Chapter 22: The Lymphatic System and Immunity

1. Chapter 22: The Lymphatic System and Immunity BIO 211 Lecture Instructor: Dr. Gollwitzer

2. Today in class we will discuss: • Body defenses and the components, mechanisms and functions of: • Nonspecific defenses • Physical Barriers • Phagocytes • Immunological surveillance • Interferons • Complement system • Inflammatory response • Fever • Specific defenses • Immune response • T cells • B cells • Types of immunity • Properties of immunity

3. Immune System • A physiological system that includes several organ systems • Primary = lymphatic system • Plus components of integumentary, cardiovascular, respiratory, digestive, and other anatomic systems • e.g., interactions between lymphocytes and Langerhans cells of skin important in defenses against skin infections

4. Immune System • Specialized sensory “megaorgan” • Enables us to detect things that are foreign or cannot be seen with the naked eye (microbes, allergens…) • Allows us to fight (defend against) pathogenic microbes while normal flora left alone

5. Body Defenses • Physical and chemical barriers that prevent or slow entry/progress of infectious organisms • 2 Types of defenses • Nonspecific defenses • Specific defenses

6. Body Defenses • Nonspecific defenses • NOT unique • Against any invading agent • Many different threats elicit same response • Present from birth (innate) • e.g., physical barriers, phagocytic cells, immunological surveillance, interferons, complement, inflammation, fever

7. Body Defenses • Specific defenses (AKA: Adaptive defenses) • Protect against specific threats (e.g., one type of bacterium or virus) • Develop after birth as a result of exposure • Depend on activities of lymphocytes • Result in specific resistance or immunity = ability to resist infection and disease through activation of specific defenses

8. Nonspecific Defenses Figure 22-11

9. Nonspecific Defenses:Physical Barriers • Keep pathogens from entering body • Epithelial linings • Skin surface layers with keratin and desmosomes water resistant, impregnable wall • Epithelial accessory structures (e.g., hair, cilia) • Protect against mechanical abrasion • Prevent hazardous contact with skin • Epithelial secretions • Mechanical barrier, e.g., mucous in respiratory tract, stomach • Antibacterial, e.g. sebum (oily secretion from sebaceous gland), lysozyme enzyme in tears • Flushing action (tears, urine, mucus in respiratory tract)

10. Nonspecific Defenses:Phagocytes • Perform “police,” “first-responder,” “janitorial” services in peripheral tissues • First line of cellular defense • Roving cells on look-out for foreign invaders • Remove pathogens and cell debris (cell eaters) • Often attack and remove invaders before lymphocytes aware of them • Attracted to chemicals (chemotaxis) • Chemicals released: • From damaged body cells • By pathogens into surrounding fluids, e.g., cytokines • Move out of bloodstream by squeezing between endothelial cells (diapedesis)

11. Nonspecific Defenses:Phagocytes • Must be activated • Respond to invasion by foreign compounds or pathogens in several ways • Engulf pathogen or foreign object and destroy with lysozymes • Bind or remove pathogen from interstitial fluid but not able to destroy without assistance from other cells • Destroy pathogen by releasing: • TNF (tumor necrosis factor), NO (nitric oxide), or H2O2 (hydrogen peroxide) • Brief lifespan for active phagocytes (30 min – 1 hr)

12. Nonspecific Defenses:Phagocytes • 2 Classes of phagocytes • Microphages (“small eaters”) • Macrophages (“big eaters”)

13. Nonspecific Defenses:Microphages • Circulating neutrophils and eosinophils that leave bloodstream and enter injured or infected tissues • Neutrophils • Abundant, quick, mobile • Engulf pathogens or cellular debris • Eosinophils • Much rarer cells • Target foreign compounds or pathogens (antigens) coated with antibodies, e.g., allergens

14. Nonspecific Defenses:Macrophages • Large, actively phagocytic cells derived from monocytes • Spend very little time in blood • 2 Types • Fixed/resident macrophages • Permanent cells in certain tissues, e.g., • Microglia in CNS, Kupffer cells in liver, alveolar macrophages in lungs • Free macrophages • Mobile; travel throughout body through tissues or blood

15. Nonspecific Defenses: Immunological Surveillance • Immune system programmed to ignore cells of own body (e.g., intestinal bacteria) unless they become abnormal • Normal tissues constantly monitored by natural killer (NK) cells looking for: • Abnormal cells (cancer cells with tumor-specific antigens) • Cells infected with viruses

