IMMUNITY
Pathogen “Path” = disease “ogen” = generating
 A pathogen is something that causes disease.
 A biological pathogen is a bacterium, virus, fungi, yeast, protozoa, worms, etc.
 A non-biological pathogen can be a toxic chemical, asbestos, etc.
 Usually, the term “pathogen” refers to a biological pathogen.
Sizes of Pathogens
Bacteria are so small that hundreds of them can fit inside one white blood cell. However,
bacteria usually do not invade body cells. They live between the cells of the body, using
up nutrients in the area, and they cause harm by secreting toxins. Viruses are so small
that thousands of them can fit inside the NUCLEUS of one white blood cell. They
always try to invade body cells because they need a piece of our DNA or RNA in order
to replicate. When a body cell has been invaded by a virus, the entire cell must be killed
by a white blood cell.
Antigen
 An antigen is anything that causes an immune response, which isn't necessarily a
biological pathogen (disease-causing organism).
 A non-biological antigen can be pollen, dust, grass, or anything that a person is
allergic to.
 Pollen can be an antigen to a person with allergies, but it is not an antigen to a
person without allergies, because no immune response was launched.
1. LEUKOCYTES (White blood cells): There are different kinds; all fight infection.
a. BASOPHILS: Few in body. Their blue granules are filled with histamines,
which help fight infection by vasodilation, increasing the number of WBCs
to the infection site. Antihistamines interfere with the function of basophils.
When a basophile leaves the circulation to enter the tissues, it becomes a
MAST CELL.
b. EOSINOPHILS: Function to fight allergies and parasitic infections.
During these conditions, their numbers increase.
c. NEUTROPHILS: The most abundant type of WBC. They are the first to
respond to infection. They phagocytize (eat) bacteria and also destroy
bacterial toxins in body fluids. Nucleus – has two to six lobes
1. Neutrophils are the white blood cells that contribute to immunity
mainly by engulfing BACTERIA and foreign bodies (thorns, dirt,
etc) in a process called phagocytosis.
2. They release the contents of their lysosomes onto the invader,
dissolving it.
3. When a bacterium has a capsule, it makes it hard to phagocytize,
so the neutrophil requires opsonization by antibodies.
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4. Some bacteria have evolved a slippery capsule around them as a
defense against phagocytosis. The neutrophil cannot engulf this
type of bacteria. Neither can a macrophage.
5. When an antibody attaches to this type of bacteria, the neutrophil
can now grab onto the antibody like a handle, enabling it to
phagocytize the bacteria.
6. This process of facilitation of phagocytosis is called
OPSONIZATION.
7. When the invader has the antibody attached to it, it is called an
ANTIGEN-ANTIBODY COMPLEX.
8. If a bacterium does not have a capsule, the neutrophil can destroy
it without opsonization. The antibody can also destroy the
bacterium by itself by popping the cell membrane.
9. But when a capsule is present, the neutrophil and antibody work
best together.
10. Neutrophils are also the ones that primarily destroy the
dissolved toxins that bacteria secrete into body fluids.
d. MONOCYTES: Like neutrophils, they phagocytize (eat) bacteria, old
cells, and foreign bodies. They have more types of lysosome enzymes
than neutrophils so they are better at killing difficult pathogens.
e. They also use antibodies for opsonization.
f. When they leave the bloodstream and enter the tissues, they are called
MACROPHAGES.
What’s the Difference between Neutrophils and Monocytes/Macrophages?
 There are 10x more neutrophils in the bloodstream than
monocytes/Macrophages. Consider neutrophils to be the most numerous white
blood cell.
 However, there are more macrophages in the tissues of the body. They are
everywhere!
 Neutrophils live only a few days. Monocytes/Macrophages live a few months.
Lymphocytes live for years.
 Monocytes/Macrophages are larger and slower than neutrophils, but they can
phagocytize larger organisms and more of them.
