Transcript Nature of The Immune System

Nature of The Immune System
I. Historical Concepts
II. Non-Specific Immunity
Terry Kotrla, MS, MT(ASCP)BB
Age of Serology
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.
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Introduction
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.
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Vaccination
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.
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Vaccination – Edward Jenner
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.
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Vaccination – Edward Jenner
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.
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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
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.
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Natural (Nonspecific , Innate) Immunity
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Non-specific immunity
First line of defense against infection
 Uses body functions

Coughing, sneezing, cilia
 HCl in stomach, wax in ears, enzymes in tears
 Circulating and tissue cells
 Circulating substances
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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
Age
 Hormones
 Drugs and chemicals
 Malnutrition
 Fatigue and stress
 Genetic determinants
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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

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
Mononuclear phagocytes
 Polymorphonuclear phagocytes
 Eosinophils
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Mediator cells
Basophils and mast cells
 Platelets
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Cells involved in specific immunity
Lymphocytes
 Plasma cells
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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
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 are easily identified due to large numbers of
bluish-black granules in the cytoplasm. These
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
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.
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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
non-specific 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 non-specific and specific immune mechanisms.
Acute Phase Reactants
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Defined-normal serum constituents that
increase rapidly because of infection,
injury, or trauma to tissues.
C-Reactive Protein
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.
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Complement
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A series of serum proteins involved in
mediation of inflammation but also
involved in
opsonization,
 chemotaxis, and
 cell lysis.
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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
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
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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.
Ceruloplasmin
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The major copper containing protein in plasma,
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 cirroses and
with all types of stress in general.
 Other effects related to elevated levels of AGP are
immunosuppression, poor response to vaccines, etc.
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/