Comprehensive Overview of the Lymphatic System and Immune Defenses

1. Chapter 12 The Lymphatic System & Body Defenses

2. Outline • Functions of the Lymphatic System • Definitions • Primary & Secondary Lymphatic Organs • First Line of Defense- Innate Immunity • Barriers to Entry • Second Line of Defense- Innate Immunity • Nonspecific Defenses • Third Line of Defense- Adaptive Immunity • Specific Defenses: The Immune Response • B-lymphocytes: Antibody-Mediated Immunity • T-lymphocytes: Cell-Mediated Immunity • Active vs. Passive Immunity

3. Functions of The Lymphatic System • Drains excess interstitial fluid (lymph) and puts it back into the blood • Formation of lymph • Refer back to capillary exchange in Chap. 21 • Flow of lymph • Skeletal muscle pump • Respiratory pump • Transports dietary lipids • Lacteals in GI tract • Carries out immune responses

4. Lymphatic System

5. Entrance of right lymphatic duct into right subclavian vein Regional lymph nodes: Cervical nodes Internal jugular vein Thoracic duct entry into left subclavian vein Figure 12.3 Distribution of lymphatic vessels and lymph nodes. Axillary nodes Thoracic duct Aorta Spleen Cisterna chyli (receives lymph drainage from digestive organs) Inguinal nodes Lymphatics KEY: Drained by the right lymphatic duct Drained by the thoracic duct

6. Tissue fluid Tissue cell Lymphatic capillary Figure 12.2a Special structural features of lymphatic capillaries. Blood capillaries Arteriole Venule (a)

7. Fibroblast in loose connective tissue Flaplike minivalve Figure 12.2b Special structural features of lymphatic capillaries. Filaments anchored to connective tissue Endothelial cell (b)

8. Lymph Node Germinal center in follicle Capsule Afferent lymphatic vessels Subcapsular sinus Figure 12.4 Structure of a lymph node. Trabecula Afferent lymphatic vessels Efferent lymphatic vessels Hilum Cortex Medullary sinus Follicle Medullary cord

9. Functions of The Lymphatic System (Cont.) • Carries out immune responses • function to defend the body against all attackers including bacteria, viruses, and cancer cells. • protects “self” from “non-self” • Immunity is the ability to react to antigens so that the body remains free of disease • Disease is a state of homeostatic imbalance • Disease can be due to infection,failure of the immune system, genetic defects, or autoimmune issues

10. Functions of The Immune System (Cont.) • Definitions • Antigen:Piece or part of a foreign attacker such as a piece of protein or cell membrane. • Antibody:Special protein produced by the immune system to bind specifically to antigens. Antibody shape fits like a glove to the surface shape of the antigen. Helps to remove attacker from the body.

11. Primary Lymphatic Organs • Lymphatic system is network of organs, tissues, cells, and cell products. • Principal cells are the lymphocytes, aided and assisted by neutrophils, macrophages. • Two types: B lymphocytes and T lymphocytes • Primary Lymphatic organs contain large numbers of lymphocytes. • Red Bone Marrow: Source of B & T lymphocytes; B lymphocytes mature here; move to lymph nodes • Thymus Gland: T lymphocytes move here from bone marrow; mature here; move to lymph nodes.

13. Lymphatic Organs

14. Thyroid gland Trachea Right common carotid artery Brachiocephalic veins Superior vena cava Right lung Thymus Left lung Fibrous pericardium Diaphragm (a) Thymus of adolescent

15. Secondary Lymphatic Organs • Secondary Lymphatic Organs: Secondary lymphatic organs are places where lymphocytes encounter and bind with antigens. • Spleen- largest single mass of lymphatic tissue- for immune monitoring of the blood • Lymph nodes • Lymphatic Nodules- not surround by capsule • MALT: Mucosa-associated lymphatic tissue • Tonsils: Lymphatic tissue at back of mouth • Adenoids: Lymphatic tissue at back of nasal passages • Peyer’s patches: Lymphatic tissue in intestines

