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Immune System
Immune System
• A functional system rather than an organ system
in an anatomical sense
• Its “structures” are a diverse number of immune
cells and molecules that are involved in the
immune response.
Pathogens
Pathogen = any living organism or virus that
is capable of causing disease. Includes:
• Bacteria, Viruses, Protozoa, Fungi,
some worms
Most don’t result in disease because of our
defense system
Before antibiotics
• Between 1345 – 1350, approx. 25,000,000
people in Europe died from ‘the plague’.
• Most people thought it was from breathing
‘bad air’, so treatments included burning nicesmelling incense.
Disease was actually
caused by a bacteria
carried by rats.
Before antibiotics
• People would either get better on their
own, or get worse and die
• Ex. 40% of people with pneumonia died
Home ‘cures’
would sometimes
hurt more than
help. Example:
leeches!
How antibiotics work against bacteria
• Antibiotics take advantage of the differences between
prokaryotic and eukaryotic cells
• There are many classes of antibiotics each with their
own method of destroying bacteria
– selectively blocks protein synthesis
(aminoglycosides, macrolides, tetracyclines)
– some inhibit new cell wall production, blocking their
ability to grow and divide (penicillins, cephalosporins),
includes amoxicillin, ampicillin, cefalexin
– Some damage cell membranes (polymixins)
– Some interfere with bacterial enzymes (quinolones,
sulfonamides)
Immune System:
2 major kinds of defense
First kind is Innate immunity
• largely nonspecific, responding to a broad range
of microbes.
- external barriers: skin and mucus membranes
- internal barriers: cellular and chemical
defenses that defend against microbes that get
past the external barrier
(macrophages and other phagocytic cells
that ingest and destroy pathogens)
Immune System:
2 major kinds of defense
Second kind is Acquired immunity:
• Develops after exposure to microbes or other
foreign substances
• Highly specific
• White blood cells (lymphocytes). 2 responses:
– Humoral response – cells derived from Blymphocytes secrete antibodies that bind to microbes
and target them for elimination
– Cell-mediated response – cytotoxic lymphocytes
directly destroy infected body cells, cancer cells, or
foreign tissue
Overview of innate and cellmediated responses
Innate
defenses
Adaptive
Defenses
(Acquired
Immunity)
Surface barriers
Skin
Mucus membranes
Internal defenses
Phagocytes
NK cells
Inflammation
Antimicrobial proteins
Fever
Humoral immunity
B cells
Cellular immunity
T cells
Ways we prevent pathogens from
entering the body
• Skin: 2 primary layers:
Dermis (underlayer) has sweat glands, capillaries,
sensory receptors, and dermal cells that give
strength and structure to skin
Epidermis (top layer) – layer of mostly dead cells.
Good barrier because its not truly alive.
Stomach acid: if pathogens
come in with food or liquid,
stomach acid helps to kill
most of them
Ways we prevent pathogens from
entering the body
Mucus
Pathogens enter in the air we breathe (mouth or nose)
Mucus is produced by cells lining entryways (trachea,
nasal passages) to trap incoming pathogens.
The cells that secrete mucus also secrete the enzyme
lysozyme which digests bacterial cell walls
Some mucus membranes are lined with cilia, which
also help move pathogens up and out
What happens when they do get in? (pt.1)
Role of phagocytic leukocytes
Leukocytes = white blood cells, many different
types, they are the main cells in bloodstream
that help fight off pathogens that enter our
bodies
- they also provide us with immunity for returning
pathogens
Macrophages – large WBC’s that can change
their shape and squeeze their way in and out of
small blood vessels. They surround invaders
and ingest them by phagocytosis.
When a macrophage finds a cell, it
determines whether its “self” or “not-self”
based on surface protein receptors on the
cell
• If its “self”? they leave it alone
• If its “not-self”? they engulf by
phagocytosis and chemically digest it with
lysosomes
– Non-specific;
just determined
to be “not-self”
Macrophages phagocytosing bacteria
4 types of phagocytic leukocytes
1) Macrophages
2) Neutrophils
• 60-70% of all WBC’s
• Attracted to and enter
infected tissue,
engulfing and
destroying microbes
there
• Self-destruct in only a
few days
3) Eosinophils
Critical for defense against
multicellular parasites like
blood flukes. Instead of
engulfing them, they position
themselves against the
parasite’s body and then
discharge destructive enzymes
that kill them
4) Dendritic cells
Can ingest by phagocytosis,
But primary role is to stimulate the
development of acquired immunity
What happens when they do get in?
