prevent the
microbial onslaught.”
Ilya Mechnikov
“Photographs taken of him
when he was working at the
Pasteur Institute show him
with long hair and an
unkempt beard. It is said of
him that at this time he
usually wore overshoes in all
weathers and carried an
umbrella, his pockets being
overfull with scientific papers,
and that he always wore the
same hat, and often, when
he was excited, sat on it.”
The Inflammatory Response
The Inflammatory Response
• When the skin is broken, damaged mast
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cells release histamine (which causes one
to burn and itch). The histamine diffuses to
the capillaries and cause them to dilate
and become leaky.
The phagocytes and components of blood
plasma move out of the leaky capillaries. This
results in redness and swelling. The
swelling puts pressure on the pain receptors.
Consequently, the inflammation leads to
pain.
In the interstitial fluid, the phagocytes
known as neutrophils rapidly engulf
microbes and dead or injured body cells.
The pus at the site of injury consists mostly
of interstitial fluid and dead neutrophils.
Stinging Nettle Causes Inflammation
Because It Contains Histamine
• The hairs of stinging
nettle contain
•
histamine, acetylcholine
and serotonin.
These molecules that
occur in the plant and
animal kingdoms cause
itching, burning,
reddening and swelling
when you touch the
hairs of the plant,
informing you that the
plant you touched is
Urtica dioica.
Phagocytes, Antioxidants and Free Radicals
• The phagocytes kill the
•
invading bacteria by
producing a dose of free
radicals (including
superoxide), which are
produced by the
phagocyte itself.
Vitamin C is necessary
as an antioxidant to
protect the phagocyte
from its own high dose
of superoxide.
Corticosteroids and Anti-Inflammation
• Cortisol released during stress
suppresses the inflammation
response. In the short term, this
minimizes the pain associated with
•
inflammation; but in the long term, it
makes it easier to succumb to
germs.
Synthetic corticosteroids
(hydrocortisone) are used topically
to treat the pain and itchiness of
dermatitis, eczema, psoriasis,
hemorrhoids, and poison ivy or nasally
to treat allergy symptoms.
Zits
• Acne occurs during puberty when androgens
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produced by the adrenal glands in men and
women stimulate secretion of oils from the
sebaceous (oil) glands beneath the skin.
The oil glands, which are exocrine glands,
continuously secrete oil in order to lubricate
the skin.
Cells that are close to the opening of an oil
gland block the duct and cause a buildup of oil
beneath the skin. Bacteria feast on this oil
and trigger the inflammation response.
If the inflammation is near the surface, you get
a pimple and if it is deeper, you get a boil.
When the oil breaks though to the surface, you
get a whitehead and the oil becomes
oxidized, it turns black and you get a
blackhead.
Causes and Preventative Measures
• The three basic causes of acne
– Oil from sebaceous glands
– Clogged pores
– Bacteria
• Three preventative measures
– Minimize oil (wipe away with
mild astringent; or kill oil
producing cells with laser).
– Unclog pores (soap and water;
alpha-hydroxy acids or betahydroxy acids)
– Kill bacteria (benzoyl peroxide)
Alpha-Hydroxy Acids
Glycolic acid (from
sugar beet and
sugar cane)
Lactic acid
(from milk)
Beta-Hydroxy Acids
• Salicylic acid, isolated from
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•
the bark of willow (Salix)
trees and Spiraea bushes, is
involved in the “systemic
immune response” of plants.
Notice the greater proportion
of CH bonds in this betahydroxy acid than in the
alpha-hydroxy acids.
This makes salicylic acid more
soluble in oil (more
nonpolar) so it penetrates
more deeply into the oil ducts.
Innate Immunity Against Viruses:
Interferons
• Interferons are proteins that
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are produced by virus-infected
cells that help other cells
become resistant to
viruses.
The interferon gene from the
infected cell is transcribed
and translated to make
interferon, which is secreted
from the cell and diffuses to
the neighboring healthy cells.
The interferon stimulates the
healthy cells to make
antiviral proteins.
