Transcript THE IMMUNE SYSTEM

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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?
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)
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ANATOMY OF THE IMMUNE SYSTEM
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• 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
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.
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reign invaders - viruses, bacteria, allergens, toxins and
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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
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INNATE IMMUNITY
Barriers
• Physical
– skin
– hair
– mucous
• Chemical
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sweat
tears
saliva
stomach acid
urine
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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
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Phagocytic cells include:
Macrophages engulf pathogens and dead cell remains
Neutrophils release chemicals that kill nearby bacteria
• pus = neutrophils, tissue cells and dead
pathogens
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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.
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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
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Macrophage and E. coli
©Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com
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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.
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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
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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.
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Neutrophil killing yeast
NEUTROPHIL
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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.
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INNATE IMMUNITY
Cellular response
Inflammatory response
• chemical and cell response to injury or localized infection
• eliminates the source of infection
• promotes wound healing
Step 1. Circulation to the site increases  tissue warm,
red and swollen
Step 2. WBCs leak into tissues  phagocytes engulf and
destroy bacteria
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INNATE IMMUNITY
Cellular response
Inflammatory response (cont’d)
The release of histamine and prostaglandin causes
local vessel dilation resulting in:
• more WBCs to site
• increased blood flow  redness and warmth
• increased capillary permeability
• phagocytes move out of vessels into
intracellular fluid (ICF)
• edema (swelling) due to fluids seeping from
capillaries
INNATE IMMUNITY
Cellular response
Inflammatory response (cont’d)
Fevers have both positive and negative effects on
infection and bodily functions
POSITIVE
NEGATIVE
• indicate a reaction to
infection
• extreme heat  enzyme
denaturation and
interruption of normal
biochemical reactions
• stimulate phagocytosis
• slow bacterial growth
– increases body temperature
beyond the tolerance of
some bacteria
– decreases blood iron levels
> 39° C (103°F) is dangerous
> 41°C (105°F) could be fatal
and requires medical
attention
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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.
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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.
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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.
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• 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/acquired immunity, the
customized second line of defense.
reign invaders - viruses, bacteria, allergens, toxins and
rasites- constantly bombard our body.
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YOUR ACTIVE IMMUNE DEFENSES
Innate Immunity
Acquire 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
YOUR ACTIVE IMMUNE
DEFENSES
reign invaders - viruses, bacteria, allergens, toxins and
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rasites- constantly bombard our body.
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
1. APCs present Ag to T cells
2. Activated T cells provide help to
B cells and kill abnormal and
infected cells
3. B cells - produce antibody
specific for antigen
STARTING AN IMMUNE
RESPONSE
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Foreign invaders - viruses, bacteria, allergens, toxins
and parasites - constantly bombard our body.
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The response to this assault is a carefully orchestrated and
controlled interaction between immune cells with the ultimate
goal to eliminate the invader by pathogen-specific
mechanisms.
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Antigen presentation
APC
T helper cell
Antigen-presenting cells
(APCs) may be
macrophages or B cells
T cells have special antigenrecognizing molecules on their
surfaces called T cell receptors
(TCR). An APC that has
ingested antigen “presents”
pieces of the Ag to T cell by
docking with its TCR. This, and
a 2nd signal, activates the T cell.
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T cell activation
Activated T helper
cells induce
effector and
memory TH cells
Presentation of antigen to a
T cell triggers its activation
into a helper T (TH) cell.
Activated TH cells produce
a cytokine called
interleukin-2 (IL-2). IL-2
causes the T cells to divide.
Some of the new T cells go
into battle (TH effector cells)
and some become memory
cells.
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B cell activation and
differentiation
Activated T
helper cell
Antibodies
Activated T cells interact with
B cells through the action of
cytokines. The B cells
become activated and
differentiate into plasma
cells. Plasma cells secrete
antibodies, which help to
inactivate the antigen.
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How lymphocytes produce
antibody
CELLS alive!
