Chap21 powerpoint l
- 1. 21-1 Chapter 21 Lecture Outline See PowerPoint Image Slides for all figures and tables pre-inserted into PowerPoint without notes. Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
- 2. 21-2 • Maintain fluid balance • Protect body from infection and disease Lymphatic and Immune Systems
- 3. 21-3 • Immunity – fluids from all capillary beds are filtered – immune cells stand ready to respond to foreign cells or chemicals encountered • Lipid absorption – Lacteals in small intestine absorb dietary lipids • Fluid recovery – absorbs plasma proteins and fluid (2 to 4 L/day) from tissues and returns it to the bloodstream • interference with lymphatic drainage leads to severe edema Functions of Lymphatic System
- 4. 21-4 Lymph and Lymphatic Capillaries • Lymph – clear, colorless fluid, similar to plasma but much less protein • Lymphatic capillaries – closed at one end – tethered to surrounding tissue by protein filaments – endothelial cells loosely overlapped • allow bacteria and cells entrance to lymphatic capillary • creates valve-like flaps that open when interstitial fluid pressure is high, and close when it is low
- 6. 21-6 Lymphatic Vessels • Larger ones composed of 3 layers – tunica interna: endothelium and valves – tunica media: elastic fibers, smooth muscle – tunica externa: thin outer layer
- 7. 21-7 Valve in a Lymphatic Vessel
- 8. 21-8 Route of Lymph Flow • Lymphatic capillaries • Collecting vessels: course through many lymph nodes • Lymphatic trunks: drain major portions of body • Collecting ducts : – right lymphatic duct – receives lymph from R arm, R side of head and thorax; empties into R subclavian vein – thoracic duct - larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, L arm, L side of head, neck and thorax; empties into L subclavian vein
- 10. 21-10 Lymphatic Drainage of Mammary and Axillary Regions
- 12. 21-12 Mechanisms of Lymph Flow • Lymph flows at low pressure and speed • Moved along by rhythmic contractions of lymphatic vessels – stretching of vessels stimulates contraction • Flow aided by skeletal muscle pump • Thoracic pump aids flow from abdominal to thoracic cavity • Valves prevent backward flow • Rapidly flowing blood in subclavian veins, draws lymph into it • Exercise significantly increases lymphatic return
- 13. 21-13 Lymphatic Cells • Natural killer (NK) cells – responsible for immune surveillance • T lymphocytes – mature in thymus • B lymphocytes – activation causes proliferation and differentiation into plasma cells that produce antibodies • Antigen Presenting Cells – macrophages (from monocytes) – dendritic cells (in epidermis, mucous membranes and lymphatic organs) – reticular cells (also contribute to stroma of lymph organs)
- 14. 21-14 Lymphatic Tissue • Diffuse lymphatic tissue – lymphocytes in mucous membranes and CT of many organs – Mucosa-Associated Lymphatic Tissue (MALT): prevalent in passages open to exterior • Lymphatic nodules – dense oval masses of lymphocytes, congregate in response to pathogens – Peyer patches: more permanent congregation, clusters found at junction of small to large intestine
- 15. 21-15 Lymphatic Organs • At well defined sites; have CT capsules • Primary lymphatic organs – site where T and B cells become immunocompetent – red bone marrow and thymus • Secondary lymphatic organs – immunocompetent cells populate these tissues – lymph nodes, tonsils, and spleen
- 16. 21-16 Lymph Node • Lymph nodes - only organs that filter lymph • Fewer efferent vessels, slows flow through node • Capsule gives off trabeculae, divides node into compartments containing stroma (reticular CT) and parenchyma (lymphocytes and APCs) subdivided into cortex (lymphatic nodules) and medulla – reticular cells, macrophages phagocytize foreign matter – lymphocytes respond to antigens – lymphatic nodules-germinal centers for B cell activation
- 17. 21-17 Lymphadenopathy • Collective term for all lymph node diseases • Lymphadenitis – swollen, painful node responding to foreign antigen • Lymph nodes are common sites for metastatic cancer – swollen, firm and usually painless
- 18. 21-18 Lymph Node Fig. 21.12 a and b
- 19. 21-19 Tonsil • Covered by epithelium • Pathogens get into tonsillar crypts and encounter lymphocytes