Recombinant DNA Technology Makes
Interferon Cheap and Accessible for the
Treatment of Hepatitis and other Viral
Infections
The Immune System:
The Mind Body Connection
Psychology Today
Psych Sci
IL-6 is produced by the white blood cells that participate in the
innate immune response. Participants looked at a 10 minute
slide show of people holding guns or people with disease
symptoms. After seeing pictures of the sick people, the
interleukin-6 (IL-6) level in the participant’s blood rose
significantly. The increased levels of IL-6 can give a boost to the
entire immune system.
Our Blood—Our Identity
• Experience with blood transfusions
•
•
indicate that our body can distinguish
between our own blood and the
blood of others.
Karl Landsteiner found that the red
blood cells in the blood seemed to
fall into four groups (A, B, AB and O).
Jean Dausset, Baruj Benacerraf and
George Snell found that the white
blood cells (as well as all the other
cells in our body) also have proteins,
now known as the major
histocompatibility complex, in their
plasma membranes that represent
our self.
Karl Landsteiner (1930):
Our Blood and Our Biological Individuality
• Anthropological Studies
– Northern Europeans are
mostly Type A.
– Asians are mostly Type B.
– American Indians are mostly
Type O.
• Forensic Studies
– Tests of blood found at a
crime scene has been used
to acquit innocent people.
• Paternity Tests
– Blood tests has been used
to exclude a putative father.
Karl Landsteiner
Jean Dausset, Baruj Benacerraf and
George Snell
John Galbraith Simmons: The Self
“The self is not just a narrative
fiction of language and mind, nor
is a physical structure its only
boundaries. The self may also
be said to exist on a
molecular level, comprised of
a group of antigenic proteins
found in all cells of the body. The
specific complexion of these
antigens is configured by a set of
genes known as the “major
histocompatibility complex”
(MHC).”
Peter Medawar and Macfarlane Burnet:
Acquired Immunity (1960)
• If the innate defenses can not eliminate an
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•
•
infection, the immune system kicks in.
The immune system provides acquired
immunity, consisting of humoral
immunity and cell-mediated
immunity.
Whereas the innate system may be
effective before one is exposed to a
microbe, the immune response develops
after exposure to microbes.
The immune system is triggered by an
antigen, a molecule that is foreign to the
host’s body.
Peter Medawar (1946):
The Uniqueness of the Individual
“Philosophy and common sense,
though often parted, have long
agreed about the uniqueness of
individual man. Different men
have different faces, sizes, shapes
and origins; different aptitudes,
skills and predilections; and
different ambitions, hopes and
fears. Science now makes it a trio of
concordant voices, for the
uniqueness of individual mice and
men is a proposition which science
can demonstrate with equal force,
perhaps with deeper cogency, and
certainly with a hundred times as
much precision.”
Books by Peter Medawar
Books by MacFarlane Burnet
Clonal Selection Theory
How does the immune system
recognize so many different
foreign particles, mobilize against
them and remember them?
MacFarlane Burnet suggested
that it “would make real sense if
cells produced a
characteristic pattern of
globulin [antibody molecule]
for genetic reasons and were
stimulated to proliferate by
contact with the
corresponding antigenic
determinant.”
Antigens Generate the Proliferation of
Antibodies
• Proteins that make up the coats of
viruses, the surfaces of protozoa and
other parasites act as antigens.
• Carbohydrates from the walls of bacteria
and fungi also act as antigens.
• Various venom and toxins that get into
the blood stream also act as antigens.
• Vaccines act as antigens.
• Unfortunately, proteins from the surface
of donated blood cells, tissues and
organs also act as antigens.
Antigen: Antibody-Generating
Substance
• An antigen triggers the immune system to
produce large quantities of the antibody that
will bind to it.
• An antibody is a protein found in the circulatory
system that specifically binds to an antigen
with high affinity.
• The immune system, like the brain, learns
about the antigens to which a host is exposed
and has a memory which allows it to react
rapidly against an antigen it has experienced
before.
Antibodies
• An antibody has two identical antigen binding sites that
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allow it to form large complexes with antigens or microbes with
exposed antigens.
This process of forming large complexes is called
agglutination.
Macrophages are a kind of phagocyte that engulfs the
insoluble agglutinated complexes of antigens and/or microbes
in a process called phagocytosis.
Paul Ehrlich (1908)
The antigen and the
antibody “…enter into a
chemical bond which, in
view of the strict
specificity is most easily
explained by the
existence of two groups
of distinctive
configuration - of groups
which according to the
comparison made by Emil
Fischer fit each other
‘like lock and key’.”
