Download Nature of The Immune System

Nature of the Immune System
I.
II.
Historical Concepts
Specific Immunity
Terry Kotrla, MS, MT(ASCP)BB
Age of Serology
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Time period from 1900 to 1950 called era of
international serology.
Immunology is a relatively new science.
Tests developed to detect presence of immune
substances in the blood.
Introduction
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Immunology defined as the study of the
reaction of a host when foreign substances are
introduced into the body.
Immunity is the condition of being resistant to
infection.
Serology is the study of the noncellular
components in the blood.
Vaccination
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Purposeful exposure of individual to
infectious material.
Early forms of vaccination were developed in
ancient China as early as 200 B.C.
Used powdered scabs from people infected
with smallpox was used to protect against the
disease.
Vaccination – Edward Jenner
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Smallpox affected all levels of society.
Noticed that milkmaids did not generally get
smallpox.
Jenner theorized that the pus in the blisters
which milkmaids received from cowpox (a
disease similar to smallpox, but much less
virulent) protected the milkmaids from
smallpox.
Vaccination – Edward Jenner
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Inoculated 8 yr old with material from pus in
cowpox blisters.
Exposed boy to infectious agents and no
disease followed.
Jenner's unique contribution was not that he
inoculated a few persons with cowpox, but
that he then proved they were immune to
smallpox.
Cow Pox versus Small Pox
Vaccination
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A vaccine - biological preparation that improves
immunity to a particular disease.
A vaccine typically contains a small amount of an
agent that resembles a microorganism.
Stimulates the body's immune system to recognize
the agent as foreign, destroy it, and "remember" it,
so that the immune system can more easily recognize
and destroy any of these microorganisms that it later
encounters.
Vaccination - Types
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Killed microorganisms
Attenuated – live organisms cultivated to disable
virulent properties
Toxoid - inactivated toxic compounds in cases where
these (rather than the micro-organism itself) cause
illness
Subunit -fragment create an immune response
Conjugate-linking outer coats to proteins which can
the lead immune system to recognize
Rabies
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Louis Pasteur applied this principle of attenuation to
a rabies vaccine.
Developed a rabies virus that was milder and had a
shorter incubation (development) period than the
wild virus.
A person bitten by a rabid animal would be
inoculated with the Pasteur virus and rapidly develop
immunity to the wild strain.
Rabies
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He developed his rabies vaccine by growing the
virus in rabbits, then drying the affected nerve tissue
to weaken the virus.
On July 6, 1885, the vaccine was administered to a
9-year-old boy who had been attacked by a rabid
dog.
The boy survived and avoided contracting rabies,
which would have almost certainly proved fatal.
Rabies
Cellular versus Humoral Immunity
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Cellular - Researchers observed that foreign
substances were removed by specialized cells
in a process known as phagocytosis.
Humoral - Other researchers postulated that
substances in the blood provided protection
from microorganisms, humoral immunity.
Natural (Nonspecific , Innate) Immunity
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Non-specific immunity
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First line of defense against infection
Uses body functions
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Coughing, sneezing, cilia
HCl in stomach, wax in ears, enzymes in tears
Circulating and tissue cells
Circulating substances
Two mechanisms – external and internal
Physical barriers – Intact Skin
Physical Barrier - Cilia
Physiological factors
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Stomach acid kills pathogens and sterilizes food.
Mucus lining of lungs traps pathogens and cilia move
particles out to throat and it is swallowed.
Tears wash away pathogens and have bacteriocidal enzymes.
Flushing action of urine
Skin: Difficult for a pathogen to penetrate, sweat creates high
salt conditions, oil layer makes an inhospitable environment.
Normal flora prevents growth of opportunistic pathogens in
mouth, large intestine and reproductive system
Factors Modify Defense Mechanisms
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Age
Hormones
Drugs and chemicals
Malnutrition
Fatigue and stress
Genetic determinants
Nonspecific Immunity: Second line of defense
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Inflammatory response - four classic signs are
redness, swelling, heat and pain.
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Dilation of capillaries (hyperemia) to increase blood
flow to area
Chemotaxis - chemicals released which cause phagocytic
white cells to migrate to the area.
