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Similar to Chapter 21: The Immune System (#2)
Chapter 21: The Immune System (#2)
- 1. CHAPTER 21: THE IMMUNESYSTEM (2): ADAPTIVE IMMUNITY Human Anatomy and Physiology II – BIOL153
- 2. Immune System –Innate vs Adaptive Innate: • Nonspecifi c • Responds quickly Adaptive: • Specific • Responds Slowly the 1st time
- 3. Goals/Objectives Compare andcontrast humoral and cellular immunity Compare and contrast the origin, maturation process, and general function of B and T lymphocytes Describe role of plasma cells and memory cells in humoral immunity Describe the structure of an antibody monomer, and name the five classes of antibodies and their characteristics Explain the functions of antibodies
- 4. Adaptive Defenses Specific– recognizes and targets specific antigens Systemic – not restricted to initial site Have memory – stronger attacks to "known" antigens Two separate, overlapping arms Humoral (antibody-mediated) immunity Cellular (cell-mediated) immunity
- 5. Humoral vs CellularImmunity Humoral Immunity Antibodies, produced by lymphocytes, circulating freely in body fluids Bind temporarily to target cell Temporarily inactivate Mark for destruction by phagocytes or complement Humoral immunity has Cellular Immunity Lymphocytes act against target cell Directly – by killing infected cells Indirectly – by releasing chemicals that enhance inflammatory response; or activating other lymphocytes or macrophages Cellular immunity has cellular targets
- 6. Antigens Substances thatcan mobilize adaptive defenses and provoke an immune response Targets of all adaptive immune responses Most are large, complex molecules not normally found in body (nonself) Only certain parts (antigenic determinants) of entire antigen are immunogenic Antibodies and lymphocyte receptors bind to them as enzyme binds substrate
- 7. Antibody A Antigen- binding sites Antibody B AntibodyC Antigenic determinants Antigen Antigens
- 8. Cells of theAdaptive Immune System Three types of cells Two types of lymphocytes B lymphocytes (B cells)—humoral immunity T lymphocytes (T cells)—cellular immunity Antigen-presenting cells (APCs) Do not respond to specific antigens Play essential auxiliary roles in immunity
- 9. Adaptive defenses Humoral immunity Cellularimmunity Primary lymphoid organs (red bone marrow and thymus) Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrowRed bone marrow Lymphocyte precursors Thymus Red bone marrow 1 Origin • Both B and T lymphocyte precursors originate in red bone marrow.
- 10. Adaptive defenses Humoral immunity Cellularimmunity Primary lymphoid organs (red bone marrow and thymus) Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrowRed bone marrow Lymphocyte precursors Thymus Red bone marrow 1 2 Origin • Both B and T lymphocyte precursors originate in red bone marrow. Maturation • Lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there. • B cells mature in the bone marrow. • During maturation lymphocytes develop immunocompetence and self-tolerance.
- 11. Adaptive defenses Humoral immunity Cellularimmunity Primary lymphoid organs (red bone marrow and thymus) Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrowRed bone marrow Lymphocyte precursors Thymus Red bone marrow Lymph node Antigen 1 2 3 Origin • Both B and T lymphocyte precursors originate in red bone marrow. Maturation • Lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there. • B cells mature in the bone marrow. • During maturation lymphocytes develop immunocompetence and self-tolerance. Seeding secondary lymphoid organs and circulation • Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. • They “seed” the secondary lymphoid organs and circulate through blood and lymph.
- 12. Adaptive defenses Humoral immunity Cellularimmunity Primary lymphoid organs (red bone marrow and thymus) Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrowRed bone marrow Lymphocyte precursors Thymus Red bone marrow Lymph node Antigen 1 2 3 4 Origin • Both B and T lymphocyte precursors originate in red bone marrow. Maturation • Lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there. • B cells mature in the bone marrow. • During maturation lymphocytes develop immunocompetence and self-tolerance. Seeding secondary lymphoid organs and circulation • Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. • They “seed” the secondary lymphoid organs and circulate through blood and lymph. Antigen encounter and activation • When a lymphocyte’s antigen receptors bind its antigen, that lymphocyte can be activated.
- 13. Adaptive defenses Humoral immunity Cellularimmunity Primary lymphoid organs (red bone marrow and thymus) Secondary lymphoid organs (lymph nodes, spleen, etc.) Red bone marrowRed bone marrow Lymphocyte precursors Thymus Red bone marrow Lymph node Antigen 1 2 3 4 5 Origin • Both B and T lymphocyte precursors originate in red bone marrow. Maturation • Lymphocyte precursors destined to become T cells migrate (in blood) to the thymus and mature there. • B cells mature in the bone marrow. • During maturation lymphocytes develop immunocompetence and self-tolerance. Seeding secondary lymphoid organs and circulation • Immunocompetent but still naive lymphocytes leave the thymus and bone marrow. • They “seed” the secondary lymphoid organs and circulate through blood and lymph. Antigen encounter and activation • When a lymphocyte’s antigen receptors bind its antigen, that lymphocyte can be activated. Proliferation and differentiation • Activated lymphocytes proliferate (multiply) and then differentiate into effector cells and memory cells. • Memory cells and effector T cells circulate continuously in the blood and lymph and throughout the secondary lymphoid organs.
