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Lymphatics and Body Defense

Lymphatics and Body Defense


                              
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Lymphatics and Body Defense:
The lymphatic system is sometimes considered to be part of the circulatory system because it transports a fluid through vessels and empties it into venous blood.  Because it consists of organs that work together to perform certain functions, it may be treated as a separate system.  The lymphatic system has a major role in the body's defense against disease.

FUNCTIONS OF THE LYMPHATIC SYSTEM

The lymphatic system has three primary functions.  
it returns excess interstitial fluid to the blood
the absorption of fats and fat-soluble vitamins from the digestive system and then the transportation of theses substances to the venous circulation
defense against invading organisms and disease

COMPONENTS OF THE LYMPHATIC SYSTEM

The lymph system consists of a fluid (lymph) vessels that transport the lymph, and organs that contain lymphoid tissue.

“Lymph” is the name for tissue fluid that enters the lymph capillaries.  Lymph is similar in composition to blood plasma.  It is derived from blood plasma as fluids pass through capillary walls at the arterial end.  As the interstitial fluid begins to accumulate, it is picked up and removed by tiny lymphatic vessels and returned to the blood.  Returning the fluid to the blood prevents edema and helps to maintain normal blood volume and pressure.

Lymphatic vessels only carry fluid away from the tissues. Lymph capillaries are very permeable and collect tissue fluid and proteins.  Lacteals are specialized lymph capillaries in the villi of the small intestine; they absorb the fat soluble end products of digestion.
Lymph capillaries unite to form larger lymph vessels, whose structure is very much like that of veins.  There is no pump for lymph but the lymph is kept moving within the lymph vessels by the same mechanism that promotes venous return.  The smooth muscle layer of the larger lymph vessels constricts and the one way valves to prevent the backflow of lymph.  Lymph vessels in the extremities are compressed by the skeletal muscles that surround them.

Pressure gradients that move fluid through the lymphatic vessels come from the skeletal muscle action, respiratory movement, and contraction of smooth muscles in vessel walls.

Where is the lymph going?  Back to the blood to become plasma again.

LYMPH NODES AND NODULES

These are masses of lymphatic tissue,  that produce lymphocytes and monocytes.  Nodes and nodules differ with respect to size and location.  

Lymph nodes are found in groups along the pathways of lymph vessels.  Lymph enters a node through several afferent lymph vessels and leaves through one or two efferent vessels.  

There are many groups of lymph nodes along all the lymph vessels throughout the body, but three paired groups deserve mention because of their strategic location.  These are the cervical, axillary, and inguinal lymph nodes.  Notice that these are at the junctions of the head and extremities with the trunk of the body.  

Anything that interferes with the flow of lymph, such as an obstruction or surgical ligation, may cause tissue fluid to accumulate, resulting in edema.  Because plasma proteins that have leaked out of the capillaries are returned to the bloodstream via the lymph, obstruction of lymph flow may cause a decrease in plasma protein concentration.
You may be familiar with the expression “swollen glands” as when a child has a strep throat.  These glands are the cervical lymph nodes that have enlarged as the macrophages attempt to destroy the bacteria in the lymph from the pharynx.
Lymph nodules are small masses of lymphatic tissue found just beneath the epithelium of all mucous membranes.  Some of these nodules have specific names like those of the small intestines called “Peyer's patches” and those of the pharynx called the tonsils.

Tonsils usually function to prevent infection from the bacteria that attempt to enter the body through the nose and mouth.  Sometimes, however, they become severely and repeatedly infected themselves and may need to be removed.  The palatine tonsils are the ones removed in a tonsillectomy.  If the pharyngeal tonsils are enlarged, they may interfere with breathing.  Removal of these tonsils is called an adenoidectomy.

The development of breast cancer often necessitates the removal of part or all of the breast tissue, a surgical procedure called a mastectomy.  There is an extensive network of lymphatic vessels associated with the breast, and the cancer cells from the breast can spread to surrounding lymph nodes through these vessels.  For this reason, the axillary nodes may be removed with the breast tissue.  Sometimes this procedure interferes with lymph drainage from the arm and the fluid accumulates, resulting in swelling or lymphedema.

