Lymphatic & Immune Systems

1. Lymphatic & Immune Systems

2. Lymphatic System • Reabsorbs about 15% of fluid filtered by blood capillaries & returns it to blood • Provides immunity & protection from foreign cells & matter in the body • Absorbs dietary lipids in small intestine & transports them to blood p 809

3. Lymph = fluid in lymphatic vessels • Usually clear, colorless fluid • Originates in lymphatic capillaries p 810

4. Lymphatic Vessels • Histology similar to veins • Thinner walls • More valves • Flow of Lymph • Like venous; low pressure & speed • Primary driving force is rhythmic contractions of vessels • Assisted by Milking & “Thoracic pump” p 811

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7. Lymph Nodes • In-line filters that cleanse the lymph as it passes through • Reticular fibers act as a filter and delay microbes & debris • Macrophages & reticular cells remove about 99% of impurities from lymph p 817

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9. Lymphatic Cells • Natural killer (NK) = lymphocytes that attack & destroy bacteria, transplanted cells, & host cells that are cancerous or viral-infected • Provide immune surveillance • T lymphocytes= mature in thymus & provide cell-mediated immunity • B lymphocytes = mature in bone marrow & provide antibody-mediated immunity

10. Lymphatic Cells • Macrophages = develop from monocytes into large highly phagocytic cells that destroy foreign matter and dead tissues & cells • Act as antigen-presenting cells (APCs) by breaking down foreign matter & displaying parts of it on their cell membrane

11. Lymphatic Cells • Dendritic cells = APCs that engulf foreign matter by endocytosis • Located in epidermis (Langerhans cells), mucous membranes, & lymphatic organs • Reticular cells = act as APCs in thymus • Form blood-thymus barrier that isolates lymphocytes from blood-borne antigens • Produce hormones that promote development & actions of T cells

12. Lymphatic Tissues • Lymphatic Nodules = dense masses of lymphocytes & macrophages • Some appear temporarily to fight infections • Permanent nodules are found in; • Lymph nodes • Tonsils • Appendix • Ileum of Sm. Intestine (Peyer’s Patches)

13. Red Bone Marrow • Source of all blood cells which enter the blood through sinusoids • Site where • B lymphocytes mature p 814

14. Thymus • Site where T lymphocytes mature • Shrinks to small size in adults • Secretes hormones that stimulate development and activities of T lymphocytes p 815

15. Tonsils. • Patches of lymphatic tissue that guard entrances to the pharynx • Surface has deep pits called crypts that help trap foreign materials p 819

16. Spleen: • Largest lymphatic organ • Acts as in-line filter for blood, with reticular fibers as filter and macrophages to ingest microbes & foreign material • “Erythrocyte graveyard” where worn out RBCs are phagocytized by macrophages p 819

17. Nonspecific Defenses • Protection against a wide range of pathogens • Pathogens = anything capable of causing disease • Bacteria • Viruses • Toxic chemicals • Radiation

18. Nonspecific Defenses • External Barriers • Leukocytes & Macrophages • Immunological Surveillance • Interferons • Complement System • Inflammatory Response • Fever

19. External Barriers • Skin • Mucous Membranes • Secretions; • Tears, saliva, urine, vaginal secretions, perspiration • Lysozymes = antibacterial enzymes that breakdown cell walls • Stomach acid

20. Leukocytes & Macrophages • Neutrophils • Phagocytosis, plus • Lysozymes release enzymes that trigger the respiratory burst, which produces; • Superoxide (O2-) • Hydrogen peroxide (H2O2) • Hypochlorite (HClO) • All highly toxic, so form a killing zone, that kills many bacteria & neutrophils

21. Eosinophils • Phagocytosis • Release toxic chemicals • Particularly effective against allergens & parasites • Basophils • Secrete histamine (vasodilator) • Secrete heparin (anticoagulant) • Stimulated by Eosinophils

22. Monocytes • Leave blood and become macrophages • Wandering (Free) macrophages • Fixed macrophages • Includes; • Dendritic cells • Microglia • Alveolar macrophages • Hepatic macrophages (Kuppfer’s cells)

23. Interferons • Small proteins • Released from viral-infected cells & bind to receptors on surface of nearby cells causing them to make antiviral proteins that prevent viral replication, thereby protecting those cells • Act as cell to cell signals to stimulate activities of macrophages and NK cells

24. Complement System • Group of 30 or more proteins • Important role in both Specific and Nonspecific defenses p 823

25. Membrane Attack Complex p 824

26. Immune SurveillanceNatural Killer (NK) Cellspatrol body looking to find & destroy bacteria, transplanted cells, viral-infected cells, & cancer cells. p 824

27. Inflammation • Inflammation is a local defensive response to injury, like trauma or infection • Purposes; • Limit spread of pathogens & eventually destroy them • Remove debris of damaged tissue • Start tissue repair • Words ending in itis denote inflammation of that tissue (arthritis, dermatitis, etc) • Signs = heat, redness, swelling, pain

28. Inflammation • Vasodilation triggered by histamine & other chemicals released from basophils, mast cells & damaged cells (flow=heat, redness) • These chemicals also cause Increased Blood Vessel Permeability as intercellular clefts widen & allow increased filtration of; • Fluids (swelling) • Leukocytes • Proteins (complement, antibodies, clotting factors)

29. Neutrophil Behavior • Margination = loose adhesion to vessel wall • Diapedesis = crawl thru gaps between cells • Chemotaxis = move toward chemical signals from damaged cells • Phagocytosis = engulf and digest foreign cells & molecules p 826

