Download David Emerine Immune system Supplemental Instruction Nov 17

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David Emerine
Immune system
Supplemental Instruction Nov 17 & 20
Blood Composition
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Immune System
First we will review the Lymphatic system which is important to the immune system.
Lymphatic system
The lymphatic system is important to the immune system and circulatory system.
There is a small net loss of fluids from blood capillaries into the
interstitial spaces (about 3 liters per day).
The lymphatics act as an accessory route by which this fluid
can return to venous system.
Lymphatics are also important for the immune system (contain many white blood cells)
Lymphatics include lymph nodes that contain large numbers of white blood cells.
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Lymphatics are distributed throughout the body.
Lymphatics contain a total of about 1 to 2 liters of fluid (i.e. “lymph”) and they
returns approximately 120 ml of lymph per hour to venous system.
Lymphatic capillaries pick up fluid and substances from the normal capillary bed.
The cells of lymphatic capillaries are not tightly joined to one another,
so fluid and other substances can enter the lympatics.
So, the lymphatics act as an accessory route for getting certain substances into
circulatory system.
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Lymph
Lymph is composed of fluid coming from interstitial spaces.
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It is similar to blood, but does not contain red blood cells and it does not
contain many of the “plasma proteins”
Lymph does contain white blood cells.
Some large fats and proteins that can’t get into blood capillaries can enter lymph
capillaries.
So lymph typically contains large amounts of fats and proteins (normally obtained
from the intestines).
Movement of lymph
Lymph vessels have one-way valves and smooth muscle to help move lymph
Additionally, contraction of skeletal muscle adjacent to lymph vessels will move
lymph in similar fashion to skeletal muscle pumps of veins.
Lymphatic vessels converge and connect to venous system at the junction of the
subclavian veins and internal jugular veins (in the upper thoracic cavity).
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Blockage of lymph flow can result in severe edema (can't return lymph fluid back to
circulatory system).
Fluid accumulates in interstitial spaces.
Example: "Filariasis" or "elephantiasis"
It is causes by a parasitic nematode worm.
Larvae transmitted to human by mosquito bite.
Adults live in, and clog lymphatics, so excess fluid accumulates in certain
interstitial spaces.
Believed to affect 120 million people, mostly in tropical and
subtropical areas (e.g. Asia, Africa, and Western Pacific).
Patients can be treated with drugs which kill the nematode and its larvae.
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Overview of the Immune System
Involves a variety of organs and tissues in the body.
Bone marrow, lymphoid tissue (lymph nodes, tonsils, gut-associated
lymphoid tissue, etc), spleen, thymus, liver
Functions:
Protects body from invading organisms that cause disease (pathogens)
Remove damaged or aged cells (in particular RBCs)
Destroys abnormal and/or mutant cells
Non Beneficial Immune Responses
a) allergies
b) autoimmune disease (example: Multiple Sclerosis, GBS, etc.)
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Immune system utilizes a variety of white blood cells
White Blood Cells
WBCs or "Leukocytes"
4000 to 11,000 per ul (in normal healthy individual)
Can increase to 25,000 or more during infections.
Most are produced in bone marrow by "stem cells", but a some are produced in lymph
nodes, spleen, and thymus.
WBCs divided into four basic groups
1) ranulocytes.
All granulocytes are very mobile and can move out of blood and into the tissues.
a) Neutrophils (polymorphonuclear leukocytes)
Most abundant type of white blood cell.
They are highly mobile and move out of the blood and into areas of
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inflammation.
They seek out, ingest (phagocytosis), and destroys bacteria,
viruses, and foreign material.
They are nonspecific in their targeting (they go after any non-self
pathogen) .
They give “pus” its yellowish/whitish color.
b) Eosinophils
They are involved in allergies, asthma, and in some parasitic infections.
They release “cytokines’ which are chemical signals that have a variety of
effects on parasites, pathogens, and on other immune system cells.
c) Basophils
They move into area of inflammation and they release histamine and
cytokines.
Histamine stimulates many of the symptoms of an allergy such as
vasodilation and edema in the inflamed area.
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2) Monocytes
They circulate in the blood and then enter tissues and become
tissue macrophage (5X increase in size).
“macrophage” means large eater
They are important in lymph nodes, liver, spleen, lungs, and bone marrow.
They ingest bacteria, viruses, and foreign substances.
The monocyte macrophages are much more powerful phagocytes in comparison
to
neutrophils
They are nonspecific in their targeting (they attack a variety of pathogens, etc..)
3) Mast cells
Similar to basophils, but they become resident in specific tissues.
In response to infections, pathogens, etc, they will release a variety of chemicals
including histamine.and cytokines.
They are nonspecific in their targeting (they respond to variety of pathogens, etc.).
4) Lymphocytes
They are initially produced in bone marrow.
Then they move to lymph nodes, spleen, and thymus.
They reenter circulation when needed.
They are “specific” in their targeting
i.e. They are important for "specific immunity" (targeting of specific
antigens).
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a) B lymphocytes (i.e. B cells)
They are important for “antibody-medicated immunity” (also calls
“humoral immunity”
“B” refers to “bursa-derived”
Their maturation was first studied in birds
Precursor cells "mature" in "Bursa of Fabricius" in birds
(hence "B" lymphocytes) It is an outcropping of the cloaca.
In humans the B lymphocytes mature in the bone marrow.
Lymphocyte maturation (both B and T) occurs during embryonic
development and early childhood.
