Lymphatic System

1. Lymphatic System • Organs, vessels and a fluid called lymph • Almost similar to interstitial fluid • Organs involved • red bone marrow • thymus • spleen • lymph nodes • diffused lymphatic tissue • tonsils, peyers patches Shina Alagia

2. Functions of the Lymphatic System • Draining excess interstitial fluid & plasma proteins from tissue spaces • Transporting dietary lipids & vitamins from GI tract to the blood • Facilitating immune responses • recognize microbes or abnormal cells & responding by killing them directly or secreting agents that cause their destruction Shina Alagia

3. Lymphatic Vessels & Circulation • Capillaries that begin asclosed-ended tubes foundin spaces between cells • Combine to form lymphaticvessels • resemble veins with thinwalls & more valves • Fluid flows through lymph nodes towards large veins above the heart (mostly subclavian vein) Shina Alagia

4. Lymphatic Capillaries • Found throughout thebody except in Avasculartissue (cartilage, epidermis& cornea) • Structure is designed to lettissue fluid in but not out • overlapping endothelial cells open when tissue pressure is high (one-way valve) • In GI tract, known as lacteals Shina Alagia

5. Lymph Trunks & Ducts • Vessels unite to form trunks & thoracic ducts • Right side head, arm & chest empty into right lymphatic duct and rest of body empties into thoracic duct • Lymph is dumped directly into left & right subclavian veins Shina Alagia

6. Formation & Flow of Lymph • Fluid & proteins escaping from vascular capillaries is collected by lymphatic capillaries & returned to the blood • Respiratory & muscular pumps promote flow of lymphatic fluid • Lymphatic vessels empty into subclavian veins Shina Alagia

7. Lymphatic Organs & Tissues • Widely distributed throughout the body • Primary lymphatic organs • provide environment for stem cells to divide & mature into B and T lymphocytes • thymus is site where pre-T cells from red marrow mature • Secondary lymphatic organs & tissues • site where most immune responses occur • lymph nodes, spleen & lymphatic nodules Shina Alagia

8. Thymus Gland • Large organ in infants (70 g) but atrophied as adult (3 g) • 2 lobed organ located in mediastinum Shina Alagia

9. Lymph Nodes • Bean-shaped organs, located along lymphatic vessels • scattered throughout body but concentrated near mammary glands, axillae & groin Shina Alagia

10. Spleen • 5 inch organ between stomach & diaphragm • consists of white pulp and red pulp • white is lymphatic tissue (lymphocytes & macrophages) around branches of splenic artery • red pulp is venous sinuses filled with blood & splenic tissue (splenic cords) Shina Alagia

11. Lymphatic Nodules • Concentrations of lymphatic tissue not surrounded by a capsule • mucosa-associated lymphoid tissue (MALT) • Peyer’s patches in the ileum of the small intestine • Tonsils form ring at top of throat • adenoids (pharyngeal tonsil) • palatine tonsils (on each side wall) • lingual tonsil in the back of the tongue Shina Alagia

12. Metastasis Through Lymphatic System • Characteristic of malignant tumors • Spread of disease from one organ to another • cancer cells travel via blood or lymphatic system • cells establish new tumors where lodge • Secondary tumor sites can be predicted by direction of lymphatic flow from primary site • Cancerous lymph nodes are firm, enlarged and nontender -- infected lymph nodes are not firm and are very tender Shina Alagia

13. IMMUNE SYSTEM Shina Alagia

14. Types : Non-specific resistance or innate immunity and specific resistance or acquired immunity Shina Alagia

15. Innate immunity • Protection against wide variety of pathogens & foreign substances • Include external mechanical & chemical barriers and internal nonspecific defenses/innate immunity • antimicrobial proteins • natural killer cells & phagocytes Shina Alagia

16. Skin & Mucous Membranes • Mechanical protection • skin (epidermis) closely packed, keratinized cells • shedding helps remove microbes • mucous membrane secretes viscous mucous • cilia & mucus trap & move microbes toward throat • washing action of tears, urine and saliva • Chemical protection • sebum inhibits growth bacteria & fungus • perspiration lysozymes breakdown bacterial cells • acidic pH of gastric juice and vaginal secretions destroys bacteria Shina Alagia

17. Innate immunity: Internal defenses • Anti-microbial proteins • Cells that seek out and destroy microbes(NK cells and phagocytes) • Response initiated: Inflammatory response causing fever Shina Alagia

18. Anti-microbial proteins: Ineterferons • Antimicrobial proteins discourage microbial growth • Interferons • produced by virally infected nucleated cells • Interferons diffuse to neighboring cells to induce synthesis of antiviral proteins • Virus may enter cells but can’t multiply Shina Alagia

19. Complement proteins • Defensive system of plasma proteins that attack and destroy microbes • System activated by 2 different pathways • Produce same result • inflammation: dilation of arterioles, release of histamine & increased permeability of capillaries • opsonization: protein binds to microbe making it easier to phagocytize • cytolysis: a complex of several proteins can form holes in microbe membranes causing leakiness and cell rupture Shina Alagia

20. opsonization Shina Alagia

21. NK cells NK cells • Recognize cell surface markers on foreign cells. Also recognize cancer cells (altered MHC) • Destroy cells with foreign antigens(surface proteins) (recognize-adhere-release perforin-punch hole in attacked cell) • Important in keeping cancer cells in check Shina Alagia

