THE LYMPHATIC SYSTEM --STRUCTURE AND FUNCTION

I) Three components:

a) Lymph (plasma like fluid---originates as interstitial fluid

b) Lymphatic vessels or lymphatics  begin as lymphatic capillaries in the peripheral tissues which form into larger lymphatics (with valves) and then into lymphatic ducts which collects the lymph and returns it into the circulatory system by way of the venous system.

----Two sets of ducts:

                    The thoracic duct (left lymphatic duct) collects lymph from the pelvis, lower limbs, left side of the head at the junction of the left internal jugular and left subclavian veins.  It arises from an enlarged sac called the cisterna chyli.    The right lymphatic duct collects lymph from the right side of the body above the diaphragm at the junction of the right internal jugular and the right subcavian veins.

****The structure of collecting vessels are like veins except that they contain more valves, anastomose more than veins, and of course carry only plasma.

***A condition known as lymphedema  (a swelling of the vessels due to blocked drainage) can occur when collecting vessels are blocked by a tumor.  Surgery is required to remove the blocked vessels.

c) Lymphoid organs (the lymph nodes, spleen, thymus, lymphoid nodules--tonsils, appendix and Peyer's patches                                           **except for the thymus,which is of endodermal origin all other organs develop from mesoderm                                                                                    ***by the 5th week the embryo has vessels and nodes forming from veins.

d) Lymphocytes (one of the classes of leukocytes--an agranulocyte) which are found predominately in the lymphatic system

II) Functions of the lymphatic system:

a) Returns fluid to the blood in all parts of the body except for the central nervous system (CNS) by the lymphatic vessels.

b) Transport of hormones, nutrients, waste products into the bloodstream by the lymphatic vessels ****highly specialized lymphatic vessels called lacteals are present in the villi of the small intestines and absorb lipids  into the lymphatic system.  This fatty lymph called chyle is also delivered to the blood via the lymphatic system.

c) Production of lymphocytes (bone marrow and the thymus are involved)

III) The lymphocytes (a type of leukocyte subclassified as an agranulocyte)

Three classes of lymphocytes:

1) T cells (thymus dependent) (forms 80% of all lymphocytes)

a) They begin production in the bone marrow as stem cells and migrate to the thymus to differentiate in the presence of thymic hormones called thymosins into three types:

-----Helper T cells (which stimulate T and B cells)

-----Suppressor T cells (which inhibit T and B cells)

-----Cytotoxic T cells also called killer T cells (provide cellular immunity) (sometimes referred to as cell mediated immunity)

****Helper T and Suppressor T cells are often referred to as regulatory T cells

2) B cells

a) Production and differentiation occurs in the bone marrow (B stands for bone marrow

b) forms 10-15% of all lymphocytes

c) change into plasma cells that produce antibodies (immunoglobins)

d) responsible for humoral (liquid) immunity also called antibody-mediated immunity

3) NK cells

a) Natural killer cells which attack foreign cells,normal cells infected by viruses, and also cancer cells using toxins called perforins.

b) responsible for immunological surveillance

c) form about 5-10% of all lymphocytes

e) produced in the bone marrow

****life span of lymphocytes: 80% live for about four years; 20% can live for as long as twenty years.

****All leukocytes develop from a cell in the bone marrow called the lymphoid stem cell (which formed from a hematocytoblast).  Some lymphoid stem cells remain in the bone marrow and develop into either B cells or NK cells. Other lymphoid stem cells migrate to the thymus and under the influence of thymic hormones called thymosins differentiate into Tcells. The T cells then differentiate further into Helper T, Suppressor T, or cytotoxic T cells. All then divide by mitosis to produce an increase in their numbers depending upon the immunity requirements of the body at any given time.

IV) Lymphoid Nodules

a) can increase or decrease in size due to the amount of lymphocytes present.

b) found beneath the epithelia of respiratory, digestive, and urinary systems (where foreign invaders may enter from our body openings)

c) have a pale central region called a germinal layer where lymphocytes divide.

d) Includes the six tonsils:

1 pharyngeal tonsil (adenoids)

2 palatine tonsils (most often infected)

2 lingual tonsils

2 tubal tonsils  (around the openings into the auditory (eustachian)tubes

***tonsils "invite" bacteria with blind ended pouches called crypts.

e) other examples of lymphoid nodules include the appendix and Peyer's patches

***Can become infected (tonsilitis and appendicitis) 

VI) Lymphoid Organs

1) Lymph Nodes:

a) 1-25 mm in diameter

b) filters and purifies the lymph before it is emptied into the venous system (there are afferent and efferent lymphatics attached)

c) 99% of antigens (foreign protein) are removed by them

d) T cells and B cells are stimulated in the lymph nodes within the germinal layer of the cortex within the lymph node producing an immune response.

e) They become swollen during an immune response  due to bacterial infection, viral infection, or cancer.

f) Cancer cells are trapped in lymphatic capillaries  of lymph nodes and lymph nodes can become secondary cancer sites (a lymphoma).

g) Swollen or infected lymph nodes are called buboes.

