The lymphatic tissues are masses of WBCs (lymphocytes and other WBCs) embedded in areolar loose connective tissue. The lymphatic system FORCES interstitial fluids to pass through a concentration of lymphocytes.  The areolar loose connective tissue is a network of collagen, reticular and elastin fibers which act as a 'filter' catching and slowing the passage of large objects.  This 'filtering' action allows phagocytes the opportunity to capture and eat anything in fluid that should not be there.

The lymphatics are a system of vessels that collect interstitial fluids into vessels and then force the interstitial fluids to pass through lymphatic organs so that foreign cells (bacteria, viruses, etc), debris (cellular wastes, cell fragments, dead cells, denatured proteins, etc), toxins (mosquito anticoagulants, snake bite, etc), abnormal self-cells (cancerous cells), and anything else that is foreign or not beneficial to the body, can be phagocytized and removed from the intercellular spaces.

The PRIMARY function of the lymphatic system is to protect the body from pathogens.
   The functional unit of the lymphatic system are the lymphocytes.
The lymphatic system achieves its function by forcing any thing that is mobile to pass through areolar loose connective tissue crammed with lymphocytes.

We study the the lymphatic system in two parts:
     The physical lymphatics and organs - the actual structures that concentrate and channel the fluids.
     The immune response - the WBCs and how they are produced and function to protect the body from pathogens.

The Lympatics:
  1.  Return of excess interstitial fluid to the vascular system

   2. Help regulate solute concentrations by transporting molecules, ions, etc from peripheral tissues to
         the blood.

   3. Distribute hormones, nutrients and waste products from their tissues of origin to the general
          circulation.  Substances unable to enter the venous system directly may do so through
          the lymph vessels.
               Example: Large lipids absorbed by the digestive tract often fail to enter circulation via
                   the vascular capillary system.  These are molecules and other structures that are too large
                   for efficient transport via diffusion.

 The Immune Response:

  1. Production, maintenance, and distribution of lymphocytes (from and to the lymphoid organs:
       spleen, marrow, and thymus)  Because lymphocytes are THE functional unit, this is
       the most important function of the lymphatic system.

What is the PRIMARY function of the lymphatic system?
 What is the functional unit of the lymphatic system?
   How does the lymphatic system achieve it's primary function?
     Why is production of lymphocytes the most important function of the lymphatic system?
         Lymphocytes identify and destroy pathogens. 
         No lymphocytes = death due to infection.

The components of the physical lymphatic system are:
     - Lymphatics, the vessels
     - Lymph, the fluid
     - and various tissues and organs: nodules, nodes, spleen and thymus.

Lymph is the fluid inside the lymphatics.
 

Interstitial fluid squeezes between the cells that make up the wall of lymphatic capillaries into the lymph capillary. Once the interstitial fluid is inside the lymphatic capillary, it is called lymph.     The body produces about 3.6 l/day, which moves very slowly through the lymphatics.  A rupture in major lymph vessel can cause dramatic and potentially lethal drop in blood volume.

Lymph fluid resembles blood plasma but contains a much lower concentration of suspended proteins.

The fluid in the body cycles between blood plasma, interstitial fluid and lymph: 

Blood plasma à interstitial fluid à lymph  à blood plasma à interstitial fluid à lymph  … and so on

Water and small solutes in blood plasma are forced out of the vascular system in the capillaries à 90% of that fluid returns to the vascular system, but 10% remains in the interstitial spaces.  This fluid builds up and increases the extracellular hydrostatic pressure à the pressure forces interstitial fluid into the lymphatic capillaries, at which point it is called lymph à eventually lymph moves through the lymphatic vessels and re-enters the venous system, at which point it is again plasma.

Describe the process that produces lymph.
  What happens to lymph once it enters the lymphatics?
     What is lymph called when it re-enters the venous system?
Describe the components of lymph.
   Compare lymph with blood and interstitial fluid. (Make a table)

Lymph moves very slowly through the lymphatics.
  What process or mechanism causes lymph to flow through the lymphatics?
         Hint: list the processes that affect blood flow through the arteries and veins?
      Now: which of these effect flow through the lymphatics?
      How does 'pressure' effect the flow of lymph?
        Hint: How does pressure affect blood flow?

Lymphatics: the vessels that transport lymph, funneling lymph through lymph nodes.
Begin in the peripheral tissues and ends at connections to the venous system. 
Note: there are anastomoses.