The lymphatic system is one route by which cancer cells can spread from a primary tumor site to other areas of the body.  As the cells travel with the lymph, they pass through the lymph nodes where the lymph is filtered.  At first this traps the cancer cells within the lymph node, and the cells are destroyed.  Eventually, the number of cancer cells may overwhelm the filtration ability of the lymph nodes, and some of the cells pass through the nodes to establish secondary tumors.

Lymphatic organs are characterized by clusters of lymphocytes and other cells, such as macrophages, enmeshed in a framework of short, branching connective tissue fibers.
Tonsils are clusters of lymphatic tissue just under the mucous membranes that line the nose, mouth, and throat.

The spleen is a lymph organ that filters the blood and also acts a reservoir for blood.  The spleen is a rather soft and fragile organ, and although it is somewhat protected by the ribs, it is often ruptured in abdominal injuries.  Because the spleen is a reservoir for blood, this results in severe internal hemorrhage and shock, which may lead to death if it is not stopped.

The thymus is a soft organ with two lobes that is located anterior to the ascending aorta and posterior to the sternum.  It is relatively large in infants and children but after puberty it begins to decrease in size so that in older adults it is quite small.

The primary function of the thymus is the processing and maturation of the T-cells or T lymphocytes.  While in the thymus, the lymphocytes do not respond to pathogens or foreign agents.  After the lymphocytes are matured, they enter the blood and go to other lymphatic organs where they help provide defense against disease.  

 The thymus also produces a hormone called thymosin, that stimulates the maturation of lymphocytes in other lymphatic organs.  Thymic hormones are necessary for what may be called “immunological competence”.  The thymic hormones enable the T cells to participate in the recognition of foreign antigens and to provide immunity.  This capability of T cells is established early in life and then is perpetuated by the lymphocytes themselves.  The newborn's immune system is not yet fully mature, and infants are more susceptible to certain infections than older children or adults.  Usually by the age of 2 years, the immune system matures and becomes fully functional.  This is why some vaccines, such as the measles vaccine, are not recommended for infants younger than 15-18 months of age.  Their immune systems are not mature enough to respond strongly to the vaccine, and the protection provided by the vaccine may be incomplete.

RESISTANCE TO DISEASE
The human body is continually exposed to disease producing organisms called pathogens.  If these enter the body, they may disrupt homeostasis and cause disease.  The body's ability to counteract the effects of pathogens and other harmful agents is called resistance and is dependant on a variety of defense mechanisms.  

Susceptibility is a lack of resistance.  Some defense mechanisms called nonspecific mechanisms, act against all harmful agents and provide non-specific resistance.  Other defense mechanisms only act against certain agents and are called specific mechanisms.  These provide specific resistance or immunity.  To maintain a state of health, all the body's defense mechanisms must act together to provide protection against invading pathogens, foreign cells that are transplanted into the body, and the body's own cells that have become cancerous.  

NONSPECIFIC DEFENSE MECHANISMS
Nonspecific defense mechanisms are directed against all pathogens and foreign substances regardless of their nature.  They present the initial defense against invading agents.  The first line of defense is the barrier against entry into the body.  If the foreign agent succeeds in passing the barrier and entering the body, then the second line of defense comes into the action.  This includes the chemical action of complement and interferon, and the processes of phagocytosis  and inflammation.

BARRIERS

Intact, or unbroken skin and mucous membranes form effective mechanical barriers against the entry of foreign substances.

Fluids such as tears flowing across the eyes, saliva that is swallowed, and urine passing through the urethra, are examples of mechanical barriers that flush pathogens out of the body before they have a chance to damage the tissues.  Enzymes in these fluids destroy bacteria.  These are all examples of chemical barriers that deter microbial invasion.
Various body chemicals, including complement, and inflammation.  Complement is a group of proteins normally found in the plasma in an inactive form.  Certain complement proteins become activated when they come in contact with a foreign substance.  Complement is a chemical defense that promotes phagocytosis and inflammation.  This is done in stages and when the final complement protein is activated it causes bacterial cells to rupture.  Interferon has particular significance because it offers protection against viruses.  When a cell becomes infected with a virus, the cell usually stops its normal functions.  The virus uses the cell's metabolic machinery or organelles for one goal-viral replication or reproduction.  When the cell is full of viruses, it ruptures and releases many viruses to infect new cells.  This is how the viral infection is established.  Interferon stimulates the uninfected cells to produce a protein that blocks viral replication.  In this way the uninfected cells are protected from the virus.

