Download The Lymphatic System

The Lymphatic System
Part 1
Chapter 12
Lymphatic System

The lymphatic system actually consists
of two semi-independent parts
• Lymphatic vessels
• Transport fluids escaped from the vascular system
back to the blood
• Lymphoid tissues and organs
• House the phagocytic cells and lymphocytes which
help the body's defenses against disease
Lymphatic Vessels



As blood circulates throughout the body
exchanges of nutrients waste and gases
occurs between the blood and the interstitial
fluid.
Hydrostatic and Osmotic pressures are
responsible for forcing fluid out of the blood at
the capillaries and then reabsorb it into the
veins
As much as 3 liters of fluid is left behind in the
tissue spaces and will become part of the
interstitial fluid.
Lymphatic Vessels



The fluid left behind along with plasma proteins
must be carried back to the blood in order for
the vascular system to have the proper amount
of blood volume to operate.
If this does not occur the fluid builds up in the
tissues and is then referred to as EDEMA.
Excessive edema will impair the ability of the
cells to make exchanges with the interstitial
fluid and eventually stop making exchanges
with the blood.
Lymphatic Vessels


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The function of the lymphatic vessels is
to pick up the excess tissue fluid (lymph)
and return it to the blood stream.
Lymph: Clear water that is found within
the tissues that was not reabsorbed by
the venous system.
Lymphatics: groups of lymphatic vessels
that form a one way system flowing only
towards the heart
Lymphatic Vessels

Lymph Capillaries: form a web between the
tissue cells and the blood capillaries in the
loose connective tissues of the body where
they absorb leaked fluid.
•
•
•
•
Extremely permeable
Contain flap like “minivalves” along their walls that act
as one way swinging doors
When fluid pressure is higher in the interstitial space
the doors open and fluid moves into the lymphatic
capillaries
When pressure is higher inside the lymphatic vessels
the flaps are forced closed and cause the fluid to be
pushed along the vessel and preventing it from
moving back into the interstitial space.
Lymphatic vessels


Lymph capillaries are so permeable that they
can also allow proteins, cell debris and
bacteria to enter and take them away from the
area where they have built up.
Lymph is transported from the capillaries
through the larger lymphatic vessels until it
returns through one of two large ducts in the
thoracic region:
•
•
Right lymphatic duct
Thoracic duct
Lymphatic Vessels

Right Lymphatic duct:
• Drains lymph from the right arm and the right
side of the head and thorax

Thoracic Duct
• Receives lymph from the rest of the body
• Both ducts will empty their lymph into the
subclavian vein on their side of the body
Lymphatic Vessels

Lymphatic vessels:
• Thin walled
• Larger ones contain valves
• Low pressure, pumpless system
• Transported by the action of skeletal muscle
•
contractions and pressure changes in the
thorax during breathing
The working of the smooth muscles of the
digestive tract also help to move the lymph
along.
Lymph Nodes

Lymph nodes:
• Protect the body by removing foreign
materials such as
• Bacteria
• Tumor cells
• They Produce lymphocytes which help in the
immune response
Lymph Nodes


When lymph moves towards the heart it is
filtered through thousands of lymph nodes that
are found in clusters along the lymphatic
vessels
The largest clusters of lymph nodes are found
in the:
•
•
•
Inguinal
Axillary
Cervical regions
Lymph Nodes

Each lymph node contains
• Macrophages: engulf and destroy bacteria,
•
•
viruses, and foreign substances so that they
cannot go back into the blood stream
Lymphocytes: type of white blood cell found in
the lymph nodes also attack foreign
substances
When the lymph nodes trap the foreign
substances we may become aware of the
swelling of the glands.
Lymph Nodes

Lymph nodes may vary in their shape
and size but most are:
• Kidney shaped
• Less than 1 inch long
• Buried within the connective tissue
•
surrounding them
Surrounded by a fibrous capsule that contains
trabeculae
Lymph Nodes



Trabeculae:
•
Extensions off of the fibrous capsule surrounding the
lymph node that extend inward dividing the capsule
into compartments.
Cortex:
•
The outer part of the node which contains collections
of lymphocytes called…
Follicles:
•
Have a dark-staining center called germinal centers
that enlarge when specific lymphocytes are generating
daughter cells called plasma cells
Lymph Nodes


