Innate_Immunity

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Transcript Innate_Immunity

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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
–
–
–
–
–
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
• a soluble factor, complement, is also involved
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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

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
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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
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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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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
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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
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
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
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This immunology curriculum and integrated laboratory modules were created by teachers
and scientists working together through a grant from the National Science Foundation to the
Nanobiotechnology Center in collaboration with the Cornell Institute for Biology Teachers,
which is funded by the Howard Hughes Medical Institute.
Collaborators for this project:
Harriet Beck, Wellsville Central School
Jim Blankenship, Cornell Institute for Biology Teachers
Rita Calvo, Cornell University
Jerrie Gavalchin, Cornell University
Mary Kay Hickey, Dryden High School
Susan Oliver, Dundee High School
Jeanne Raish, Avoca Central School
Anna Waldron, Nanobiotechnology Center
This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement
No. ECS-9876771. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the
author(s) and do not necessarily reflect the views of the National Science Foundation.
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Permission to use images were secured by the NBTC from various sources:
KUBY IMMUNOLOGY by Richard A. Golsby and Thomas J. Kindt and Barbara A. Osborne. © 1992,
1994, 1997, 2000 by W.H. Freeman and Company. Used with permission.
© 2001 From Immunobiology: The Immune System in Health and Disease, Fifth edition by Charles A.
Janeway, Paul Travers, Mark Walport and Mark Shlomchik. Reproduced by permission of Routledge, Inc.,
part of The Taylor & Francis Group.
© 2000 From The Immune System by Peter Parham. Reproduced by permission of Routledge, Inc., part
of The Taylor & Francis Group.
Dennis Kunkel Microscopy, Inc., www.DennisKunkel.com
CELLS alive! www.cellsalive.com
Mike Clark, www.path.cam.ac.uk/~mrc7/
This material is based upon work supported in part by the STC Program of the National Science Foundation under Agreement
No. ECS-9876771. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the
author(s) and do not necessarily reflect the views of the National Science Foundation.