The Lymphatic and Immune System

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The Lymphatic and Immune System
Lymphatic System
Lymphatic System Functions  The lymphatic system has three main functions: i. lymphatic vessels return excess tissue fluid to the bloodstream ii. lacteals receive and transport lipoproteins iii. lymphatic organs work with the immune system to combat disease  The walls of lymphatic capillaries consist mostly of simple squamous (scaled) epithelium

Lymphatic Vessels   Small, lymphatic capillaries join to form lymphatic vessels. The lymphatic vessels collect fat molecules at the intestinal villi and excess tissue fluid at blood capillaries; they carry lymph to the subclavian veins. The fluid inside lymphatic vessels is called lymph. Lymphatic Ducts  Lymphatic vessels merge before entering one of two ducts: i. Thoracic Duct: collects and returns lymph from below the thorax, left arm, and left side of head and neck; leads to the left subclavian vein ii. Right Lymphatic Duct: collects and returns lymph from right arm and right side of head and neck; returns to right subclavian vein





Note: the thoracic duct is bigger than the right lymphatic duct Lymph Vessels





Lymph vessels are similar in structure to cardiovascular veins:  have one way valves  dependent upon muscle contraction Edema is the retention of fluids in the tissues (failure of lymphatic system to drain them) Lymphatic Organs

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Lymphoid organs, which contain large numbers of lymphocytes, are separated into primary (the red bone marrow and the thymus gland) and secondary (lymph nodes and spleen). Lymphocytes, which are produced and mature in the primary lymphatic organs, accumulate in the cortex of these organs. Recall: the two types of lymphocytes are B-lymphocytes and T-lymphocytes

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Red Bone Marrow produces stem cells that become blood cells. It is only found in certain locations in adults. B-lymphocytes mature here. The thymus gland is divided into lobes and it is the site of T-lymphocyte maturation. Secondary Lymphatic Organs

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In secondary lymphatic organs, lymphocytes encounter and bind to antigens, after which they proliferate and engage foreign material in the body. Blood is cleansed of pathogens and their toxins in the larger spleen. Lymph Nodes

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Lymph nodes are small ovoid structures found near lymph vessels which cleanse lymph. This organ is made of many nodules. Each nodule contains a sinus. Macrophages filter lymph in sinuses by engulfing pathogens. T-lymphocytes fight infections and attack cancerous cells.

Questions 1. What is metastasis?  Metastasis is the spread of cancer far from its place of origin. The lymphatic system sometimes assists metastasis as cancer cells can enter lymphatic vessels and move undetected to other regions of the body, where they produce secondary tumours. 2. Where is red bone marrow found in children? What about in adults?  Red bone marrow can be found in most bones in children. From birth until the age of about seven, all human marrow is red because the need for new blood formation is high.  Thereafter, fat tissue gradually replaces the red marrow, which is present only in the bones of the skull, the sternum, the ribs, the clavicle, the pelvic bones, and the vertebral column for adults. 3. What occurs at the sinuses of red bone marrow?  At the sinuses of red bone marrow, differentiated blood cells enter the bloodstream. 4. Where is the thymus gland located? Draw a stick figure and place it inside the figure.  The thymus gland is located in the thoracic cavity between the trachea and Thymus the sternum, superior to (above) the heart. Gland 5. Where are T-lymphocytes produced? Where do they mature?  T-lymphocytes are produced in red bone marrow and mature in the thymus. 6. Which T-lymphocytes leave the thymus?  The T-lymphocytes which leave the thymus are the ones which are mature and have the ability to react to antigens on foreign cells, being capable of distinguishing between “self” and “nonself.” T cells that have the potential to react to the body’s own cells are destroyed. 7. Why is the thymus gland critical to immunity?  The thymus gland is critical to immunity because of its role in the maturation of T cells. It produces thymic hormones that are thought to help T cells mature and play other roles in immunity. During this maturation process, T cells gain the ability to bind to antigens and thus, perform their function in specific immunity. 8. What is the spleen made of, and what is the function of the spleen? What happens if the spleen is damaged/destroyed/removed?  Most of the spleen is made out of red pulp, with some white pulp on the inside consisting of little lumps of lymphatic tissue. It has an outer capsule which is relatively thin.  Red pulp filters the blood: it contains blood vessels and sinuses where macrophages remove old and defective blood cells, while lymphocytes cleanse the blood of foreign particles.  If the spleen is damaged, destroyed, or otherwise removed, the person becomes more susceptible to infections and may have to receive antibiotic therapy indefinitely. 9. A sick person comes to visit the doctor. Why might they feel the patient’s neck during an examination?  The doctor might feel the patient’s neck during an examination to feel for the presence of swollen, tender lymph nodes, indicating that the body is fighting an infection. This is a non-invasive, preliminary way to help make such a diagnosis. Video: The Lymphatic System, Part 1: http://www.youtube.com/watch?v=BX8fBlme9vQ