- 20. 21-20 Location of Tonsils • Palatine tonsils – pair at posterior margin of oral cavity – most often infected • Lingual tonsils – pair at root of tongue • Pharyngeal tonsil (adenoid) – single tonsil on wall of pharynx
- 21. 21-21 Thymus
- 22. 21-22 Thymus • Capsule gives off trabeculae, divides parenchyma into lobules of cortex and medulla • Reticular epithelial cells – form blood thymus barrier in cortex • isolates developing T lymphocytes from foreign antigens – secretes hormones (thymopoietin, thymulin and thymosins) • to promote development and action of T lymphocytes • Very large in fetus; after age 14 begins involution – in elderly mostly fatty and fibrous tissue
- 24. 21-24 Spleen • Parenchyma appears in fresh specimens as – red pulp: sinuses filled with erythrocytes – white pulp: lymphocytes, macrophages; surrounds small branches of splenic artery • Functions – blood production in fetus – blood reservoir – RBC disposal – immune reactions: filters blood, quick to detect antigens
- 25. 21-25 Spleen
- 26. 21-26 Defenses Against Pathogens • Nonspecific defenses - broadly effective, no prior exposure – first line of defense • external barriers – second line of defense • phagocytic cells, antimicrobial proteins, inflammation and fever • Specific defense - results from prior exposure, protects against only a particular pathogen – third line of defense • immune system
- 27. 21-27 External Barriers • Skin – toughness of keratin – dry and nutrient-poor – defensins: peptides, from neutrophils attack microbes – lactic acid (acid mantle) is a component of perspiration • Mucous membranes – stickiness of mucus – lysozyme: enzyme destroys bacterial cell walls • Subepithelial areolar tissue – tissue gel: viscous barrier of hyaluronic acid • hyaluronidase: enzyme used by pathogens to spread
- 28. 21-28 Leukocytes and Cutaneous Defenses • Neutrophils • Eosinophils • Basophils • Monocytes • Lymphocytes
- 29. 21-29 Neutrophils • Phagocytize bacteria • Create a killing zone – degranulation • lysosomes discharge into tissue fluid – respiratory burst • toxic chemicals are created (O2 .- , H2O2, HClO)
- 30. 21-30 Eosinophils • Phagocytize antigen-antibody complexes • Antiparasitic effects • Promote action of basophils, mast cells • Enzymes block excess inflammation, limit action of histamine
- 31. 21-31 Basophils • Aid mobility and action of WBC’s by release of – histamine (vasodilator) ∀↑ blood flow to infected tissue – heparin (anticoagulant) • prevents immobilization of phagocytes
- 32. 21-32 Monocytes • Circulating precursors to macrophages • Specialized macrophages found in specific localities – dendritic cells • epidermis, oral mucosa, esophagus, vagina, and lymphatic organs – microglia (CNS) – alveolar macrophages (lungs) – hepatic macrophages (liver)
- 33. 21-33 Lymphocytes • Circulating blood contains – 80% T cells – 15% B cells – 5% NK cells
- 34. 21-34 Antimicrobial Proteins • Interferons • Complement system
- 35. 21-35 Interferons • Secreted by certain cells invaded by viruses – generalized protection – diffuse to neighboring cells and stimulate them to produce antiviral proteins – activate natural killer cells and macrophages • destroy infected host cells • stimulate destruction of cancer cells
- 36. 21-36 Complement System • Complement (C) proteins in blood that must be activated by pathogens • Pathways of complement activation: C3 split into C3a and C3b – classical pathway • requires antibody; specific immunity – alternate pathway • nonspecific immunity – lectin pathway • nonspecific immunity
- 37. 21-37 Complement System • Mechanisms of action – enhanced inflammation – phagocytosis • promoted by opsonization – cytolysis • membrane attack complex forms on target cell – immune clearance • RBCs carry Ag-Ab complexes to macrophages in liver and spleen
- 39. 21-39 Membrane Attack Complex • Complement proteins form ring in plasma membrane of target cell causing cytolysis
- 40. 21-40 Immune Surveillance • NK cells – destroy bacteria, transplanted cells, cells infected by viruses, and cancer cells • release perforins and granzymes
- 41. 21-41 Action of NK cell Fig. 21.17
- 42. 21-42 Inflammation • Defensive response to tissue injury 1. limits spread of pathogens, then destroys them 2. removes debris 3. initiates tissue repair • Cytokines – small proteins regulate inflammation and immunity; include • interferons, interleukins, tumor necrosis factor, and chemotactic factors