 Neutrophils usually just phagocytize bacteria until they die. Macrophages
phagocytize and then take pieces of the dead bacteria and present them to
lymphocytes so a larger immune response can occur.
 There are two types of phagocytes: Neutrophils and macrophages.
 Neutrophils and macrophages both mainly function by phagocytizing
bacteria (not viruses).
 Neutrophils and macrophages eat bacteria more easily after an antibody attaches
to the bacteria. This is called an antigen-antibody complex. The antibody enables
the neutrophil or macrophage to grab onto the bacteria more easily.
 Lymphocytes are mostly needed to kill off body cells infected by viruses.
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 Neutrophils just phagocytize bacteria and secrete chemicals to recruit more white
blood cells to the site.
 Unlike neutrophils, macrophages have surface receptors; these "recognize" the
surface of the pathogen’s cell membrane.
 Macrophages phagocytize the bacteria, pop their lysosomes onto it, and dissolve
it, except for some pieces of the bacteria’s cell membrane.
 The macrophage places these pieces of bacteria on its own cell membrane, and
finds a lymphocyte to present it to.
 Macrophages present these pieces to T cell lymphocytes and to B cells
lymphocytes.
 The lymphocyte feels the shape of the bacteria pieces on top of the macrophage,
(this is called “antigen presentation”) and the lymphocyte can then launch an
attack on the rest of the bacteria still alive in the body.
 In this way, the macrophage recruits even more lymphocytes to join the war.
So, what is a lymphocyte?
g. LYMPHOCYTES: Effective in fighting infectious organisms like body
cells infected with viruses They act against a specific foreign molecule
(antigen)
Two main classes of lymphocyte
– B cells – Originate in the bone marrow, mature into plasma cells. A
mature plasma cell fights infection by producing antibodies
– T cells – Originate in the thymus gland. They attack foreign cells directly
(including organ transplants!)
B CELLS: – mature into plasma cells
 PLASMA CELLS secrete antibodies; the antibodies are what kill the
attacking cell. Antibodies attack in two ways:
– They attach to bacteria and pop the cell membrane
– They attach to encapulated bacteria to help neutrophils phagocytize them.
Mononucleosis: Epstein Barr virus attacks B lymphocytes. It is characterized by
inflammation of lymph vessels (lymphangitis). Lymphangitis: lymph vessel
inflammation; usually from infection. Infected lymphocytes have a
characteristic scalloped edge where they touch RBC’s
T CELLS
1. Coordinate the immune response by recruiting other white blood cells
2.They can directly destroy bacteria by popping their cell membrane.
3.They can also destroy body cells infected with viruses.
4. T cells attack foreign cells directly by popping the cell membrane.
5.They do not need to phagocytize the invading cell. They do not need the assistance
of antibodies.
6.T-cells can therefore kill a body cell that has become infected with viruses.
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7.T cells are the cells that attack organ transplants!
8.Immunosuppression drugs are designed to inhibit the action of T cells.
9.T cells are attacked by the HIV (AIDS) virus.
10.The thymus gland secrets certain hormones which can cause T cells to become
immunocompetent (makes the cells mature and start to work)
There are several types of T cells. The main types are
 Cytotoxic (Killer) T cells
– Go out and directly kill bacteria or infected host cells
 Helper T cells
– Release chemicals called “cytokines” to stimulate the B cells to produce
antibodies against the bacteria. Cytokines also call in more white blood
cells of all types to join in the war.
 Suppressor T cells
Stop the immune process when it is over, and also "tell" some B-Cells to "remember"
how to destroy that specific pathogen. Those B-cells then become Memory B-Cells. They
can react to the same pathogen faster, the next time it invades. Memory B-cells already
have the proper antibodies stored up for that pathogen.
Summary
 A pathogen somehow gets past the body's physical and chemical barriers and the
inflammation response.
 The pathogen is engulfed by a macrophage (or neutrophil).
