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LYMPHATIC SYSTEM and IMMUNITY

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					                     Chapter 16: LYMPHATIC SYSTEM and IMMUNITY

Defined as all the cells, tissues and organs responsible for:
1) Returning fluid to the blood from body tissues
   a) Maintains normal blood volume and prevents tissue swelling
2) the defense of the body from infection and disease
   a) lymphocytes respond to pathogens, abnormal body cells, and foreign proteins
3) the distribution of hormones, fats, and waste products from their tissues of origin to the
   general circulation
   a) larger substances that are unable to enter capillaries, enter lymph vessels that drain
      into venous circulation

Components

1) Lymph – mostly extracellular fluid; resembles plasma with lower protein concentration

2) Lymphatic vessels
   a) Capillaries – comprised of simple squamous epithelium (but more permeable)
       a) Originate as “blind pockets” and are large in diameter (as compared to blood
          capillaries) have thin walls and look flatter in sectional view
       b) Present in almost every tissue and organ except in areas that lack a blood supply
          as well as bone marrow and CNS
       c) Capillaries drain into larger vessels that lead toward the trunk
       d) Bulge at valves to create a beaded appearance
             valves – prevent back flow and direct it toward the thoracic cavity

   b) Major lymph collecting vessels
       a) Superficial (skin and membranes) and Deep (muscles and organs) vessels
          eventually converge to form two large collecting ducts
             Named for their location (mammary, femoral, etc)
          (1) Thoracic duct (left lymphatic duct) ~16 inches long
              (a) anterior to the level of vertebrae L2 up to the level of the left clavicle
              (b) receives lymph from left side of head, neck and thorax and entire body
                  inferior to the diaphragm
                 (i) Cisterna chyli – a receiving pouch at the inferior end of this duct
              (c) empties into left subclavian vein
          (2) Right lymphatic duct (short duct)
              (a) Lies below the right clavicle
              (b) receives lymph from delivering lymph from the right side of the body superior
                  to the diaphragm
   c) Lymph is moved through the vessels in the same manner as blood through veins
       a) Rhythmic contractions, valves, skeletal muscle contractions, and the respiratory
          pump keep lymph flowing back towards the heart
       b) The more lymph, the more contractions and pressure to return

Lymphedema (Box 16-1)
Edema is tissue swelling due to excess fluid in the tissue. Blockage of lymphatic tissue due
to infection (filarial worms) will prevent fluid drainage from tissue. Limbs will become grossly
distended, a condition known as elephantiasis. Other blockages can come from loss of
lymphatic tissue, malignant growths that block vessels, or other infections. Edema may
increase the chance of infection because filtering is diminished and protective measures are
diluted.

3) Lymphoid tissue
   a) Lymph nodes (kidney shaped) – locations (cervical, axillary, mesenteric, inguinal)
       a) Range in diameter from 1-25mm
       b) Collagen fibers surround and extend into the node (trabeculae) which is dominated
          by immune cells
       c) Blood vessels and nerves attach at the hilus (indentation)
          (1) afferent vessels – carry lymph to lymph node
          (2) efferent vessels – carry lymph to venus circulation out the hilus
       d) 99% of the lymph that passes through the node is cleared of its antigens (outer
          cortex to medulla)
       e) Designed as an early warning system (infection presents antigens)
   b) Spleen
       a) Contains the largest collection of lymphoid tissue in the body
       b) takes it shape by the organs that are around it (5-7” long. 2-3” wide)
       c) contains pulp
             red (RBC’s) vs white pulp (lymphoid nodules)
       d) Main functions:
          (1) Removes abnormal blood cells and other components by filtration and
              phagocytosis. Initiates an immune response (T-cells and B-cells)
          (2) storage of iron from recycled RBCs
          (3) Produces RBCs before birth
          (4) Blood reservoir which can be used during hemorrhage

Surgical removal of the spleen (splenectomy) when damaged is well tolerated. The capsule
around the spleen is too thin to repair. There are plenty other lymphatic tissues to do the job.
   c) Thymus
       a) located in the mediastinum (pink and grainy) posterior to the sternum
       b) grows through puberty then diminishes in size and becomes fibrous (involution)
       c) divided into lobules where each has an outer cortex and central medulla
       d) T cells mature in the cortex then migrate to the medulla to be released
       e) releases hormones collectively known as thymosins
   d) Tonsils
       a) large nodules in the walls of the pharynx
       b) R & L palatine tonsils located on the soft palate (referred to as “tonsils”)
       c) Pharyngeal tonsil (adenoids) located on the roof of the pharynx
       d) Lingual tonsils - pair at the base of the tongue
          (1) Not noticeable unless swollen
       Tonsillitis (Box 16-3): bacterial infection of the tonsils in the throat
             Breathing and swallowing become difficult
             Once an abscess forms, surgery is required to drain the fluid
             Removal of tonsils (tonsillectomy) to prevent reoccurring infection
   e) Other tissues that are dominated by lymphocytes
       a) MALT (mucosa-associated lymphoid tissue)
              (a) clusters of lymphoid nodules linked to the digestive system
              (b) Peyer’s patches exist within the mucous membrane of GI tract
       b) Appendix (7-10 cm long)
          (1) Slender tube of lymphatic tissue attached to the cecum of the large intestine
       Appendicitis: breakdown of the epithelial lining of the appendix which creates
       inflammation.
             The organ becomes distended and may rupture
             Toxins and bacteria are released into the peritoneal cavity

