Chapter 22 The Lymphatic and Immune Systems

1. Chapter 22The Lymphatic and Immune Systems

2. The Lymphatic System • Basic organization • Lymph fluid in lymph vessels • Structures, organs w/ lymph tissue, red bone marrow • Functions • drain interstitial fluid and proteins • transport dietary fats • protect against invasion • resistance - fight off disease • nonspecific resistance - general protection against disease • immunity - specific protection • susceptibility - lack of resistance

3. Lymphatic Vessels • Lymphatic capillaries • Blind ended vessels between cells, larger than blood capillaries • Not in avascular tissues, CNS, splenic pulp, bone marrow

4. Lymphatic Capillaries • Structure/Function regulates fluid flow • Anchoring filaments - from lymphatic endothelium attach to surrounding tissues • Endothelial cells overlap • high hydrostatic fluid pressure separates cells, fluid into caps • hydrostatic fluid pressure in cap prevents fluid movement out

5. The Lymphatic System • Lymph flow follows venous circulation • Lymph vessels have same organization as vascular tree • Smaller vessels drain into larger vessels

6. The Lymphatic System (cont.) • Lymph returns to venous blood through R,L lymphatic ducts • Enter at internal jugular and subclavian veins

7. The Lymphatic System • Lymph ducts • Right lymphatic duct • about ½ inch long • drains lymph from upper right side of body • Thoracic (left) duct • main collecting duct of lymph system • 38-45 cm long • drains 75% of body • begins as a dilation known as cisterna chyli located anterior to lumbar disk #2

8. The Lymphatic System Flow of Lymph More fluid out of blood capillaries by filtration than returns by absorption - Starling’s Law 3Ll day of lymph fluid Proteins from blood returned by lymphatics Lymph flow by muscle pump, respiratory pump, valves

9. Lymphatic Tissue - General • 1ºlymphatic organs - site of B and T cell production • bone marrow - produces B cells, pre-T cells • thymus gland - migrate to thymus gland • 2 º lymphatic organs • site of most immune responses • lymph nodes, spleen – surrounded by connective tissue capsule • lymphatic nodules – not surrounded by capsule

10. Thymus Gland • Thymus Gland • Between sternum, heart • 2 lobes • Atrophies w/ age • Structure/Function • Outer cortex • pre-T cells migrate to thymus • proliferation • Maturation • dendritic cells • macrophages • Inner medulla – more of the same

11. Lymph Nodes • Lymph Node Structure • oval, bean shaped structures along lymph vessels • may be deep or superficial scattered throughout body • concentrated in mammary glands, axillae, groin • filter lymph fluid

12. Lymph Nodes • Connective tissue capsule w/ trabeculae extending into cortex • Stroma -supportive network of reticular fibers, fibroblasts

13. Lymph Nodes Cortex Medulla • Parenchyma • Outer cortex - lymphatic nodules • inner germinal center site of B-cell proliferation • Site of B-cell maturation and plasma cell formation • Inner medulla - medullary cords of lymphycytes, macrophages, plasma cells

14. Lymphatic Tissue - Specific • Node fluid flow • Enter cortex through afferent vessels • Filter, remove damaged cells, microorganisms, foreign substances by reticular fibers • macrophages phagocytize some, lymphocytes destroy others • exit medulla from hilus by efferent vessels • Metastasis • cancer cells from tumor • trapped in lymph nodes

15. Lymph Nodes • Histology

16. Lymphatic Tissue - Specific • Spleen • largest mass of lymphoid tissue in body • Left side of body between stomach/diaphragm • thick fibrous capsule w/ artery, vein, efferent lymph vessel • organ function: • immune function • removal of worn out, damaged RBC’s • storage of platelets • production of RBC’s during fetal life

17. Lymphatic Tissue - Specific • Lymphatic nodules (tonsils) • oval-shaped non-encapsulated groups of lymphatic tissue • scattered in mucous membranes, GI tract, respiratory tract, urinary tract, reproductive tract • protect against invasion of inhaled or ingested foreign substances

18. Nonspecific Resistance to Disease • Summarized in Table 22.1 • Surface Barrier – Skin and mucosa • Internal Defenses • Antimicrobial proteins • Natural killer cells and Phagocytosis • Inflammation • Fever