NOTE: the blood vessels are a circular tube beginning and ending with the heart.  Blood stays inside the blood vessels – BUT – LYMPH begins in the interstitial spaces as extracellular fluid.  This fluid enters the lymphatic vessels from the interstitial fluid and then flows eventually, into the venous system at the subclavian veins.

Lymphatic capillaries – this is the BEGINNING of the lymphatics. They start in the tissues and are blind pockets, cul de sacs. The wall of the lymphatic capillaries are endothelial cells arranged with the cells overlapping each other so that as the extracellular hydrostatic pressure increases, the pressure forces the fluid to flow between the cells, into the capillary – this is a one-way flow, since the structure of the lymphatic capillary walls is functionally a valve.
This fluid flows into larger diameter lymph vessels.

  How does the construction of the wall of the lymphatic capillary aid the formation of lymph?
Why does lymphatic fluid flow from one place to another?

   NOTE: the WALL of the capillary is a single layer of cells that overlap each other, BUT without cell junctions that hold them tightly together.  Extracellular fluid easily pushes BETWEEN the cells and into the lymphatic capillary.
 

Lymph vessels - the walls are similar to veins with more valves. Lymphatic pressures are extremely low (why) and lack pressures of circulatory system (which ones?) and valves are essential! 

The lymph flows into trunks.

Trunks: Thoracic collecting duct – lower abdomen, pelvis, lower limbs left half of head, neck, chest (left upper limbs, too). Dumps into the venous system near the junction between the left internal jugular vein and the left subclavian vein.

Right lymphatic duct – drains lymph from the right side of the body above the diaphragm.  Dumps into the venous system near the junction of the right internal jugular and right subclavian vein.

Lymphedema –blockage of lymph vessel causing fluid build up in vessels, tissues.

Describe the parts of the lymphatic system.
List the functions of each part.

Interstitial fluid contains many solutes and suspended molecules such as minerals (electrolytes), hormones (produced by endocrine cells), bits and pieces of debris (broken proteins, lipids), etc.  Hydrostatic pressure (water pressure) forces this fluid PLUS all the solutes and suspended particles into the lymphatic capillary.   This is a primary method by which large molecules, such as large hormones, enter the vascular system and large pieces of debris are removed from the interstitial spaces.  Any mobile, intercellular substance (bacteria, cancer cells, hormones, whatever) is able to enter the lymphatics along with the interstitial fluid.  Anything that gets into the lymphatics has access to the vascular system, and therefore, can be transported throughout the body.

As the lymph flows through the lymphatics it has to pass through a series of lymph nodes. At each node, phagocytes remove bacteria and foreign molecules and debris from the lymph. It passes from small diameter lymphatics to larger diameter lymphatics and eventually is dumped into the subclavian veins near the superior vena cava and the right atrium.

Cancer cells that 'break free' of the cancer origin can enter the lymphatics. Under normal conditions, NK-Cells recognize cancerous cells as 'abnormal' and phagocytize them.  If the cancer cells are NOT recognized as 'abnormal', the cancer cells can establish in the node and begin to grow in the lymph nodes - while also, shedding cancerous cells that flow along the lymphatics to the next lymph node.  In this way, cancers can move rapidly through out the body from the point of origin.  The lymphatics are a very efficient distribution system.

List the parts of the Lymphatics.
  What are the smallest lymphatics called?
      Where are these smallest lymphatics located?
  What are the largest lymphatics?
      What are the names of the two largest lymphatics?
       Where are these two largest lymphatics located?
         What part of the body does each 'drain'?

Lymphatic nodules are lymphatic tissues found interspersed with and between the cells of the mucous membranes found in the mouth, nose, anus, vagina, digestive tract, etc. These mucous membranes are a barrier between the environment outside the body and that inside the body.  Any bacterium or molecule that enters the body through these membranes must pass through lymphatic nodule tissues, too.

Picture a donut. Put your finger in the ‘hole’ – is your finger inside the donut itself – or outside? Now, stretch that donut so it is real tall – with high walls and a ‘tube’ (the donut hole) running through the middle. Anything inside the ‘hole’ is still OUTSIDE the donut itself. Now, the top of the hole is your mouth, the bottom is your anus. Anything INSIDE your intestines is STILL OUTSIDE your body!!!  Anything that enters the INSIDE of the body must pass through the mucous membranes and the lymphatic nodule tissues.

The mucous membranes that line the digestive tract are a barrier between the environment outside the body and that inside the body.

Lymphatic nodules contain phagocytes and antibodies that destroy foreign particles BEFORE the bad stuff can get inside the body! Anything that tries to enter the body through the mucous membranes must pass through lymphatic nodules first!