Increased capillary permeability allowing white cells to
go to injured area, a process known as “diapedesis”
Formation of exudate - same composition as plasma and
it contains antibacterial substances, phagocytic cells, and
drugs and antibiotics, if present.
Inflammatory Response
Inflammatory Response
Inflammatory Response
Second Line of Defense
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If bacteria are not successfully killed locally, may further
invade the host by way of the lymphatics to the regional
lymph nodes.
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within lymph nodes the bacteria meet other phagocytic cells
bacteria may overcome these and gain access to the
bloodstream where they meet circulating phagocytes
(neutrophils and monocytes).
may pass through the bloodstream and reach organs such as the
liver and spleen where they come into contact with tissue
macrophages.
although a powerful defense system, this final phagocytic
barrier may be overcome, with seeding of the microorganism to
organs such as bone, brain, and kidney, terminating in fatal
septicemia.
Phagocytosis
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Initiation is caused by damage to the tissues, either by trauma or as a
result of microbial multiplication.
Chemotaxis, attraction of leukocytes or other cells by chemicals.
Opsonization - Opsonization coating a pathogen by substances so as to
enhance phagocytosis.
Adherence, firm contact between phagocyte and microorganism.
Engulfment into cytoplasm and enclosed in a vacuole.
Digestion enzymatic contents in vacuole destroy the microorganism.
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Number of killing mechanisms operating in the vacuoles of phagocytic cells.
One of the major mechanisms involves hydrogen peroxide which, acting
along with an intracellular enzyme, is rapidly lethal to many bacteria.
Phagocytosis
Phagocytosis
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http://www.cellsalive.com/ouch.htm
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http://health.howstuffworks.com/adam-200096.htm
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http://tinyurl.com/6oa779
Cells of the Non-Specific Immune System
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Cells involved in non specific immunity.
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Phagocytic cells
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Mononuclear phagocytes
Polymorphonuclear phagocytes
Eosinophils
Mediator cells
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Basophils and mast cells
Platelets
Cells involved in specific immunity
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Lymphocytes
Plasma cells
Origin of immune cells
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Origin of all these cell types are stem cells found in the bone
marrow.
These self replicating cells differentiate into two types of
"committed" stem cells.
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One group differentiates further and matures to become platelets,
erythrocytes (red blood cells), monocytes or granulocytes.
Second group produces cells of the lymphoid line only.
The lymphoid line will develop into 2 different types, T and B
cells, depending upon where they complete their maturation,
thymus or bone marrow.
Phagocytic Cells
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Mononuclear phagocytes - include both circulating blood
monocytes and tissue macrophages found in various tissues
of the body.
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Arise from bone marrow stem cells
Not end cells, they may divide.
Ingest and destroy material such as bacteria, damaged host cells or
tumor cells (non-specific immunity).
Stay in peripheral blood 70 hours - migrate to tissues, double in size,
then called tissue macrophages.
Tissue macrophages named according to tissue locationliver=Kupffer cells, brain-microglial cells, etc.
Phagocytosis takes place to a greater degree in tissues.
Monocyte and Tissue Macrophage
Polymorphonuclear phagocytes
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AKA Neutrophils
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Characterized by a large nucleus, usually with 3 - 5 lobes,
and the presence of numerous, specific granules in the
cytoplasm.
Arise from bone marrow stem cells.
They are end cells.
Primary function is ingestion (phagocytosis).
Clear body of debris such as dead cells and thrombi.
Able to move into tissues by diapedesis -wander
randomly
Neutrophil Involved in Phagocytosis
Eosinophils
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Easily distinguished by the presence of large granules in their
cytoplasm which appear red when stained by routine
hematology stains.
Much less phagocytic than macrophages or neutrophils
Function is far from clear, however the numbers increase
greatly in certain parasitic diseases and allergic diseases.
Both neutrophils and eosinophils contain specific granules,
the granules contain various enzymes which are released
under certain circumstances.
Eosinophil
Mediator Cells
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Influence the immune response by releasing various
chemical substances into the circulation.
Have a variety of biological functions
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Increase vascular permeability
Contract smooth muscle
Enhance the inflammatory response
Two types
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basophils/mast cells
Platelets
Basophils and Mast cells
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Basophils easily identified due to large numbers of bluishblack granules in the cytoplasm.