- 43. 21-43 Inflammation • Suffix -itis denotes inflammation of specific organs • Cardinal signs –redness (erythema) caused by hyperemia (↑ blood flow) –swelling (edema) caused by ↑ capillary permeability and filtration –heat caused by hyperemia –pain caused by inflammatory chemicals (bradykinin, prostaglandins) secreted by damaged cells, pressure on nerves
- 44. 21-44 Inflammation • Three major processes 1. mobilization of body defenses 2. containment and destruction of pathogens 3. tissue clean-up and repair
- 45. 21-45 Mobilization of Defenses • Kinins, histamine, and leukotrienes are secreted by damaged cells, basophils and mast cells – stimulates vasodilation that leads to hyperemia • causes redness and heat ∀ ↑ local metabolic rate, promotes cell multiplication and healing • dilutes toxins, provides O2, nutrients, waste removal – stimulates ↑ permeability of blood capillaries • allows blood cells, plasma proteins (antibodies, complement proteins, fibrinogen) into tissue • clotting sequesters bacteria, forms scaffold for tissue repair
- 46. 21-46 Mobilization of Defenses • Leukocyte Deployment – margination • selectins cause leukocytes to adhere to blood vessel walls – diapedesis (emigration) • leukocytes squeeze between endothelial cells into tissue space
- 47. 21-47 Containment and Destruction of Pathogens • Fibrinogen now in tissue clots, trapping pathogens • Heparin prevents clotting at site of injury – pathogens are in a fluid pocket surrounded by clot • Chemotaxis – leukocytes are attracted to chemotactic chemicals • Neutrophils are quickest to respond – phagocytosis – respiratory burst – secrete cytokines for recruitment of macrophages and neutrophils – macrophages and T cells secrete colony-stimulating factor to stimulate leukopoiesis
- 48. 21-48 Tissue Cleanup • Monocytes the primary agents of cleanup arrive in 8 to 12 hours, become macrophages, • Edema ↓ venous flow, ↑ lymphatic flow that favors removal of bacteria and debris • Formation of pus – mixture of tissue fluid, cellular debris, dying neutrophils and microbes
- 49. 21-49 Tissue Repair • Blood platelets and endothelial cells in injured area secrete a cytokine, PDGF, that stimulates fibroblasts to multiply and synthesize collagen • Facilitated by hyperemia that provides materials needed and heat that increases metabolism • Fibrin clot may provide a scaffold for repair • Pain limits use of body part allowing for repair
- 50. 21-50 Fever • Defense mechanism: does more good than harm – promotes interferon activity – accelerating metabolic rate and tissue repair – inhibiting pathogen reproduction • A cytokine, interleukin 1, called a pyrogen – secreted by macrophages, stimulates anterior hypothalamus to secrete PGE which resets body thermostat higher > 105°F may cause delirium, 111°F- 115°F, coma-death • Stages of fever – onset, stadium, defervescence
- 51. 21-51 Course of a Fever
- 52. 21-52 Specific Immunity • Specificity and memory • Cellular immunity: cell-mediated (T cells) • Humoral immunity: antibody mediated (B cells)
- 53. 21-53 Passive and Active Immunity • Natural active immunity (produces memory cells) – production of one’s own antibodies or T cells as a result of infection or natural exposure to antigen • Artificial active immunity (produces memory cells) – production of one’s own antibodies or T cells as a result of vaccination • Natural passive immunity (through placenta, milk) – temporary, fetus acquires antibodies from mother • Artificial passive immunity (snakebite, rabies, tetanus) – temporary, injection of immune serum (antibodies)
- 54. 21-54 Antigens • Trigger an immune response • Complex molecules – > 10,000 amu, unique structures – proteins, polysaccharides, glycoproteins, glycolipids • Epitopes (antigenic determinants) – stimulate immune responses • Haptens – too small, host macromolecule must bind to them to stimulate initial immune response
- 55. 21-55 Lymphocytes • Specific immunity depends on lymphocytes
- 56. 21-56 Life Cycle of T cells • Stem cells in red bone marrow • Mature in thymus – thymosins stimulate maturing T cells to produce antigen receptors – immunocompetent T cell has antigen receptors in place • Deployment – naïve T cells colonize lymphatic tissue and organs