Antibody-Antigen: Lock and Key
• The part of the antigen that the
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•
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•
antibody recognizes is called the
antigenic determinant or
epitope.
The antibody has amino acids with
the correct chemical properties to
bind the epitope.
If the epitope be positively
charged, the binding site will be
negatively charged.
If the epitope be negatively
charged, the binding site will be
positively charged.
If the epitope be polar, the binding
site will also be polar.
If the epitope be nonpolar, binding
site will be nonpolar.
The Complement System “Complements the
Antibody-Macrophage System”
• The complement
proteins
•
recognize the
antibodies when
they bind to an
antigen on a
microbe.
The complement
proteins poke
holes in the
plasma
membrane of
the microbe and
the microbes die.
B (bone marrow) Cells and T (thymus) Cells
• The cells that produce antibodies are
called lymphocytes. They are derived
from lymphocyte stem cells.
• The lymphocyte stem cells are derived
from pluipotent stem cells in the
bone marrow.
• Lymphocytes that mature in the bone
marrow are known as B cells.
Lymphocytes that move to the thymus
and mature there are known as T
cells.
• The mature B and T cells enter the
lymphatic system and go to the
spleen, lymph nodes, tonsils,
adenoids and appendix.
The Lymphatic System
• The lymphatic system
is an open
conducting system
•
that returns fluid from
the interstitial fluid
back to the circulatory
system.
When the lymph
fights a large microbe
attack, the
lymphocytes and
macrophages
accumulate in the
lymph glands and one
gets “swollen
glands.”
Humoral Immunity: B cells
• B cells, with
antibodies on their
surfaces, travel
•
through the
circulatory and
lymphatic systems.
The B cells also
secrete antibodies
that circulate in the
blood stream,
interstitial fluid and
lymph.
Susumu Tonegawa (1987):
Generation of Immune Diversity by Splicing
Distant Segments of DNA
How can lymphocytes create
antibodies to millions of antigens
when there are approximately
20-30 thousand different genes
in a person?
Susumu Tonegawa discovered
that, in each lymphocyte clone,
the antibody genes are
formed by splicing segments
of DNA in a unique way.
By recombining segments of
DNA, millions of genes and
antibodies can be created.
Revolutionary Idea
Before Susumu Tonegawa obtained
experimental evidence that the DNA
that encodes a single polypeptide in
an antibody occurs in two widely
separated regions of the genome in
non-lymphocyte cells, this
revolutionary theory, originally
proffered by W. J. Dreyer and J.
Bennett in 1965, was not taken
seriously because it contradicted
two of the most widely accepted
dogmas of biology:
– one gene encodes one polypeptide
– the genome is constant during
ontogeny and cell differentiation
B Cells
• When a B cell develops, its antibody gene is
transcribed, the mRNA is translated and the
resultant antibody proteins move through the
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secretory system until 100,000 of them become
incorporated into the plasma membrane.
These antibodies, which can be considered
receptors for antigens, stick out of the
plasma membrane.
Some of the antibodies produced are in the
exocytotic vesicles and are not incorporated into
the plasma membrane, but are secreted from
the B cells into the blood (one of the four
humors).
B Cells
• There are
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millions of
different kinds of
B cells.
Each B cell has a
different gene
and produces a
different
antibody.
B cells that have
the antibody to
an antigen that
enters the body
become
activated.
B Cells
• The activated B
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•
cells divide to
produce plasma
cells and
memory cells.
The memory
cells have the
antibody on the B
cell surface.
The plasma cells
live for 4-5 days
producing and
secreting a given
antibody at a rate
of 2000 molecules
per second.
B Cells
The memory
cells, which
live as long as
the person
does, are
poised to divide
into plasma
cells that will
rapidly produce
antibodies and
memory cells
following a later
exposure to the
same antigen.
Only B Cells that Encounter their Antigen
Propagate
Every minute our body produces several
million lymphocytes—each one
expressing its unique antibody. If a B
cell encounters its antigen, it will divide
to form plasma cells and memory cells,
which will last a lifetime. If a B cell does
not encounter its antigen, it will die.
