David EmerineImmune systemSupplemental 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.

.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)] granulocytes.

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 "antibody-

mediated 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 be low . For some reason I am not able to delete them****

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