- 57. 21-57 Negative Selection of T cells • Immunocompetent T cells must be able to 1. bind to RE cell 2. not react to self antigens • Failure results in negative selection via – clonal deletion: destruction of offending T cells – anergy: inactive state, alive but unresponsive • Leaves body in a state of self-tolerance • Only 2% of T cells succeed
- 58. 21-58 Positive Selection of T cells • Immunocompetent T cells that are able to 1. bind to MHC on RE cell 2. not react to self antigens divide rapidly and form clones of T cells with identical receptors for a specific antigen – these cells have not encountered target antigens, constitute naïve lymphocyte pool • Deployment - cells ready to leave thymus
- 59. 21-59 B Lymphocytes (B cells) • Sites of development – other fetal stem cells remain in bone marrow • B cell selection – B cells should not react to self antigens • or suffer clonal deletion or anergy • Self-tolerant B cells form B cell clones – synthesize antigen receptors, divide rapidly, produce immunocompetent clones
- 60. 21-60 Antigen-Presenting Cells (APCs) • Function depends on major histocompatability complex (MHC) proteins – act as cell ID tag • B cells and macrophages, display antigens to T cells
- 62. 21-62 Interleukins • Chemical messengers between leukocytes • Used by lymphocytes and APCs to communicate
- 63. 21-63 Cellular Immunity • T cells attack foreign cells and diseased host cells; memory of Ag • Three classes of T cells 1. Cytotoxic T cells (Tc cells) carry out attack 2. Helper T cells: help promote Tc cell and B cell action and nonspecific defense mechanisms 3. Memory T cells: provide immunity from future exposure to antigen
- 64. 21-64 TC cell Recognition • Antigen presentation – MHC-I proteins • found on nearly all nucleated body cells • display peptides produced by host cells • TC cell activation 1. binding of cytotoxic T cells (CD8 cells) to abnormal peptides on MHC-I and 2. costimulation via a cytokine – triggers clonal selection: clone of identical T cells against cells with same epitope
- 65. 21-65 TH cell Recognition • Antigen presentation –role of MHC-II proteins • found only on antigen presenting cells • display only foreign antigens • stimulate helper T cells (CD4 cells)
- 66. 21-66 TH cell Activation 1. binding of helper T cells (CD4 cells) to epitope displayed on MHC-II of APC 2. costimulation via a cytokine 3. triggers clonal selection
- 68. 21-68 Attack Phase: Role of Helper T Cells • Secretes interleukins – attract neutrophils, NK cells, macrophages – stimulate phagocytosis – stimulate T and B cell mitosis and maturation • Coordinate humoral and cellular immunity
- 69. 21-69 Attack Phase: Cytotoxic T Cells • Only T cells directly attack enemy cells • Lethal hit mechanism – docks on cell with antigen-MHC-I protein complex 1. releases perforin, granzymes - kills target cell 2. interferons - decrease viral replication and activates macrophages 3. tumor necrosis factor: kills cancer cells
- 70. 21-70 Cytotoxic T Cell Function • Cytotoxic T cell binding to cancer cell
- 71. 21-71 Destruction of Cancer Cell
- 72. 21-72 Memory • Memory T cells – following clonal selection some T cells become memory cells – long-lived; in higher numbers than naïve cells • T cell recall response – upon reexposure to same pathogen, memory cells launch a quick attack
- 73. 21-73 Humoral Immunity • Recognition – B cell receptors bind antigen, take in and digest antigen then display epitopes on its MHC-II protein – After costimulation by TH cell, divide repeatedly, differentiate into plasma cells, produce antibodies specific to that antigen • Attack – antibodies bind to antigen, render it harmless, ‘tag it’ for destruction • Memory – some B cells differentiate into memory cells
- 74. 21-74 Humoral Immunity - Recognition
- 75. 21-75 B cells and Plasma cells
- 77. 21-77 Antibody Classes • By amino acid sequences of C region of antibody • IgA: monomer in plasma; dimer in mucus, saliva, tears, milk, intestinal secretions, prevents adherence to epithelia • IgD: monomer; B cell membrane antigen receptor • IgE: monomer; on mast cells; stimulates release of histamines, attracts eosinophils; immediate hypersensitivity reactions • IgG: monomer; 80% circulating, crosses placenta to fetus, 2° immune response, complement fixation • IgM: pentamer, 10% in plasma, 1° immune response, agglutination, complement fixation