22. How Natural Killer Cells Kill Cellular Targets Shina Alagia

23. Phagocytes • Cells that ultimately take over to provide isolation,destruction and clean up of pathogen and its products. • Also helps in acquired immunity • Closely associated with inflammation Shina Alagia

24. Types of Phagocytes Shina Alagia

25. Inflammation • Damaged cell initiates • Signs of inflammation • redness • heat • swelling • pain • Function is to trap microbes, toxins & begin tissue repair Shina Alagia

26. Stages of inflammatory response • Localized vasodilation • Localized edema • Isolation of invader • Phagocyte migration • Phagocytosis Shina Alagia

27. Localized Vasodilation • Vasodilation & increased permeability of vessels • caused by histamine from mast cells(basophils) • occurs within minutes producing heat, redness & edema • blood-clotting factors leak into tissues trapping microbes Shina Alagia

28. Localized Edema • As clotting factors deposit into tissue, the pressure balance between tissue fluid and plasma get altered. • Huge quantities of nutrients and fluid get released into the interstitial space Shina Alagia

29. Isolation of Pathogen • Clotting proteins now present in ISF initiate cascade • Resulting fibrin clots surround the pathogen and prevents or slows down its escape - Streptococcus example of exception Shina Alagia

30. Phagocyte migration • Phagocyte migration within an hour, neutrophils and then monocytes arrive and leave blood stream by -Margination: Phagocytes move slowly over CAMs (selectin) protruding out of capillary wall - Diapedesis: Phagocytes squeeze out of capillaries into interstitial space Shina Alagia

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32. Phagocytosis • Microbes and clot eaten and digested by phagocytes • Pus: Dead phagocytes and tissue debris Shina Alagia

33. Fever • Abnormally high body temperature that occurs because the hypothalamic thermostat is reset • Occurs during infection & inflammation • bacterial toxins trigger release of fever-causing cytokines such as interleukin-1 • Benefits • intensifies effects of interferons, inhibits bacterial growth, speeds up tissue repair Shina Alagia

34. Specific Resistance: Acquired Immunity • Differs from innate immunity • specificity----recognize self & non-self • memory----2nd encounter produces even more vigorous response • Carried out by lymphocytes B and T cells. Phagocytes help Shina Alagia

35. Chemical Nature of Antigens • Molecules or bits of foreign material • entire microbes, parts of microbes, bacterial toxins, pollen, transplanted organs, incompatible blood cells • small part of antigen that triggersthe immune response is epitope Shina Alagia

36. Major Histocompatibility Complex Antigens • All our cells have unique surface markers (1000s molecules) • MHC-I molecules are built into cell membrane of all cells except red blood cells • MHC-II markers seen only on membrane of antigen presenting cells (macrophages, B cells, thymus cells) • Function Shina Alagia

37. Antigen Processing • B and T cells must recognize a foreign antigen before beginning their immune response • B cells can bind to antigen in extracellular fluid • T cells can only recognize fragments of antigens that have been processed and presented to them as part of a MHC molecule Shina Alagia

38. Processing of Bacterial Antigens • Foreign antigen in body fluid is phagocytized by APC • Mostly macrophage • Antigen is digested and fragments are bound to MHC-II molecules stuck into antigen presenting cell membrane Shina Alagia

39. Processing of Viral Antigens • Foreign proteins produced within a body cell --- viral or cancerous • Fragments of weird proteins become part of MHC-I molecules displayed at surface of cell Shina Alagia

40. Cytokines • Small protein hormones involved in immune responses • secreted by lymphocytes and antigen presenting cells Shina Alagia

41. Cell-Mediated Immunity (CMI Response) • Begins with activation of T cell by a specific antigen • Result is T cell capable of an immune attack • elimination of the intruder by a direct attack Shina Alagia

42. Types of Mature T Cells • Helper T cells • Cytotoxic (killer) T cells • Memory T cells • Suppressor T cells Shina Alagia

43. Helper T Cells • Also known as CD4cells or TH cells • Recognize antigen fragments associated with MHC-II molecules & activated by APCs • Function is to costimulate all other lymphocytes • secrete cytokines (interleukin-2) Shina Alagia

44. Cytotoxic T Cells • Known as CD8 or Tc cells • Recognize antigen fragments associated with MHC-I molecules • cells infected with virus • tumor cells • Co-stimulation required by cytokine from helper T cell Shina Alagia

45. Memory T Cells • T cells from a clone that did not turn into cytotoxic T cell during a cell-mediated response • Available for swift response if a 2nd exposure should occur Shina Alagia

46. Activation, Proliferation & Differentiation of Helper T(CD4) Cells • CD4 cell binds to foreign antigen fragment associated with MHC-II on APC • CD4 cell Proliferates & differentiates into population (clone) of CD4 cells and long-lived memory CD4 cells Shina Alagia

47. Activation, Proliferation & Differentiation of Cytotoxic T(CD8) Cells • CD8 cell binds to foreign antigen fragment part of MHC-I • Costimulation from helper T cell • Proliferates & differentiates into population (clone) of Tc/CD8 cells and memory Tc cells Shina Alagia

48. Killing by Tc cell • Tc cells migrate to site of infection or tumor formation • Recognize, attach & attack • secrete perforin that punches holes in target cell Shina Alagia

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50. Antibody-Mediated Immunity (AMI Response) • Millions of different B cells that can recognize different antigens and respond • B cells sit still and let antigens be brought to them • Once activated, differentiate into plasma cells that secrete antibodies • Antibodies circulate in lymph and blood • combines with antigen similarly to key fits a specific lock Shina Alagia