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Plasma cells are responsible for the
release of antibodies.
The rest of the cells within the cortex are
lymphocytes in transit or better known
as…
T-Cells
• Circulate between the blood, lymph nodes
and lymphatic “stream” checking for foreign
substances.
Lymph Nodes

Medulla:
•
Center area of the lymph node that houses the
phagocytic macrophages\
Lymph enters the convex side of the lymph node through
afferent lymphatic vessels from there it flows through a
number of sinuses within the lymph node and then
exits the node through an indented portion known as
the Hilus and then through the efferent lymphatic
vessels
Lymph Nodes


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There are fewer of the efferent vessels than
afferent vessels which makes the flow of lymph
through the lymph node is very slow.
Since it is so slow this allows the lymphocytes
and macrophages to perform their cleansing
and protecting functions.
It will become completely “cleansed” after
passing through several lymph nodes.
Homeostatic Imbalance of the
Lymph Nodes
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
When lymph nodes become overwhelmed by
the foreign substances they are trying to
destroy the nodes will become inflamed and
tender to touch.
They can also become secondary cancer sites,
mostly in cancers that use the lymphatic
system to spread.
When the lymph nodes have cancerous tissue
within them they are inflamed but do not
become tender to the touch and are easily
distinguished from just a viral/bacterial
infection
Lymph Organs
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Spleen
Thymus gland
Tonsils
Payers patches
Lymphatic tissue within the epithelial and
connective tissue
Other Lymph organs

Common feature of other lymph organs
• Reticular connective tissue
• Lymphocytes
• Their function is to protect the body – only
lymph nodes filter lymph
The spleen

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
Blood-rich organ that filters blood
Location:
•
Upper left side of the abdominal cavity
Function:
•
•
•
•
Filters and cleanses blood of bacteria, viruses and
other debris.
Destroys worn out red blood cells and returns their
broken down products to the liver to create something
else.
Stores platelets, acts as a blood reservoir
Produce Lymphocytes
The Thymus

Lymphatic mass that is most active
during youth
Location:

Function:

• Low in the throat, overlying the heart
• Produces hormones that function in the
programming of lymphocytes so that they can
carry out their protective role
The Tonsils
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
Small masses of lymphatic tissue that surround
the pharynx (throat)
Location:
•
Found within the mucosa of the throat
Function:
•
•
Trap and remove bacteria or other foreign material
entering the body
When they become too full of bacteria or foreign
material they swell and become irritated = tonsillitis
Peyers Patches

Resemble tonsils
Location:

Function:

• In the wall of the small intestine
• Capture and destroy bacteria preventing it
from penetrating the intestinal wall
Mucosa-Associated-Lymphatic
Tissue (MALT)



Collections of small lymphoid tissues
Peyers patches and Tonsils are part of
this group
MALT acts as to protect the upper
respiratory and digestive tracts from
foreign matter entering those cavities
Body Defenses

Non-specific defense system:
•
•
Responds immediately to protect the body from all
foreign substances
Provided by:
• Intact skin
• Mucus membranes
• Inflammatory response
• Proteins produced by the body
Prevents entry and spread of micro-organisms through the
body
Body Defenses

Specific Defense System:
• Most commonly called the Immune System
• Attacks PARTICULAR foreign substances
• Its structures are
• Molecules
• Immune cells
• Lymphocytes
• Macrophages
Body Defenses

Specific Defense system
• When immune system is working properly it
•
protects us from bacteria, viruses,
transplanted organs/grafts and even our own
cells that have turned against us
It does this by
• Directly attacking the cells and indirectly by
releasing chemicals and protective antibodies
• Immunity: the highly specific resistance to disease
Non-Specific Body Defenses



Defined: Mechanical barriers that cover
body surfaces and cells and chemicals
that act to protect body from invading
pathogens
Pathogen: harmful or disease causing
micro-organism
Some non-specific responses to disease
is inherited
Non-Specific body Defense

Surface Membrane Barriers
• First line of defense against invasion of
disease causing micro-organisms
• Skin
• Strong barrier of keratinized epidermis
• Produce protective chemicals
• Mucus Membranes
• Line all body cavities open to the exterior
• Produce protective chemicals
Non-Specific Body Defense

