PowerPoint ® Lecture Slide Presentation by Patty Bostwick-Taylor, Florence-Darlington Technical College Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings PART B 12 The Lymphatic System and Body Defenses

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Immune response is the immune system’s response to a threat  Immunology is the study of immunity  Antibodies are proteins that protect from pathogens

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Three aspects of adaptive defense  Antigen specific—recognizes and acts against particular foreign substances  Systemic—not restricted to the initial infection site  Memory—recognizes and mounts a stronger attack on previously encountered pathogens

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Types of Immunity  Humoral immunity = antibody-mediated immunity  Provided by antibodies present in body fluids  Provided by B lymphocytes  Cellular immunity = cell-mediated immunity  Targets virus-infected cells, cancer cells, and cells of foreign grafts  Provided by T lymphocytes

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Antigens (nonself)  Any substance capable of exciting the immune system and provoking an immune response  Examples of common antigens  Foreign proteins (strongest)  Nucleic acids  Large carbohydrates  Some lipids  Pollen grains  Microorganisms

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Self-antigens  Human cells have many surface proteins  Our immune cells do not attack our own proteins  Our cells in another person’s body can trigger an immune response because they are foreign  Restricts donors for transplants

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Allergies  Many small molecules (called haptens or incomplete antigens) are not antigenic, but link up with our own proteins  The immune system may recognize and respond to a protein-hapten combination  The immune response is harmful rather than protective because it attacks our own cells

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Cells of the adaptive defense system  Lymphocytes respond to specific antigens  B lymphocytes (B cells)  Produce antibodies and oversees humoral immunity  T lymphocytes (T cells)  Cell-mediated immunity  Macrophages help lymphocytes

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Immunocompetent—cell becomes capable of responding to a specific antigen by binding to it  Cells of the adaptive defense system  Lymphocytes  Originate from hemocytoblasts in the red bone marrow  B lymphocytes become immunocompetent in the bone marrow (remember B for B one marrow)  T lymphocytes become immunocompetent in the thymus (remember T for T hymus)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte Differentiation and Activation Figure Site of lymphocyte origin KEY: Site of antigen challenge and final differentiation to mature B and T cells Sites of development of immunocompetence as B or T cells; primary lymphoid organs Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop immunocompetence there. B cells develop immuno-competence in the bone marrow. After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the infected connective tissues (especially lymphoid tissue in the lymph nodes), where the antigen challenge occurs and the lymphocytes become fully activated. Activated (mature) lymphocytes circulate continuously in the bloodstream and lymph, and throughout the lymphoid organs of the body. and Bone marrow Lymph nodes and other lymphoid tissues Immature lymphocytes Circulation in blood Immunocompetent, but still naive, lymphocytes migrate via blood Mature immunocompetent B and T cells recirculate in blood and lymph Thymus

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte Differentiation and Activation Figure 12.11, step 1a Site of lymphocyte origin KEY: Site of antigen challenge and final differentiation to mature B and T cells Sites of development of immunocompetence as B or T cells; primary lymphoid organs Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop immunocompetence there. and Bone marrow Immature lymphocytes Circulation in blood Thymus

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte Differentiation and Activation Figure 12.11, step 1b Site of lymphocyte origin KEY: Site of antigen challenge and final differentiation to mature B and T cells Sites of development of immunocompetence as B or T cells; primary lymphoid organs Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop immunocompetence there. B cells develop immuno-competence in the bone marrow. and Bone marrow Immature lymphocytes Circulation in blood Thymus

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte Differentiation and Activation Figure 12.11, step 2 Site of lymphocyte origin KEY: Site of antigen challenge and final differentiation to mature B and T cells Sites of development of immunocompetence as B or T cells; primary lymphoid organs Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop immunocompetence there. B cells develop immuno-competence in the bone marrow. After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the infected connective tissues (especially lymphoid tissue in the lymph nodes), where the antigen challenge occurs and the lymphocytes become fully activated. and Bone marrow Lymph nodes and other lymphoid tissues Immature lymphocytes Circulation in blood Immunocompetent, but still naive, lymphocytes migrate via blood Thymus