16. Nonspecific Defenses: Immunological Surveillance • NK cells • Lymphocyte “spy system” in peripheral tissue • Recognize/respond to wide variety of proteins on cell membranes • vs. T cells or B cells that can be activated only by exposure to a specific antigen at a specific site on a cell membrane • Respond immediately on contact with abnormal cell • Much more rapidly than T or B cells whose activation is complex and time consuming

17. Nonspecific Defenses: Immunological Surveillance • NK cell • Attaches to abnormal cell • Producess protein (perforin) that creates large pores in cell membrane  lyses cell • Especially important opponent for cancer cells

18. How NK Cells Kill Cellular Targets Fig. 22-12

19. Nonspecific Defenses:Interferons • Small protein chemical messengers (type of cytokine) produced by: • Macrophages • Cells infected with viruses • Activated lymphocytes • Interfere with spread of disease • Coordinate local defenses against viral infection • Stimulate macrophages and NK cells • Signal WBCs and lymphatic system (“tattle tales”) • Increase resistance of cells to viral infections • Trigger production of antiviral proteins that inhibit replication within cells

20. Nonspecific Defenses:Complement System • System of 11 blood proteins that interact in a chain reaction (cascade) • Assists (complements, supplements) antibodies in destroying pathogens • Begins when first complement protein (C1) binds to antibody (Ab) attached to its specific antigen • Ends with pore formation and lysis of target cell membrane

21. Complement System Figure 22–12, 7th edition

22. Nonspecific Defenses:Complement System • Attracts phagocytes to injury or infection (via chemotaxis) • Enhances phagocytosis of antibody-antigen (pathogen) complex • Stimulates inflammation • Enhances histamine release by mast cells (basophils in tissues) • Increases local inflammation and accelerates blood flow

23. Nonspecific Defenses:Inflammation • Local tissue response to injury or infection • Stimulus • Anything that changes cell and alters chemical composition of interstitial fluid • Anything that kills cells, damages CT fibers, or injures tissue • e.g., impact, abrasion, chemical irritation, infection by pathogens, extreme temperatures

24. Nonspecific Defenses:Inflammation • Stimulus causes mast cells  • Histamine • Heparin •  • Local vasodilation  increased blood flow redness and heat • Increased capillary permeability  blood proteins into injured tissue  local swelling • Stimulation of pain receptors  pain

25. Nonspecific Defenses:Inflammation • Inflammatory response • Walls off region, slows spread of injury/ pathogens from site • Combats infection by activating: • Phagocytes • Complement • Specific defenses • Performs temporary repair and prevents access of other pathogens • Mobilizes regeneration (permanent repair)

26. Figure 22-15

27. Nonspecific Defenses:Fever • High body temperature (>99 F) • Caused by pyrogens • = Proteins released by macrophages that can raise body temperature • Affect temperature-regulating center in hypothalamus • Stimuli for pyrogens • Pathogens • Bacterial toxins • Antigen-antibody complexes • Act directly as pyrogens • Stimulate release of pyrogens by macrophages

28. Nonspecific Defenses:Fever • Beneficial phenomenon • Increases body’s metabolic rate so more enzyme made to fight infection • Inhibits pathogenic enzymes • Stimulates cell repair

29. Specific/Adaptive Defenses:The Immune Response • Immunity • Specific resistance to injury and disease caused by foreign compounds, toxins, or pathogens • Provided by coordinated effort of 2 types of lymphocytes: T and B cells • Lymphocytes • Respond to presence of specific antigens • “Organize” the defense

30. Figure 22-17

31. Specific Defenses:The Immune Response • T cells (thymus-dependent) • Initiate, maintain, control the immune response • Responsible for cell-mediated immunity • Defend against abnormal cells and pathogens inside cells (do not respond to pathogens in body fluids) • 3 Major types of T cells • Cytotoxic • Helper • Suppressor

32. Specific Defenses:The Immune Response • B cells (bone marrow-derived) • Responsible for antibody-mediated (humoral) immunity • Differentiate into plasma cells that produce antibodies • Defend against antigens and pathogens in body fluids (antibodies can’t cross cell membranes)

33. Specific Defenses:The Immune Response • Types of immunity • Innate immunity • Present at birth (genetically determined) • Does not require exposure to antigen or antibody production •  Diseases that are species specific • Acquired/Adaptive immunity • Not present at birth • Produced by prior exposure to specific antigen or antibody production • 4 types