Chemicals that protect:
•
Acid pH of the skin
•
Stomach mucosa
• Inhibits bacterial growth
• Sweat (sebum) contains chemicals that are toxic to bacteria
• Secretes Hydrochloric acid and protein digesting enzymes that
kill pathogens
•
Saliva and Lacrimal fluid
•
Sticky mucus
• Contains lysozyme that destroys bacteria
• Traps micro-organisms that enter the digestive and respiratory
passages
Non-Specific Body Defense

Structural modifications that fend off
invaders:
• Mucus coated hairs – trap inhaled material
• Cilia – sweep dust and bacteria away from the
lungs
Non-Specific Body Defense

Cells and Chemicals
• The second line of defense
• These defenses rely on
• Phagocytes
• Natural killer cells
• Inflammatory response
• Chemical substances
• Fever
Non-Specific Body Defense

Phagocytes:
• Cell eating
• Macrophages and Neutrophils engulf the
•
foreign particle then their cytoplasmic
extensions bind the particle pulling it inside
enclosing it within the vacuole
The vacuole then fuses with the enzymatic
contents of a lysosome and its contents are
then broken down and digested
Non-Specific Body Defense

Natural Killer Cells
• Unique group of defensive cells that can lyse and
•
•
•
kill cancer cells and virus infected body cells
before the immune system is involved
They can act spontaneously against any invader
by recognizing certain sugars on the surface of
the foreign material
They are NOT phagocytic
They attack the cells membrane and release
chemicals that disintegrate the entire cell and its
contents
Non-Specific Body defense

Inflammatory Response
•
•
•
Nonspecific response that is triggered whenever the
body tissues are injured
Occurs in response to physical trauma, intense heat,
irritating chemicals as well as infection of viruses and
bacteria
Four cardinal signs and symptoms of inflammation
are:
• Redness
• Heat
• Swelling
• Pain
Non-Specific Body Defenses

Inflammatory response:
• When cells are injured they release
inflammatory chemicals including histamine
and kinins that:
• Cause blood vessels in the involved area to dilate
and capillaries leak
• Activate pain receptors
• Attract phagocytes and white blood cells to the
area (chemotaxis)
Non-Specific Body Defense

Inflammatory response:
• Prevents spread of damaging agents to
•
•
nearby tissues
Disposes of cell debris and pathogens
Sets the stage for repair
Inflammatory Response

Within the first hour of an injury the
inflammatory response occurs
•
•
•
Neutrophils squeeze through the capillary walls and
begin cleaning up by engulfing dead or damaged
materials
Monocytes (poor phagocytes) leave the bloodstream
following the neutrophils into the inflamed area and
within 8-12 hours will become macrophages with big
appetites
Macrophages take over for the neutrophils as the final
disposal for cell debris
Inflammatory Response

Once the phagocytosis is finished clotting
begins
• Clotting proteins leak in from the blood and
•
•
close off the damaged area so that pathogens
and other harmful substances cannot spread.
This fibrous mesh also forms the “blueprint” for
the permanent repair of the damaged tissue
Local heat raises the metabolic rate of the tissue
cells and speeds up the defensive action and
repair processes.
Homeostatic Imbalance
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

If the injured area becomes severly infected a
yellow pus may form in the wound
Pus: mixture of dead or dying neutrophils,
broken down tissue cells and living and dead
pathogens.
If the inflammatory response fails to fully clear
all the debris and the sac of pus is “blocked off”
it forms an Abscess that must be surgically
drained before healing can take place
Non-Specific Body Defense

Antimicrobial Chemicals:
• The most important antimicrobial chemicals
are the:
• Complement proteins
• Interferons
Non-Specific Body Defenses

Complement Proteins:
• Complement: groups of at least 20 plasma
•
•
proteins that circulate in the blood in an
inactive state
Once the complement attaches itself to
another material it becomes a factor in
fighting foreign cells
Complement fixation: occurs when
complement proteins bind to sugars or
proteins on a foreign cells surface
Non-Specific Body Defense

Complement fixation:
• Membrane attack complexes: produce lesions
•
•
in the surface of a foreign cell, allowing water
to rush in and cause the cell to burst
Activated complements also amplify the
inflammatory response by vasodilatation or
releasing chemotaxis chemicals which draw
neutrophils and macrohages to the area
Opsonization: causes the cell membrane to
become sticky and easier to phagocytize (eat)
Non-Specific Body Defense