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Lymphocyte Differentiation and Activation Figure 12.11, step 3 Site of lymphocyte origin KEY: Site of antigen challenge and final differentiation to mature B and T cells Sites of development of immunocompetence as B or T cells; primary lymphoid organs Lymphocytes destined to become T cells migrate from bone marrow to the thymus and develop immunocompetence there. B cells develop immuno-competence in the bone marrow. After leaving the thymus or bone marrow as naive immunocompetent cells, lymphocytes “seed” the infected connective tissues (especially lymphoid tissue in the lymph nodes), where the antigen challenge occurs and the lymphocytes become fully activated. Activated (mature) lymphocytes circulate continuously in the bloodstream and lymph, and throughout the lymphoid organs of the body. and Bone marrow Lymph nodes and other lymphoid tissues Immature lymphocytes Circulation in blood Immunocompetent, but still naive, lymphocytes migrate via blood Mature immunocompetent B and T cells recirculate in blood and lymph Thymus

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Adaptive Defense System: Third Line of Defense  Cells of the adaptive defense system (continued)  Macrophages  Arise from monocytes  Become widely distributed in lymphoid organs  Secrete cytokines (proteins important in the immune response)  Tend to remain fixed in the lymphoid organs

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Functions of Cells and Molecules Involved in Immunity Table 12.3 (2 of 2)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Humoral (Antibody-Mediated) Immune Response  Stage One of B cell development  Inactive B cells are released from bone marrow and circulate to lymph nodes, spleen and other lymphatic structures  Stage Two is when B cell becomes activated  B lymphocytes with specific receptors bind to a specific antigen  One the antigen is an epitope  Epitope is protein molecule that has a sequence that determines its shape

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Humoral (Antibody-Mediated) Immune Response  The binding event activates the lymphocyte to undergo clonal selection  Family of identical B cells are produced  A large number of clones are produced (primary humoral response)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Humoral Immune Response  Most B cells become plasma cells  Produce antibodies to destroy antigens  Activity lasts for 4 or 5 days  Some B cells become long-lived memory cells (secondary humoral response)  A Second exposure causes a rapid response  Secondary response is stronger and lasts longer

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive) Proliferation to form a clone B lymphoblasts Plasma cells Secreted antibody molecules Clone of cells identical to ancestral cells Subsequent challenge by same antigen Memory B cell Memory B cells Plasma cells Secreted antibody molecules Secondary Response (can be years later)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.12, step 1 Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.12, step 2 Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive) Proliferation to form a clone B lymphoblasts

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.12, step 3 Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive) Proliferation to form a clone B lymphoblasts Plasma cells Secreted antibody molecules Memory B cell

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.12, step 4 Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive) Proliferation to form a clone B lymphoblasts Plasma cells Secreted antibody molecules Clone of cells identical to ancestral cells Subsequent challenge by same antigen Memory B cell Secondary Response (can be years later)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.12, step 5 Humoral Immune Response Primary Response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (lymphocyte) (B cells with non-complementary receptors remain inactive) Proliferation to form a clone B lymphoblasts Plasma cells Secreted antibody molecules Clone of cells identical to ancestral cells Subsequent challenge by same antigen Memory B cell Memory B cells Plasma cells Secreted antibody molecules Secondary Response (can be years later)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure Humoral Immune Response

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Active Immunity  Occurs when B cells encounter antigens and produce antibodies  Active immunity can be  Naturally acquired during bacterial and viral infections  Artificially acquired from vaccines  Amount of antibodies produced in response to a vaccination is called an antibody titer  Booster shots may intensify the immune response at a later meeting with the same antigen

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Passive Immunity  Occurs when antibodies are obtained from someone else  Conferred naturally from a mother to her fetus (naturally acquired)  Conferred artificially from immune serum or gamma globulin (artificially acquired)  Immunological memory does not occur  Protection provided by “borrowed antibodies”

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Passive Immunity  Monoclonal antibodies  Antibodies prepared for clinical testing or diagnostic services  Produced from descendents of a single cell line  Examples of uses for monoclonal antibodies  Diagnosis of pregnancy  Treatment after exposure to hepatitis and rabies  Inherited Immunity- immunity you are born with

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Types of Acquired Immunity Figure 12.14

