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THE IMMUNE SYSTEM
We all get sick sometimes...but then
we get better.
What happens when we get sick?
Why do we get better?
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• Let's start at the
beginning. What does it
mean when someone
says "I feel sick today?"
What is a disease? By
understanding the
different kinds of
diseases it is possible to
see what types of
disease the immune
system helps you
handle.
• When you "get sick", your body is not able to
work properly or at its full potential. There are
many different ways for you to get sick - here are
some of them:
Mechanical damage. If you break a bone or tear
a ligament you will be "sick" (your body will
not be able to perform at its full potential). The
cause of the problem is something that is
easy to understand and visible.
• Organ degradation - In
some cases an organ is
damaged or weakened.
For example, one form of
"heart disease" is caused
by obstructions in the
blood vessels leading to
the heart muscle, so that
the heart does not get
enough blood.
• Genetic disease - A genetic disease is
caused by a coding error in the DNA. The
coding error causes too much or too little of
certain proteins to be made, and that causes
problems at the cellular level. For example,
albinism is caused by a lack of an enzyme
called Tyrosinase. That missing enzyme
means that the body cannot manufacture
melanin, the natural pigment that causes hair
color, eye color and tanning.
• Cancer - Occasionally a cell will change in
a way that causes it to reproduce
uncontrollably. For example, when cells in
the skin called melanocytes are damaged
by ultraviolet radiation in sunlight they
change in a characteristic way into a
cancerous form of cell. The visible cancer
that appears as a tumor on the skin is
called melanoma.
• Viral or bacterial infection - When a virus
or bacteria (also known generically as a
germ) invades your body and reproduces,
it normally causes problems. Generally the
germ's presence produces some side
effect that makes you sick.
– The polio virus releases toxins that destroy
nerve cells (often leading to paralysis)
• Your body is a multi-cellular organism
made up of perhaps 100 trillion cells.
• The cells in your body are fairly
complicated machines. Each one has a
nucleus, energy production equipment,
etc.
• Bacteria are singlecelled organisms that
are much simpler. For
example, they have
no nucleus. They are
perhaps 1/100th the
size of a human cell
and might measure 1
micrometer long.
• Bacteria are completely independent organisms
able to eat and reproduce - they are sort of like
fish swimming in the ocean of your body.
• Under the right conditions bacteria reproduce
very quickly: One bacteria divides into two
separate bacteria perhaps once every 20 or 30
minutes.
• At that rate, one bacteria can become millions in
just a few hours.
• A virus is a different
breed altogether.
• A virus is not really
alive.
• A virus particle is
nothing but a
fragment of DNA in a
protective coat.
• The virus comes in contact with a cell, attaches
itself to the cell wall and injects its DNA (and
perhaps a few enzymes) into the cell.
• The DNA uses the machinery inside the living
cell to reproduce new virus particles. Eventually
the hijacked cell dies and bursts, freeing the new
virus particles; or the viral particles may bud off
of the cell so it remains alive. In either case, the
cell is a factory for the virus.
The Lytic
Cycle
• Viral and bacterial infections are by far the
most common causes of illness for most
people. They cause things like colds,
influenza, measles, mumps, malaria, AIDS
and so on. The job of your immune system
is to protect your body from these
infections. The immune system protects you
in three different ways:
1. It creates a barrier that prevents bacteria and
viruses from entering your body.
2. If a bacteria or virus does get into the body, the
immune system tries to detect and eliminate it
before it can make itself at home and reproduce.
3. If the virus or bacteria is able to reproduce and
start causing problems, your immune system is
in charge of eliminating it.
ANATOMY OF THE IMMUNE SYSTEM
• The immune system is
localized in several
parts of the body
– immune cells
develop in the
primary organs bone marrow and
thymus (yellow)
– immune responses
occur in the
secondary organs
(blue)
ANATOMY OF THE IMMUNE SYSTEM
• Thymus – glandular organ near the heart – where T cells learn
their jobs
• Bone marrow – blood-producing tissue located inside certain
bones
– blood stem cells give rise to all of the different types of blood cells
• Spleen – serves as a filter for the blood
– removes old and damaged red blood cells
– removes infectious agents and uses them to activate cells called
lymphocytes
• Lymph nodes – small organs that filter out dead cells, antigens,
and other “stuff” to present to lymphocytes
• Lymphatic vessels – collect fluid (lymph) that has “leaked” out
from the blood into the tissues and returns it to circulation
• All white blood cells are known officially as
Leukocytes.