Interferon:
•
•
•
Viruses cannot create ATP for energy and therefore
enter the tissues and take over the cellular
“machinery” needed to reproduce themselves.
The cell that is infected with the virus can now no
longer defend itself but can help defend other cells
that have not been infected yet by releasing
Interpherons
Interpherons are small proteins that diffuse to nearby
cells and bind to their membrane receptors and hinder
the ability of the virus to multiply within the cell
Non-Specific Body Defense

Fever:
•
•
•
•
•
•
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Abnormally high body temperature
Systemic response to invading micro-organisms
Temperature is regulated by the hypothalamus and is normally set
at 98.2˚f but can be reset upwards in response to pyrogens
Pyrogens: chemicals secreted by white blood cells and
macrophages exposed to foreign cells or substances within the
body
Excessive fever is dangerous to the body but a moderate fever has
benefits
Bacteria must have large amounts of iron and zinc to multiply and
during a fever the liver and spleen take up these nutrients making
them less available
Increases the metabolic rate of tissue cells speeding up their repair
process
Specific Body Defenses:
The Immune System

Immune response:
• The immune systems response to a threat
• Increases the inflammatory response
• Provides protection targeted against specific
•
antigens
Initial exposure to an antigen prepares the
body to react more vigorously the next time it
sees it.
Specific Body Defenses:
The Immune System

Immune System:
•
•
•
•
Body’s third line of defense
Functional system that recognizes foreign molecules
and acts to destroy or inactivate them
Protects from variety of pathogens as well as
abnormal body cells
Failure of this system to work results in devastating
diseases such as:
• Cancer
• AIDS
• Rheumatoid arthritis, etc.
Specific Body Defenses:
The Immune System

Immunology: the study of immunity
•
•
•
Fairly new science
Basis began when scientists in the early 1800’s
noticed that animals who survived a serious illness
had factors in their blood that protected them from
getting those illnesses again
They also found that the antibody containing serum
injected into animals who had never before suffered
the illness would also be protected from getting it.
Specific Body Defenses:
The Immune System

Because of these scientists we found
that the immune system:
• Is antigen specific
• It can recognize and act against PARTICULAR
pathogens or foreign substances
• Is systemic
• Immunity is not restricted to the initial infection site
• Has a “memory”
• It can recognize and create stronger attacks on
previously encountered pathogens
Specific Body Defenses:
The Immune System
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
Humoral Immunity:
•
•
Also known as antibody-mediated immunity
Provides antibodies present in the body’s own fluids
(Humor’s)
Cell-mediated immunity:
•
•
•
When lymphocytes themselves defend the body
Act against specific targets – virus infected cells, cancers
and cells of foreign grafts
Lymphocytes act against these targets either directly, by
lysing the cell or indirectly, by releasing chemicals
Specific Body Defenses:
The Immune System

Antigens:
• Any substance capable of exciting our
•
•
•
immune system and provoking an immune
response
Large complex molecules that are not
normally present in the body
Foreign intruders to our body referred to as
NONSELF
Substances that act as antigens:
• Foreign proteins, nucleic acids, large
carbohydrates, lipids
Specific Body Defenses:
The Immune System

SELF antigens:
• Antigens that our body can recognize
• Proteins found within the body
• They do not trigger an immune response in
our body but are antigenic to other people
and is the reason why our bodies reject
foreign grafts unless medication or special
measures are taken to cripple the immune
response.
Specific Body Defenses:
The Immune System


Generally small molecules are not
antigenic but when combined with other
proteins the immune system may not
recognize the combination and attack it.
Hapten or Incomplete antigen:
• The troublesome small molecule being
•
attacked
Drugs and some chemicals act as haptens
and cause an allergic type reaction
Cells of the Immune System

Main cells involved with the immune system
are:
•
Lymphocytes
• B lymphocytes/B cells: produce antibodies to help with
•
•
humoral immunity
T Lymphocytes/T cells: are non-anti-body producing and
are part of the cell-mediated arm of immunity
Macrophages
• Do not respond to specific antigens but play a role in
helping the lymphocytes that do.
Lymphocytes