Although interferon has not proved to be the great cancer cure that was hoped when it was discovered in the 1950's, some useful therapies have emerged.  It is produced naturally in such small amounts that its harvest and use were impractical until researchers developed genetic engineering techniques that utilize bacteria to make it in sufficient quantities for clinical use.  

phagocytosis is the ingestion and destruction of solid particles by certain cells.  The cells are called phagocytes, and the particles may be microorganisms or their parts, foreign particles. an individual' s own damaged or dead cells or cell fragments.  The primary phagocytic cells are neutrophils and macrophages.

Neutrophils are usually the first cells to leave the blood and migrate to the site of an infection, where they phagocytize the invading bacteria.  This is a suicide mission because the neutrophils die after engulfing only a few bacteria.  Pus is primarily an accumulation of dead neutrophils, cellular debris, and bacteria.  The number of neutrophils greatly increases in acute infections.

Macrophages are monocytes that have left the bloodstream and have entered the tissues.  When they leave the blood they become larger and develop additional lysosomes.  Remember them?   What are they?  Macrophages usually appear at the scene of an infection after the neutrophils and are responsible for cleaning up the debris and the dead neutrophils during the latter stages of an infection.

Macrophages are present in uninfected tissues as the lymph nodes.  They cleanse the lymph as it filters through the node.  

Inflammation is a non-specific defense mechanism that occurs in response to tissue damage from microorganisms or trauma.  Localized inflammation is contained in a specific region.  It is evidenced by redness, warmth, swelling, and pain.  A combination of these effects frequently causes loss of function, at least temporarily and the irritation sometimes makes inflammation more harmful than beneficial.

Despite this, it is usually a worthwhile process because it is aimed at localizing the damage and destroying the source.  Inflammation also sets the stage for tissue repair.  The unpleasant signs and symptoms have a protective function because they warn that tissue damage has occurred so that the source of the damage may be removed.  Below are the steps of the inflammatory process.
bacteria or foreign particles enter the body
tissues are damaged
damaged tissues release chemical mediators
chemical mediators have three effects
attract neutrophils and macrophages
increase blood flow through vasodilation
increase capillary permeability
chemical mediators are to bring additional phagocytes to the damaged area
phagocytes are successful and destroy bacteria
area is cleansed of debris
tissues are repaired
if the phagocytes are not successful, steps 2-5 continue to result in chronic inflammation
 Systemic inflammation is not contained in a localized region, but is widespread throughout the body.  The warmth, redness, swelling, pain, and loss of function associated with localized inflammation may be present at specific sites, but the systemic nature of the inflammation is evidenced by three additional responses.

bone marrow is stimulated to produce more WBC's especially neutrophils and monocytes, so there is a condition of leukocytosis.
chemical mediators include pyrogens that influence the hypothalamus and cause an increase in body temperature or fever.  The fever speeds up the metabolic reactions in the body, including those directed at destroying the invading pathogens.
vasodilation and increased capillary permeability may become so generalized that there is a drastic and dangerous decrease in blood pressure.  Systemic inflammation is a medical crisis and needs immediate attention.
Systemic inflammation shows leukocytosis, fever, and decreased blood pressure.

SPECIFIC DEFENSE MECHANISMS

In contrast to the nonspecific defense mechanisms that react to all foreign agents, the specific defense mechanisms are programmed to be selective.  This characteristic is called specificity.  Another characteristic of specific defense mechanisms is memory.  Once the system has been exposed to a particular invading agent, components of the specific defense mechanisms “remember” that agent and launch a quicker attack if it enters the body again.  Specific defense mechanisms provide the third line of defense against microbial infection.  This third line of defense is specific resistance, or immunity.  The primary cells involved are lymphocytes and macrophages.  Nonspecific mechanisms and immune responses take place at the same time, and resistance to disease depends on the interaction of all the mechanisms.

