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.

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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.

LEUKOCYTES (White blood cells)
all fight infection

BASOPHILS
– MAST CELL
EOSINOPHILS
 NEUTROPHILS
 MONOCYTES

– MACROPHAGES

LYMPHOCYTES
– B CELLS
– T CELLS
BASOPHILS

Basophils – only about
0.5% of all leukocytes
– Granules secrete
histamines (vasodilation;
more WBCs can get to the
infection site)
– Antihistamines interfere
with the function of
basophils.
– Mast Cell: a basophil that
leaves the blood vessel
and enters the tissues.
Eosinophils

Eosinophils –
compose 1-4% of all
WBCs
– Play roles in:
 Ending allergic
reactions, parasitic
infections
 During these conditions
they increase in
numbers: eosinophilia
 (too many is ___philia
 too few is ___penia)
Neutrophils
Neutrophils – most
numerous WBC
 First to respond to
infection

– Phagocytize and destroy
bacteria
– Also destroy bacterial
toxins in body fluids
– Nucleus – has two to six
lobes
Neutrophils
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.
 They release the contents of their
lysosomes onto the invader, dissolving it.
 When a bacterium has a capsule, it makes
it hard to phagocytize, so the neutrophil
requires opsonization by antibodies.

Opsonization
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.
 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.
 This process of facilitation of phagocytosis
is called opsonization.

When an invading bacteria has the antibody
attached to its cell membrane, the entire
structure is now called an antigen-antibody
complex.
 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.
 But when a capsule is present, the neutrophil
and antibody work best together.
 Neutrophils are also the ones that
primarily destroy the dissolved toxins that
bacteria secrete into body fluids.

Monocytes

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Comprise about 5% of all WBC’s.
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.
They also use antibodies for
opsonization.
When they leave the
bloodstream and enter the
tissues, they are called
MACROPHAGES.
WBC’s leave the blood vessel
to enter the tissues
What’s the Difference between Neutrophils and
Monocytes/Macrophages?

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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.
Differences in Function


There are two types of phagocytes: Neutrophils and
macrophages.
– Neutrophils and macrophages both mainly function by
phagocytizing bacteria (not viruses).
Lymphocytes are mostly needed to kill off body cells
infected by viruses.
Differences in Function
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.

Differences in Function
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?

Lymphocytes

20–45% of WBCs
– The most important cells of the
immune system
– There are two types of
lymphocytes; one type is
effective in fighting infectious
organisms like body cells
infected with viruses
– Both types of lymphocytes act
against a specific foreign
molecule (antigen)
Lymphocytes
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!). They can also kill
viruses.
Lymphocytes
B cells – mature into plasma cells
Plasma cells secrete antibodies; the
plasma cell’s antibodies are what
kills the attacking cell.
Antibodies attack in two ways:


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–
–
They attach to bacteria and pop the cell
membrane
They attach to encapsulated bacteria to
help neutrophils and macrophages to
phagocytize them.
Disorder of B-cell Lymphocytes
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
Function of a B Lymphocyte
Figure 17.6b
T-cell Lymphocytes

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T cells – coordinate the immune response by
recruiting other white blood cells.
They can directly destroy bacteria by popping their cell
membrane.
T cells can also directly destroy foreign cells by
popping the cell membrane.
They do not need to phagocytize the invading cell.
They do not need the assistance of antibodies.
T-cells can therefore kill a body cell that has become
infected with viruses.
T-Cell
T-cell Lymphocytes

T cells are the cells that attack
organ transplants!



Immunosuppression drugs are designed to
inhibit the action of T cells.
T cells are attacked by the HIV (AIDS)
virus.
The thymus gland secrets certain
hormones which can cause T cells to
become immunocompetent (makes the
cells mature and start to work)
T Cells
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 call in more white blood
cells of all types to join in the war. They also present the
macrophage’s antigen to a B cell, which causes it to produce
antibodies against that particular bacteria. The B cell is now
called a plasma cell
 Suppressor T cells
– Stop the immune process when it is over, and also "tell" some
plasma cells to "remember" how to destroy that specific
pathogen. Those plasma B-cells are then called Memory B-Cells.
They can react to the same pathogen faster, the next time it
invades because Memory B-cells already have the proper
antibodies stored up for that pathogen.
Killer TCell
Virus-Infected Cell
Function of a T- Lymphocyte
Figure 17.6a
Summary
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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.
Summary
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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 turn into plasma cells which make the 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 by
secreting cytokines.
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 (plasma cells) to "remember"
how to destroy that specific pathogen.
Those B-cells (plasma cells) now become Memory B-Cells.
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”

A Typical
Antibody
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.
Antibodies
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.

Antibodies

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
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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.
#1
#2
#3
Precipitation/agglutination
38
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
Capsule
Pops
the cell
Virus
Opsonization
Bacteria
Bacteria
Antibodies
Plasma
Cell
Pops the cell
Cytokines
Phagocytosis
STOP
Presentation
Neutrophil
Macrophage
(Monocyte
in bloodstream)
B-Cell
Helper
T-Cell
Killer
T-Cell
Lymphocytes
Suppressor
T-Cell
IMMUNITY

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.

Fig. 9-1
Hematopoiesis
44
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.

BLOOD TYPING


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
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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.
BLOOD TYPING





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- blood is called the universal donor,
because there are no antigens, so that blood
can be donated to anyone.
Type AB+ 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.

RH FACTOR

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).
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

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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 (or
miscarriage), the placenta tears away and that’s when
the baby’s blood cells get into the mother’s bloodstream.
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 have an infected cut, the
body goes through a series of events called an
inflammatory reaction.
 Four outward signs:

–
–
–
–
Redness (erythema or rubor)
Heat (calor)
Swelling (edema)
Pain (dolor)
INFLAMMATORY REACTION

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
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
You can also think
of it this way
– 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
Naturally Acquired
Active Immunity
This is when the body is exposed to an
infectious agent and the body has to work to
produce antibodies which specifically attack that
infectious agent.
 The white blood 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.

Naturally Acquired
Active Immunity
– 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.
Active vs. Passive Immunity
Active immunity is long-lived, and may last
for years or even a life time.
 Passive immunity is short lived, and may
last only for a few months.

NOTE: A vaccination is not the same as
receiving an anti-toxin or anti-venom
injection. More on that in Micro class.
ALLERGIES

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:
Immediate
Delayed
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 epinephrine
that will stop the reaction.
Delayed allergic response
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.
Common
allergens
71
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
72
Symptoms of allergy
dependent upon site of allergen exposure
 wheal-and-flare reaction

– Pruritis (itching), erythema
– skin
bronchoconstriction
 mucous secretion
 vasodilation (shock)

73
74
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

75
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 lifethreatening (<5% severe asthma)
76
AUTOIMMUNE DISEASE

A hereditary problem where the body
thinks its own tissues are foreign bodies,
and it constantly tries to kill off its own
tissues.