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
Originate from hemocytoblasts in red
bone marrow
Immunocompetent: the ability to respond
to a specific antigen by binding to it.
T-Cells: originate from the lymphocytes
that migrate to the thymus
B-Cells: develop in the bone marrow
Lymphocytes
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Once the lymphocyte is immunocompetent it can
react to one distinct antigen only because all of
the antigen receptors on its surface are the same.
During their maturation process the lymphocytes
become immunocompetent before they ever meet
the antigens they will attack.
Our genes determine what foreign substances our
immune system will be able to attack and resist.
Once the cells are immunocompetent they travel
to the lymph nodes and spleen where they begin
fighting the antigens and become fully mature T
cells and B cells
Macrophages




Originate from monocytes formed in the bone
marrow
Widely distributed throughout the lymphoid
organs and connective tissues
Role: engulf foreign particles and present
fragments of the antigens on their surfaces
where they can be recognized by the
immunocompetent t cells
Sometimes called: Antigen presenters
Macrophages
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

Secrete proteins called monokines
Activated T-cells will release chemicals that
cause macrophages to become killer
macrophages
Macrophages remain fixed in the lymphoid
organs where lymphocytes circulate through
the body.
The lymphocytes and macrophages must
constantly communicate so that the immune
system as a whole can respond to antigens
Humoral Immune Response


An immunocompetent, immature B cell/lymphocyte
is stimulated to complete its maturity when an
antigen binds to its surface receptor.
This event sensitizes/activates the lymphocyte to
“turn on” and undergo clonal selection.
•
•
•
The lymphocyte multiplies rapidly and forms cells exactly
like itself with the same antigen specific receptors
These identical cells from the same ancestor cell are clones
Clone formation is the primary humoral response to that
antigen.
Humoral Immune Response


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
Most of these B-cell clones become plasma
cells
Plasma cells: antibody producing cells produce
the same highly specific antibodies at a rate of
approximately 2000 antibody molecules per
second
This lasts approximately 4-5 days and then the
plasma cells begin to die.
Antibody levels in the blood during this period
of time peak within 10 days and then slowly
decline
Humoral Immune Response

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The B-cell clones that do not become plasma
cells become longer living – memory cells
Memory cells: are capable of responding to the
same antigen at later meetings with it.
They are responsible for our immunological
“memory”.
This is the secondary response to antigens
which is much faster, more prolonged and
more effective because the preparation for an
attack has already been made
Humoral Immune Response



Hours after the recognition of an “oldenemy” antigen new plasma cells are
generated and antibodies are flowing in
the blood stream
Within 2-3 days the blood antibody levels
peak and they will remain high for weeks
to months after.
Much faster than the initial response
Active and Passive
Humoral Immunity

Active Immunity:
• When B-cells encounter antigen and produce
•
•
•
antibodies against them
It is naturally acquired during bacterial and
viral infections – when we develop symptoms
and suffer them.
Or they may be artificially acquired when we
receive a vaccine
Either way the body’s immune response will
be the same
Active Immunity

Vaccines:
• Contain dead or attenuated – living but
•
extremely weakened – pathogens
There are two benefits of vaccines:
• We are spared the signs and symptoms of the
disease that would occur during the primary
response
• The weakened antigens are still able to stimulate
antibody protection and promote an immunological
memory
Active Immunity

Booster Shots:
• Intensify the immune response at a later
meeting with the same antigen

Vaccines:
• Fight against micro-organisms that cause
•
pneumonia, smallpox, polio, tetanus, measles
and many other diseases
In the US a number of deadly childhood
diseases have been almost completely wiped
out through the use of vaccines
Passive Immunity


Antibodies are made from the serum of
an immune human or animal donor.
B-cells are not challenged by the antigen
and therefore immunological memory will
not occur and the protection they provide
will eventually disappear when the
antigens die naturally
Passive Immunity



Passive immunity may occur naturally when a
mother’s antibodies cross the placenta and
enter fetal circulation.
The baby will be protected for several months
after birth from the antigens that the mother
was exposed to
It is artificially created when a person receives
an immune serum or gamma globulin
Passive Immunity




Gamma globulin: Commonly administered after
exposure to hepatitis
Immune serum: used to treat poisonous snake
bites, rabies and tetanus because these
diseases would kill a person before the active
immunity could take over
Donated antibodies provide immediate
protection but only survive 2-3 weeks
During this time the body’s own defenses will
take over
Passive Immunity