19. Nonspecific Resistance to Disease • Surface Barrier – Skin and mucosa • Mechanical protection • intact epidermis • mucous membranes • line body cavities, mucus prevents drying, traps foreign bodies • nose hairs, respiratory tract cilia • lacrimal apparatus • saliva - dilute microbes, wash them from teeth surface • urine flow, vaginal secretions – flow and pH help kill microorganisms • defecation and vomiting - expel microbes

20. Nonspecific Resistance to Disease • Surface Barrier – Skin and mucosa • Chemical protection • Skin • sebum (unsaturated FA’s) forms layer, prevents bacterial growth • perspiration has fatty acids, lo pH • lysozyme - enzyme breaks down bacterial walls • gastric juice - stomach nearly sterile due to lo pH, 2ish

21. Nonspecific Resistance to Disease • Antimicrobial substances produced against pathogens that penetrate 1º defense • Interferons • Released from infected cells • Stimulate production of antiviral proteins from neighboring cells • Complement system • 20 plasma and cell membrane proteins • Function to complement (enhance) certain immune, allergic and inflammatory systems • Transferrins – inhabit bacterial growth by binding iron

22. Nonspecific Resistance to Disease • Natural killer (NK) cells and phagocytosis • NK • nonspecific killers that respond before immune system is activated • ability to kill virus infected body cells and some tumor cells by poking holes in cells and stimulating cell death

23. Nonspecific Resistance to Disease • Natural killer (NK) cells and phagocytosis • Phagocytosis • ingestion of microbes or foreign material by phagocytes • 2 kinds of phagocytosis - neutrophils and macrophages • steps • chemotaxis • adherence • ingestion • digestion • killing

24. Nonspecific Resistance to Disease • Inflammation • 4 symptoms: • Redness • Pain • Heat • Swelling • 3 steps in process • Vasodilation/increased vessel permeability • Phagocyte migration • Tissue repair

25. Nonspecific Resistance to Disease • Step 1. Vasodilation and increased vessel permeability • Release of factors from leukocytes stimulate vascular changes • Histamine, kinins, prostaglandins, leukotrienes • Vasodilate, increase permeability, stimulate emigration and chemotaxis • Cause heat, redness and swelling

26. Nonspecific Resistance to Disease • Step 2. Phagocyte migration • leukocytosis-inducing factors • chemotaxis • Emigration • neutrophils - rapid • monocytes - slower

27. Nonspecific Resistance to Disease • Step 3. Tissue repair • Tissue regrowth and repair of damage • Pus • dead phagocytes, damaged tissue • if too numerous for easy removal may form abscess

28. Nonspecific Resistance to Disease • Fever • increase effects of antimicrobial substances • inhibits some microbes • increase rate of body repair

29. Nonspecific Resistance to Disease • Surface Barrier – Skin and mucosa • Internal Defenses • Antimicrobial proteins • Natural killer cells and Phagocytosis • Inflammation • Fever

30. Immunity • Immunity • ability of body to defend itself against specific invaders • specificity and memory differentiate this from non-specific system • two types • Humoral (antibody mediated) immunity • Cellular (cell mediated) immunity

31. Antigens • Antigen - substances that provoke immune response • Epitope • antigen part that triggers immune response • most antigens have many epitopes

32. Antigens (cont.) • Chemical nature of antigens • large, complex molecules - mostly proteins, nucleo-, lipo-, glyco- • smaller substances may be incomplete antigens - hapten • react with antibodies but not cause immune response • poison ivy toxin • usually foreign substances

33. Antigens (cont.) • Antigen receptor diversity • >1 billion different epitopes recognized by body • diversity - genetic recombination, shuffle, reorganize different genes • Major Histocompatibility Complex antigens (MHC) • unique to each individuals cells, help in identifying foreign bodies • 2 classes of MHC antigens • class I MHC - all body cells but RBC's • class II MHC - only on antigen presenting cells (APC’s), thymus cells, activated T cells

34. Pathways of Antigen Processing • For immune response to occur, B and T cells must recognize foreign antigen • B cells can recognize, bind to antigens in ECF, blood, lymph • T cells only recognize antigen protein fragments presented w/ MHC self-antigens - good/bad proteins