Immune Response of B cells
In response to exposure to specific antigens, B lymphocytes differentiate
into “plasma cells” and “memory cells”
Plasma cells are the antibody producing cells responsible for "antibodymediated immunity".
Antibodies are produced against specific antigens
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They are “specific” in their targeting
They identify specific antigens on the pathogens.
Memory cells are produced so that antibody response can occur
rapidly upon second or later exposure to antigen.
i.e. “adaptive or acquired immunity”
This is the purpose of vaccinations: exposure to an antigen results
in the production of memory cells.
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Actions of antibodies
1) Neutralize toxins directly
2) Agglutination of antigens
Clumping of antigenic cells.
Formation of clumps which hinders pathogen’s ability
to affect cells
(Agglutination refers to antibody/antigen reaction. Do not confuse
this with coagulation which refers to blood clotting).
3) Mark invading cells
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Allows for binding of monocyte/macrophage, neutrophils, etc
b) T lymphocytes
They are important for “cell-mediated immunity”
They are specific in their targeting and will bind directly to their
targets.
Precursor cells "mature" in thymus during embryonic development and
early childhood.
They differentiate into four types of cells:
1) Cytotoxic T Cells (killer T cells)
2) Helper T cells
3) Regulatory T cells (i.e. Suppressor T Cells).
4) Memory T cells
1) Cytotoxic T cells (i.e. killer T cells) or aka natural killer/NK cells
They are specialized for killing virus-infected cells
Cells infected by virus display viral antigen on cell surface
cytotoxic T cells destroy cells with specific antigen
i.e. they are specific in their targeting
Cytotoxic T cell binds to cell and then releases
substances that kills the cell..
They releases "perforin" which is a protein that inserts
itself into the cell membrane of infected cells
creates holes in membrane that kills cell
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2) Helper T cells enhance both "antibody and cellular-mediated immunity"
They are the most numerous of the T cells (60 to 80% of
circulating T cells).
They activate other immune cells, including both B and T cells
As such, they are considered a “master switch” for turning on
the specific immunity portion of immune system.
They produce "lymphokines" which stimulate both B and T cells
Lymphokines are chemicals released by lymphocytes
They can have a variety of effects.
Helper T cells are the target of the HIV virus.
Results in a decreasing levels of Helper T cells
This eventually compromised the immune systems ability
to respond to infection.
3) Regulatory T Cells (Suppressor T cells)
They suppress immune responses and prevent over activity of the
immune system.
Helps maintain tolerance to self antigens.
Researcher are trying to use these to treat autoimmune diseases.
4) Memory T Cells
Produced during initial exposure to pathogen.
Allow for rapid production of other T cells and strong immune
response during second and subsequent
exposure to pathogen.
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"Clonal selection theory"
During embryonic development millions of different T and B
lymphocytes are formed, each capable of
identifying a specific antigen.
This is done by the reshuffling of gene fragment to produce
millions of different types of T and B cells.
Each of the lymphocytes can produce "clones" of itself
Antigen on invading organism selects for a clone and
"activates" it
Clone will then begin to divide and produce large numbers
of lymphocytes specific for a particular antigen
Nonspecific Immune Responses
i.e. “Inflammation”
Nonspecific response to tissue damage and/or foreign invasion
Inflammation functions to isolate and destroy invading organisms
as well as remove debris to prepare for healing
Following the invasion of tissue by pathogens:
1) Tissue macrophage migrate into the area and ingest and destroy invading
organisms
2) Mast cells in the tissue release histamine in response to tissue damage and
invading organisms
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Histamine results in:
a) local vasodilation
b) increased capillary permeability
So plasma proteins leak into interstitial spaces
and cause edema by attracting water osmotically
allows for movement of white blood cells out of capillary
and into affected area..
3) Increase number of phagocytic WBCs (neutrophils and
monocytes/macrophage move into inflamed area due to
a) edema
b) and they are attracted to area by chemoattractants release by
mast cells and macrophage.
They ingest and destroy foreign organisms and materials
"Pus" is an accumulation of the phagocytic WBCs and the
material they have digested
4) Inflamed area is "walled off"
Edema also results in more of the plasma protein fibrinogen entering
inflamed area.
Fibrinogen is the precursor to fibrin which is used to form blood clots
and to wall off inflamed areas
Fibrinogen is converted to fibrin by thrombin
which is activated by factors in the damaged tissue
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A mesh of fibrin walls off inflamed area.
This delays or prevents spread of pathogens.
After inflammation
Cells in surrounding tissue may repair damaged area (e.g. skin)
or in the case of nonregenerating tissue (e.g. muscle) tissue is
replaced by scar tissue.
Primary Organs/Tissues involved with Immune System
1) Bone marrow
Important for blood cell production
Important for B lymphocyte maturation
2) Lymphoid Tissue:
Lymph nodes, lymph vessels, gut-associated lymphoid tissue (Peyer's
patches in small intestines), tonsils, and adenoids.
It helps produce lymphocytes for lymph and blood.
It has resident lymphocytes that produce antibodies and
sensitize T cells when needed..
It has resident macrophage that ingest microbes
3) Spleen
Same functions listed above for lymph nodes, but they do these
functions for blood system
Additionally:
macrophage in spleen remove old RBCs
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4) Liver
Blood sinuses lined with specialized macrophage (called Kupffer cells).
They destroys large numbers of bacteria and other invading
organisms in blood coming from intestines
5) Thymus
Site of T lymphocyte maturation
****Please ignore the pictures presented below. For some reason I am not
able to delete them****
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