RECOGNITION OF SELF VERSUS NONSELF

In order for the immune system to function properly, lymphocytes have to distinguish between self and nonself.  During their development and maturation process, the lymphocytes learn to recognize the proteins and other large molecules that belong to the body.  They interpret these as self.  Molecules that are not recognized as self are interpreted as nonself, and defense mechanisms are set in motion to destroy them.  A molecule that is interpreted as nonself and that triggers an immune response is called a foreign antigen.  Normally, antigens that cause problems are foreign molecules that enter the body, but sometimes the body fails to recognize its own molecules and triggers and immune reaction against itself.  This damages normal body tissues and is the basis of autoimmune diseases such as rheumatoid arthritis.

Antigens are molecules that trigger an immune response.  

DEVELOPMENT OF LYMPHOCYTES

Like all other blood cells, lymphocytes develop from stem cells in the bone marrow.  During fetal development, the bone marrow releases immature and undifferentiated lymphocytes into the blood.  Some of these go to the thymus gland where they acquire the ability to distinguish between self and nonself molecules.  The lymphocytes differentiate to become T-cells in the thymus gland.  For several months after birth the thymus gland continues to process the T cells for specific activities in immune reactions.  Differentiated T cells leave the thymus

There are two major types of lymphocytes: T cells and B cells.  In the embryo T cells are produced in the bone marrow and the thymus.  They must pass through the thymus, where the thymic hormones bring about their maturation.  The T cells then migrate to the spleen, lymph nodes and lymph nodules, where they are found after birth.  Produced in the embryo bone marrow, B cells then migrate directly to the spleen and lymph nodes and nodules.  When activated during an immune response, some B cells will become plasma cells that produce antibodies to a specific foreign antigen.

IMMUNITY

Immunity can be defined as the ability to destroy pathogens or other foreign material and to prevent further cases of certain infectious disease.  This ability is of vital importance because the body is exposed to pathogens from he moment of birth.  Malignant cells, which may be formed within the body as a result of mutations of normal cells, are also recognized as foreign and are usually destroyed before they can establish themselves and cause cancer.  Unfortunately, organ transplants are also foreign tissue, and the immune system may reject (destroy) a transplanted kidney or heart.  Sometimes the immune system mistakenly reacts to part of the body itself and causes an autoimmune disease.  Most often the immune mechanisms function to protect the body from the microorganisms around us and within us.

ANTIGENS AND ANTIBODIES

Antigens are chemical markers that identify cells.  Human cells have their own antigens that identify all the cells in an individual as “self”.  When antigens are foreign or “nonself” they may be recognized as such and destroyed.  Bacteria, viruses, fungi, protozoa, malignant cells, and organ transplants are all foreign antigens that activate the immune response.

Antibodies, also called immune globulins or gamma globulins, are proteins produced by plasma cells in response to foreign antigens.  Antibodies so not themselves destroy foreign antigens, but rather become attached to such antigens to “label” them for destruction.  Each antibody produced is specific for only one antigen.  Since there are so many different pathogens, you might think that the immune systems would have to be capable of producing many different antibodies and in fact, this is so.  It is estimated that millions of different antigen specific antibodies can be produces, should there be a need for them.  See the attached chart on the classes of antibodies.

MECHANISMS OF IMMUNITY

The first step in the destruction of a pathogen is recognition of its antigens as foreign.  Both T and B cells are capable of this,  but the immune mechanisms are activated especially well when recognition is accomplished by macrophages and a specialized group of T lymphocytes called helper T cells.  

The foreign antigen is first phagocytized by a macrophage, and parts of it are presented on the macrophage's cell membrane.  Also on the macrophage's cell membrane are “self” antigens that are representative of the antigens found on all of the cells of the individual.  Therefore, the helper T cell that encounters this macrophage is presented not only with the foreign antigen but also with the “self” antigens for comparison.  The helper T cell now becomes sensitized to and specific for the foreign antigen, the one that does not belong to the body.

The recognition of an antigen as foreign initiates one or both of the mechanisms of immunity.  These are cell-mediated immunity, in which the T cells and the macrophages participate and humoral immunity which involves T cells and B cells and macrophages.