- 14. © 2013 PearsonEducation, Inc.
- 15. Antigen-presenting Cells (APCs) Engulfantigens Present fragments of antigens to T cells for recognition Major types Dendritic cells in connective tissues and epidermis Macrophages in connective tissues and lymphoid organs B cells (not as much as macrophages)
- 16. Adaptive Immunity: Summary Uses lymphocytes, APCs, and specific molecules to identify and destroy nonself substances Depends upon ability of its cells to Recognize antigens by binding to them Communicate with one another so that whole system mounts specific response
- 17. Goals/Objectives Compare andcontrast humoral and cellular immunity Compare and contrast the origin, maturation process, and general function of B and T lymphocytes Describe role of plasma cells and memory cells in humoral immunity Describe the structure of an antibody monomer, and name the five classes of antibodies and their characteristics Explain the functions of antibodies
- 18. Adaptive defenses Humoralimmunity Primary response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B lymphocyte (B lymphocytes with noncomplementary receptors remain inactive) Proliferation to form a clone Activated B cells Plasma cells (effector B cells) Memory B cell— primed to respond to same antigen Secreted antibody molecules Humoral Immunity
- 19. Immunological Memory Primaryimmune response Cell proliferation and differentiation upon first antigen exposure Lag period: three to six days Peak levels of plasma antibody are reached in 10 days Antibody levels then decline Secondary immune response Re-exposure to same antigen gives faster, more prolonged, more effective response Sensitized memory cells respond within hours Antibody levels peak in two to three days at much higher levels Antibodies bind with greater affinity
- 20. Antibodytiter(antibodyconcentration) inplasma(arbitraryunits) 100 101 102 103 104 0 7 1421 28 35 42 49 56 First exposure to antigen A Second exposure to antigen A; first exposure to antigen B Primary immune response to antigen A occurs after a delay. Secondary immune response to antigen A is faster and larger; primary immune response to antigen B is similar to that for antigen A. Time (days) Anti- Bodies to A Anti- Bodies to B
- 21. Antibodies Immunoglobulins—gamma globulinportion of blood Proteins secreted by plasma cells Capable of binding specifically with antigen detected by B cells Grouped into one of five Ig classes
- 22. Adaptive defenses Humoralimmunity Antigen-binding site Heavy chain variable region Heavy chain constant region Light chain variable region Light chain constant region Disulfide bond Hinge region Stem region Antibody Structure
- 23. Classes of Antibodies IgM Pentamer (snowflake, larger than others); first antibody released Readily fixes and activates complement IgA (secretory IgA) Monomer or dimer; in mucus and other secretions Helps prevent entry of pathogens IgD Monomer attached to surface of B cells Functions as B cell receptor IgG Monomer; 75–85% of antibodies in plasma (most abundant) From secondary and late primary responses IgE Monomer active in some allergies and parasitic infections Causes mast cells and basophils to release histamine B cells can switch antibody classes but retain antigen specificity IgM at first; then IgG Almost all secondary responses are IgG
- 24. © 2013 PearsonEducation, Inc. Adaptive defenses Humoral immunity Antigen Antigen-antibody complex Antibody Inactivates by Fixes and activates Neutralization (masks dangerous parts of bacterial exotoxins; viruses) Agglutination (cell-bound antigens) Precipitation (soluble antigens) Complement Enhances Enhances Leads to Phagocytosis Inflammation Cell lysis Chemotaxis Histamine release
- 25. Summary of AntibodyActions Antigen-antibody complexes do not destroy antigens; prepare them for destruction by innate defenses Antibodies do not invade solid tissue unless lesion present (ex. Cancer) Can act intracellularly if attached to virus before it enters cell Activate mechanisms that destroy virus
- 26. Cellular Immune Response T cells provide defense against intracellular antigens Some T cells directly kill cells; others release chemicals that regulate immune response
- 27. Cellular Immunity Twopopulations of T cells based on which glycoprotein surface receptors displayed CD4 cells usually become helper T cells (TH); activate B cells, other T cells, macrophages, and direct adaptive immune response Some become regulatory T cells – which moderate immune response Can also become memory T cells CD8 cells become cytotoxic T cells (TC) Destroy cells harboring foreign antigens Also become memory T cells Helper, cytotoxic, and regulatory T cells are activated T cells Naive T cells simply termed CD4 or CD8 cells
- 28. Adaptive defenses Cellularimmunity Immature lymphocyte Red bone marrow T cell receptor Maturation T cell receptor Class II MHC protein displaying antigen CD4 cell Thymus CD8 cell Class I MHC protein displaying antigen Activation Activation APC (dendritic cell) APC (dendritic cell) Memory cells CD4 CD8 CD4 cells become either helper T cells or regulatory T cells Lymphoid tissues and organs CD8 cells become cytotoxic T cells Effector cells Blood plasma