Lymphatic NODULES are lymphatic tissues interspersed within the membrane tissues.
     The tonsils are lymphatic nodules.  There are 5 tonsils:
          Lingual tonsils - 1 pair
          Palatine tonsils - 1 pair
          Pharyngeal tonsil - aka Adenoids

What is tonsilitis?
  What is a tonsilectomy?
     Why were so many tonsilectomies performed in the past?
       Why did the AMA 'stop' the practice of routine tonsilectomies?

Remember: Lymphatic tissues are lymphocytes embedded in areolar loose connective tissue.

Lymph ORGANS are lymphatic tissue surrounded by a capsule.
   What is a capsule made of?
     What is the function of the capsule?

Describe the lymph organs, state the location and function of each

Lymph nodes are lymphatic tissues (lymphocytes in areolar loose connective tissues) surrounded by a CAPSULE, INSIDE the body, distributed ALONG the lymphatics. Nodes contain phagocytes that eat ‘bad’ stuff in the lymph – i.e. BAD STUFF that has already gotten INSIDE the body!! They are lymphatic tissues surrounded by a CAPSULE, and are found at intervals along the lymphatics.

Lymphatic NODULEs do NOT have a capsule.
Lymph NODEs HAVE a capsule.

Compare and contrast Nodules vs Nodes. (make a table)
   What is the function of nodules vs nodes?
    Where is each located?
      What do nodes have that nodules do NOT have?
    How do nodes 'clean/filter' lymph?
       How do phagocytes support the function of lymphatic nodules vs nodes?

Define filter.
  How does the node 'filter' lymph?

Nodes are located throughout the body.  Examples include:
       Cervical                                                         
       Axillary
           Cubital - Near elbow
       Mammary 
       Lumbar     
       Pelvic
       Inguinal
            Popliteal - near Knee

List some examples of lymph nodes.

Spleen: the largest collection of lymphatic tissue in body, this organ is a huge mass of lymphocytes embedded in areolar loose connective tissue and surrounded by a very FRAGILE capsule. The spleen is wedged between the stomach, left kidney, and diaphragm and contains large quantities of blood. As blood flows through the spleen, macrophages identify and engulf any damaged or infected cells. Local presence of lymphocytes ensure microorganisms, abnormal antigens, will stimulate immune response.

Function: the Spleen cleans the blood (it does for blood what nodes do for lymph fluid.)
   1) remove abnormal blood cells and components, Review RBC life cycle.
   2) initiate the immune response by B and T cells in response to antigens in the
        circulating blood,
   3) stores iron from recycled RBCs.

Rupture of the capsule (easily accomplished) causes severe internal bleeding leading to circulatory shock. The fragile structure of the capsule is difficult to repair surgically, therefore, resulting in a Splenectomy.

How long do RBCs live? Review Chapter 11
  What happens to RBCs at the end of their life cycle?
    Where does this normally occur?
      How does the spleen 'filter' blood?

What is a splenectomy?
  Why does damage to the spleen often result in a splenectomy?
What does the suffix '-ectomy' mean?
  Define: appendectomy, tonsillectomy, mastectomy.

Describe the Thymus

The thymus is located caudal to the thyroid, superior to the heart, anterior to the trachea, and posterior to the sternum.

The function: the thymus produces thymosins (hormones) that cause immature T-Cells to
become mature T-Cells.

The T-Cells function in Immunity.

List all the lymphatic tissues.
List the Organs of the Lymphatic System.
List the vessels of the lymphatic system.
Compare and contrast lymph organs with the lymphatic tissues: name, location, specific function, structure, location of pathogens intercepted, etc.  Make a table.
 

The body has two basic methods to defend against pathogens.

Pathogens
   Bacteria - when they cause disease, they are usually located INSIDE the body, in the interstitial
          spaces... i.e. extracellular.
   Viruses - when they cause disease, they are usually located INSIDE the body, within the
          cell... i.e. intracellular.
   Fungi - when they cause disease, they are usually EXTERNAL, on an epithelial surface.
   Parasites - these are multicellular microorganisms that when they cause disease, usually burrow
           through tissues causing damage.
   Micro organisms - various prokaryotes, ameoba, protozoans, etc.

Pathogens cause disease when the total pathogen population is large enough that collectively their effects pull the body out of homeostasis.  The body can absorb the effects of just a few pathogens, but when the pathogen population reaches billions of bacteria - the total effects of all the bacteria are too great and the body is pulled away from homeostasis.

Host - An organism that is infected by a pathogen. The pathogen is present and is using the host's
      resources to meet the needs of the pathogen.