- 78. 21-78 Antibody Diversity • Immune system capable of as many as 1 trillion different antibodies • Somatic recombination – DNA segments shuffled and form new combinations of base sequences to produce antibody genes • Somatic hypermutation – B cells in lymph nodules rapidly mutate creating new sequences
- 79. 21-79 Humoral Immunity - Attack • Neutralization – antibodies mask pathogenic region of antigen • Complement fixation – antigen binds to IgM or IgG, antibody changes shape, initiates complement binding; primary defense against foreign cells, bacteria • Agglutination – antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them • Precipitation – antibody binds antigen molecules (not cells); creates antigen-antibody complex that precipitates, phagocytized by eosinophil
- 82. 21-82 Hypersensitivity (Allergy) • Excessive immune reaction against antigens that most people tolerate - allergens • Type I Antibody mediated (IgE), acute reaction • Type II Antibody mediated (IgG, IgM), subacute • Type III Antibody mediated (IgG, IgM), subacute • Type IV Cell mediated, delayed
- 83. 21-83 Type I (acute) Hypersensitivity • Anaphylaxis – occurs in sensitized people – allergen caps IgE on mast cells, basophils – release inflammatory chemicals • Asthma – most common chronic illness in children – inhaled allergens, histamines, bronchiole constriction • Anaphylactic shock – bronchiole constriction, dyspnea, vasodilation, shock, death; treatment- epinephrine
- 84. 21-84 Type II Hypersensitivity (Antibody-Dependent Cytotoxic) • IgG or IgM – binds to antigens on cells; complement activation and lyses or opsonization – may bind to cell surface receptors and either interferes with function or over-stimulate cell
- 85. 21-85 Type III Hypersensitivity (Immune Complex) • IgG or IgM form widespread antigen- antibody complexes • Complexes precipitate and trigger intense inflammation – involved in acute glomerulonephritis and in systemic lupus erythematosus
- 86. 21-86 Type IV Hypersensitivity (Delayed) • 12 to 72 hour delay • APC’s in lymph nodes display antigens to helper T cells, which secrete interferon and cytokines that activate cytotoxic T cells and macrophages • Cosmetic and poison ivy allergies - haptens • TB skin test
- 87. 21-87 Autoimmune Diseases • Failure of self tolerance – cross-reactivity – abnormal exposure of self-antigens – changes in structure of self-antigens • Production of autoantibodies
- 88. 21-88 Immunodeficiency Diseases • Severe Combined Immunodeficiency Disease – hereditary lack of T and B cells – vulnerability to opportunistic infection
- 89. 21-89 • AIDS – HIV structure (next slide) – invades helper T cells, macrophages and dendritic cells by “tricking” them to internalize viruses by receptor mediated endocytosis – reverse transcriptase (retrovirus), uses viral RNA as template to synthesize DNA, new DNA inserted into host cell DNA, may be dormant for months to years Immunodeficiency Diseases
- 91. 21-91 AIDS • Signs and symptoms – early symptoms: flulike chills and fever – progresses to night sweats, fatigue, headache, extreme weight loss, lymphadenitis – normal TH count is 600 to 1,200 cells/µL of blood but in AIDS it is < 200 cells/µL • person susceptible to opportunistic infections (Toxoplasma, Pneumocystitis, herpes simplex virus, CMV or TB) – thrush: white patches on mucous membranes – Kaposi sarcoma: cancer originates in endothelial cells of blood vessels causes purple lesions in skin
- 93. 21-93 HIV Transmission • Through blood, semen, vaginal secretions, breast milk, or across the placenta • Most common means of transmission – sexual intercourse (vaginal, anal, oral) – contaminated blood products – contaminated needles • Not transmitted by casual contact • Undamaged latex condom is an effective barrier to HIV, especially with spermicide nonoxynol-9
- 94. 21-94 Treatment Strategies • Prevent binding to CD4 proteins of TH cells • Disrupt reverse transcriptase, inhibit assembly of new viruses or their release from host cells • Medications – none can eliminate HIV, all have serious side-effects – HIV develops resistance, meds used in combination – AZT azidothymidine • first anti-HIV drug, inhibits reverse transcriptase – Protease inhibitors • inhibit enzymes HIV needs to replicate – now more than 16 anti-HIV drugs