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The Immune System Overview
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The skin is the first defense in the immune system.  Internally, the immune system is the first responder to any injury, or introduced microbes and germs.  Billions of cells defend the body every minute against illness or injury, but they also play an important part in our everyday lives.  The immune system performs everyday functions such as disposing of dead cells and waste byproducts.  Whether it’s normal maintenance or a response to an infection or cut, the immune response is unleashed by a complex set of signals in our body.

 

The bloodstream and lymph system ushers the immune components around the body.  The bloodstream is comprised of four basic parts, each with a particular function: red blood cells, platelets, plasma and white blood cells.

 

Red blood cells are responsible for carrying oxygen molecules from the lungs to tissues.  Red blood cells do not actually contact all tissues, rather, proteins in interstitial fluid (fluid between cells) pull oxygen and nutrients through the blood vessel walls and carry them to the cells. Red blood cells remove carbon dioxide molecules, carrying them to the lungs where they can be exhaled. Red blood cells are also called erythrocytes.  A protein in the red blood cell, hemoglobin, binds to oxygen molecules allowing the cell to carry them.

 

Platelets help the blood to clot, springing into action when we have a cut or injury. They help staunch the flow of blood leaking out of broken or torn blood vessels.  Scientists are showing that platelets also stimulate the immune system to adapt its response to a specific microbial assault.  Immune components have the ability to recognize and remember specific pathogens and so respond with particular white blood cells to fight the type of infection invading the body.  (This is known as adaptive immunity, or adaptive immune response.) 1  Platelets can release proteins that rapidly kill bacteria and some other microbes, and that triggers other immune components. 2  

 

Plasma is the watery fluid that constitutes over half of the volume of our blood.  Dissolved in it are nutrients and vitamins, electrolytes, hormones, clotting factors, proteins, enzymes, fats, sugars, metabolic wastes and other substances. The other blood cells (red, white and platelets) float in the plasma as it is circulated through the body.  Unlike the red blood cells, the plasma seeps from the blood vessels into spaces between cells (becoming interstitial fluid), carrying nutrients with it, and picks up waste by-products for later disposal. Plasma is the clear fluid that seeps out when someone has a minor skin scrape or brush burn. When plasma leaves the bloodstream, it becomes part of the lymph system and is called lymph.

 

White blood cells are part of the body’s immune system.  They are also called leukocytes.  Leukocytes are found throughout the body, including the blood and lymphatic system. Several different and diverse types of leukocytes exist, but they are all produced in the bone marrow, each having a particular function: lymphocytes, granulocytes, monocytes, phagocytes and macrophages.

 

The lymphocytes are nearly colorless cells found in the blood, lymph fluid, and lymphoid tissues, constituting approximately 25 percent of white blood cells.  They are normally maintained within preset normal ranges, but respond rapidly to immune challenges.  Lymphocytes respond to specific antigens (foreign substances).  There are three types of lymphatic cells, T cells and B cells and natural killer cells.  B cells function in humoral immunity (elements in the blood or other body fluids), and T cells function in cellular immunity and natural killer cells destroy cells infected by a virus or that have become cancerous.  B cells and T cells work together to mount an immune response.  B cells make antibodies to counter a specific threat. They bind antigens and present certain antigen markers to the T cells.  T cells “remember” the antigen and how to kill them, and in a future exposure, activate a rapid immune response by triggering B cells to produce the specific antibody to destroy the antigen.

 

The granulocytes are types of white blood cells filled with little sacs containing enzymes (“granules”) that ingest and chemically attack and destroy microorganisms. They often are the first responders to an infection or foreign substance, attacking and ingesting the microorganisms until they themselves die.  They also trigger the inflammation response.  These cells are known as polymorphonuclear cells and are of three types: neutrophils, basophils, and eosinophils.  They are part of the innate immune system and have somewhat nonspecific, broad-based activity and are normally maintained within preset normal ranges.  Increased production of them is made in immunological response to infections, allergic reactions and other stimuli.  They do not respond exclusively to specific antigens, (substances carried by germs that make the immune system respond) as do B-cells and T-cells. 