Vector.  the mechanism by which a pathogen is transmitted from one host to the another host. 
      Microscopic Mucous droplets suspended in the air we breath is the vector for the common cold.
      Bodily fluids exchanged during intercourse are the vector for STDs (sexually transmitted disease).
      Mosquitoes are the vector for malaria, west nile virus, st louis encephalitis, etc.
      Water is the vector for water-borne diseases: diphtheria, typhoid, cholera, giardia, amoebic
          dysentery, etc.

The two defense mechanisms:
     Non specific - defense against whatever is attacking
     Specific - defense against only a single pathogen for which the body has created a specific response.

Nonspecific defense mechanisms defend the body against all threats.

Physical barriers – the skin and mucous membranes, hair, nails, etc – defend against abrasion, bacteria, virus, water loss, etc. ALL things.

      List the 4 types of membranes found in the body. Review Chapter 4, Tissues
        Which are 'dry'?
        Which are 'wet'?
        Which are exposed only to the internal environment?
        Which are exposed to the external environment?
     Which are physical barriers?

WBCs – basophils (mast cells) and some phagocytes defend against ALL threats.
      When a threat has been identified, these WBCs attack and phagocytize the pathogen.

Fever – kills ALL types of bacteria.
   HEAT denatures the proteins. I.e. enzymes which control and regulate metabolism.

Inflammatory response - a generalized response to damage to tissues (and connective tissues).
   Redness
   Swelling
   Heat
   Pain
   Loss of function

 Mast cells - basophils attached to collagen fibers in the interstitial spaces. When the tissues
      and collagen damaged, mast cells release Histamine. Histamine promotes the
      inflammatory response.

 

Once a pathogen has been discovered, the body immediately sets off an array of all its defenses.  The nonspecific defenses are implemented simultaneously and the specific defenses are activated.  Once the specific defenses have been created, discovery of a 'known' pathogen initiates the total defense response much more rapidly: both specific and nonspecific defenses.

What 'triggers' the inflammatory response?
  The MAST cell releases histamine, serotonin and heparin, which triggers the inflammatory response.

Specific defense mechanisms defend against A SPECIFIC pathogen. The measles defense mechanism defends against measles ONLY. Not against mumps, chickenpox, or any other pathogen – specifically against measles only. The chickenpox defense mechanism defends against chickenpox ONLY. Likewise the mumps defense mechanism.

The Specific Defense consists of two mechanisms:
   - Specialized cells that are programmed to recognize a specific threat,
   - Antibodies, specialized proteins, that are programmed to recognize a specific threat.

How does a nonspecific defense differ from a specific defense?
  List the types of nonspecific defenses.
List the symptoms of the inflammatory response.
   What are mast cells?
     Where are mast cells located?
        How do mast cells function in defense?

The characteristics of the Specific Defenses are:
    Memory- the ability to remember a specific pathogen and rapidly respond to subsequent infection
        by that pathogen.
    Specificity - the ability to rapidly respond to a SPECIFIC species of pathogen without responding to
        NONpathogenic cells or substances. 
    Tolerance - the ability to distinguish between SELF cells, nonpathogenic substances and pathogenic
        or foreign cells.  Phagocytes do NOT eat normal, self-cells.
    Versatility - the ability to respond to any and all foreign cells and substances that may be encountered.

The lymphocytes are the functional unit of the Immune system. There are three types of lymphocytes:

T-cells - phagocytosis - individual T-cells become specific for a single species of pathogen
B-cells - produce antibodies that are specific to a single species of pathogen.
NK-cells - phagocytosis - specifically function for immunological surveillance, the recognition
        of abnormal self cells.

These cells and antibodies 'recognize/identify' a specific pathogen and trigger a pre-created defense that is specific to that specific pathogen.

List the three Lymphocytes.
  What is the function of each?
     How are T-cells and antibodies a SPECIFIC defense?
  Describe immunological surveillance.

List and describe the 'characteristics of Specific Defenses'.

Immunological surveillance - NK cells wander through tissues and monitor (surveillance = keep an eye on) the normal self-cells that make up the tissues.  When a self-cell becomes 'abnormal' the NK cell phagocytizes it. 
    Viruses enter a normal cell, and that cell produces antigens and chemicals that tell the surrounding cells
        that it is no longer 'normal'.
    Cancer is a self-cell that goes through repeated cycles of mitosis without stopping between cycles to
         be 'functional'.   NK cells recognize 'cancerous' cells, going through uncontrolled mitosis, and
         remove the 'abnormal' cells.
                     It is estimated that everyday, throughout your entire life, more than
                           2 million cancer cells are identified and phagocytized.
Immunological escape - an abnormal self-cell is NOT identified by the NK cells, allowing the abnormal
   cell to continue reproducing and spreading and using resources.  This produces the condition that we
   know as 'Cancer'.