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies (Immunoglobulins or Igs)  Soluble proteins secreted by B cells (plasma cells)  Carried in blood plasma  Capable of binding specifically to an antigen

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure 12.15a Antibodies (Immunoglobulins or Igs)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies  Antibody structure  Four amino acid chains linked by disulfide bonds  Two identical amino acid chains are linked to form a heavy chain- 400 amino acids  The other two identical chains are light chains  Specific antigen-binding sites are present

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibody Structure Figure 12.15b

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies  It is Y shaped and the ends have variable regions  Variable region is region where the sequence varies in different antibodies (epitope)  Also has a complement binding site

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies  Antibody classes  Antibodies of each class have slightly different roles  Five major immunoglobulin classes (MADGE)  IgM—can fix complement  IgA—found mainly in mucus, saliva, tears  IgD—important in activation of B cell  IgG—can cross the placental barrier and fix complement and is most abundant  IgE—involved in allergies

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Table 12.2 Immunoglobin Classes

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies  Antibody function  Antibodies inactivate antigens in a number of ways  Neutralization-antibodies bind to specific sites on bacteria and viruses and turns them into harmless cells  Agglutination- clumping so easy for phagocytosis; happens in blood mixing

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibodies  Antibody function  Complement fixation- alters shape of antibody to expose previously hidden complement site  Binding to these sites causes a hole in the middle of the enemy cell and water runs in and cell bursts  cytolosis  Precipitation

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Antibody Function Figure 12.16

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response  Antigens must be presented by macrophages to an immunocompetent T cell (antigen presentation)  T cells must recognize nonself and self (double recognition)  After antigen binding, clones form as with B cells, but different classes of cells are produced

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response Figure 12.17

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response  T cell clones  Cytotoxic (killer) T cells  Specialize in killing infected cells  Insert a toxic chemical (perforin)  Helper T cells  Recruit other cells to fight the invaders  Interact directly with B cells to differentiate into plasma cells

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response Figure 12.18

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Cellular (Cell-Mediated) Immune Response  T cell clones (continued)  Regulatory T cells  Formerly called suppressor T cells  Release chemicals to suppress the activity of T and B cells  Stop the immune response to prevent uncontrolled activity  A few members of each clone are memory cells

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Functions of Cells and Molecules Involved in Immunity Table 12.3 (1 of 2)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Functions of Cells and Molecules Involved in Immunity Table 12.3 (2 of 2)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure Summary of Adaptive Immune Response

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure (1 of 2) Summary of Adaptive Immune Response

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Figure (2 of 2) Summary of Adaptive Immune Response

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Organ Transplants and Rejection  Major types of grafts  Autografts—tissue transplanted from one site to another on the same person  Isografts—tissue grafts from an identical person (identical twin)  Allografts—tissue taken from an unrelated person  Xenografts—tissue taken from a different animal species

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Organ Transplants and Rejection  Autografts and isografts are ideal donors  Xenografts are never successful  Allografts are more successful with a closer tissue match  Immunosuppressive therapy needed to prevent rejection  Includes drugs, radiation, and controlling inflammation  May have side effects

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Organ Transplants and Rejection  Host vs. Graft rejection- destroys donated tissue  Graft vs. Host rejection- destroys tissue in hosts body and may lead to death

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Allergies (Hypersensitivity)  Abnormal, vigorous immune responses  Types of allergies  Immediate hypersensitivity  Triggered by release of histamine from IgE binding to mast cells  Reactions begin within seconds of contact with allergen  Runny nose, watery eyes, itching, hives, constricted airways, irregular heart beat  Antihistimines may help  When allergen inhaled- asthma

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Allergies (Hypersensitivity)  Anaphylactic shock—dangerous, systemic response  Occurs when allergen enters the blood and rapidly circulates through body  Bee stings and spider bites  Can happen with penicillin in some people

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Allergies (Hypersensitivity)  Types of allergies (continued)  Delayed hypersensitivity  Triggered by the release of lymphokines from activated helper T cells  Symptoms usually appear 1–3 days after contact with antigen  Use corticosteroid drugs  Contact dermatitis (poison ivy), cosmetics, detergents

