Bio 12 - Chapter 13 Lymphatic and Immune System CHAPTERS NOTES

Lymphatic & Immune system

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13.1 The Lymphatic System Lymphatic System Functions  has three main functions:  The 1. Lymphatic vessels return excess tissue fluid to the bloodstream bloo dstream 2. lacteals receive and transport lipoproteins 3. lymphatic organs work with the immune system to combat disease c apillaries consist mostly of  The walls of lymphatic capillaries

Lymphatic Vessels  Small, lymphatic capillaries join to form 

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The lymphatic vessels collect fat molecules at intestinal villi and excess tissue fluid at blood carry lymph to the veins The fluid inside lymphatic vessels ve ssels is called

Lymphatic Ducts  Lymphatic vessels merge before entering one of two 1. : collects and returns lymph from below thorax, and from left arm, left side of head and neck and leads to left subclavian vein 2. : collects and returns lymph from right arm, right side of head and neck and returns to subclavian vein Q: Which one is bigger and why? The  (left lymphatic duct) is larger; it returns lymph collected from the body below the thorax, the left arm, left side of the head and neck into the left subclavian vein. The right lymphatic duct only returns lymph from the right arm and right side of the head

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and neck into right subclavian vein.

Lymphatic Vessels (ctd’ (ctd ’)   are similar in structure to cardiovascular veins: o Have one way valves Dependent upon muscle contraction o   is retention of fluids in the tissues (failure of lymphatic system to drain them) Lymphatic Organs 

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, which contain large numbers of lymphocytes, are separated into  (the red bone marrow and the thymus gland) and  (lymph nodes and spleen) , which are produced and mature in the primary lymphatic organs, accumulate in the cortex of these organs Q: What are the two types of lymphocytes again?   s  l l  e   c  T  d   n   a   s  l l  e   c  B :    A

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Red Bone Marrow  o

o

Produce  that become blood cells Only found in certain locations in adults

o

Thymus Gland  The : Divided into lobes o o

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

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Lymph Nodes  Small ovoid structures found near lymph vessels  Clean lymph; made of many 

Each nodule Contains a o o Macrophages filter lymph in sinuses by engulfing pathogens T-lymphocytes fight o infections and attack cancerous

Questions Q: What is Metastasis?  is the spread of cancer from the place of origin throughout the body, which is A: caused by the ability of cancer to migrate and invade tissue. Q: Where is bone marrow found in children? What about in adults?  is found in most bones in a child. In adult, adu lt, it is present in the bones of the A: skull, the sternum, the ribs, the clavicle, the pelvic bones, and the vertebral column. Q: What occurs at the sinuses of red bone marrow?  that are filled with venous blood can be found outside o utside the reticular A: The thin-walled cells, the stem cells and their progeny. Differentiated blood cells will enter the bloodstream at these sinuses. Q: Where is the thymus gland located? Have a figure that indicates the thymus gland.  is located in the thoracic cavity between A: the trachea and the sternum above the heart. Q: Where are T-lymphocytes produced? Where do they mature?  develops in the primary lymphoid organs A: the bone marrow, and matures in the thymus Q: Which T-lymphocytes leave the Thymus? of the T-cells which are  leave the A: Only thymus. Q: Why is the thymus gland crucial to immunity? A: Thymus gland is crucial to the adapting immune system, since it allows the T cells to mature. Q: Of what is the spleen made and what is the spleen’s function? What happens if the spleen is damaged/destroyed/removed? A: Red pulp consists of blood vessels and sinuses where macrophages remove old and defective blood cells; lymphocytes cleanse the blood of foreign particles. To conclude, . The spleen also has white pulp that is inside the red pulp and Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 5 | 18

consists of small areas of lymphatic tissue. If the spleen of a person is damaged/burst due to an infection of trauma, the person is often slightly more susceptible to infections and may have to receive antibiotic therapy indefinitely. Q: A sick person comes to visit the doctor. Why might he/she feel the patients’ neck during an examination?  are abnormal.  lymph nodes A: This is to check whether or not the might be evidence that the body is .