2) The Thymus:

a) Site of T cell maturation

b) only lymphatic organ that does not directly fight antigens

c) located primarily in the mediastinum

d) has a right and a left lobe and each is subdivided into lobules by septae

e) It is the first lymphatic organ to develop in the embryo and produces hormones that stimulate the development of other lymphatic organs

f) Each lobule contains a dark cortex  where lymphocytes divide and turn into T cells and a paler medulla where the T cells migrate to from the cortex before being sent out to fight disease.

g) Epithelial cells in the lobules produce the hormones known as thymosins which stimulate T cell production.

h) The thymus is larger in infants and decreases in size after puberty.  We therefore have less immune response as we age. 

3) The Spleen

a) Contains the largest collection of lymphatic tissue in the body and therefore is the largest lymphatic organ.

b) Removes abnormal blood cells, marophages store iron in the spleen, and blood platelets are also stored in the spleen

c) site of erythrocyte production in the fetus

d) contains white pulp--immunological function (filters the blood  and red pulp --- functions of the blood (the white pulp actually appears as islands in a sea of red pulp

THE LYMPHATIC SYSTEM---BODY DEFENSES

I) Nonspecific Defenses

a) Physical Barriers:

---The skin is a physical barrier due to the presence of keratin which besides being so hard to penetrate,  resists bacterial toxins and enzymes. Secretions from the sebaceous and the sweat glands produce an acidic covering over the skin that prevents bacterial growth (pH of 3 to 5). Sebaceous secretions also include an enzyme called lysozyme that destroys bacteria.--

---The mucous membranes lining our digestive, respiratory, urinary and reproductive tracts produce secretions that inhibit bacterial growth.   Glandular secretions in the reproductive tract such as vaginal secretions of adult females are very acidic and prevents bacterial growth.  The stomach mucosa secretes a concentrated hydrochloric acid along with protein-digesting enzymes which destroy bacteria. Saliva is secreted into the mouth and lacrimal fluid is secreted by the lacrimal glands in the eye. Both secretions also contain the enzyme lysozyme which destroys bacteria.  Mucous membrane in the respiratory tract will secrete mucus which entraps dust particles containing bacteria as they are breathed into the lungs and eventually expelled by a cough.

b) Phagocytes:

---The first line of cellular defense (can destroy foreign microorganisms before the lymphocytes are aware of the incident---

---Two classes of phagocytes:

1) microphages (neutrophils and eosinophils)

2) macrophages ( larges cells derived from monocytes of the blood)

***phagocytes can squeeze through capillary walls by a process called diapedesis

c) Immunological Surveillance:

---involves NK (natural killer cells) which kills abnormal cells (cancer cells, or virally infected cells) before they spread. ***cancer cells can undergo immunological escape and spread anyway---

d) Interferons:

---small proteins produced by tissues infected with viruses and by activated lymphocytes, and macrophages----

----exposed cells respond by producing these proteins which interfere with viral replication---

----classified among the hormones called ctyokines (hormones of the immune system----

e) Complement System:

---20 special plasma proteins that bind to invading bacteria and enhance phagocytosis by a process called opsonization ("to make tasty"), destroy the cell membranes of bacteria, and promote inflammation. 

f) Inflammation:

---a local sensation of swelling , redness , heat, and pain---

---Occurs when injured cells, mast cells, basophylls, and blood proteins release inflammatory mediators (histamine, heparin, kinins, PGs, complement, cytokines) which cause dilation of blood vessels, attraction of phagocytes (chemotaxis), and finally clot formation.----

g) Fever :

---pyrogens cause a rise in body temperature released by macrophages in response to pathogens in the blood--\

---body temperature becomes greater than 99 degrees F in an attempt to destroy pathogens by heat or slow their spread--

--fever can also be harmful to the host organism---

  II) Specific Defenses

A) Forms of Immunity

1) Innate (inborn) immunity is found within specific organisms. We can't get distemper and a dog can't get smallpox.

2) Acquired Immunity:

a) Active Immunity: results in exposure to antigens and can be either naturally acquired immunity, or induced (artificially) acquired immunity in which immunization of antigens occur.

b) Passive Immunity: results in exposure to antibodies and can be either natural passive immunity (transfer of antibodies from mother to fetus), or induced passive immunity in which immunization of antibodies occur.