Antibody Production
(pt.2)
Antibodies = proteins that we produce in
response to a specific type of pathogen
-Y-shaped
Each antibody is different because each type has
been produced in response to a different
pathogen
Antigens =
foreign substances that
stimulate the production
of antibodies
• Each type of antibody
recognizes one specific
antigen
• Antibodies have binding sites
specifically for those antigens
How are antibodies produced
• When antigens are
found, the body gears
up to produce large
amounts of
antibodies needed
• Each type of
lymphocyte
recognizes one
specific antigen and
responds by dividing
to form clones
• These clones then
secretes specific
antibodies against the
antigen
How are antibodies produced
A B-cell´s recognition of
a target structure
quickly leads to the
production of
numerous antibodies
ready to attack this
target. Memory cells
ensure a quick
response in case the
target reappears at a
later time. B-cells
which don’t recognize
the target (here the
cells 1 and n), don’t
produce antibodies
Immune Response animation
• http://highered.mcgrawhill.com/sites/0072507470/student_view0/chapter22/ani
mation__the_immune_response.html
Immune Response
1. A macrophage discovers an antigen
2. When it determines it to be “not-self”, it engulfs it by
phagocytosis, but pieces are purposely left on the cell
membrane of the macrophage
3. Helper T cells chemically recognize the antigen being
presented and become activated
4. Helper T cells then chemically communicate with
(activate) the specific B cell that is able to produce the
antibody needed
Immune Response
(B lymphocytes are the leukocytes that produce antibodies)
1.
2.
3.
4.
5.
B cells are activated to clone themselves by mitosis to
make many more of themselves
- (antibody-secreting plasma cells and memory
cells)
The newly formed ‘army’ begins antibody production
Antibodies circulate in the blood until they find their
antigen match
Antibodies destroy the pathogens
Some of the cloned lymphocytes stay in bloodstream
and give immunity from a second infection by the
same pathogen. (they are called memory cells)
•HIV infects cells in the
immune system, specifically
helper T cells
•Once helper T cells are
destroyed, there is no longer
communication between cells
and antibodies are not
produced, so the individual
cant fight off pathogens
•HIV can be dormant in host
cells for years before
becoming active
HIV
•Once active, secondary infections occur, and symptoms of
AIDS begin to appear
Issues related to AIDS
What are some cultural and economic
reasons for differences in the prevalence
of AIDS?
Principles of Immunity
• Challenge and response: The immune
system must be challenged by an antigen
during the first infection in order to develop
an immunity.
– All the cellular events (involving
macrophages, helper-T cells, and B cells) are
part of the response which leads to immunity
to this pathogen
Principles of Immunity
• Clonal selection: when B cells encounter
a specific antigen to which their antibody
binds, they multiply many times to form
clones.
• Memory cells: These are the cells that
provide long-term immunity. You must
experience a pathogen once in order to
produce these and be truly immune.
Active vs. Passive Immunity
• Active immunity: Immunity due to the production
of antibodies after the body’s immune cells have
been stimulated by antigens.
• Passive immunity: when one organism acquires
antibodies which were produced in another
organism.
– Only the organism which produced the
antibodies has the memory cells and so has
long-term immunity. Getting antibodies from
somewhere else acts only short-term.
Examples of Passive Immunity
• Antibodies passed from mother to fetus
through the placenta
• Antibodies passed from mother to baby
through the colostrum. Colostrum is the
breast milk produced in late pregnancy
and first few days after birth; high antibody
concentration.
• Injection of antibodies in antisera. Ex.
antivenom if you’ve been bitten by a
poisonous snake
Production of monoclonal antibodies
Process by which large quantities of antibodies
(targeted against a particular antigen) can be
produced
• A mouse (or other laboratory animal) is injected
with a specific antigen
• Then the animal is given time to go through an
immune response
• The mouse’s body will
stimulate the production of
antibodies
against the
antigen
Production of monoclonal antibodies
• The spleen is taken out as a
source of many B cells
• B cells are fused with tumor
(cancer) cells to produce
hybridomas
Production of monoclonal antibodies
Each hybridoma
proliferates and
produces mass
quantities of
antibodies called
monoclonal
antibodies
Uses of monoclonal antibodies:
Diagnosis
One common use: pregnancy testing.
Early in pregnancy, the embryo starts to produce a
hormone called HCG (Human Chorionic
Gonadotrophin).
Only pregnant women would have this hormone
which shows up in blood and urine.
Hybridomas are produced by injecting a
mouse with HCG, the B cells produced
secrete antibodies which recognize HCG as
an antigen. These anti-HCG antibodies are
bonded to an enzyme which shows a color
change when the antibody encounters HCG.
why pregnancy tests
change color when
positive
Uses of monoclonal antibodies:
Treatment
• Cancer cells produce
cancer-cell specific antigens
on their cell membranes
• One possible treatment for
cancer is to produced
monoclonal antibodies that
target those antigens
• Big advantage is that they
target the cancer cells
directly
Vaccination
• A vaccine is developed by
weakening a virus by heating
it or chemically treating it, then
injecting it into the body
• The body will recognize it as ‘notself’ and the primary immune
response takes place (including
formation of memory B cells for
quick response if needed later)
Note that a second infection of the same
pathogen results in a faster response with more
antibodies produced
Benefits of vaccination
• Possible total elimination of the disease, as has
occurred with smallpox
• Decrease in spread of pandemics (worldwide
infections) and endemics (local infections).
Increased international travel has made this very
important: an infection started on one side of the
world could be on other side of the world in < 1
day
• Preventative medicine is cheaper than treating
diseases
• Prevention of harmful side-effects of diseases
Dangers of vaccination
• Possible toxic effects of mercury; prior to
1999, a mercury-based preservative was
used
• Multiple vaccines in a short period of time
may ‘overload’ the immune system
• Possible links to autism (?)