Nonspecific and Specific Defenses
Immunity  Immunity is the body’s ability to defend against infection and involves nonspecific and specific defenses.

Nonspecific Defenses  There are 4 types of nonspecific defenses: i. Barriers to Entry ii. Inflammatory Reaction iii. Natural Killer Cells iv. Protective Proteins  Barriers to Entry: all of the following contribute to keeping pathogens from entering the body…  skin and mucous membranes lining the respiratory, digestive, and urinary tract (mechanical barrier against entry)  oil glands (secretes chemicals that weaken or kill bacteria on skin)  ciliated cells (sweep particles trapped in mucus up into the throat for expectoration (coughing))  an acidic stomach (kills or inhibits growth of bacteria)  beneficial bacteria also prevent pathogens from taking up residence  Inflammatory Reaction:  The inflammatory reaction involves redness, heat, swelling, and pain, which are all due to changes in the capillary, such as dilation and increased permeability.  The release of histamine (an inflammatory chemical) and kinins from damaged tissue cells and mast cells causes redness, heat, and swelling.  The swollen area and kinins stimulate free nerve endings, causing the sensation of pain.  Macrophages migrate to the site of injury and can engulf pathogens. They also release colonystimulating factors that cause the bone marrow to release more white blood cells (ie. stimulate other immune cells).  Anti-inflammatory drugs act against the chemical mediators, such as histamine, released by white blood cells. Chemical mediators may cause chronic inflammation.





Natural Killer Cells:  Natural killer (NK) cells kill virus-infected cells and tumour cells by cell-to-cell contact.  NK cells are granular lymphocytes that look for ‘self-proteins’ on cells; virus-infected or cancer cells sometimes have altered ‘self-proteins,’ which NK cells look for and then attack.  NK cells are not specific like some other white blood cells, so they have no memory; their numbers do not increase when exposed to a specific antigen. Protective Proteins:  Complement proteins, a large part of the complement system (often simply called complement), are a number of plasma proteins that assist nonspecific immunity.  They can amplify (complement) the inflammatory reaction by attracting phagocytes and promoting phagocytosis; trigger histamine release; bind to pathogens already coated with antibodies to ensure phagocytation by a neutrophil, dendritic cell, or macrophage.  Some complement proteins join to form a membrane attack complex which produces pores in the surface of bacteria or viruses, allowing fluids and salts to enter until the pathogens eventually burst.  Interferon is a protein produced by virus-infected cells that prepares non-infected cells for possible attack and interferes with viral replication; it is specific to a species. Specific Defenses

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Takes effect when non-specific defenses have failed to stop an infection. Takes 5-7 days to become fully activated and have a lasting effect (able to stop or impede subsequent infections from the same pathogen). Antigens: Foreign substances, usually proteins or carbohydrates, that stimulate the immune system.  The body does not consider its own proteins foreign; therefore the immune system must distinguish self from non-self.  Lymphocytes have a large number of antigen receptors.



B and T Cells:  Specific defenses require B and T lymphocytes, which are produced in the bone marrow.  B cells give rise to antibodies that are shaped as an antigen receptor.



 T cells do not produce antibodies; they differentiate into helper T cells and cytotoxic T cells.  Each lymphocyte is specific to only one receptor. Our bodies contain lymphocytes that recognize hundreds of thousands (to millions) of different types of pathogens. B Cells and Antibody-Mediated Immunity:  When B cells encounter an antigen in a lymph node or the spleen, its BCR (B cell receptor) is activated and the B cell divides clonally many times, through mitosis.  The resulting cells are plasma cells, mature B cells that mass-produce antibodies which are specific to the antigen that triggered the BCR.  Some members of the clone become memory B cells that remain in the body and produce antibodies if the same antigen enters the body at a later date.  When infection passes, plasma cells undergo apoptosis (programmed cell death).