13.2 Innate (Nonspecific) and Acquired (Specific) Immunity Immunity is the body’s ability to defend against infection and involves

 o o

Non-specific Defenses  There are 4 types of non-specific defenses:

Barriers to Entry  All of the following contribute to keeping pathogens from entering the body o

o o o

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(mechanical barrier against entry)  (contains chemicals that awaken or kill bacteria on skin)  (sweep particles in mucus for expectoration (coughing)) an  (kills or inh ibits growth)  also prevent pathogens from taking up residence

Inflammatory Reaction

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The involves 1) redness, ii) heat, iii) swelling, and iv) pain, which are all due to changes in the capillary, such as dilation and increased permeability. The release of  (an inflammatory chemical) and  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 . Macrophages migrate to the site of injury and can engulf pathogens and also release – stimulating factors that cause the bone marrow to release more white blood cells (aka – stimulate other immune cells)  act against the  (histamine is a chemical mediator) released by white blood cells. Chemical mediators may cause chronic inflammation.

Natural Killer Cells 

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 kill virus – infected cells and tumor cells c ells by cell-to-cell contact NK cells are that look for “ o ” on cells; virus-infected virus-infected or cancer cells sometimes have altered “self“self-proteins,” which NK cells look for and then attack. NK cells  like some other white blood cells, o they have , and their numbers do n ot increase when exposed to a specific antigen. , a large part of the ) are a number of plasma proteins that assist nonspecific immunity They can amplify (complement) the inflammatory reaction by attracting phagocytes and o promoting phagocytosis o trigger histamine release o bind to pathogens already coated with antibodies to ensure phagocytation by a neutrophil, dendritic cell of macrophage o Some complement proteins join to form pores in the surface of bacteria and cause them to burst

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Interferon is a protein produced by virusinfected cells that prepares non-infected non-infe cted cells for attack and interferes with viral replication; it is specific to a species Specific Defenses  to  Take effect when stop an infection to become fully activated, and  Take have  (able to stop or impede subsequent infections from same pathogen) Antigen  An  is a foreign substance. The body does not consider its own proteins foreign; therefore the immune system must distinguish self from non-self  have a large number of  o

B- and T- cells  Specific defenses require , which are 

B cells give rise to antigen receptor

 that are shaped as an

T-cells T-cells do not produce antibodies; they differentiate into  Each lymphocyte is specific to only one receptor; our bodies contain lymphophytes that recognize hundreds of thousands (to millions) of different type of pathogens pathog ens B-Cells and Antibody - Mediated Immunity  As B-cells encounter an antigen in a lymph node or , its is activated and the B-cell clonally divides many times. The resulting cells are , mature B-cells that can mass-produce antibodies which are specific to the antigen that triggered the BCR Memory B-cells  that  Some members of the clone become 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 ( ) 

After clearing the body of an invading organism, the B-cell retains memory of its target and rests until another infection occurs.

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Structure of an antibody (i.e. IgG)  The most common type of antibody, the , is a Y-shaped molecule that has  for a specific antigen. Each one has

IgGs (cont'd)  often mark the antigen for destruction and/or activate

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complement Some portions of the IgG have fixed amino-acid chains, while others have variable amino-acid chains, which allows them to

Other Types of Antibodies 

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 include a total of five types including IgG. They activate the complement system  are responsible for . All differ in structure and function as described in Table 13.1

Table 1302A: Classes of Antibodies IgG

Main antibody type in circulation

IgM

Antibody type found in circulation; largest antibody Main antibody type in secretions such as saliva and milk

IgA

IgD IgE

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Antibody type found on surface of immature B cells Antibody type found as antigen receptors on eosinophils in blood and on mast cells in tissues

Binds to pathogens, activates complement, and enhances phagocytosis Activates complement, clumps cells Prevents pathogens from attaching to epithelial cells in digestive and respiratory r espiratory tract Presence signifies readiness of B cell to respond to antigens Responsible for immediate allergic response and protection against certain parasitic worms

. Like B cells, each T-cell bears a However, for a T-cell to recognize an antigen, the antigen must be presented by an  such as a dendritic cell or macrophage Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 9 | 18

MHC 

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An APC will travel to the spleen or lymph node and present a portion of a digested pathogen to a groove in an MHC When a viral or cancer cell antigen is presented, the antigen is first linked to a . After presentation:

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Human MHC  Human MHC proteins are called 

.  are signal chemicals 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   kill infected cells that bear a foreign antigen on contact   stimulate other immune cells and produce cytokines, which enhance the response of all types of immune cells  that will jump-start an immune reaction upon reinfection.  Some T cells are

Questions Q: From what is pus made, and what does it indicate is happening in the body?  is a protein-rich liquid, usually yellowish (to green) gre en) that is formed at the site of A: inflammation during infection and is composed com posed of white blood cells, bacteria and cellular debris. Q: What do aspirin, ibuprofen and cortisone all do?  are all A: minimize the effects of various chemical mediators. m ediators.