Monoclonal antibodies:
•
•
•
•
Passive immunity antibodies prepared commercially
for use in research or diagnostic purposes.
Produced by descendants of a single cell and exhibit
specificity for only one antigen
They can be used to deliver cancer fighting drugs to
cancerous tissue or diagnosis of pregnancy, hepatitis
and rabies
They can also be used for early diagnosis and tracking
the extent of cancers that are harder to find within the
body
Antibodies




Also known as Immunoglobins (Igs)
Make up the gamma globulin part of
blood proteins
Soluble proteins secreted by activated B
cells or by their plasma cell offspring in
response to an antigen
Capable of binding to that specific
antigen of the B-Cell
Antibodies


Antibodies are formed in a response to
many different antigens
They all contain a basic anatomy that
allows them to be grouped into five Ig
categories, each with a slightly different
structure and function.
Basic Antibody Structure

Each antibody has a basic structure regardless
of its Ig class:
•
•
•
•
Four amino acid (polypeptide) chains linked together
by disulfide bonds
Two of the four chains are identical and contain
approximately 400 amino acids each = Heavy chains
The other two chains are identical as well but only half
as long = Light chains
When the four chains are combined the antibody
molecule has two identical halves each consisting of
one heavy and one light chain and the molecule as a
whole is either T or Y shaped
Basic Antibody Structure



Each of the four chains making up the antibody
has a variable (v) region at one end and a
constant (C) region at the other which is much
larger
Antibodies that respond to different antigens have
different variable regions but their constant
regions remain the same
The variable regions of the heavy and light chains
combine to form an antigen binding site that is
uniquely shaped to fit its specific antigen
Basic Antibody Structure


The constant regions form the “stem” of
the antibody and performs common
functions to all antibodies
They determine the type of antibody
formed as well as how the antibody will
carry out its immune role in the body and
the cell type or chemical that it can bind
with
Antibody Classes

There are five major immunoglobin
classes:
• IgM, IgA, IgD, IgG, and IgE (MADGE)
• IgD, IgG and IgE all have a Y shaped
•
•
structure and are referred to as monomers
IgA antibodies are found in both monomer
and dimer (two linked monomers) forms
IgM antibodies are huge and consist of five
linked monomers and called pentamers
Antibody Classes

The antibody classes have slightly different
roles and locations in the body.
•
•
•
•
IgG is the most abundant antibody in blood plasma
and is the only one that can cross the placental barrier
IgM and IgG can fix complement
IgA is found mainly in mucus and other secretions that
bathe body surfaces and plays a role in preventing
pathogens from getting into the body
IgE are “troublemakers” involved in allergies by
triggering the histamines that bring about an allergic
response
Antibody Function

Antibodies inactivate antigens in various
ways:
• Complement fixation
• Neutralization
• Agglutination
• Precipitation
• Complement fixation and neutralization are
the most important to body protection
Antibody Function



Complement: chief antibody ammunition used
against cellular antigens such as bacteria or
mismatched red blood cells
Complement is activated (fixed) during nonspecific body defenses
It is also activated very efficiently when it binds
to antibodies attached to cellular targets
•
This triggers events that result in lysis of the foreign
cell and release of molecules that enhance the
inflammatory process
Antibody Function


Neutralization: occurs when antibodies bind to
specific sites on bacterial exotoxins or on viruses
that can cause cell injury
Agglutination: clumping of foreign cells that are
bound to multiple antigens
•

Occurs when mismatched blood is transfused and is the
basis of tests used for blood typing
Precipitation: Cross linking that involves soluble
antigenic molecules that result in large complexes
that are insoluble and settle out of a solution.
•
Agglutinated and precipitated antigen molecules are much
more easily captured and engulfed by the body’s
phagocytes than freely moving antigens
Cellular Immune Response



Like the B-cell immunocompetent T-cells are
activated to form a clone by binding with a
“recognized” antigen
T cells are not able to bind with Free antigens
but must be presented by a macrophage and
“double recognition” must occur
Macrophages engulf the antigens, process
then internally and then display the parts of the
processed antigen on their outer surface in
combination with their own (self) protein
Cellular Immune Response



T-cells must recognize the “nonself” (antigen
part presented by the macrophage) and also
“self” by coupling with a specific glycoprotein
on the macrophages surface at the same time.
This binding alone is not enough to sensitize
the T-cell the macrophages must “feed” them
to the T-cell
Antigen Presentation: major role of the
macrophages and is essential for activation
and clonal selection of t-cells
Cellular Immune Response