- 29. MHC Proteins andAntigen Presentation T cells respond only to processed fragments of antigens displayed on surfaces of cells Antigen presentation vital for activation of naive T cells and normal functioning of effector T cells
- 30. T cell Activation:Proliferation and Differentiation Primary T cell response peaks within a week T cell apoptosis occurs between days 7 and 30 Benefit of apoptosis: activated T cells are a hazard – produce large amount inflammatory cytokines hyperplasia, cancer Effector activity wanes as amount of antigen declines Memory T cells remain and mediate secondary responses
- 31. Roles of HelperT (TH) cells Play central role in adaptive immune response Activate both humoral and cellular arms Once primed by APC presentation of antigen, they Help activate T and B cells Induce T and B cell proliferation They release cytokines recruit other immune cells Without TH, there is no immune response
- 32. Cytotoxic T (TC)cells Directly attack and kill other cells Activated TC cells circulate in blood and lymph and lymphoid organs in search of body cells displaying antigen they recognize Targets Virus-infected cells Cells with intracellular bacteria or parasites Cancer cells Foreign cells (transfusions or transplants)
- 33. Cytotoxic T cells Lethal hit – two methods: TC cell releases perforins and granzymes by exocytosis Perforins create pores through which granzymes enter target cell Granzymes stimulate apoptosis TC cell binds specific membrane receptor on target cell, and stimulates apoptosis
- 34. Adaptive defenses Cellularimmunity Cytotoxic T cell (TC) TC identifies foreign antigens on MHC I proteins and binds tightly to target cell. TC releases perforin and granzyme molecules from its granules by exocytosis. Perforin molecules insert into the target cell membrane, polymerize, and form transmembrane pores (cylindrical holes) similar to those produced by complement activation. Perforin Granule TC cell membrane Target cell membrane Target cell Perforin pore Granzymes The TC detaches and searches for another prey. Granzymes enter the target cell via the pores. Once inside, granzymes activate enzymes that trigger apoptosis. A mechanism of target cell killing by TC cells. Scanning electron micrograph of a TC cell killing a cancer cell (2100x). Cytotoxic T cell Cancer cell 1 2 3 4 5
- 35. Natural Killer cells Recognize other signs of abnormality Lack of class I MHC Antibody coating target cell Different surface markers of stressed cells Use same key mechanisms as TC cells for killing their target cells Immune surveillance—NK and TC cells prowl for markers they recognize
- 36. Regulatory T (TReg)cells Dampen immune response by direct contact or by inhibitory cytokines such as IL-10 and TGF- β Important in preventing autoimmune reactions Suppress self-reactive lymphocytes in periphery (outside lymphoid organs) Research into using them to induce tolerance to transplanted tissue
Editor's Notes
- #3 Innate immune system: acts quickly but is nonspecific (ex. Someone enters a classroom, we don’t know who they are but we know they don’t belong) Adaptive immune system: takes longer (esp. first time) but is specific (identifies it to attack it the best way possible)
- #5 Once the system sees a foreign pathogen, it will recognize it in the future and can attack it quicker
- #6 Humoral (ANTIBODY) bind to antigens and exert marks/tags for phagocytes to be engulfed or cause them problems
- #7 Both arms of immune system can recognize antigens Antigen is a substance that can be recognized; NOT ALL antigens trigger an immune response; only ones considered foreign ex. Antigens that determine blood type will not be attacked (type A person won’t have an immune system attacking A antigens)
- #8 Antigen is not directly recognized as foreign; only ANTIGENIC DETERMINANTS are recognized by cells/antibodies
- #9 APCs take in antigen, chop it up and present it to T cells/B cells to become activated
- #10 All begin from hematopoietic stem cells in bone marrow; environment determines cell produced
- #11 T cells go to thymus to mature and know what antigens to attack B cells mature in the bone marrow Learning tolerance to non-foreign cells/antigens
- #12 Haven’t come into contact with antigen; no “practice” Go to secondary lymphoid organs to encounter antigens
- #16 Mostly phagocytes
- #24 Know key structural characteristic and functions IgM: first antibody found in circulation
- #25 Neutralization: prevents pathogen from being destructive; does not mean it is killing pathogen Agglutination: antibody binds to antigen on cell, clumping all together Precipitation: antibodies take little foreign molecules and clump together to make a more visible target to phagocytes
- #28 CD4 and CD8 names given when they are developing; after activation they are named for the job they do: CD4 -> helper cells, CD8 -> cytotoxic cells
- #37 Prevent auto immune actions, and aid when tissue is transplanted to not destroy the new tissue