 that may be used to

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Q: a) What do helper T cells do? b) What do cytotoxic T cells do? , once stimulated by antigen-presenting cells (APC), TH cells secrete various A: a) cytokines. The cytokines produced by TH cells may help activate cytotoxic c ytotoxic T cells, as well as B cells. b) . They have storage vacuoles that contain many molecules of perforin and enzymes called granzymes. Activated TC cell binds to a virusinfected or cancer cell c ell that is presenting foreign antigen on o n its MHC class I molecules, it releases perforin molecules, which form pores in the plasma membrane of the abnormal cell. This allows the granzymes to enter the target cell, which is induced to undergo apoptosis and die. Q: Why are plasma cells larger than B cells? A: Plasma cells are larger than regular B cells because they have extensive rough endoplasmic reticulum for the mass production and a nd secretion of antibodies to a specific antigen. Antibodies are the secreted form of the B-cell receptor of the B cell that was activated. Q: What is the clonal selection theory?  states that an antigen binds to the antigen receptor of only one A: The type of B cell or T cell, and then this B-cell or T-cell divides, forming clones of itself. Q: What is antibody-mediated immunity?  because the various types of A: Defense by B cells is called the activated B cells become plasma cells that produce antibodies. It is also called c alled humoral immunity because these antibodies are present in blood and lymph.

Q: What is “humor”? (Not humour)  is any fluid normally occurring in the body. A: Q: What are the characteristics of B cells?  Provide antibody-mediated immunity against pathogens  Produced and mature in bone marrow  Reside in lymph nodes and spleen; circulate in blood and lymph  Directly recognize antigen and then undergo clonal selection  Clonal expansion produces antibody-secreting plasma cells as well as memory B cells Q: Why is an antigen-antibody like a lock and a key? A: The variable regions of antibodies become hypervarible at their tips and form antigen-binding sites; their shape is specific for a particular p articular antigen. It is the variable and hypervarible h ypervarible regions that allow that antibody to bind to a specific antigen. The antigen combines with the antibody at the antigen-binding site in a lock and key manner. Q: What are the 5 main types of antibodies (or Igs)*? Where are they present? What is each one’s function? A: Refer to Page 9 of this note package- Table 1302A: Classes of Antibodies Q: What happens when apoptosis does not occur as it should? What may also happen in the thymus? Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 11 | 18

A: When apoptosis does not occur as it should, T-cell cancers (i.e., lymphomas and leukemias) can result. Q: What are perforins and granzymes? A: TC have storage vacuoles that contain many molecules of perforin and enzymes called granzymes. Q: How does AIDS affect the immune system? Where does it reside hide in the body? A: AIDS infects helper T cells and other cells of the immune system, it suppresses many components of acquired immune responses and makes HIV-infected individuals susceptible to opportunistic infections. Infected macrophages and dendritic cells also serve as reservoirs for HIV. Q: What are the characteristics of T cells?  Produced in bone marrow, mature in thymus  Function in cell-mediated immunity against virus-infected cells and cancer cells  Reorganize antigens presented in groove of an MHC molecule  Cytotoxic T cells destroy nonself protein-bearing cells  Helper T cells secrete cytokines that control the immune response * The original question asks for the “5 main types of IgG”, which does not exist as IgG only has 4 subclasses according to Wi kipedia, and are not included within the Biology 12 curriculum. This should be a typo and “antibodies”or “Igs (Immunoglobulins ( Immunoglobulins)” )” should be in place for “IgG”

13.3 (Active vs. Passive) / (Induced) Immunity Active immunity  A person naturally develops immunity after infection  are available to induce long-lived active immunity when a person is well. After  exposure to a vaccine - usually u sually an a virulent (non-harmful) disease agent - antibodies are produced   can be used to mass produce proteins (aka - from pathogens) that can be used as a vaccine  With a  (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 

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 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. Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 12 | 18

Cytokines and Immunity  are signalling molecules produced by white blood cells.   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 

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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  produce only one type of antibody. Monoclonal antibodies are most often used in diagnostic procedures such as  but could carry isotopes to destroy cancerous tumors