NK-cells via Immunological surveillance remove abnormal self-cells.
T-cells and B-cells via the immune response remove PATHOGENS.

Define immunity

Immunity - the ability to resist infection and disease through the activation of specific defenses
      against a specific pathogen

Immunity begins with antigen recognition.

Define antigen.
  An antigen is a identifier protein on the surface of the cell membrane.

Define antibody.
  An antibody is a protein molecule (i.e. a chemical) with a specific segment that 'identifies' a specific antigen.

Genetic Immunity - immunity to a pathogen due to species differences. You do not get the fish disease ‘ick’ because you are a human – not a fish. Fish don’t get measles because they are fish, not humans.

This is 'innate' immunity - the organism is born with this immunity.
   i.e. - the fish 'pathogen' cannot cause disease in humans.

Acquired Immunity – The body has specific defenses that protect it against a specific pathogen that CAN make the body sick.
   This is immunity to a pathogen as a result of activated T-cells and B-cells
   (plasma cells à antibodies).

Two types of Acquired Immunity:
   Passive acquired immunity - the immune response is GIVEN to the body.
       Two types:
          Passive NATURAL acquired immunity - antibodies from the MOTHER (first 6 months of life).
             This is the primary source of immunity for newborn infants.
          Passive INDUCED acquired immunity - antibodies received from an artificial setting.
              Doctor gives an injection containing antibodies.
              Army docs give 'gamma globulin' injections to soldiers going to areas of the world where the
              soldier will be exposed to such pathogens as scarlet fever, typhoid, diphtheria, etc.

   Active Acquired Immunity-  The body must first expend resources and energy to CREATE this
           immunity.
    The pathogen CAN make you sick – but you have the antibodies and T-cells to fight it.

The FIRST exposure to a pathogen makes you sick – remember getting the measles?
   After that first time, though, subsequent exposures to the measles will no longer make
   you sick.

You DO get sick on the First exposure.
You do NOT get sick on the Second (subsequent) exposure.

      Two types:
          Active NATURAL acquired immunity - exposure to a pathogen in the natural environment. Measles
                 that you got from the neighbor kid, or from a fellow kindergartener.
          Active INDUCED acquired immunity - exposure to a pathogen in a 'controlled' environment
                 Immunization and Vaccination - exposure via an artificial vector.
                   Immunity to Polio due to getting a Polio vaccination 

What does genetic immunity mean?
What is acquired immunity?
Which type of immunity must the body expend energy to create?

The thymus produces hormones called Thymosins, which stimulate the immature T-Cells to become mature T-Cells. Immature T-Cells are a bland slate - they do not know who their specific pathogen is.  Mature T-cells know which specific pathogen they will respond against.
   Measles T-Cells respond to the measles pathogen. 
   Chicken pox T-Cells respond to the Chicken pox pathogen.

Cell mediated immunity begins with a T-Cell recognizing an antigen on a pathogen.
 

Antibody (aka Humoral) mediated immunity begins with an ANTIBODY recognizing an antigen.

What recognizes the antigen in cell mediated immunity?
What recognizes the antigen in antibody mediated immunity?

When the body 'discovers' a pathogen, the body creates both Cells and antibodies that specifically recognize that pathogen. 

The immune response begins with what event?

T cells and Cell Mediated Immunity: Immature T cells recognize BAD-antigens bound to special receptors on the CM of other cells. These receptors are called Major Histocompatibility Complex (MHC) proteins found on the surface of all our cells.

Macrophages (WBCs) engulf foreign cells, break down the foreign antigens, creating antigenic fragments that are bound to MHC proteins and displayed on the cell surface. Immature T-cells, contacting this macrophage membrane become activated, initiating an immune response.

Virus infected cells display antigen-MHC proteins on their CM also – this rallies a defense against a virus. THIS makes a ‘self-cell’ abnormal.

Once the T-cells have been activated they divide (mitosis) and produce:

Cytotoxic/Killer T cells: Cell mediated immunity; track down and attack pathogens with
        the target antigen.
Memory T cells – remain ‘in reserve’ to respond to subsequent exposure to the same
       antigen,  by differentiating into anti-body secreting plasma cells.
Helper/ Regulatory T cells – release cytokines, chemicals that regulate the immune
        response.