T-Cell clone classes
• Cytotoxic (killer) t-cells: cells that specialize in
killing virus-infected cancer or foreign graft cells
• They work by binding to them and inserting a toxic
chemical (perforin) into the foreign cells plasma
membrane and shortly after the cell will rupture and die.
• Helper T-cells: T-cells that act as the “directors” or
“managers” of the immune system.
• Once they are activated they will circulate through the
body and recruit other cells to fight the invaders
Cellular Immune Response

T-cell clone classes:
•
Helper T-cells (continued)
• Interact directly with B-cells to provoke them to divide faster
•
and then signal antibody formation to begin
Release a variety of cytokine chemicals called lymphokines to
indirectly rid the body of antigens by:
•
•
•
•
Stimulating killer t-cells and B-cells to grow and divide
Attract other types of white blood cells such as neutraphils into
the area
Enhance the ability of the macrophages to engulf and destroy
micro-organisms
Immune response gains momentum and antigens cannot fight
against the immune elements acting against them
Cellular Immune Response

T-cell clone classes:
• Suppressor T-cells: release chemicals that
suppress the activity of the T and B cells
• Vital to winding down and stopping the immune response
after an antigen has been successfully activated or
destroyed
• Prevents unnecessary immune system activity
• Delayed Hypersensitivity T-cells
• Effector cells that play major role in cell-mediated
allergies and long-term/chronic inflammation
• When activated release lymphokines that promote an
intense inflammatory response
Organ Transplants and
Rejection


Organ transplant can be a lifesaving treatment
option but because the immune system is so vigilant
rejection can be a real problem.
There are four major types of grafts:
•
•
•
•
Autografts: tissue grafts transplanted from one site to
another in the same person
Isografts: tissue grafts donated by a genetically identical
person (related)
Allografts: tissue grafts taken from an unrelated person
Xenografts: Tissue grafts harvested from a different animal
species.
Organ Transplants and
Rejection



Autografts and Isografts are the
preferred donor organ or tissue because
they have a high success rate with
adequate blood supply to the new
organ/tissue.
Xenografts are never successful
Allografts are most commonly taken from
a cadaver
Organ Transplants and
Rejection



When doing an alograft the ABO and other
blood group antigens of both the donor and
recipient must be determined and must match.
Once this is done the cell membrane antigens
of the tissue cells are typed to determine how
closely they will match.
At least 75% match is needed to attempt the
graft – making it harder for a good tissue
match between unrelated people.
Organ Transplants and
Rejection

Immunosuppressive therapy:
•
•
Once the transplant has been done to prevent rejection
this type of therapy must be done.
Therapy includes:
• Corticosteroids: to suppress inflammation
• Cytotoxic drugs
• Radiation therapy
• Immunosuppressor drugs
When going through the immunosuppresive therapy it is very
hard for the body to fight against other foreign agents and
the most common cause of death in these patients is a
bacterial and viral infection.
Disorders of Immunity

Allergies/Hypersensitivities:
• Abnormally vigorous immune responses in
•
which the immune system causes tissue
damage as it fights off a perceived threat that
would normally be harmless to the body.
Allergen:
• Type of antigen which produces the irritation
Disorders of Immunity

Types of Allergies:
• Immediate hypersensitivity:
• Also called Acute hypersensitivity
• Triggered by the release of histamine when the IgE
antibodies bind to mast cells.
• Histamine causes small blood vessels in the area
to become dilated and leak and causes symptoms
such as – runny nose, watery eyes, itching, etc.
• Antihistamines: anti-allergy drugs which counteract
the effects of the allergen
Disorders of Immunity

Anaphylactic shock:
•
•
•
•
•
Acute allergic response
Occurs when the allergen directly enters the blood and
circulates quickly throughout the body
It may also follow an injection of a foreign substance in
a susceptible individual
The mechanism is the same as an allergic response
but much more life threatening because the entire
body is involved – constriction of blood vessels,
constriction of the bronchioles and other lung
passages.
Epinephrine is the most common and effective drug
used to reverse these effects.
Disorders of Immunity