“After the great randomized gene lottery
natural selection will pick the winners,
thereby generating specific immunity,
the cheapest and most efficient
protection there is against infections.”
Memory Cells and Acquired Immunity
• Acquired
immunity
•
results from
the buildup of
memory cells
in your body.
The number of
types of B
memory cells
your body has
depends on
prior exposure
to various
antigens.
Childhood Immunity
• A mother’s antibodies, but not her
lymphocytes, are passed through the
placenta from mother to child. Her
antibodies and macrophages are
passed through her breast milk.
• These antibodies provide a child with
immunity to many germs, including polio.
• While the child is immune, he/she can
come in contact with these germs and
build up his/her own acquired
immunity, so that an infection will be
fought in the child for the rest of his/her
life by the powerful secondary immune
response and he/she would not even
realize they were infected.
Dropped Pacifiers, Dirty Hands and
Faces
• Exposure to some amount
•
of dirt and germs during
childhood primes the
immune system so that
the secondary immune
response is armed and
ready.
Antibacterial soaps kill
germs, but they also
slow down the priming
of the immune system.
How Polio Became a “Disease of the Clean”
• Polio is a contagious disease.
• The polio virus enters the body
•
through the mouth and leaves
the body in the feces. By not
flushing the toilet or washing
one’s hands, the polio virus can
be transferred between infected
and uninfected people by the
fecal-oral route.
There was a polio epidemic in the
United States in the 1950s.
• Consequently, health officials
and scientists recommended
good sanitary practices to
prevent the spread of polio.
How Polio Became a “Disease of the Clean”
• However, the recommended sanitary
•
•
measures, including washing one’s
hands, cleaning ones house and
ensuring a polio virus-free water
supply, prevents a child from
developing acquired immunity to
the polio virus while still being
protected by his/her mother’s
antibodies.
Consequently, a child or an adult, who
has lost the protection of the maternal
antibodies, but had not developed
his/her own acquired immunity, could
easily come down with polio.
Consequently, polio predominantly
infected those who followed the new
sanitary guidelines.
Polio Vaccines Virtually Eradicated Polio
• Jonas Salk found that humans became
•
•
immune to the polio virus when they were
injected with a “formaldehyde-killed”
virus.
Albert Sabin found that people became
immune to the polio virus after eating a
lump of sugar containing a live
attenuated virus. The dead virus
vaccine could be prepared quickly, but it
took a while to find the conditions that
would yield a live virus that could enter
the body through the digestive system by
itself and was safe.
The live-attenuated virus has an
advantage in that it easily passes from the
immunized person to his/her family and
friends by the fecal-oral route resulting in
the immunization of many people.
Comic Book about Polio Vaccines
Eckard Wimmer (2002), who was Driven by
Curiosity, Created a Synthetic Poliovirus that
is Identical to the Natural Virus
“Research on viruses is
driven not only by an urgent
need to understand, prevent,
and cure viral disease. It is
also fueled by a strong
curiosity about the minute
particles that we can view
both as chemicals and as
“living” entities.”
Should Scientists Create
Synthetic Disease-Causing
Viruses?
Allergies
• Allergies are an overreaction to
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common environmental antigens.
Antigens that cause (or generate)
allergies are known as
allergens.
When a person is first exposed to
an allergen, the allergen binds to
the B cell with a complementary
receptor. The activated B cells
divide to form plasma cells which
secrete antibodies to the
allergen.
Allergic Response
• These antibodies bind to receptors on Mast cells.
• When the antibodies on the mast cell recognize and
bind the allergen, the mast cells secrete histamine,
which triggers the inflammation response.
Antihistamine
• Histamine released from
damaged mast cells causes
blood capillaries to become
leaky so the phagocytes can get
to the region where the cells are
damaged.
• In the case of allergies,
histamine released from mast
cells does the same thing, but
the fluid is just a nuisance
causing nasal irritation and
watery eyes.
• Antihistamines block the
histamine receptor on the
capillaries and consequently
reduce the release of fluid.
The Histamine Receptors in the Stomach
Differ from those in Blood Vessels
• Histamine increases the
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•
production of gastric acid.
James Whyte Black discovered that
antihistamines, which successfully
block the allergic reactions, do not
inhibit the production of' gastric
acid because the histamine
receptors in the stomach (H-2
receptors) are different.