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure Antigen (allergen) invades body Plasma cells produce large amounts of class IgE antibodies against allergen Mast cell with fixed IgE antibodies Granules containing histamine IgE IgE antibodies attach to mast cells in body tissues (and to circulating basophils) Sensitization stage More of same allergen invades body Allergen binding to IgE on mast cells triggers release of histamine (and other chemicals) Histamine causes blood vessels to dilate and become leaky, which promotes edema; stimulates release of large amounts of mucus; and causes smooth muscles to contract Subsequent (secondary) responses Antigen Histamine Mast cell granules release contents after antigen binds with IgE antibodies Outpouring of fluid from capillaries Release of mucus Constriction of bronchioles

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 1 Antigen (allergen) invades body Sensitization stage

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 2 Antigen (allergen) invades body Plasma cells produce large amounts of class IgE antibodies against allergen Sensitization stage

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 3 Antigen (allergen) invades body Plasma cells produce large amounts of class IgE antibodies against allergen Mast cell with fixed IgE antibodies Granules containing histamine IgE IgE antibodies attach to mast cells in body tissues (and to circulating basophils) Sensitization stage

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 4 More of same allergen invades body Subsequent (secondary) responses Antigen

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 5 More of same allergen invades body Allergen binding to IgE on mast cells triggers release of histamine (and other chemicals) Subsequent (secondary) responses Antigen Histamine Mast cell granules release contents after antigen binds with IgE antibodies

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 6 More of same allergen invades body Allergen binding to IgE on mast cells triggers release of histamine (and other chemicals) Histamine causes blood vessels to dilate and become leaky, which promotes edema; stimulates release of large amounts of mucus; and causes smooth muscles to contract Subsequent (secondary) responses Antigen Histamine Mast cell granules release contents after antigen binds with IgE antibodies Outpouring of fluid from capillaries Release of mucus Constriction of bronchioles

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Allergy Mechanisms Figure 12.20, step 7 Antigen (allergen) invades body Plasma cells produce large amounts of class IgE antibodies against allergen Mast cell with fixed IgE antibodies Granules containing histamine IgE IgE antibodies attach to mast cells in body tissues (and to circulating basophils) Sensitization stage More of same allergen invades body Allergen binding to IgE on mast cells triggers release of histamine (and other chemicals) Histamine causes blood vessels to dilate and become leaky, which promotes edema; stimulates release of large amounts of mucus; and causes smooth muscles to contract Subsequent (secondary) responses Antigen Histamine Mast cell granules release contents after antigen binds with IgE antibodies Outpouring of fluid from capillaries Release of mucus Constriction of bronchioles

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Immunodeficiencies  Production or function of immune cells or complement is abnormal  May be congenital or acquired  Includes AIDS (Acquired Immune Deficiency Syndrome) and Severe Combined Immunodeficiency Disease (SCID)

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Autoimmune Diseases  The immune system does not distinguish between self and nonself  The body produces antibodies and sensitized T lymphocytes that attack its own tissues

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Autoimmune Diseases  Examples of autoimmune diseases  Multiple sclerosis—white matter of brain and spinal cord are destroyed  Myasthenia gravis—impairs communication between nerves and skeletal muscles  Type I diabetes mellitus—destroys pancreatic beta cells that produce insulin

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Disorders of Immunity: Autoimmune Diseases  Examples of autoimmune diseases  Rheumatoid arthritis—destroys joints  Systemic lupus erythematosus (SLE)  Affects kidney, heart, lung and skin  Glomerulonephritis—impairment of renal function  Reynaud’s Disease

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Self Tolerance Breakdown  Inefficient lymphocyte programming  Appearance of self-proteins in the circulation that have not been exposed to the immune system  Eggs  Sperm  Eye lens  Proteins in the thyroid gland

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Self Tolerance Breakdown  Cross-reaction of antibodies produced against foreign antigens with self-antigens  Rheumatic fever

Copyright © 2009 Pearson Education, Inc., publishing as Benjamin Cummings Developmental Aspects of the Lymphatic System and Body Defenses  Except for thymus and spleen, the lymphoid organs are poorly developed before birth  A newborn has no functioning lymphocytes at birth, only passive immunity from the mother  If lymphatics are removed or lost, severe edema results, but vessels grow back in time