Cytokines from T cells activate B cells

B-cellls divide (mitosis) producing:
     Memory B cells
     Plasma cells, which produce antibodies.

The 5 Classes of Antibodies or Immunoglobulins: IgG, Ig A, IgM, IgE and IgD
     IgG: the largest group, make up about 80% of all antibodies. Longest life
     IgA: 15%, antibodies in mucous
     IgM: 5-10%. 1^st produced, 1^st to act against an infection; cross reactions between
                  incompatible blood types.
     IgE: attached to and activate mast cells and basophils
     IgD: help B-Cells

(Note:  spells:  G A M E D)

Antibodies defend against antigen in several ways:

1. Neutralize: bind to toxins or viruses- the pathogen therefore cannot bind to CM and/or cause damage.
2. Agglutinate & precipitate: clumping of many antigen-antibody complexed cells. (IgM). Smaller antigens form insoluble masses that settle out (precipitate) of fluids.
3. Activate Complement: expose binding sites on complement proteins à antigen destruction
4. Attract phagocytes: antibody labeled antigens attract eosinophils, neutrophils, macrophages
5. Enhance phagocytosis: coating of antibodies and complement proteins increase effectiveness of phagocytosis.
6. Stimulate inflammation: stimulate basophils, mast cells (IgE) – help mobilize nonspecific defenses and slow spread of infection.

When an antibody binds to an antigen - the antibody may cause any one, a combination, or all of the above actions by the immune system.

List the ways that antibodies can 'defeat' a pathogen.
  Explain the 'method' by which each achieves defeat of a pathogen.

T-Cells activate B-Cells.  If the T-Cells do not get activated, then the B-Cells do not get activated - NO plasma cells are produced, so NO antibodies are produced.

Memory T-Cells and Memory B-Cells:  these lymphocytes are produced as part of the specific defense mechanism - but are NOT active/functional at the time they are created.  The Memory Cells become functional during a subsequent exposure to its specific pathogen.

The FUNCTION of the Memory Cells is to be ready to immediately go through mitosis and rapidly produce a new group of functional phagocytes (cytotoxic/killer T-Cells) and functional antibodies against a pathogen that has been previously encountered.

Example:

When the body is exposed to the measles, the immune system activates T-Cells against the measles, producing Cytotoxic/Killer T-Cells which are immediately functional against the current invasion of measles.  It also creates Memory T-Cells which are nonfunctional against the current invasion - but become functional against a subsequent invasion.  Regulatory T-Cells against the measles activate B-Cells that are also specific against the measles.  These B-Cells produce Plasma Cells and Memory B-Cells.  The Plasma cells produce antibodies that are immediately functional against the measles.  The Memory B-Cells are inactive - waiting till the NEXT invasion by the measles.

On each subsequent invasion by the measles, Memory T-Cells under mitosis, immediately producing active Cytotoxic/Killer T-Cells and a new group of Memory T-Cells and Regulatory T-Cells.  Memory B-Cells are activated, undergo mitosis and immediately produce Plasma Cells and a new group of Memory B-Cells.  The new Plasma cells produce a new group of antibodies against the measles.

What is the function of the Memory Cells?
 When do Memory T-Cells and Memory B-Cells become active?

Immediately functional lymphocytes and antibodies defend against current pathogens.
Memory Lymphocytes are a rapid response defense against future pathogens.

There are trillions of Lymphocytes in the body. Some live for a few years, some, about 80%, live more than 4 years, and a few live more than 20 years.  Antibodies are molecules that 'hang' out in the extracellular fluid, waiting till their 'target' antigen comes along. 

Long-lived lymphocytes and antibodies give long lasting immunity, especially if there is subsequent exposure to the pathogen every couple of years.

What is the first line of cellular defense against pathogens?
        Which 'characteristic of specific defense' is this?
  Why are antibodies NOT the first line of cellular defense?
  Why are T-cells NOT the first line of cellular defense?
What role do antibodies play in 'immunity'?
  Which 'characteristic of specific defense' is this?
What is the function of Memory T-Cells and Memory B-Cells in immunity?
     Which 'characteristic of specific defense' is this?
What is the role of NK-cells in immunity?
Describe Tolerance (the characteristic of immunity) and how each of the above exhibit 'tolerance'.   

Immunity means that the body is exposed to a pathogen and creates a specific defense against that pathogen.  The first time a pathogen is encountered, the body must use resources to create the defense - this takes time - during which a live, virulent pathogen is causing disease and damage.  The body immediately recognizes and defends against that pathogen in any subsequent exposure to that pathogen- the body does not need the 'time' to create the defense, and the pathogen does not have time to reproduce to population levels that can cause disease.