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Production of cytotoxic T cells
Activated T
helper cell
Cytotoxic T
cell (Tc)
Memory Tc
Effector Tc
T cells may be activated by
IL-2 from T helper cells.
Some will become
cytotoxic T cells (Tc ) that
kill abnormal and infected
cells. Others will become
memory cytotoxic T cells.
PUTTING IT ALL TOGETHER…
APC
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T helper cell
Activated T helper cell
Cytotoxic
T cell (Tc)
Antibodies
Memory Tc
Effector Tc
Lysis
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IMMUNE RESPONSE
There are two phases in the generation of an immune
response:
• primary response – when the Ag is first encountered
– the response is slow because, at first, there are only a few B cells that react
with the Ag
– the weak response allows the invader enough time to cause illness
– a type of antibody (IgM) and memory B cells are produced
• secondary response – the next time the antigen is encountered
– the response is quicker and stronger each time
– memory B cells recognize antigen and they all begin to divide quickly
– lots of plasma cells are produced which make lots of a different type of
antibody called IgG
The course of a typical antibody
response
The first encounter with an antigen produces a primary response.
Antibody against antigen A (blue) appears; its concentration rises to a
plateau, and then declines. When antigen A and a new antigen, B, are
encountered later, a very rapid and intense secondary response to A
occurs due to immunologic memory. This is the main reason for giving
booster injections after an initial vaccination. A primary response occurs
to antigen B.
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How does an immune response
end?
• The immune response will end when the antigen that caused the
response is no longer present
– this is what happens when antibiotics are used to treat a bacterial
infection. Once the bacteria are killed and cleared from the body,
the production of a specific immune response to the bacteria will
stop, including the activation of T cells and the production of
specific antibodies. Suppressor T cells may help in this process.
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What makes us sick?
• “enemies” in the environment in the form of microbes and
chemicals are constantly attacking our bodies, disrupting
homeostasis
• sometimes immune system homeostasis is disrupted on its own
it may over-react to
antigens such as
with allergies
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it may under-react as
with human
immunodeficiency
virus infection (HIV)
it may react to self
proteins as with
autoimmune disease
Why does the immune system
attack the body that it’s supposed
to protect?
• failure to recognize some cells as “self”
– in rheumatic fever, the streptococcus antigen is very similar to a protein in
heart tissue, so the body mistakenly identifies heart tissues as foreign
• cells seen as foreign are attacked and destroyed
– may be only a few select cells or organs (organ-specific) – e.g., multiple
sclerosis, juvenile diabetes, rheumatic fever
– may be systemic - e.g., systemic lupus erythematosus, rheumatoid
arthritis
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Acquired immunodeficiency
syndrome
(AIDS)
• first identified in 1981
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• caused by the human immunodeficiency virus (HIV) and is spread by
contact with body fluids
• infects CD4+ (helper) T cells, which decrease in number
• decreased numbers of CD4+ T cells lead to increased susceptibility to
opportunistic infections.
• treatments include drugs that inhibit the activity of HIV proteins, thereby
preventing production of the virus
Worldwide HIV infection,
1999
HIV virus particle
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THE IMMUNE SYSTEM IN
HEALTH AND DISEASE
How does your everyday life affect your
immune system?
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Exercise and stress
• exercise has been shown to boost the immune response
– moderate exercise increases the immune response in all age groups
– intensive exercise can stress the immune system
• lack of sleep and exhaustion decrease immune function
• psychological stress has also been found to decrease
immune function
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Diet
• a well-balanced diet is essential for good immune system
health
– fats are very important in the production of WBCs, cytokines and
natural killer cells
– selenium, zinc, and copper are required in small amounts, which
you get if you eat a balanced diet
– vitamin E has been shown to boost antibody production in the
elderly
– vitamin B6 aids in antibody synthesis
• but mega-dosing can be harmful, too!
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Environment
Exposure to certain things in their environment may
activate the immune systems of some people
• Chemicals
– dioxin
– pesticides
– solvents
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Viruses
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Bacteria
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Food
• Sunlight
• Medication