Structure of an Antibody (IgG):  The most common type of antibody, the IgG (immunoglobulin) antibody, is a Y-shaped molecule that has two binding sites for a specific antigen. Each one has a light and heavy chain.  Antigen-antibody complexes often mark the antigen for destruction and/or activate complement.









 Some portions of the IgG have fixed amino-acid chains, while others have variable amino-acid chains which allow them to recognize all sorts of different pathogens. Other Types of Antibodies:  There are five types of immunoglobulins, including IgG, which activates the complement system.  All differ in structure and function as described in Table 13.1.  IgE antibodies are responsible for immediate allergic responses. T Cells and Cell-Mediated Immunity:  T cells mature in the thymus. Like B cells, each T cell bears a specific receptor (TCR).  However, in order for a T cell to recognize an antigen, the antigen must be presented by an antigenpresenting cell (APC), such as a dendritic cell or macrophage. MHC - Major Histocompatibility Complex:  An APC will travel to the spleen or lymph node and present a portion of a digested pathogen in the groove of an MHC protein on its surface.  When a viral or cancer cell antigen is presented, the antigen is first linked to a major histocompatibility complex protein. After presentation,  MHC I  activates T cells to form cytotoxic T cells  MHC II  activates T cells to form helper t cells  Human MHC proteins are called HLA (human lymphocyte-associated) antigens.  Cytokines are chemical signals that stimulate various immune cells.  Many copies of activated T cells are produced. Types of T Cells: The two main types of T cells are cytotoxic T cells and helper T cells.  Cytotoxic T cells kill infected cells that bear a foreign antigen on contact.  Helper T cells stimulate other immune cells and produce cytokines, which enhance the response of all types of immune cells.  Some T cells are memory cells that will jumpstart an immune reaction upon reinfection.  B cells cannot be activated without T cell help. Questions

1. From what is pus made, and what does it indicate is happening in the body?  Pus is a whitish material made from dead phagocytes, dead tissue cells, dead bacteria, and living white blood cells. Its presence indicates that the body is trying to overcome an infection. 2. What do aspirin, ibuprofen, and cortisone all do?  Aspirin, ibuprofen, and cortisone are anti-inflammatory agents which act against chemical mediators, such as histamine, released by the white blood cells in the damaged area. 3. What do helper T cells do? What do cytotoxic T cells do?  Helper T cells secrete cytokines that control the immune response, while cytotoxic T cells destroy cells bearing “nonself” proteins. 4. Why are plasma cells larger than B cells?  Plasma cells are larger than B cells because they have extensive rough endoplasmic reticulum (REM) in order to mass produce and secrete antibodies for a specific antigen. 5. What is the clonal selection theory?  The clonal selection theory states that an antigen selects and binds to the BCR of only one type B cell or type T cell. This B cell or T cell then undergoes clonal expansion and produces more lymphocytes with the same type of antigen receptor. 6. What is the antibody-mediated immunity?  Antibody-mediated immunity is a specific defense mechanism in which plasma cells derived from activated B cells produce antibodies that bind to antigens.