Vaccines/immunizations expose the body to a NONvirulent pathogen so that the body can create the specific defense response prior to being exposed to that pathogen in conditions where the pathogen will cause disease.

The body is exposed to the pathogen in a controlled setting:
   the pathogen is either dead or weakened so that it cannot cause disease.

However – the antigens that identify the pathogen are present.

This is the FIRST exposure.

Your body recognizes the antigen and builds a population of T-cells and B-cells (plasma cells) as well as memory T-cells and memory B-cells against that pathogen.

When next you encounter the pathogen (second exposure) – this time in a natural, uncontrolled setting – the pathogen is virulent – the antibodies, activated T-cells, B-cells, and memory T & B- cells immediately recognize the ANTIGENS on the pathogen and destroy the pathogen before it can make you sick.

Describe the Immune Disorders

Immune disorders – The Immune system is a complex system = MANY opportunities for malfunctions.

Immunodeficiency – these conditions are rare, which is clear evidence of the effectiveness of
   the immune system's control mechanisms.
These conditions arise when the Immune system fails to develop normally or becomes
   blocked in some way (example: AIDS and HIV).

Autoimmune disorders – also rare, and therefore, clear evidence of the effectiveness of the immune system's control mechanisms.
    -  Immune response mistakenly targets normal body cells.  Rheumatoid arthritis occurs when
          autoantibodies attack joint surfaces. 
          NK cells start to identify normal self-cells as abnormal.

    - Mistaken identity: proteins associated with measles, influenza, and other viruses contain amino
         acid sequences similar to those on the myelin proteins.  Antibodies that target these viruses
         may also attack myelin sheaths, producing the neurological complications sometimes associated
         with a vaccination or viral infection.

    - MHC (major Histocompatibility complex) proteins are linked to at least 50 clinical disorders;
          psoriasis, rheumatoid arthritis, myasthenia gravis, multiple sclerosis, narcolepsy, Type 1 diabetes,
          Graves’ disease, Addison’s disease, pernicious anemia, systemic lupus erythmatosus, and
          chronic hepatitis.
         These are CHRONIC conditions/diseases

What is an antigen?
   What triggers or activates the 'immune response'?
      How do antigens affect immune disorders?
        What happens when a normal, self antigen is recognized by T-Cells or antibodies as a 'threat' - i.e.
             an antigen that identifies that self cell as a foreign cell?

Stress, either acute or chronic, plays a role in the development of Autoimmune disorders.  Stress causes the body to use resources to 'fight' it, rather than using those resources for tissue repair, maintaining overall homeostasis, efficiently creating immune responses to pathogens, etc. 

Allergy – an inappropriate or excessive immune response to allergens.
   Inappropriate - a response to an antigen that is NOT pathogenic, such as a response to
       ragweed pollen, mountain cedar pollen, grass clippings, pet dander, etc.
   Excessive - a response that greatly exceeds threat, such as a response to bee or wasp sting/toxins

Some allergies can be both Inappropriate and Excessive - such as food allergies. 

Allergens - Antigens that trigger allergic reactions.

Neutrophils or cytotoxic T cells – may destroy normal cells while attacking the antigen or the antigen-antibody complex may trigger a massive inflammatory response.

Immediate hypersensitivity (Type I) allergy – B cells and helper T cells are first exposed and sensitized to an allergen and produce large quantities of IgE antibodies. The IgE antibodies attach to basophils and mast cells throughout the body. Subsequent exposure to the antigen triggers a response from the mast cells.

The most common type of Allergy is the Immediate Hypersensitivity Allergic Response.

-  T-Cells and B-Cells are first 'sensitized' to an antigen, creating active functional T-Cells,
      Plasma Cells and antibodies against that antigen.
-  Antibodies are produced, and especially IgE, deploy to the mast cells in the areolar
     loose connective tissues.  (Review Chapter 4, Tissues)
-  The antigen comes into contact with the antibody or a T-Cell that 'recognizes' the antigen,
      and the whole inflammatory and immune/allergic response is triggered.

Local, epithelial exposure causes a local allergic response.
    What is an epithelium?
       Which are the most common allergies and how does this result from an epithelial exposure?
          Poison Ivy or other 'rashes'.
          Plant allergies in which the allergen enters the nasal cavity and is trapped in the nasal mucous
             membranes.  Antibodies 'recognize/identify' the allergen and trigger an inflammatory response
             which triggers the immune (allergic) response.
          Usually NOT lethal.