Questions Q: What is a "booster" shot? Draw a graph with titer level [antibodies] on y-axis and time on x-axis. Label 1st and 2nd exposure to vaccine. is the second exposure of a vaccine to a person’s body. For graph refer to A: A the diagram at the top of this page. Q: What is a gamma globulin injection, and why is it used?  is serum that contains antibodies, perhaps taken from individuals A: who have recovered from the illness. It is used to prevent illness in a patient who has been expectedly expose to disease. Q: Why are cancer cells more susceptible to cytotoxic T cells? How might cytokines help in the fight against cancer? A: Because many cancer cells carry altered proteins on cell surface, they should be attacked and destroyed by cytotoxic T cells. Cytokines could activate the cytotoxic T cells and awaken the immune system, leading to the destruction of the cancer. Q: How are monoclonal antibodies related to pregnancy tests? How does it works? A: A particular hormone is present in the urine of a pregnant women. A monoclonal antibody can be used to detect this hormone; if it is present, the woman is pregnant.

13.4(-13.5*) Adverse Effects (and Disorders) of Immune Responses th

*Textbook 12  Edition Only

Sometimes, the immune system    

harms the

body

Develop allergies Incompatible blood Tissue rejection Autoimmune disease Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 13 | 18

Allergies 

 occur when t he 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 Response 

 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 Response , such as contact dermatitis, are due to the activity of memory T

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cells. This skin test for tuberculosis is an example, as is allergy to poison ivy, jewelry, etc. Occurs at site of contact of allergen with skin/part of body.

Blood type and reactions

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The  may contain In the  there are two possible p ossible antibodies: . 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. o 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. o receiving the wrong blood type is like injecting something someone is allergic to o into their blood system.(bad)

Rh System The  is also a blood type. Rh antigen is important during pregnancy because an Rh-mother may form antibodies to 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 

o

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o

A  uses stimulate the mother to produce her own antibodies

 before they can

Tissue rejection 

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 occurs when cytotoxic T cells bring about the destruction of foreign tissue t issue in the body. A close match between donor and recipient can reduce rejection.  act by inhibiting the response of T cells to cytokines, but can result in kidney damage.

Diseases of the immune system  occur when  as if they bear foreign antigens Autoimmune diseases include: myasthenia gravis, multiple sclerosis, systemic lupus, rheumatoid arthritis, and heart damage after rheumatic fever 

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Diabetes, AIDS and SCID  

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It has been suggested that  is an autoimmune disease  results when the immune system is unable to protect the body against diseases Examples (Severe combined autoimmune deficiency disorder), a genetic disorder in which the immune system fails to develop.

Questions Q: How are IgE related to immediate allergic responses? Q: IgE leads to immediate allergic responses, as they are attached to receptors on the plasma membrane of mast cells in the tissues and also to eosinophils and basophils in the blood. When an allergen attached to IgE, these cells release histamine that bring about allergic symptoms. Q: What causes the symptoms for i) Hay fever ii) Asthma A: i) When pollen is an antigen, histamine stimulates the mucous membranes of the nose an d eyes, causes runny nose and watery eyes typical of . ii) In , the airways leading to the lungs constrict, resulting in difficult breathing accompanied by wheezing. When food contains an allergen, nausea, vomiting, and diarrhea often result. Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 15 | 18

Q: What is anaphylactic shock? What causes it? What are its characteristic symptoms and what can be done to slow it down?  is an immediate allergic response that occurs because the allergen has A: entered the blood steam. It is often caused by bee stings and penicillin shots, and characterized by a sudden and life-threatening drop in blood pressure due to increased permeability of the capillaries caused by histamines.  can counteract this reaction until medical help is available. Q: What happens if you give someone with Blood type A an infusion of type B blood? A: Type A blood would have type A antigen, which the person with type B blood would contain anti-B antibodies in their blood to attack. Q: What percent of people are Rh+ and Rh-? A: 85% of people are Rh+, and 15% of people are Rh-. Q: What is xenotransplantation? (it is not growing plants for the aliens)  is the use of animal organs instead of human organs o rgans in transplant A: patients.

The lymphatic system consists of lymphatic vessels and the lymphoid org ans. It is closely associated with the cardiovascular system. Lymphatic Vessels Lymphatic vessels form a one-way system that begins with lymphatic capillaries that take up excess tissue fluid. The fluid inside lymphatic vessels is called lymph. Lymphoid Organs The primary lymphoid organs are red bone bon e marrow and the thymus gland. The Th e secondary lymphoid organs are the spleen and lymph nodes. nod es. Primary Lymphoid Organs Red bone marrow is the site of o f stem cells that are ever capable of dividing and producing blood cells. The thymus gland is largest in children and shrinks as we get older. Immature T cells migrate from the bone bon e marrow through the blood stream to the thymus, where they mature. Secondary Lymphoid Organs Lymphocytes migrate to the secondary lymphoid organs. Here they encounter foreign molecules or cells, after which they proliferate pro liferate and become activated. The spleen filters the blood. Lymph nodes are packed with B and T cells.