• White blood cells are not like normal cells
in the body - they actually act like
independent, living single-cell organisms
able to move and capture things on their
own.
•White blood cells behave very much
like amoeba in their movements and are
able to engulf other cells and bacteria.
• Many white blood cells cannot divide and
reproduce on their own, but instead have a
factory somewhere in the body that
produces them. That factory is the bone
marrow.
• Antibodies are produced
by white blood cells.
• They are Y-shaped
proteins that each respond
to a specific antigen
(bacteria, virus or toxin).
• Each antibody has a
special section (at the tips
of the two branches of the
Y) that is sensitive to a
specific antigen and binds
to it in some way.
• When an antibody binds to the outer coat of
a virus particle or the cell wall of a
bacterium it can stop their movement
through cell walls. Or a large number of
antibodies can bind to an invader and signal
to the complement system that the invader
needs to be removed.
• The complement system, like antibodies, is a
series of proteins. There are only a handful of
proteins in the complement system, and they are
floating freely in your blood.
• Complements are manufactured in the liver.
• The complement proteins are activated by and
work with (complement) the antibodies, hence the
name.
• They cause lysing (bursting) of cells and signal to
phagocytes that a cell needs to be removed
PASSIVE IMMUNITY
While your immune system was developing, you were
protected by immune defenses called antibodies. These
antibodies traveled across the placenta from the maternal
blood to the fetal blood.
Antibodies (Y) are also found
in breast milk.
The antibodies received
through passive immunity
last only several weeks.
reign invaders - viruses, bacteria, allergens, toxins and
rasites- constantly bombard our body.
YOUR ACTIVE IMMUNE DEFENSES
Innate Immunity
Adaptive Immunity
- invariant (generalized)
- early, limited specificity
- the first line of defense
- variable (custom)
- later, highly specific
- ‘‘remembers’’ infection
INNATE IMMUNITY
When you were born, you brought with you several
mechanisms to prevent illness. This type of immunity
is also called nonspecific immunity.
Innate immunity consists of:
• Barriers
• Cellular response
– phagocytosis
– inflammatory reaction
– NK (natural killer) and mast cells
• Soluble factors
INNATE IMMUNITY
Barriers
• Physical
– skin
– hair
– mucous
• Chemical
–
–
–
–
–
sweat
tears
saliva
stomach acid
urine
INNATE IMMUNITY
Cellular response
• nonspecific - the same response works against many
pathogens
• this type of response is the same no matter how often it
is triggered
• the types of cells involved are macrophages,
neutrophils, natural killer cells, and mast cells
• a soluble factor, complement, is also involved
Cell Types
1. Lymphocytes: derived in bone marrow from
stem cells 10^12
A) T cells: stored & mature in thymus-migrate
throughout the body
-Killer Cells
Perform lysis (infected cells)
Cell mediated immune response
-Helper Cells
Enhance T killer or B cell activity
-Supressor Cells
Reduce/suppress immune activity
May help prevent auto immune disease
Lymphocytes (cont.)
B) B-Cells: stored and mature in spleen
• secrete highly specific Ab to bind foreign
substance (antigen: Ag), form Ab-Ag complex
• responsible for humoral response
• perform antigen processing and presentation
• differentiate into plasma cells (large Ab
secretion)
2. Neutrophils- found throughout body, in blood
-phagocytosis of Ab-Ag CX
3. Macrophages- throughout body, blood, lymphatics
-phagocytose non-specifically (non Ab coated Ag)
-phagocytose specifically Ab-Ag CX
-have large number of lysosomes (degradative enzyme)
-perform Ag processing and presentation
-present Ag to T helper cell
-secrete lymphokines/ cytokines to stimulate T helper
cells and immune activity
4. Natural Killer Cells-in blood throughout body
-destroy cancer cells
-stimulated by interferons
Phagocytic cells include:
Macrophages engulf pathogens and dead cell remains
Neutrophils release chemicals that kill nearby bacteria
• pus = neutrophils, tissue cells and dead
pathogens
Phagocyte migration
CELLS alive!
Neutrophils and macrophages recognize chemicals
produced by bacteria in a cut or scratch and migrate
"toward the smell". Here, neutrophils were placed in a
gradient of a chemical that is produced by some bacteria.
The cells charge out like a "posse" after the bad guys.
Macrophages
• WBCs that ingest bacteria, viruses, dead cells, dust
• most circulate in the blood, lymph and extracellular
fluid
• they are attracted to the site of infection by chemicals
given off by dying cells
• after ingesting a foreign invader, they “wear” pieces
of it called antigens on their cell membrane receptors
– this tells other types of immune system cells what
to look for
Macrophage and E. coli
©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com
Macrophage ingesting yeast
CELLS alive!