 The macrophage releases the contents of its lysosomes onto the bacterium and
dissolves most of it. There are still some pieces of the bacterium’s cell membrane
left. The macrophage then forces the surface proteins of the bacterium (antigens)
to it's own cell surface.
 Helper T-Cells touch these surface antigens, make a copy of their shape, and
present them to B-cells to make antibodies against them.
 These Helper T-Cells begin to multiply and have two main roles.
 The first is to activate B-Cells and "tell" them how to neutralize the pathogen by
presenting the pieces of the bacterium cell membrane so the B-cells can make
antibodies.
 The B-Cells (now called Plasma cells because they have been activated)
begin to multiply and produce the antibodies to neutralize this specific
pathogen.
 The second role of Helper T-Cells is to activate the Killer T-Cells.
 Killer T-Cells can either destroy the pathogen itself (bacteria), or destroy the
entire body cell which is infected (viruses).
 When the immune response is over, Suppressor T-Cells stop the process and also
"tell" some B-Cells to "remember" how to destroy that specific pathogen. Those
B-cells now become Memory B-Cells.
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Antibodies
 Antibodies (also known as immunoglobulins, abbreviated Ig) are proteins made
by plasma cells.
 They are used to identify and neutralize foreign objects, such as bacteria and
viruses.
 They are typically made of basic structural units—each with two large heavy
chains and two small light chains—to form a unit shaped like the letter “Y”
 The tips of the “Y” have receptors that are specific for a particular antigen.
 The stem of the “Y” can be grasped by a phagocyte.
 The small region at the tip of the protein is extremely variable, allowing millions
of antibodies with slightly different tip structures, or antigen binding sites, to
exist.
 This region is known as the hypervariable region. Each of these variants can bind
to a different target, known as an antigen.
 This huge diversity of antibodies allows the immune system to recognize an
equally wide diversity of antigens.
 Some of these “Y” shaped units exist by themselves (monomers)
 Some are in pairs (dimers)
 Some are in a cluster of five (pentamers)
 There are five different antibody types , which perform different roles, and help
direct the appropriate immune response for each different type of foreign object
they encounter.
Antibodies attack in three ways:
1) Opsinization (helps phagocytes)
2) Neutralization by agglutination. This is when antibodies surround the bacteria and
cause it to drop out (precipitation) of the environment, where it can be walled off
in a capsule or phagocytized.
3) Complement Activation. This is a process where the antibody causes a series of
reactions that causes the cell membrane of the bacteria to pop.
Types of Antibodies
IgD – initiation of immune response
IgE – stimulates allergic reactions, good for
worm infections
IgG – highest concentration in blood, highest
amounts in most secondary responses,
crosses the placenta
IgA – secretory Ig, found in secretions,
highest concentration in body
IgM – produced first, best at C’ activation
J-Protein is what attaches the antibody segments
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 IMMUNITY: B Cells that have matured into plasma cells which have made
antibodies are now called Memory lymphocytes, after their first war.
Most people are sick more often as children than as adults in their 20s through 30s
because we build up many varieties of MEMORY LYMPHOCYTES during childhood,
providing immunity from more and more antigens during adulthood.
Myasthenia gravis
 Myasthenia gravis (MG): autoimmune disease where antibodies destroy or block
receptors for acetylcholine, a neurotransmitter.
 Causes muscle paralysis.
 First attacks small muscles especially those that keep eyes open; will spread to
diaphragm  death. To stave off effects, do thymectomy.
Aspirin
 One baby aspirin a day can help prevent blood clots.
 It blocks the ability of an enzyme called COX (cyclo-oxidase) to cleave
arachidonic acid into a molecule called a prostaglandin.
 Prostaglandins are needed for inflammatory reactions and for making clotting
factors.
 COX inhibitors, such as aspirin, block pain from inflammation, but they also
INCREASE blood clotting time.
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Life span, from longest-lived to shortest-lived: lymphocytes, erythrocytes, platelets,
neutrophils.