Histamine-2 receptor blockers,
including Tagamet, Zantac and
Pepcid are effective treatments for
ulcers.
Anaphylactic Shock
• When a person is
hypersensitive to a given
•
allergen (e.g. peanut protein, bee
venom and penicillin), an
exposure to the antigen will cause
all their mast cells to release
histamine simultaneously.
This will cause all the capillaries to
become leaky and the blood
pressure will suddenly and
drastically drop.
• Anaphylactic shock can be
thwarted by injecting adrenaline
into the patient.
Cell-Mediated Immunity: T Cells
• T cells proliferate into cytotoxic T cells, Helper T
•
cells and memory T cells.
Cytotoxic T cells recognize and destroy the body’s
own cells that have become infected or cancerous.
Cytotoxic T Cells
• Cytotoxic T cells bind to body’s cells that have a
non-self antigen bound to the surface.
• The cytotoxic T cells then synthesize and secrete a
number of deadly proteins, one of which is known as
perforin, a protein that kills the infected host cell by
making holes in its membrane.
Helper T Cells
• The macrophages that digest microbes interact with
•
the rest of the immune system. They have receptor
proteins that bind the antigen from the microbe.
The antigen-receptor complex then migrates to the
surface of the macrophage.
Helper T Cells
• Helper T cells have receptors that bind to the
macrophage receptor-antigen complex.
• Each Helper T cell has only one type of receptor that
recognizes only one macrophage receptor-antigen
complex.
Interleukins (or Cytokines)
• The macrophage secretes a protein known as
interleukin-1 that promotes the binding of the
•
•
Helper T cell to the macrophage.
The Helper T cell, once bound to the
macrophage receptor-antigen complex, secretes
a protein known as interleukin-2, which
activates B cells and T cells to divide in order to
form B and T memory cells and more plasma B
cells and cytotoxic T cells that can be used right
away.
The protein is called interleukin because it is
involved in communication between (inter)
white blood cells (leukocytes).
Interleukin-1 and Fever
• Interleukin-1 travels to the
hypothalamus and causes it to
•
•
change the set-point for your body
temperature higher than 98.6 ̊ F.
Even though you have a fever, you
feel cold when your temperature
is less than the temperature of the
set-point.
When you have a fever, your
blood is diverted from the skin to
the core of the body to heat up the
core. You also shiver to heat up
your body core. All this makes you
want to bundle up in bed.
Interleukin-1 Makes you Feel Crummy
• Interleukin-1 also causes
•
the hypothalamus to secrete
releasing factors that
activate the flight or flight
response, which kills your
appetite.
Interleukin-1 also lowers the
threshold of the nerves that
carry stimuli from pain
sensing neurons to the
brain. Consequently, your
joints begin to ache.
Interleukin-1, Prostaglandins and
Aspirin
• Interleukin-1 causes fever, loss
•
of appetite and pain through a
signal transduction chain that
involves the synthesis of
prostaglandins.
Luckily, aspirin blocks
prostaglandin synthesis and
prevents the crummy feelings
caused by interleukin-1 that are
associated with being sick.
Acetaminophen
The action of
acetaminophen is not
well understood. It
blocks prostaglandin
synthesis and it may
also prevent pain by
binding to the
endogenous
cannabinoid receptor
in the brain.
Recombinant DNA Technology Makes
Immuno-Boosters (Interleukins) Cheap and
Accessible for People with Immune
Deficiency Diseases (Although it also makes
them feel crummy)
HIV Causes a Deficiency in the Immune
System
• HIV (human
•
immunodeficiency virus),
which is the cause of AIDS
(Acquired Immune Deficiency
Syndrome), specifically binds
to and destroys Helper T
cells.
The depletion of Helper T cells
drastically impairs the body’s
ability to fight infections
through cell-mediated
immune responses.
Severe Combined Immunodeficiency
Disease (SCID)
• One form of SCID results
•
from the production of a
mutant form of adenosine
deaminase (ADA) by B
cells and T cells.
Some clinical trials are
underway to treat this
immunodeficiency
disease with gene
therapy.
• Other clinical trials have
been suspended because
the random gene insertions
has caused leukemia.