Immunity is the body’s capability of removing or o r killing foreign foreign substances, pathogens, and cancer cells. Mechanisms of innate immunity are fully functional without p revious exposure to these substances, while Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 16 | 18

adaptive immunity is enhanced by exposure to specific antigens. An antigen is any molecule that stimulates an immune response. Innate Immunity The four types of innate immunity include physical and chemical barriers, inflammation, phagocytes and natural killer cells, and protective proteins. Physical and Chemical Barriers Skin and mucous membranes lining the th e respiratory, digestive, and urinary tracts serve as mechanical barriers to entry of pathogens. The secretions of oil glands in the skin contain chemicals that weaken or kill certain bacteria on the skin. The stomach has an acid pH, which kills many types of bacteria or inhibits their growth. Inflammation An inflamed area has four signs: redness, heat, swelling, and pain. Phagocytes and Natural Killer Cells Neutrophils and macrophages migrate to the area of tissue damage where they engulf pathogens. Natural killer cells kill abnormal cells by cell-to-cell co ntact. Protective Proteins The complement system is composed of a number of blood blo od plasma proteins that form a membrane attack complex to destroy invading b acteria. Interferons are proteins produced by virus-infected virus-in fected cells as a warning to noninfected cells. Adaptive Immunity In adaptive immunity, the body is able to distinguish “self” from “nonself”. Adaptive defenses primarily depend on the action of lymphocytes, lympho cytes, which differentiate as either B cells or T cells. B Cells and Antibody-Mediated Immunity When a B cell is activated by binding to a specific antigen, it is activated and makes many copies of itself. Activated B cells become plasma cells that produce antibodies. Structure of an Antibody Antibodies are also called immunoglobulins. They are typically Yshaped molecules with two binding sites for foreign antigens. Types of Antibodies There are five major classes of antibodies: IgG, IgM, IgA, IgD, and Ig E. T Cells and Cell-Mediated Immunity T cells can only recognize an antigen when it is displayed to them by an antigen presenting cell in conjunction with an MHC (major histocompatibility complex) protein. There are two major types of T cells: helper T cells and cytotoxic T cells. Helper T cells secrete various cytokines while cytotoxic T cells d estroy the target cell.

In active immunity, the individual alone produces an immune response against an antigen; in passive immunity, the individual is given prepared antibodies or cells via an injection. Active Immunity Active immunity usually develops naturally after a person is infected with a pathogen. Immunization involves the use of vaccines to initiate immunity. Passive Immunity Passive immunity occurs when an individual is given prepared antibodies o r immune cells to combat a disease. This occurs naturally from mother to fetus. Immune Therapies Cytokines and Immunity Biology 12 Chapter 13 – Lymphatic and Immune System Notes Ve 1.50) P a g e 17 | 18

Cytokines are chemical messengers produced by T cells, macrophages, and other cells. They regulate white blood cell formation and/or fun ction. They may be used as immunotherapeutic drugs in the future. Monoclonal Antibodies Monoclonal antibodies can be produced in vitro. Currently these are being used for quick and certain diagnosis of o f various conditions. These may be used u sed to treat cancer.

Allergies Allergies are hypersensitivities to substances, such as pollen, food, or animal hair that ordinarily would do no harm to the body. An immediate allergic response can can occur within seconds seconds of contact with the antigen and may result in anaphylactic anaphylactic shock, a life- threatening problem. A delayed allergic response is initiated by memory T cells. Blood-Type Reactions The ABO blood system is the most important of the blood typing systems. ABO System The presence or absence of type A and type B antigens on red blood cells determine a person’s blood type. Transfusion with with the wrong type blood can be fatal. Rh System Another important antigen in matching blood types is the Rh factor. A mismatch can be fatal. Tissue Rejection The immune system is responsible for rejection of transp lanted tissue. Organ rejection can be controlled by administering immunosuppressive drugs.

When a person has an autoimmune disease, cytotoxic T cells or antibodies antibodies mistakenly attack the body’s own cells. Examples include myasthenia gravis, multiple sclerosis, and systemic lupus erythematosus. In an immune deficiency, the immune system is unable to protect the b ody against disease. Examples include AIDS and severe combined immunodeficiency disease (SCID).

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