30. Neutrophils release signaling molecules to attract more phagocytes (neutrophils & macrophages) through chemotaxis • Macrophages engulf & destroy pathogens, and casualties, like tissue cells & neutrophils • Macrophages secrete colony-stimulating factors, that trigger increased production of more leukocytes (reinforcements)

31. What remains is Pus which is the dead cells, tissue debris & fluid that are eventually absorbed • Pain receptors are stimulated by; • Direct injury • Pressure from edema • Chemicals released by damaged cells (like prostaglandins & bradykinin) and bacterial toxins

32. Fever • Fever is an abnormal increase in body temp due to hypothalamus raising the set point for body temp. • Pyrogen (fever-causing agent) = interleukin-1, that triggers hypothalamus release of prostaglandin E (PGE) which raises set point for temp p 827

33. Specific Immunity • Specific immunity is directed at • one and only one specific pathogen • An initial exposure to a pathogen will create a memory • When exposed again to the same pathogen the body reacts so quickly that there is no noticeable illness.

34. Specific Immunity • Cellular (cell-mediated) immunity = lymphocytes directly attack & destroy foreign cells or diseased host cells where • Pathogen is inside human cells • Intracellular Viruses, Bacteria, • Protozoans, & Yeast • Cells of Transplanted Tissue & Cancer Cells

35. Specific Immunity • Humoral (antibody-mediated) immunity = antibodies tag or mark the pathogen for destruction by other mechanisms • Indirect attack by antibodies, • instead of immune cells directly • Extracellular Viruses, Bacteria, • Protozoans, & Yeast • Molecular (noncellular) pathogens • like, toxins, venoms and allergens

36. Antigens • Antigen = any molecule that triggers an immune response, normally proteins, polysaccharides, glycoproteins, & glycolipids • Antigenic Determinant Sites (epitopes) • = portions of the exposed surface of the antigen that actually make it an antigen, (trigger an immune response) • = sites where antibodies bind • Immune system must distinguish between; • Self vs. Nonself molecules

37. Haptens • Too small to be an antigen • Bind host macromolecule = then antigenic • Second exposure may not require binding • Include many allergens; • Cosmetics • Detergents • Industrial chemicals • Poison ivy • Animal dander

38. T Lymphocytes (T Cells) • “Born” in bone marrow, then to thymus where they become immunocompetent, meaning they get receptors on their surface for one antigen • Must pass a test to be sure they can recognize foreign antigens, but not attack self-antigens (only 2% pass) • Graduation = multiple & form clones of identical T cells that recognize that one specific antigen, then leave thymus as naive T lymphocytes

39. B Lymphocytes (B Cells) • Born and become immunocompetent in bone marrow (develop receptors on surface for specific antigen) • Must pass same test to be sure they will tolerate “self” cells and recognize foreign or “nonself” cells • Then multiple & form clones of identical B cells that recognize that one specific antigen and leave marrow as naive B lymphcytes

40. Major Histocompatiblity Complex (MHC) Proteins • Complex = genes are on chromosome #6 • Glycoproteins on surface of cells (except RBC), about 200,000 per cell • Unique to each person • Shaped like hotdog bun, they pick up antigens from inside the cell, migrate to the surface & hold them in their central groove • Class I on all cells (except RBC)

41. . Acting like an information relay, the MHC Class I (MHC-I) molecules retrieve bits and pieces of the proteins from inside the cell and display them on the cell surface. • MHC complexes essentially give • a read out of what's inside the cell

42. Antigen-Presenting Cells (APCs) • Phagocytosis of antigen • Break down into molecular fragments • Display (present) the epitopes on its MHC proteins • Class II MHC proteins on APCs only • macrophages, B cells, reticular & dendritic cells p 831

43. Cellular Immunity • Cytotoxic T (TC) cells = carry out direct attack on enemy cells • Also known as T8, CD8, or CD8+ cells because they have a surface glycoprotein for binding to other cells called CD8 • Helper T (TH) cells = promote actions of TC cells and play a key role in humoral immunity & nonspecific defenses • Also known as T4, CD4, or CD4+ cells due to CD4 glycoprotein

44. Cellular Immunity • Memory T (TM) cells = descended from cytotoxic T cells and provide memory of initial exposure to an antigen, providing for a very rapid response if exposed again

45. Immunity as a Three Act Play • Act One = Recognition • Act Two = Attack • Act Three = Memory • OR • “the three Rs of immunity” • Recognize • React • Remember

46. Recognition • Naive T cells inspect cells MHC proteins & antigens • Self antigens = okay • Viral proteins, abnormal antigens made by cancer cells = Respond • Like a sign that says, • “I’m infected” or • “I’m a cancer cell” • TC cells only MHC-I • TH cells only MHC-II p 833

47. T Cell Activation • Receptor on T cell surface must match foreign antigen on MHC • = binds MHC • Second binding called costimulation required for activation • Triggers clonal selection, repeated mitosis which produces a clone of T cells with receptors for same epitope p 833

48. T Cell Attack • Helper T cells secrete interleukins that; • Attract neutrophils & natural killer cells • Atrract macrophages & stimulate phagocytosis • Stimulate T and B cell mitosis & maturation p 833

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50. T Cell Attack • Cytotoxic T cells attack & destroy cell with a release of chemicals • For example, Perforin creates pores in cell membrane that kill it • Recall the Membrane Attack Complex p 833