Autoimmune Diseases
• An out-of-control immune system
•
•
•
causes trouble when the lymphocytes
make antibodies directed against
the body itself.
Lupus (→) occurs when the B cells
make antibodies against the normal
molecules in the body. The antibodies
can be directed against a variety of
organs.
Type 1 diabetes occurs when the
insulin-producing cells of the pancreas
are the targets of Cytotoxic T cells.
Multiple sclerosis occurs when the
oligodendrocytes in the central
nervous system are the targets of
Cytotoxic T cells.
lupus.org
Lymphoma and Leukemia
• Lymphomas are
•
cancers that occur in
the lymphatic system
and are caused by
malignant lymphocytes
(T cells and B cells).
Leukemias are
typically cancers that
occur in the bone
marrow or circulatory
system and are caused
by other kinds of
malignant white blood
cells.
Development of Lymphoid and Myeloid
Cells
[Granulocytes]
Biotechnology: Monoclonal Antibodies
• A mouse can be injected
with an antigen and after it
•
produces antibodies to the
antigen, its B cells are isolated
from its spleen.
The B cells are then fused
with cultured cancer cells
and the fusion cells divide
often and grow
indefinitely, producing an
antibody to the antigen
injected into the mouse.
• Single fusion cells are
isolated and grown on
culture plates. They produce
a single kind of antibody.
Biotechnology: Monoclonal Antibodies
A monoclonal
antibody produced this
way can become part of
a diagnostic kit to
detect molecules, like
human chorionic
gonadotropin, which is
an indicator of
pregnancy; or the
antibody to HIV,
which is an indicator of
HIV infection.
Cell Mediated Immunity and Organ
Transplants
• Unless one gets an organ from an identical twin,
•
•
a transplanted organ will have cells whose
surface is coated with antigens that are not
recognized as “self” by the recipient’s immune
system.
Consequently, the recipient’s Cytotoxic T cells
will begin to kill the cells of the donated organ.
Luckily, cell-mediated immunity can be
suppressed by the immunosuppressant
drugs Cyclosporin and Tacrolimus. These
immunosuppressant drugs are important in
making organ transplants possible.
Immunosuppressants are Isolated from
Fungi and Actinobacteria
Cyclosporin is produced by
the fungus, Tolypocladium
inflatum.
Tacrolimus is produced by
the Actinobacterium,
Streptomyces tsukubaensis.
Individuality: How Our Blood Defines Us
• Agglutination or clumping will
occur if the blood contains
antibodies and antigens that
bind to each other.
• Blood Group A (A antigen on
•
•
•
RBCs, B antibody in blood serum—
can donate to A and AB).
Blood Group B (B antigen on
RBCs, A antibody in blood serum—
can donate to B and AB).
Blood Group AB (A and B
antigens on RBCs, no antibodies in
blood serum—universal
recipient).
Blood Group O (No antigens on
RBCs, A and B antibodies in blood
http://nobelprize.org/educational_games/
serum—universal donor).
Aside: Abraham Lincoln Contracted Small
Pox Just Before He Delivered the
Gettysburg Address
This portrait of
President Abraham
Lincoln was taken
on November 8,
1863 by Alexander
Gardner eight days
before he delivered
the Gettysburg
Address.
Abraham Lincoln at Gettysburg
rmc.library.cornell.edu
Abraham Lincoln Probably Had a Mild Case of
Small Pox While He Delivered his Address at
Gettysburg on November 19, 1863
• Dr. Washington van Bibber told Abraham Lincoln when he
•
•
returned from Gettysburg that he had "a touch of the
varioloid."
Lincoln responded: "Then am I to understand that I have the
small pox?” Van Bibber nodded his head, “yes”.
Lincoln responded, "How interesting. I find every now and then
that even unpleasant situations in life have certain
compensation. As you came in just now, you passed through a
room full of people. Do you have any idea what they are there
for…they are there, every mother's son of them, for one
purpose only: namely, to get something from me. For once in
my life as president, I find myself in a position to give
everybody something!"
While Lincoln Survived Small Pox, William H.
Johnson, Lincoln’s Valet, Was Not as Lucky
William H. Johnson, Lincoln’s valet, traveled with him
to Gettysburg. Johnson died of small pox two months
later, and was buried at what is now Arlington
National Cemetery.