Terms
 Excess neutrophils: neutrophilia
 Few neutrophils: neutropenia
 Excess platelets: thrombocytophilia
 Few platelets: thrombocytopenia
WBC Count
 White blood cell (WBC) count is a count of the actual number of white blood
cells per volume of blood. Both increases and decreases can be significant.
 White blood cell differential looks at the types of white blood cells present. There
are five different types of white blood cells, each with its own function in
protecting us from infection. The differential classifies a person's white blood
cells into each type: neutrophils (also known as segs, PMNs, granulocytes, grans),
lymphocytes, monocytes, eosinophils, and basophils.
BLOOD TYPING: The ABO SYSTEM
Blood typing is the technique for determining which specific protein type is present on
RBCs.
Only certain types of blood transfusions are safe because the outer membranes of the red
blood cells carry certain types of proteins that another person’s body will think is a
foreign body and reject it.
These proteins are called antigens (something that causes an allergic reaction). There are
two types of blood antigens: Type A and Type B.
A person with Type A antigens on their blood cells have Type A blood.
A person with Type B antigens have Type B blood.
A person with both types has type AB blood.
A person with neither antigen has type O blood.
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If a person with type A blood gets a transfusion of type B antigens (from Type B or Type
AB, the donated blood will clump in masses (coagulation), and the person will die.
The same is true for a type B person getting type A or AB blood.
Type O negative blood is called the universal donor, because there are no antigens, so
that blood can be donated to anyone. Type AB positive blood is considered the universal
acceptor, because they can use any other type of blood. This blood type is fairly rare.
The rarest blood type is AB negative.
RH FACTOR
There is another term that follows the blood type. The term is “positive” or “negative”.
This refers to the presence of another type of protein, called the Rh factor. A person with
type B blood and has the Rh factor is called B-positive.
A person with type B blood and no Rh factor is called B-negative.
The reason this is so important is that if an Rh- mother has an Rh+ fetus in her womb
(from an Rh+ father), her antibodies will attack the red blood cells of the fetus because
her body detects the Rh protein on the baby’s red blood cells and thinks they are foreign
objects. This is called Hemolytic Disease of the Newborn (HDN).
This can be prevented if the doctor knows the mother is Rh- and the father is Rh+,
because that means the baby has a 50% chance of being Rh+ like the father.
Therefore, anytime a mother is Rh-, even if the mother says the father is Rh-, you can’t
be sure who the father is, so they will proceed as though the baby may be Rh +.
They will give her an injection of a medicine (rhogam) that will prevent her immune
system from attacking the baby.
Rhogam
 Rhogam is given at 18 weeks into the pregnancy and again within 72 hours after
giving birth.
 It is usually given within 2 hours after giving birth since you can’t trust the patient
to return after they leave the hospital.
 The first baby is not at risk; during the first birth, the placenta tears away and
that’s when the baby’s blood cells get into the mother’s bloodstream.
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 She then forms antibodies against the Rh factor, which are ready to attack the
second fetus.
 The baby does not make the Rh factor until about 18 weeks into the pregnancy.
IMMUNE SYSTEM
INFLAMMATORY REACTION: When you get stuck by a thorn or inhale a
cold virus, the body goes through a series of events called an inflammatory reaction.
Four outward signs:
1. Redness
2. Heat
3. Swelling
4. Pain
Redness is caused from the blood vessels dilating to allow more blood flow to the area.
Within the blood are platelets to clot the blood, proteins to repair the damage, and
macrophages, which are white blood cells that eat up the foreign body, bacteria, or the
dead cells.
Heat is caused because of the extra amount of warm blood flow to the area.
Swelling is caused from the plasma that leaks out of the swollen blood vessels.
Pain is caused from the pressure of the extra fluid pressing on nerves in the area.