35. Pathways of Antigen Processing • During protein digestion and production in cell, small peptides used to stabilize MHC proteins • if peptides from normal body cells, no response • if peptides from antigens • T cells recognize them • immune response! • preparation of foreign antigen for cell surface known as processing and presenting of antigen • Antigen Presenting Cell's (APC’s) • macrophages, activated B cells, dendritic cells • process exogenous antigens present them w/ MHC class II molecules to T cells

36. Pathways of Antigen Processing • Processing of exogenous antigen – produced outside cell • phagocytosis/endocytosis • digestion • vesicles fuse, peptide fragments bind to MHC-II’s • exocytosis to membrane • move to lymphatic tissue, present antigen to T-cells

37. Pathways of Antigen Processing • Processing of endogenous antigen – produced within body cells • viral proteins from viral infection of cell • produced, incorporated into MHC-I molecules during normal cell growth • put on surface of cell • identifies cell as infected, signals that cell needs help

38. T and B cell formation • Both B and T cells produced from stem cells in bone marrow • Development of immunocompetence occurs in different sites • B cells complete maturation in Bone marrow • Pre-T cells move to Thymus - complete maturation in thymus

39. Immunity - General • Before mature cells leave home: • both types acquire surface proteins - antigen receptors • T cells exit as CD4+ or CD8+ cells w/ different functions • CD4+ cells become helper T cells

40. Immunity - General • 2 Types of immune responses • Cell-mediated immunity • Antibody-mediated immunity • General • Initial activation of Helper T cells • Helper T cells aid both types of immune responses • Pathogens often activate both types of responses

41. Immunity - General • Cell-mediated immune (CMI) responses • CD8+ cells change into killer T cells with aid from Helper T cells • directly attack infecting antigen • Effective against: • intracellular pathogens • some cancer cells • foreign tissue transplants

42. Immunity - General • Antibody-mediated immune (AMI) responses • B cells transform into plasma cells with aid of Helper T cells • synthesize, secrete specific proteins (antibodies or immunoglobulins) • antibodies bind and inactivate antigens • Effective against: • antigens in body fluids • EC pathogens (bacteria)

43. Cell -Mediated Immunity • Basic steps • Recognition of APC antigen by T cell receptors (TCR’s) – first signal • Costimulation for activation • Proliferation and differentiation • Clone effector cells capable of recognizing initial activator (antigen) • Elimination of intruder

44. Cell-Mediated Immunity (cont.) • T cell recognition, proliferation, differentiation • APC presents antigen • TC’s recognize, bind foreign antigen - millions of T cells each specific for 1 antigen • Need co-stimulator • 20 known, cytokines, interleukins, needed for full immune response • prevent false activation?

45. Cell-Mediated Immunity (cont.) • T cell enlarges, makes clones capable of recognizing antigen

46. Cell-Mediated Immunity (cont.) • Clones • Helper T (TH) cells - CD4+ • after co-stimulation helpers secrete co-stimulators • co-stimulates helper T cells, cytotoxic T cells, B cells • Cytotoxic T (TC) cells - CD8+ • recognize antigen fragments associated w/ MHC-I molecules, some tumor cells and tissue transplant cells • become cytolytic need stimulators from helper T cells

47. Cell-Mediated Immunity (cont.) • Tc elimination of invaders • Migrate from lymph to infection site • Recognize, attach to target antigen/cell • Kill invaders • Detach, seek out another invader w/ proper antigen

48. Cell-Mediated Immunity (cont.) • More Clones • Suppressor T (TS) cells • produced with other clones • downregulate immune system by producing other cytokines • Memory T (TM) cells • recognize original invading antigen • second response rapid due to large numbers of TM cells present

49. Antibody-Mediated Immunity • Body contains millions of B cells • located in lymphoid tissue • each responds to specific antigen • Become activated in presence of foreign antigen • unprocessed antigen weak response • need to process antigen for stronger response

50. Antibody-Mediated Immunity • Unprocessed antigen taken into cell • incorporated into MHC-II self-antigen • activates helper T cells • Costimulation - production of cytokines