7. What is ‘humor’?  Humor is any fluid normally occurring in the body. 8. What are the characteristics of B cells?  B cells participate in antibody-mediated immunity against pathogens by recognizing an antigen and undergoing clonal expansion to produce antibody-secreting plasma cells as well as memory B cells.  They are produced and matured in bone marrow, reside in lymph nodes and spleen, and circulate in blood and lymph. 9. Why is an antigen-antibody complex like a lock and key?  The antibody has hyper-variable regions at its tips that form antigen binding sites with a shape specific to the particular antigen. 10. What are the 5 main types of IgGs? Where are they present? What is each one’s function?  IgGs are the major type of antibodies in blood, lymph and tissue fluid. They bind to pathogens and their toxins, activate the complement system, and enhances phagocytosis.  IgM antibodies appear in blood soon after an infections begins and disappear before it is over. They can activate the complement system and cause red blood cells to clump.  IgA antibodies are the main type found in body secretions such as tears, saliva, gastric juice, and mucous secretions, and they are also present as monomers in blood and lymph. Their function is to bind to pathogens before they reach the bloodstream and to prevent pathogens from attaching to epithelial cells in the digestive and respiratory tract.  IgD molecules appear on the surface of B cells which are ready to be activated, so their presence signifies the readiness of the B cell.  IgE antibodies are found as antigen receptors on basophils in blood and on mast cells in tissues. Although they also provide protection against certain parasitic worms, they are most noted for their function in immediate allergic responses, including anaphylactic shock. 11. What happens when apoptosis does not occur as it should? What may also happen in the thymus?  When apoptosis does not occur as it should, T cells cancers, such as lymphomas and leukemias, can result. Apoptosis may also occur in the thymus while the T cells are maturing, as any T cell with the potential to destroy the body’s own cells undergoes suicide. 12. What are perforins and granzymes?  Perforins are molecules which perforate the plasma membrane of a virus-infected cell or a tumor cell, forming a pore.  Enzymes known as granzymes are then delivered into the pore, where they cause the cell to undergo apoptosis and die. 13. How does HIV affect the immune system? Where does it reside/hide in the body?  HIV destroys the immune system by killing off T helper cells, making the individual susceptible to many unusual infections which would not cause disease in a person with a healthy immune system.  The virus infects helper T cells and other cells of the immune system, residing in infected macrophages and dendritic cells. 14. What are the characteristics of T cells?  T cells participate in cell-mediated immunity against viruses and cancer cells.  They are produced in the bone marrow and matured in the thymus.  T cells are unable to recognize an antigen present in lymph, blood, or the tissues without help; the antigen must be presented to them by an antigen-presenting cell. This antigen is first linked to a major histocompatibility complex protein on the surface of the APC. MHC I activates T cells to form cytotoxic T cells, while MHC II activates T cells to form helper t cells.  There are two types of T cells: helper T cells and cytotoxic T cells.

Immunity
 A person naturally develops immunity after infection. Active Immunity     Vaccines are available to induce long-lived active immunity when a person is well. After exposure to a vaccine – usually an avirulent (non-harmful) disease agent – antibodies are produced. Bacteria can be used to mass produce proteins (from pathogens) that can be used as a vaccine. With a booster shot or second exposure, the antibody titre (count of antibodies in a fixed volume) rises to a much higher level. Active immunity is long-lived because there are memory B cells and memory T cells that will respond to lower doses of antigen in the body. Passive Immunity   Passive immunity occurs when an individual is given antibodies from an outside source. For example, nursing passes antibodies from mother to child. However, passive immunity is short-lived since the antibodies were not produced by the person’s own B cells. Cytokines and Immunity  Cytokines are signaling molecules produced by white blood cells. Both interferon and interleukins are cytokines that are used to improve a person’s own T cell performance in fighting against cancer. Monoclonal Antibodies     All plasma cells derived from a B cell secretes an identical antigen. These are called monoclonal antibodies. B lymphocytes can therefore be exposed to a particular antigen and will produce monoclonal antibodies that are quick and certain indicators of various, specific conditions. Activated B lymphocytes are fused with myeloma cells and these hybridomas produce only one type of antibody. Monoclonal antibodies are most often used in diagnostic procedures such as pregnancy tests but can also carry isotopes to destroy cancerous tumours. Questions 1. What is a ‘booster’ shot? Draw a graph with titre level (antibodies) on the y-axis and time on the xaxis. Label the 1st and 2nd exposure to vaccine.  A “booster” shot exposes a person to an 1st Exposure antigen a second time, inducing a secondary to Vaccine response which boosts the antibody titre to a higher level than in the primary response. This 2nd Exposure high antibody titre is then expected to help to Vaccine prevent disease symptoms if the person is Time exposed to that particular pathogen again. 2. What is a gamma globulin injection, and why is it used?  A gamma globulin injection is a serum that contains antibodies, and it is used to prevent illness in a patient who has been unexpectedly exposed to an infectious disease.

Titre Level

3. Why are cancer cells more susceptible to cytotoxic T cells? How might cytokines help in the fight against cancer?  Cancer cells carry an altered protein on their cell surface, so they should be attacked and destroyed by cytotoxic T cells. However, whenever cancer develops, there is a possibility that the cytotoxic T cells have not been activated yet, and cytokines are needed to awaken the immune system, allowing the body to destroy the cancer. 4. How are monoclonal antibodies related to pregnancy tests? How does it work?  Pregnant women have a particular hormone present in their urine. Monoclonal antibodies can be used to detect this hormone, so if it is present, the woman knows she is pregnant.