The granules are a source of mediators such as histamine
(vasoactive amine that contracts smooth muscle) and heparin.
Basophils and platelets are found in the circulation, mast cells
are situated in the tissues of skin, lung and GI tract.
Circulating basophils greatly resemble tissue mast cells and it
is likely that they are closely related in function.
Both of these cells play a role in hypersensitivity (allergic)
reactions.
Basophil
Platelets
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Small non-nucleated cells derived from
megakaryocytes of the bone marrow.
Important in blood clotting.
Contribute to the immunological tissue injury
occurring in certain types of hypersensitivity
reactions by releasing histamine and related
substances which are contained within
specialized granules in their cytoplasm.
Megakaryocyte & Platelets
Soluble Factors
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Many soluble tissue and serum substances help to suppress
the grow of or kill microorganisms.
Interferons - family of proteins which are important nonspecific defense mechanisms against viral infections.
Transferrin - Bacteria do not thrive well in serum that
contains low levels of iron but high levels of transferrin.
Complement - a group of proteins that are essential for
bacterial destruction and plays an important role in both nonspecific and specific immune mechanisms.
Acute Phase Proteins
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Defined-normal serum constituents that increase rapidly
because of infection, injury, or trauma to tissues.
Acute-phase proteins are a class of proteins whose plasma
concentrations increase or decrease in response to
inflammation.
This response is called the acute-phase reaction .
In response to injury local inflammatory cells (neutrophils,
granulocytes and macrophages) secrete a number of cytokines
into the bloodstream, most notable of which are the
interleukins.
The liver responds by producing a large number of acutephase reactants.
C-Reactive Protein
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Increases rapidly within 4-6 hours of infection
or injury.
Returns to normal rapidly once condition
subsides.
Used to monitor healing and has also
increased in usefulness in diagnosing
Myocardial Infarction.
Complement
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A series of serum proteins involved in
mediation of inflammation but also involved
in
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opsonization,
chemotaxis, and
cell lysis.
Alpha-1 Antitrypsin
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Plays important role preventing breakdown of
enzymes in various organs of the body and protects
the lungs so they can work normally.
When the lungs do not have enough alpha-1
antitrypsin, neutrophil elastase is free to destroy lung
tissue.
As a result, the lungs lose some of their ability to
expand and contract (elasticity). This leads to
emphysema and sometimes makes breathing
difficult.
Haptoglobin
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Binds irreversibly to free hemoglobin to
protect kidneys from damage and prevent loss
of iron by urinary excretion.
Haptoglobin - hemoglobin complex removed
by RES, mainly spleen.
Used to monitor hemolysis
Fibrinogen
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A coagulation factor integral to clot formation
which serves as a barrier to prevent spread of
microorganisms further in the body.
Levels increase with tissue inflammation or
tissue destruction.
Thought to play a key role in the
inflammatory response and development of
rheumatoid arthritis.
Ceruloplasmin
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The major copper containing protein in plasma, plays a role
in iron metabolism and histamine regulation.
Stimulates the immune system to fight infections, repair
injured tissues and promote healing.
Depletion found in Wilson’s disease, causes the body to
absorb and retain excessive amounts of copper.
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Copper deposits in the liver, brain, kidneys, and the eyes.
The deposits of copper cause tissue damage, necrosis (death of the
tissues), and scarring, which causes decreased functioning of the
organs affected.
Liver failure and damage to the central nervous system (brain, spinal
cord) are the most predominant, and the most dangerous, effects of
the disorder.
Alpha-1 Acid Glycoprotein(AGP)
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An acute phase protein manufactured in the liver and found in
the blood of humans and animals.
In simplest form, detection of elevated levels of AGP has
been shown to indicate background illness or other stressors
when animals appear clinically normal.
Acute phase proteins such as AGP are elevated during acute
or chronic periods of inflammation or infectious diseases,
following surgery, with malignant tumors, in autoimmune
diseases, liver cirrhoses and with all types of stress in general.
Other effects related to elevated levels of AGP are
immunosuppression, poor response to vaccines, etc.
Immunity – Very Complex System
References
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http://www.horton.ednet.ns.ca/staff/Selig/isu/Immunity/Innate.htm
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http://www.metacafe.com/tags/neutrophil/most_popular/