This human macrophage, like the neutrophil, is a professional
"phagocyte" or eating cell (phago = "eating", cyte = "cell").
Here, it envelops cells of a yeast, Candida albicans. After
ingestion, the white cell must kill the organisms by some
means, such as the oxidative burst.
Neutrophils
• WBCs – are phagocytic, like macrophages
• neutrophils also release toxic chemicals that destroy
everything in the area, including the neutrophils
themselves
Neutrophil phagocytosing
S. pyogenes, the cause of strep throat
CELLS alive!
Human neutrophils are WBCs that arrive quickly at the site of
a bacterial infection and whose primary function is to eat and
kill bacteria. This neutrophil ingesting Streptococcus
pyogenes was imaged in gray scale with phase contrast optics
and colorized.
Neutrophil killing yeast
NEUTROPHIL

YEAST 
CELLS alive!
One way that neutrophils kill is by producing an antibacterial compound called “superoxide anion“, a process
called oxidative burst. Here, an amoeboid human
neutrophil senses, moves toward and ingests an ovoid
yeast. In the next two panels, oxidation can be seen by
using a dye, and is colorized here.
INNATE IMMUNITY
Cellular response
Complement
• complement is not a cell but a group of proteins
• these proteins circulate in the blood
• complement plays a role in inflammatory responses of
both the innate and adaptive immune responses
INNATE IMMUNITY
Cellular response
Complement
• complement is not a cell but a group of proteins
• these proteins circulate in the blood
– help to recruit phagocytes to site of inflammation and
activate them
– bind to receptors on phagocytes, helping to remove agent of
infection
– form pores in the invader or infected cell’s membrane (like
the NKs do)
– activate mast cells to release histamine and other factors
• complement plays a role in inflammatory responses
of both the innate and adaptive immune responses
Complement
Series of enzymes which are sequentially
activated and result in lysis of cell
membrane of infected cell at bacterium
Permeablizes membrane
leaky
Complement binding and
activation
~35 enzymes and factors
involved in cascade
Natural killer cells (NK cells)
• instead of attacking the invaders, they attack the
body’s own cells that have become infected by
viruses
• they also attack potential cancer cells, often before
they form tumors
• they bind to cells using an antibody “bridge”, then kill
it by secreting a chemical (perforin) that makes holes
in the cell membrane of the target cell. With enough
holes, the cell will die, because water rushing inside
the cell will induce osmotic swelling, and an influx of
calcium may trigger apoptosis.
Mast cells
• are found in tissues like the skin, near blood vessels.
• are activated after antigen binds to a specific type of
antibody called IgE that is attached to receptors on the
mast cell.
• activated mast cells release substances that contribute to
inflammation, such as histamine.
• mast cells are important in allergic responses but are also
part of the innate immune response, helping to protect
from infection.
INNATE IMMUNITY –
Soluble factors
• Interferon
– a chemical (cytokine) produced by virus-infected
cells that contributes to their death by apoptosis
• Acute phase proteins
– proteins in the plasma that increase during
infection and inflammation
– can be used diagnostically to give an indication of
acute inflammation
Apoptosis or cell death
CELLS alive!
Human neutrophils released into the blood "commit suicide“
after only 1 day. A neutrophil (left) undergoes apoptosis, a
series of changes including violent membrane blebbing and
fragmentation of DNA. Apoptotic cells break into smaller pieces
called apoptotic bodies that other body cells recognize and eat.
• Your mom’s antibodies were effective for
just a short time at birth, but your innate
immune system can be activated quickly.
It is always your first line of defense
during an infection, but it can’t always
eliminate the germ.
• When this happens, your body initiates a
focused attack against the specific
pathogen that is causing the infection.
This attack may lead to long-term
protection against that pathogen.
• This type of immunity is called adaptive
immunity, the customized second line of
defense.
reign invaders - viruses, bacteria, allergens, toxins and
rasites- constantly bombard our body.
YOUR ACTIVE IMMUNE DEFENSES
Innate Immunity
Adaptive Immunity
- invariant (generalized)
- early, limited specificity
- the first line of defense
- variable (custom)
- later, highly specific
- ‘‘remembers’’ infection
1. Barriers - skin, tears
2. Phagocytes - neutrophils,
macrophages
3. NK cells and mast cells
4. Complement and other proteins