Disorders of the Lymphatic Tissue
Lymphangitis is the inflammation of a lymphatic vessel which creates red streaks along the
skin in the area of the infection. Shows the spread of bacteria in the lymphatic system.
      If lymph system isn’t able to stop the infection, it will get into the bloodstream and
       cause septicemia (blood poisoning)


Lymphocytes that have become cancerous that exist in lymph tissue are called lymphomas
      40% of these cases are considered Hodgkin’s Disease, the rest are grouped as non-
       Hodgkin’s lymphoma
       a) cause unknown, but linked to infections and in more common in males than
          females
       b) again early diagnosis and treatment is the key to successful prognosis, but
          unfortunately most are not detected early because it mimics more traditional “every
          day” diseases
Epstein-Barr virus (EBV) causes a chronic infection that is known as Mononucleosis
(Increases monocyte production)
      Transmitted orally (kissing disease)
      Virus invades the lungs, bone marrow, and lymphoid tissue causing fever, sore throat,
       enlarged spleen, and other lymphadenopathies (disease of lymph nodes)
      Can only treat symptoms; no defense against the virus; cautionary to damaging the
       spleen

Nonspecific vs Specific Defenses

Immune response or immunity
   the ability to resist infection and disease through the activation of specific defenses

Why do infections occur? (portal of entry, virulence of an organism, dose of pathogens, and
an individual’s predisposition)


Nonspecific Defenses
1) Physical Barriers
   a) the skin provides the first outer defense against antigens/pathogens from entering the
      body
   b) epithelial tissue with hair, mucous, sebaceous and sweat glands (pH and enzymes)


2) Phagocytes (white blood cells)
   a) Police and clean up cellular debris in response to an invasion usually before
      lymphocytes detect their presence
   b) Microphages
       a) Neutrophils and eosinophils that circulate in the blood
       b) Leave the blood and enter peripheral tissue subjected to injury or infection
   c) Macrophages
       a) Large phagocytic cells that are fixed or move freely
       b) Fixed macrophages: are permanent residents of specific tissues and organs,
          incapable of movement, scattered within the connective tissue of organs
       c) Free macrophages: travel throughout the body and migrate to damaged or infected
          tissue


3) Immunological Surveillance
   a) Monitoring of normal tissues by NK cells
   b) NK cells recognize abnormal cells by detecting the antigens on it’s surface
   c) Immunological escape
       a) When cancer cells lack or cover antigens, or destroy NK cells that detect them


4) Inflammation: localized tissue response to injury
   a) most cells release chemicals into the local environment (histamine increase blood flow
      and capillary permeability)
       a) increase blood flow, increase temperature, increase enzyme activity
   b) clotting factors begin to form a clot around the general area
   c) neutrophils in the area move to the damaged area releasing chemicals that attract
      other neurophils and macrophages
   d) macrophages engulf pathogens and continue to attract other macrophages
   e) some cytokines released by the mast cells start to stimulate local sensory neurons to
      elicit pain
   f) this general response allows for specific defenses to be activated


5) Fever:
   a) maintenance of a body temperature greater than 99 degrees Fahrenheit
   b) pyrogen- proteins that reset the thermostat in the hypothatlmus
   c) interleukin –1: increase 1 degree Celsius in body temperature increase metabolism
      10%


6) Interferons (“interferes” with multiplication and spread of the virus)
   a) Small proteins released by activated lymphocytes and macrophages (cytokines)
   b) Binds to surface receptors on cell and releases antiviral proteins (don’t destroy but
      interfere with replication)
   c) Stimulate activities of macrophages and NK cells
   d) Named with a Greek letter to indicate different categories



Lymphocytes – 20-30% of the circulating white blood cells

   a) T-cells (thymus dependant cells) 80% of lymphocytes
       a) Cytoxic T cells- directly attacks foreign cells or body cells infected by viruses
          (cellular immunity)
               Responsible for rejection of skin grafts and transplants
       b) Helper T cells- stimulate the activation and function of both T cells (secrete
          interleukins) and plasma B cells (secrete antibodies)
       c) Suppressor T cells- inhibit the activation and function of both T cells and B cells
       d) Memory T cells – stay in reserve for subsequent attacks


   b) B cells (bone marrow derived) – 10-15% of lymphocytes
       a) Responsible for the production and secretion of antibodies (immunoglobulins)-
          soluble proteins (read Box 17-1)
       b) Immunoglobulins bind to specific chemical targets called antigens (pathogens)
          (foreign material)


   c) NK cells (Natural Killer) – 5-10% of lymphocytes
       a) large granular lymphocytes that “police” body tissues
       b) attack foreign cells, infected cells, and cancer cells within normal tissue

   d) Lymphocytes circulate through the body at different rates and exist in the body at
      different rates
      a) Most have long life spans (20+ years)