34. Figure 22-14, 7th edition

35. Specific Defenses: Acquired Immunity • Active immunity • Appears after exposure to an antigen • Requires active response by body, i.e., antibody production (immune response) • Two types • Naturally acquired (active) immunity • Through environmental exposure to pathogens • Induced (active) immunity • Through vaccines containing dead/inactive pathogens or antigens • Antibody production stimulated before possible future exposure

36. Specific Defenses: Acquired Immunity • Passive immunity • Requires no response by body • Produced by transfer of antibodies from one individual to another • Two types • Natural passive immunity • Antibodies acquired from mother during development (across placenta) or in early infancy (through breast milk) • Induced passive immunity • Antibodies (developed in another body) administered via injection • e.g., IG injected into Rh- mother after first Rh+ baby; antirabies virus antibodies injected into person bitten by rabid animal, antivenom…snake bite

37. Specific Defenses:The Immune Response • Properties of immunity that enable body to respond with a specific defense • Specificity • Versatility • Memory • Tolerance

38. Specific Defenses:4 Properties of Immunity • Specificity • Specific defenses activated by one specific antigen • Immune response targets that antigen ONLY • Each T and B lymphocyte has receptors that bind to only one specific antigen and ignore all others • T or B cells will destroy or inactivate that antigen without affecting other antigens or normal tissues

39. Specific Defenses:4 Properties of Immunity • Versatility • Ability of immune system to confront any antigen any time • Results from large diversity of lymphocytes in body • During development, cell differentiation in lymphatic system produces millions of different lymphocyte populations (each has several 1000 identical cells) • Each lymphocyte population responds to a different antigen • Several 1000 lymphocytes not enough to overcome pathogenic invasion, but begin dividing when activated in presence of appropriate antigen • Produce more lymphocytes with same specificity  clone

40. Specific Defenses:4 Properties of Immunity • Memory • Lymphocytes remember antigens they’ve encountered before • During initial response to antigen, lymphocytes undergo repeated cycles of cell division • Produce 2 types of cells • Activated lymphocytes that attack antigen invader • Memory cells that remain inactive until exposed to same antigen again at a later time • After second exposure, response is faster, stronger, and lasts longer than first time

41. Specific Defenses:4 Properties of Immunity • Tolerance • Immune system • Ignores “normal” (self) antigens • Attacks foreign (nonself) antigens • Can also develop in response to chronic (long-term) exposure to antigen in environment; lasts only as long as exposure continues • Failure  autoimmune diseases

42. Today in class we will discuss: • The immune process • Antigens • T cells • B cells • Types of immune responses • Cell-mediated immunity • Antigen presentation • Antigen recognition • T cell activation • Destruction/elimination of target cell/antigen

43. Immune Response Process • Antigen • = Foreign substance capable of inducing antibody production • Triggers immune response • Activates • Phagocytes  activation of T cells • B cells

44. Immune Response Process • T cells • Initiate, maintain, control immune response • Carry out direct physical/chemical attack on antigen • Stimulate activation of B cells • B cells • Mature into plasma cells that produce antibodies • Antibodies in bloodstream bind to/attack antigen  antigen-antibody complex that is eliminated from system

45. Figure 22-17

46. Immune Responses • 2 types • Cell-mediated immunity (T cells) • Antibody-mediated (humoral) immunity (B cells)

47. Immune Responses • Cell-mediated immunity • Involves T cells • Process • Antigen presentation • Antigen recognition • T cell activation • Destruction/elimination of target cell/antigen (cytotoxic T cells)

48. T Cells and Cell-mediated Immunity • Antigen presentation • = Process whereby foreign antigen is displayed (“presented”) on cell membrane • Requires combining foreign antigen + glycoprotein (e.g., MHC protein) Antigen = foreign peptide that has potential to induce antibody formation

49. T Cells and Cell-mediated Immunity • MHC proteins • Membrane glycoproteins • Synthesis controlled by group of genes called the major histocompatability complex (MHC) • Bind antigens • Differ among individuals • Two classes of MHC proteins • MHC I • MHC II

50. T Cells and Cell-mediated Immunity • MHC I proteins • Continuously being formed in allnormal, healthy cells that have a nucleus • MHC II proteins • In: • Antigen-presenting cells (APCs) • Present only when cell actively processing foreign antigen • Lymphocytes (B cells and helper T cells) NOTE: these cells also have MHC I proteins