Delayed Hypersensitivity:
•
•
•
•
Take longer to appear than any of the acute reactions produced by
the antibodies
Instead of histamine the chemicals mediating these reactions are
lymphokines released by activated T cells
Corticosteroid drugs are used to provide relief of symptoms
because the typical antihistamine will be useless
Most common types of delayed hypersensitivies are:
•
•
Allergic contact dermititis: allergens that act as haptens and when
traveling through the body are perceived as foreign to the immune
system causing a rash like reaction.
Mantoux and tine tests: tests where an antigen is injected or scratched
into the skin to determine if someone has been sensitized to the
antigen. If not an allergic type reaction appears.
Disorders of immunity

Immunodeficiencies:
•
•
•
Include congenital and acquired conditions
Production or function of immune cells or complement is
abnormal.
Severe combined immunodeficiency disease (SCID): most
devastating congenital condition where there is a marked
deficit of both B and T cells. Since T cells are necessary for
the function of the immune system afflicted children have no
protection against pathogens of any type. A simple infection
or virus can be deadly to these children.
• Bone marrow transplants have helped with some cases others
have survived by being behind a protective barrier constantly to
keep out all infectious agents – living in a plastic “bubble”
Immunodeficiencies

Acquired Immune deficiency syndrome
(AIDS):
• Cripples the immune system by interfering
•
with the activity of helper T cells
Most devastating of the acquired
immunodeficiencies
Disorders of Immunity

Autoimmune Diseases:
• When the immune system loses its ability to
•
•
distinguish good antigens or tolerate self
antigens and attack foreign antigens.
When this happens the body produces
antibodies and sensitized T cells that attack
and damage its own tissues.
5% of adults in North America are afflicted
with autoimmune diseases – two thirds of
them being women
Disorders of Immunity

Autoimmune disorders:
•
•
•
•
•
•
•
Multiple Sclerosis: destroys the white matter of the brain and
spinal cord
Myasthenia gravis: impairs communication between nerves
and skeletal muscles
Grave’s disease: thyroid gland produces excessive amounts
of thyroxine
Juvenile diabetes (type 1): destroys pancreatic beta cells
resulting in deficient production of insulin
Systemic Lupus erythematosus: systemic disease that
occurs mainly in young females and particularly affects the
kidneys, heart , lungs and skin
Glomerulonephritis: severe impairment of kidney function
Rheumatoid arthritis: systemically destroys joints
Immune Disorders

Autoimmune diseases:
• Therapies for these conditions include
•
treatment that depresses certain aspects of
the immune response.
Triggers for these diseases:
• Inefficient lymphocyte programming: instead of
being silenced or eliminated self reactive B or T
lymphocytes escape to the rest of the body. (MS)
Immune Disorders

Autoimmune diseases:
• Triggers:
• Appearance of self proteins in the circulation that
were previously exposed to the immune system
• Cross reaction of antibodies produced against
foreign antigens with self antigens.
Developmental aspects of the
Lymphatic system




Lymphatic vessels bud from the veins of the
blood vascular system
Clusters of lymph nodes are obvious by the
fifth week of development
Except for the thymus and spleen the lymphoid
organs are poorly developed before birth
Shortly after birth these organs become heavily
populated with lymphocytes as the immune
system begins to function.
Developmental Aspects of the
Lymphatic System

Problems with the lymphatic system are
relatively rare but are usually painfully
obvious:
• Elephantiasis: tropical disease in which the
•
lymphatics become clogged with parasitic
worms.
When lymphatics are removed and severe
edema is the result. Lymphatic vessels
removed will grow back with time
Developmental Aspects of the
Lymphatic System




Stem cells of the immune system originate in the
spleen and liver during the first month of
embryonic development
Later bone marrow is the predominant source of
stem cells until late adult life
In late fetal life and shortly after birth the young
lymphocytes develop self tolerance and
immunocompetence in their programming organs
and populate other lymphoid tissues
When meeting their antigens T and B cells
complete their development into fully mature
immune cells.
Development Aspects of the
Lymphatic System


Our genes play a large role in recognizing
foreign substances but our nervous system
helps to control the activity of this immune
response.
Because of the nervous systems large
involvement of how the immune system works
it can have large impacts on how well it works.
•
•
Stress will decrease the efficiency of the immune
system
As we age the immune system becomes less efficient
and the body is less able to fight foreign invaders.