IF the antigen gets into the blood stream, the exposure becomes systemic resulting in the IgE triggering basophils and mast cells throughout the body. All these basophils secrete histamine, which results in an inflammatory response throughout the body – massive edema throughout the body or- Anaphylactic shock, which can be lethal – since it pulls all the fluid out of the vascular system, putting the fluid into the interstitial spaces and the heart has nothing to pump.
        Food allergies - the antigen gets into the blood/vascular system from the digestive system.
        Insect stings (wasp, bee, etc) - venom enters vascular system from the interstitial spaces.
        Potentially FATAL.

Define 'systemic':
   system-wide: affecting the entire system, rather than just a local area.

What are basophils?
What are mast cells?
  Where are mast cells located?
      Which antibody is attached directly to mast cells?
    What do they secrete?
        What are the 5 signs of inflammation?
            What causes each?  Review Chapter 4, Tissues.

Histamine triggers the Inflammatory response, which triggers the entire array of defenses, both nonspecific and specific.

Define edema.
  How does edema affect blood volume?
    How does low blood volume affect 'life'?  Hint: review Frank Starling's Law.
       What is 'anaphylactic shock'?

When the antibodies and cells are located throughout the entire body (systemic), then the response becomes system wide.  IgE antibodies recognize wasp toxin in the left arm, trigger a response of mast cells throughout the entire body. This can result in systemic release of histamine and heparin with a subsequent systemic inflammatory response.  Massive, systemic edema ... anaphylactic shock.

There is not enough wasp toxin to actually kill the body.  The excessive immune/allergic response does the killing.

Over time, the body is exposed many, many times to the same and many, many different antigens.  There are multiple opportunities to develop Autoimmune Disorders such as diabetes, arthritis, etc, as well as allergies.

T-Cells and B-Cells become less sensitive to antigens.
       Remember, T-Cells activate B-Cells.  No T-Cell activation -->  no B-Cell activation --> no
              antibodies -->  much diminished response to pathogens.

NK-Cells, the cells responsible for keeping an eye out for cancerous cells, may become insensitive to a particular type of cancerous cell - allowing that cancer to continue growing.

Chronic stress maintains a low-level stress response
   - release of glucocorticoids which suppress the immune response and allow pathogens to gain a
       larger more problematic foot hold in the body
   - norepinephrine and epinephrine stimulate the stress response which allocates resources to
       fight or flight, rather than to tissue repair, internal homeostasis, and accurate functioning of the
       tissues and systems.  Since the lymphatic system is undersupplied with resources, the specific
       responses are either not created or not well regulated.

When the immune response slows, there is more opportunity for disease.

Remember – all the systems have to work together to maintain homeostasis.

List the WBCs.
 What are the 4 characteristics of WBCs?
   How do diapedesis and chemotaxis support 'immunity' and resistance to disease?

How does the skin support immunity?
How does the endocrine system support immunity?

What is areolar loose connective tissue?
  Where is it found?
   What WBC is specifically found attached to the collagen fibers in Areolar Loose CT?

Every system has 'defense' functions, which integrate both the nonspecific and specific defenses.
  Describe the 'defense' mechanisms of the tissues and systems that we have studied to date.

Hygiene Theory: Studies suggest that exposure to bacteria in the environment, especially as newborn to about 6 months, lead to individuals with more effective immune systems.  There is a reported correlation that individuals living in a sterile environment tend to have more asthma and allergy problems than folks who are exposed to bacteria and antigens.  The theory is that individuals from extremely sterile environments exhibit some immunodeficiency disorders.

• Lymphatic capillaries
• Lymphatics

• Thoracic collecting duct
• Right lymphatic duct

• Lymph nodules
  • Lining of the intestinal tract

   

• Lymph nodes
  • Tonsils
  • Lymphatics of upper limb
  • Cervical
  • Axillary
  • Lympharics of mammary gland
  • Lymphoid nodules of intestines
  • Lumbar lymph nodes
  • Pelvic lymph nodes
  • Inguinal lymph nodes
  • Lymphatics of lower limb

   

• Thymus
• Spleen

• T-cells
  • Cytotoxic T cells
  • Memory T cells
  • Suppressor T cells
  • Helper T Cells
• B-cells
  • Memory B cells
  • Plasma cells
• NK cells

Review the Cell Membrane structure
  Note the proteins in the CM

• Receptors
• Identifiers
• Anchors
• Channels
• Carriers
• Enzymes