CELL MEDIATED IMMUNITY

T cells are responsible for cell mediated immunity in which the T cells directly attack the invading antigen.  Cell mediated immunity is most effective against virus infected cells, cancer cells, foreign tissue cells, fungi, and protozoan parasites.  

These activated T cells, which are antigen specific, divide many times, forming memory T cells and killer T cells.    The memory T cells will remember the specific foreign antigen and become active if it enters the body again.  Killer T cells are able to chemically destroy foreign antigens by disrupting the cell membranes.  Killer T cells also produce a chemical that attracts macrophages to the area and activates them to phagocytize the foreign antigen.  Other activated T cells called suppressor T cells will stop the immune response once the foreign antigen has been destroyed.

ANTIBODY MEDIATED OR HUMORAL IMMUNITY

B cells are responsible for antibody or humoral immunity.  Like T cells, each type of B cell can respond to only one specific antigen.  Unlike T cells, B cells do not directly assault the antigen.  Instead, they are responsible for the production of antibodies that react with the foreign antigen or substances produced by the antigen.  Since the antibodies are found in body fluids, it is sometimes called humoral immunity.  Antibody mediated immunity is most effective against bacteria, viruses that are outside the body, and toxins.  It is also involved in allergic reactions.  

The production of antibodies after the first exposure to an antigen is different from that following a second or subsequent exposure.  Plasma cells produce antibodies.  The primary response normally takes 3-14 days to produce enough antibodies to be effective against the antigen,  In the meantime, the individual usually develops disease symptoms because the antigen has had enough time to cause tissue damage.

There are memory B cells that are also produced during this type of exposure and immune response.  This happens when the immune system has been exposed to an antigen against which it has already produced a primary response.  The second response provides better protection than the primary reponse for two reasons: the time required to produce antibodies is less from a few hours to a few days, and more antibodies are produced.  Consequently, the antigen is quickly destroyed and no disease symptoms develop and the person is immune.  

The memory response also includes the formation of new memory cells, which provide protection against additional exposures to a specific antigen.  Memory cells are the basis of specific resistance,  After destruction of the antigen, plasma cells die, the antibodies they released are degraded and the antibody levels decline to the point where they can no longer provide adequate protection.    However memory cells persist for many years and probably for life in some cases.    If memory cells are not stimulated, or if memory cells produced are short lived, it is possible to have repeated infections of the same disease.  For example, the same cold virus can cause the common cold more than once in the same person.

TYPES OF IMMUNITY

There are four ways to acquire specific resistance:  active natural, active artificial, passive natural and passive artificial.  Natural and artificial refer to the method of exposure.  Natural exposure implies that contact with the antigen occurred as a part of everyday living and was not deliberate.  Artificial exposure is a deliberate introduction of an antigen or antibody into the body.

Active immunity results when an individual is exposed to an antigen (either naturally or artificially) and the response of the individual's own immune system is the cause of the immunity.  Passive immunity occurs when another person or animal develops immunity and the immunity is transferred to a nonimmune individual.

Active natural immunity-   results when a person is exposed to a harmful antigen, contracts the disease, and recovers.  An example of this is the child who gets chickenpox, recovers and then never gets it again.  

Active artificial immunity-  develops when a specifically prepared antigen is deliberately introduced into an individual's system.  This is called vaccination.  The prepared antigen or vaccine usually consists of weakened (attenuated), inactivated, or dead pathogens or their toxins.  Examples include MMR, TD, DpT etc.

Passive natural immunity-  results when antibodies are transferred from one person to another through natural means.  This occurs only in the prenatal and postnatal relationships between mother and child.  Some antibodies can cross the placenta and enter the fetal blood.  This provides some protection for the child for a short time after birth, but eventually these deteriorate and the infant must rely on it's own immune system.  Antibodies may also be transferred through breast milk.

Passive artificial immunity-  results when antibodies that developed in another individual or animal are injected into an individual.  Antiserum is the general term that is used for the preparation that contains antibodies.  Passive artificial immunity provides immediate but short term protection.

After a period of time, the number of antibodies against a particular antigen may decrease.  A booster is an additional dose of a vaccine that may be given to increase the number of antibodies.



                                                                                                                                                                                                                                                                                                           

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