B) The Immune Response (T cell Activation)

1) Begins when a macrophage or a neutrophyll  engulfs a bacteria or a virus by phagocytosis. The bacteria and virus will contain a foreign protein that we call an antigen in their cell membrane and protein capsule respectively.

2) Present in the membrane of the macrophage are special proteins called MHC proteins that will display the foreign antigen (antigenic fragment)on the outside of their cell. Cells that display the antigen in such a way are called APC cells (antigen presenting cells). 

3) Stem cells produced in the bone marrow will migrate to the thymus where they are changed into immunocompetent T cells (able to recognize and attack only "foreign antigens".  The nature of the foreign antigens is predetermined or preprogrammed.  It is our genes, not antigen exposure that determines what specific foreign substances our immune system will be able to recognize and resist. An antigen only determines which of the existing T or B cells will proliferate and mount an attack against it.  T cells that would mount an attack on our own bodily antigens are "weeded out" and destroyed in the thymus.  The others that are not destroyed are declared immunocompetent.  These naive (still immature) T cells are transported to the lymph nodes, spleen, and other secondary lymphoid organs  (the primary lymphoid organs are the bone marrow and the thymus) from the thymus. Meanwhile the B cells (which became immunocompetent in the bone marrow) are also transported to the lymph nodes, spleen, and other secondary lymphoid organs. Here both the T cells are exposed to the foreign antigen by the APCs  (antigen presenting cells) and begin differentiating into cytoxic T cells, suppressor T cells, helper T cells and memory T cells.

---Cytotoxic T cells function in cell mediated immunity, are also called killer T cells, and hunt down and destroy anything containing the antigen that it was exposed to in the thymus. Cytotoxic T cells destroy the foreign invaders by a) releasing a destructive protein called perforin which ruptures the antigenic cell membrane  b) by killing cells with a poison called lymphotoxin or by c) apoptosis ---genetically programmed cell death--- Cytotoxic T cells are also responsible for the resjection of skin grafts and organ transplants---

---Memory T cells will "remember" antigin and if antigen appears again will change into more killer T cells for a second immune response.----

---Suppressor T cells secrete suppression factors to slow down the immune response. Suppressor T cells are activated after other T cells are activated.--

--- Helper T cells "help" other lymphocytes respond to infection by releasing cyotkines which stimulate the activation of B cells. Helper T cells are also the host cell for the HIV virus.---

C) The Immune Response (B cell activation):

1) B cell activation begins when helper T cells gather in the lymph nodes and spleen secreting cytokines onto the surfaces of B cells. The B cells then begin dividing into two cell types plasma cells and memory B cells. Plasma cells will then begin producing antibodies, and memory B cells will be kept in reserve for a second attack by the same antigen at a later time.

C) Antibody Structure

1) two parallel pairs of polypetide chains

2) one pair of long heavy chains

3) one pair of shorter heavy chains

4) constant and variable segments compose each chain

5) variable segments make one antibody different from another ( one billion are possible

6) antigen binding sites are found at tips of the variable segments.

D) Classes of Antibodies

1) Five classes of antibodies or immunoglobins (IG)

IgM, IgA,IgD, IgG, IgE  (MADGE)

IgG (most important of all) consists of 80% of all antibodies and are responsible for resistance to many viruses, bacteria and toxins as well as incompatible blood types.

IgM : pentamer

IgA : monomers and dimers

IgD,IgG,IgE: mononers

E) Antibody Function

Antibodies will destroy antigens by the formation  of antigen-antibody complex. Each organism has antigen determinant sites on its surface.  Two complete sites are called an antigen. An organism could have thousands of antigens. Each antibody will bind to two antigen determinant sites due to their "Y" shaped structure forming the antigen-antibody complex.  The antigens are destroyed by....

a) neutralization ( makes the antigen incapable of attaching to a cell)

b) agglutination and precipitation -clumping of antigenic cells (smaller antigens settle out by precipitation)

c) Activation of complement-antibodies change shape on exposed surfaces and attract complement proteins (opsonization)

d) attraction of phagocytes and enhancement of phagocytosis(opsonization) 

e) stimulation of inflammation

F) Primary and Secondary Humoral Responses ( Figure 22.10)

Primary exposure is called immuniztion

Secondary exposure (response) is what actually prevents the disease during which there is a second exposure to antigen A (figure 22.10), memory cells differentiate into plasma cells  which produces and immediate rise in IgG to levels many times higher than the primary response (can occur years after the initial response). Less time is required during the second exposure due to previous T an B cell activation to antigen A

G) Autoimmune Disorders:

---"friendly fire" --the body produces antibodies (autoantibodies) and cytotoxic T cells that destroys its own tissue---