Lymphopoiesis
  a) lymphocyte production involving bone marrow, thymus, and peripheral lymphoid tissue
   b) two distinct populations of lymphoid tissue are produced in the bone marrow
       a) B-cells mature in the bone marrow. NK cells develop in the bone marrow enter the
          bloodstream and mature in the blood stream.
       b) the other group of cells migrates to the thymus
          (1) there they are isolated from general circulation (blood-thymus barrier) and
              divide producing the different types of T-cells
          (2) after they have developed they reenter the blood stream and take on specific
              roles.
All lymphocytes have the ability to divide by mitosis. An important concept for the immune
response.




Specific Defenses (immunity)

Inborn immunity - immunity we have at birth. No relationship to previous exposure
      passed along within genetic lines (species immunity or individual immunity)
Acquired Immunity (active) - immunity to a specific antigen after you have been exposed
             Naturally active – contact with a specific disease
             Passive immunity – transfer of antibodies from an other source
              (placenta/mother’s milk or induced)
             Artificially acquired (vaccination or immunization)
                 1. live, dead, or attenuated vaccines
                 2. toxoids
             Boosters (table 17-2)
Research Examples of Bacterial and Viral Vaccines

Cell Mediated Immunity
1) Activated T-cells mount a direct attack on foreign or infected cells
2) Completed by cytoxic T cells, memory T cells, Helper T cells
   a) Antigen Presentation occurs when an antigen-glycoprotein combination capable of
      activating T cells appears on a cell membrane (ie. Virus infected cell)

Antibody-mediated immunity (Humoral immunity)
1) Activated B cells differentiate into Plasma cells which secrete a specific antibody that
   attacks specific antigens
       a) activated by a specific antigen presentation or interleukins secreted by helper T
          cells
       b) divide numerous times to create plasma cells or Memory B cells
             Cells that are not activated after cell division; stay in reserve

Primary and Secondary Responses
1) Primary response – Helper T cell activation which stimulates B cells which result in
   antibody production (lag time between activation and sufficient production)

2) Secondary Response – upon second exposure to the same antigen, b cells immediately
   begin synthesizing antibodies in massive quantities


Immune Disorders

With advancing age, the immune system becomes less effective. Vaccines are strongly
recommended

Physical examination includes observing or palpating for Lymphadenopathies, percussion
of the spleen, observation of skin disorder linked to certain infections, and experiencing
weakness and fatigue.

Disorders of the immune system may result from an inadequate or suppressed immune
response, an excessive immune response, or an inappropriate mechanism of the immune
response.


1) AIDS (late stage HIV disease)
   a) Retrovirus (Box 17-3) that injects RNA into healthy cell (typically Helper T cells) which
      ultimately decreases the cell population
   b) Without T cells, the body’s immune defense against other pathogens is greatly
      reduced
   c) Current chemotherapies are extending the lifespan of individuals by supporting
      immune defenses along with maintaining healthy lifestyles


2) Immunosuppressant drugs (radiation and some chemotherapy) destroy stem cells and
   lymphocytes leading to complete suppression of immunity
   a) Bone marrow transplants, if not rejected, begin creating new RBCs and WBCs within
      two weeks
   b) Graft rejections are reduced by matching lymphocytes and administering
      immunosuppressant drugs


3) Allergies – excessive immune responses
   a) Certain antigens create an excessive T cell response that in turn produces plasma
      antibody production that attacks normal cells as well as the antigen
   b) Allergens are antigens that trigger allergic reactions
   c) The most common type of allergy is immediate hypersensitivity (allergic rhinitis –
      hay fever)
      a) Starts first with sensitization
          (1) The first exposure doesn’t create the symptoms, but antibody production occurs
              which attach to basophils and mast cells so that a second exposure will create
              a massive inflammation in the surrounding tissue.
             (a) Lethal if the reaction happen systemically

Anaphylaxis – a circulating allergen affects mast cells throughout the body
1) The response can occur in a few minutes
2) Swelling and edema in the dermis and respiratory constriction occurs with possible
   vasodilation which will decrease venous return and lower blood pressure (faint)
   a) Anaphylactic shock
   b) Anihistamines required, in some cases epinephrine and corticosteroids are required as
      well


Stress and the immune response (Box 17-2)

   o Depression of the inflammatory response

   o Reduction in the number and activity of phagocytes in peripheral tissue

   o Inhibition if interleukin secretion

				
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