ADAPTIVE IMMUNITY
 Two types of Adaptive Immunity
– ACTIVE immunity
 Naturally Acquired
 Artificially Acquired
– PASSIVE immunity
 Naturally Acquired
 Artificially Acquired
ACTIVE IMMUNITY
 Naturally Acquired
– The body is naturally exposed to an infectious agent and launches an
immune reaction
 Artificially Acquired
– The person is injected with a weakened (attenuated) or killed organism, as
found in a vaccination
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Naturally acquired active immunity
This is when the body is exposed to an infectious agent and produces antibodies which
specifically attack that infectious agent so the person never gets that disease again. The
plasma cells secrete these antibodies which will continue to circulate sometimes for
years, ready to attack that type of bacteria and cause them to pop like a balloon before the
body can become sick.
– You catch a cold and eventually get better. You can never get the same
cold virus twice because you will have become immune to it. Your next
cold is from a different virus. There are hundreds of thousands of cold
viruses; that’s why there is no cure for the common cold.
– Another example is when an unvaccinated child is exposed to the measles
at school and gets the disease, but never gets the disease again.
However, there are some diseases that you don’t want to get, even once, such as polio,
diphtheria, tetanus, and influenza, because the first exposure could kill or disable you.
For these diseases, we have vaccines which are made of those organisms which have
been altered (attenuated) so that the body recognizes them as foreign, but they can’t cause
disease. That way, if the person is exposed to the real organism later, the antibodies are
already there to kill it off without the body getting sick.
Artificially acquired active immunity
– An example is when a child is vaccinated against measles as a baby, so when
he gets to school and is exposed to the disease, he doesn’t get sick.
PASSIVE IMMUNITY
 Naturally Acquired
– Example is the passing of antibodies from mother to infant in breast milk
 Artificially Acquired
– Example is when a person receives an infusion of antibodies from
someone else.
ALLERGIES are from a hypersensitivity to substances such as pollen or animal hair that
would not ordinarily cause a reaction. There are two types of allergic responses:
1. Immediate allergic response occurs within seconds of contact with the thing
causing the allergy. This is the case with anaphylactic allergies, where someone
who is allergic to seafood or peanuts can actually die within minutes because the
allergic reaction is so severe the throat swells shut and they can’t breathe . They
need an injection immediately of something that will stop the reaction.
2. Delayed allergic response is when the body’s first exposure to the substance will
not cause a reaction, but all exposures afterward will trigger the response. An
example is poison ivy. You won’t itch the first time you touch it.
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Chemical mediators of allergies
 Preformed
– histamine - ↑ vascular permeability; smooth muscle contraction
– proteases – mucous secretion, generation of complement split products
 Newly formed (30-60seconds)
– leukotrienes - ↑ vascular permeability;
contraction of pulmonary smooth muscles
– platelet activating factor – platelet aggregation;
contraction of pulmonary smooth muscles
– prostaglanin D2 – vasodilation; contraction of smooth muscles
– cytokines – chemotactic and inflammatory
Symptoms of allergy
 dependent upon site of allergen exposure
 wheal-and-flare reaction
– Pruritis (itching), erythema
– skin
 bronchoconstriction
 mucous secretion
 vasodilation (shock)
Localized anaphylaxis (atopy)
 reaction limited to the site of allergen exposure
 pruritis (itchy) and urticaria (hives)
 allergic rhinitis (hay fever)
 asthma (atopic asthma)
 atopic dermatitis (eczema)
 food allergies
Allergic asthma
 stimulation of ‘allergy attack’
– airborne allergens – pollen, dust, insect parts
– blood borne allergens – viral antigens
– degranulation of mast cells due to IgE cross-linking
 lower respiratory tract
 symptoms
– airway edema
– mucous secretion
– inflammation
– = airway obstruction and damage
 asthmatics are hypersensitive to allergens; ~5% of U.S. population
 symptoms can range from somewhat mild to life-threatening (<5% severe asthma)
AUTOIMMUNE DISEASE is a hereditary problem where the body thinks its own
tissues are foreign bodies, and it constantly tries to kill off its own tissues.
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