 

The monocytes are a type of granular leukocyte that functions in the ingestion of bacteria.  The number of monocytes is regulated within normal ranges, but a rapid increase in their numbers is a response to infections.  Monocytes eventually leave the bloodstream to become tissue macrophages.  The key functions of monocytes and macrophages are to remove cell debris and our own dead cells when they reach the end of their useful life, as well as to attack foreign microorganisms and remove pathogens.  Significantly, another function of monocytes and macrophages is to create important immune proteins and peptides.  They are responsible for synthesizing transferrin (an iron-binding protein), complement proteins and various cytokines necessary for immune function. 3

 

Phagocytes

 

Phagocytes are specialized immune cells in blood, lymph, and other body tissues that find, engulf and digest dead or injured body cells, bacteria, and viruses and other foreign matter.  This process of engulfing and digesting foreign material is known as phagocytosis.  Phagocytes are strategically positioned throughout the body.  There are three main types: granulocytes, (discussed above), macrophages, and dendritic cells.

 

The macrophages differ in size and lifespan from the granulocytes.  They are larger and live longer than granulocytes, and are known as “big eaters” because they have far greater capacities to ingest debris and foreign substances than monocytes.  Large numbers of mature macrophages are found throughout the body, but scavenge mainly in the lymph, connective tissues, along the digestive tract and the lungs, where they ingest fibers, dust, and other inhaled particles.  Macrophages also play a key part in alerting the rest of the immune system to foreign microorganisms, with neutrophils reinforcing their immune response by coming to the site of infection in large numbers.

 

The dendritic cells (dendrites) are another type of phagocyte that devour intruders, like the granulocytes and the macrophages.  At certain development stages they grow branched projections that look like tentacles.  Like the macrophages, the dendritic cells help with the activation of the rest of the immune system.  Having devoured intruders, they migrate to the lymphoid tissues where they interact with T cells and B cells to initiate and shape the adaptive immune response.  They are also capable of filtering body fluids to clear them of foreign organisms and particles.

 

Cytokines:

 

Cytokines are small secreted proteins that are a means of communication between cell types.  This communication allows a highly remarkable, self-regulated, blood cell production system that is extremely responsive to the demands put upon it.  Cytokines are produced by many types of cells, but the predominant producers are found in the immune components--the helper T cells and macrophages.  They mediate and regulate immunity, inflammation, and the production of all types of blood cells (hematopoiesis).  They act by binding to specific membrane receptors, which then signal the cell via second messengers, to alter its behavior.

 

The largest group of cytokines stimulates immune cell proliferation and differentiation.  A certain type of stimulation, the Interleukin 3, Interleukin 7 and Granulocyte Monocyte Colony-Stimulating Factor, encourages the production of all types of blood cells—red, white (immune components), and platelets.  These blood cells are produced in response to a particular need.  When the demand for production of a particular type of cell increases (e.g. immune components), or the levels of a cell type fall in blood, cytokines are released which stimulates production of the needed cells.

 

Cytokines may act on the cells that secrete them (autocrine action), on nearby cells (paracrine action), or in some instances on distant cells (endocrine action).  It is common for different cell types to secrete the same cytokine or for a single cytokine to act on several different cell types.  Cytokines are redundant in their activity; similar functions can be stimulated by different cytokines. They are often produced in a cascade, as one cytokine stimulates its target cells to make additional cytokines.  They can also act together to produce the same result, or antagonistically, where the cytokines cause opposing actions.

 

The cytokine protein Interleukin 1 (IL-1) activates T cells; IL-2, stimulates proliferation of antigen-activated T and B cells; IL-4, IL-5, and IL-6 stimulate proliferation and differentiation of B cells; Interferon gamma (IFNg) activates macrophages. 

 

Cytokines stimulate stem cells in the bone marrow to generate new mature blood cells, usually occurring in the few days required for blood cell maturation.  The production of blood cells is largely controlled by feedback from the type of mature cells to which the cytokines are responding.

 

When cytokine production is interrupted or weakened, or other problems with blood cell production are encountered, blood cell production is disturbed.  The first cells to drop are usually the short-lived neutrophils (within hours). Platelets have a 10-day life span and anemia will develop over a 120-day time span unless hematopoiesis is restored. 4

1.  Immunologic Research; Nov. 2007

 

2.  Michael Yeaman; Infection and Immunity, December 2002

 

3.  Microvet.arizona.edu/Courses/MIC419/Tutorials/ cytokines.html; Janet M.

     Decker, PhD

 

4.  Microvet.arizona.edu/courses/MIC419 /Tutorials/cytokines.html

 
 
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