Immunity Side Effects
 Sometimes, the immune system harms the body:  develops allergies  incompatible blood type Allergies    Allergic responses occur when the immune system reacts vigorously to substances (allergens) that would not normally harm the body. The response itself can cause some degree of tissue damage. Immediate allergic responses occur within seconds of contact with an allergen. Hay fever is an example. Anaphylactic shock is a severe reaction that may cause a fatal drop in blood pressure. Delayed allergic responses, such as contact dermatitis, are due to the activity of memory T cells. This occurs at the site of contact of the allergen with the skin or part of the body. The skin test for tuberculosis is an example, as is an allergy to poison ivy, jewelry, etc. Blood-Type Reactions  tissue rejection  autoimmune disease

ABO System   The membranes of red blood cells may contain type A, B, AB or no antigens (type O). In the plasma, there are two possible antibodies: anti-A and anti-B. If the corresponding antigen and antibody are put together, clumping, or agglutination, occurs. In this way, the blood type of the individual may be determined:  Antigen-A is an antigen, but not to people with type A blood.

 Antigen-B is an antigen, but not to people with type B blood.  Receiving the wrong blood type is like injecting something someone is allergic to into their blood system (ie. this is bad for the person). Rh System  The Rh antigen is also a blood type. It is important during pregnancy because an Rh-mother may form antibodies to the Rh antigen while carrying or at the birth of a child who is Rh+.  These antibodies can cross the placenta to destroy the red blood cells of any subsequent Rh+ child.  A Rho-Gm shot uses anti-Rh antibodies to attack Rh+ cells before they can simulate the mother to produce her own antibodies.

Tissue Rejection   Rejection occurs when cytotoxic T cells bring about the destruction of foreign tissue in the body. A close match between donor and recipient can reduce rejection. Immunosuppressive drugs (eg. cyclosporine, tacrolimus) act by inhibiting the response of T cells to cytokines, but can result in kidney damage and make the person more susceptible to disease. Diseases of the Immune System  Autoimmune diseases occur when T cells or antibodies mistakenly attack the body’s own cells as if they bear foreign antigens.  include myasthenia gravis, multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis  it has also been suggested that heart damage after rheumatic fever and type I diabetes are autoimmune illnesses Immunodeficiency results when the immune system is unable to protect the body against diseases.  Examples include AIDS and SCID (Severe Combined Autoimmune Deficiency disorder), a genetic disorder in which the immune system fails to develop.



Questions 1. How are IgE antibodies related to immediate allergic responses?  IgE antibodies attached to the plasma membranes of mast cells in the tissues and basophils in the blood cause immediate allergic responses. When an allergen attaches to the IgE antibodies on these cells, mast cells release histamine and other substances which bring about the allergic symptoms. 2. What causes the symptoms for i) Hay fever and ii) Asthma?  Hay fever: When pollen is an allergen, histamine stimulates the mucous membranes of the eyes and nose to release fluid. This causes the watery eyes and runny nose characteristic of hay fever.  Asthma: The airways leading to the lungs constrict, resulting in difficulty breathing and wheezing. 3. What is anaphylactic shock? What causes it? What are its characteristic symptoms and what can be done to slow it down?  Anaphylactic shock is an immediate allergic reaction which occurs as a result of an allergen entering the bloodstream. For example, bee stings and penicillin shots have been known to cause anaphylactic shock since both inject the allergen into the blood.  It is characterized by a sudden and life-threatening drop in blood pressure, caused by increased permeability of the capillaries as histamine is released.  Taking epinephrine can delay this reaction until medical help is available. 4. What happens if you give someone with blood type A an infusion of type B blood?  If you give someone with blood type A an infusion of blood type B, agglutination will result. Red blood cells will clump together, potentially causing blood to stop circulating in small blood vessels and leading to organ damage. It is also followed by hemolysis, the bursting of red blood cells, and this could in turn cause the death of the individual. 5. What percent of people are Rh+ and Rh-?  85% of the U.S. population are Rh+, while the other 15% are Rh-. 6. What is xenotransplantation?  Xenotransplantation is the use of animal organs instead of human organs in transplant patients. Scientists choose to use pigs for this purpose, as they are already being raised as a meat source and are prolific. Genetic engineering can make pig organs less antigenic.

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