16. Lymph Node Germinal center in follicle Capsule Afferent lymphatic vessels Subcapsular sinus Figure 12.4 Structure of a lymph node. Trabecula Afferent lymphatic vessels Efferent lymphatic vessels Hilum Cortex Medullary sinus Follicle Medullary cord

17. Lymphatic System

18. The Immune System Figure 12.6 An overview of the body’s defenses. Adaptive (specific) defense mechanisms Innate (nonspecific) defense mechanisms First line of defense Second line of defense Third line of defense • Skin • Mucous membranes • Secretions of skin and mucous membranes • Phagocytic cells • Natural killer cells • Antimicrobial proteins • The inflammatory response • Lymphocytes • Antibodies • Macrophages and other antigen-presenting cells

19. The First Line of Defense • Barriers to Entry • Skin • Layers of dead keratinized cells • Constant sloughing of cells • Sweat glands; low pH, dermicidin • Tears, Saliva, Earwax • Tears, saliva contain lysozyme • Earwax; very sticky traps microbes • Mucous Membranes • Mucus moved by ciliated cells, e.g.respiratory tract • Stomach • Acid in stomach; pH 1-2.

20. The First Line of Defense (Cont.) • Barriers to Entry (Cont.) • Vaginal Acids • Vaginal secretions are acidic, prevent growth • Vomiting, Urination, Defecation • Remove bacteria & toxins from stomach • Constant flushing of urinary tract • Diarrhea-increase outflow of pathogen • Resident Bacteria (vagina, intestinal tract) • Out compete pathogens for nutrients • Secrete compounds to inhibit growth of pathogens

21. The Second Line of Defense: Nonspecific Defenses • Phagocytes Engulf Foreign Cells • Phagocytic cells: white blood cells that surround & engulf invading bacteria • Neutrophils, monocytes, eosinophils • Monocytes become macrophages in tissues

22. 1 2 3 Phagocyte adheres to pathogens. Phagocytosis Phagocyte engulfs the particles, forming a phagosome. Phagosome (phagocytic vesicle) Figure 12.9b Phagocytosis by a macrophage. Lysosome Lysosome fuses with the phagocytic vesicle, forming a phagolysosome. Acid hydrolase enzymes 4 Lysosomal enzymes digest the pathogens or debris, leaving a residual body. 5 Exocytosis of the vesicle removes indigestible and residual material. (b) Events of phagocytosis

23. The Second Line of Defense: Nonspecific Defenses • Natural Killer Cells • A type of lymphocyte that attacks tumor cells & virus-infected cells

24. The Second Line of Defense: Nonspecific Defenses • Inflammatory Reaction. • Tissue damage causes tissue cells and mast cells to release chemical mediators. • Histamine and kinins. • Capillaries dilate and become more permeable. • Skin reddens and becomes warm. • Proteins and fluids escape from capillaries. • Swelling.

26. The Second Line of Defense: Nonspecific Defenses • Inflammatory Reaction. • Swelling stimulates free nerve endings, causing the sensation of pain. • Neutrophils and monocytes migrate to site of injury; engulf pathogens. • Monocytes become macrophages; engulf pathogens; spit out antigens.

28. The Second Line of Defense: Nonspecific Defenses • Inflammatory Reaction Movies 1. Rolling Leukocytes 2. Lymphocyte Homing 3. Chemotaxis of Neutrophils 4. Neutrophil Chase

29. The Second Line of Defense: Nonspecific Defenses • Complement system: Group of proteins in blood that help to destroy pathogens. • Complement proteins are activated when antibodies coat pathogens in the body. • They form membrane attack complex that knocks holes in the membrane of pathogen. • Complement coated pathogens also attract neutrophils and macrophages.

30. 1 2 3 Activated complement proteins form complexes of proteins that create holes in the bacterial cell wall. Water and salts diffuse into the bacterium through the holes. The bacterium swells and eventually bursts. Water and salts Complement proteins Bacterium Cell wall of bacteria Photomicrograph of an intact bacterium A bacterium after lysis by activated complement proteins Figure 9.8

31. The Second Line of Defense: Nonspecific Defenses • Interferons • Viral infected cells secrete proteins called interferons • Interferons stimulate neighboring non-infected cells to produce proteins that interfere with synthesis of viral proteins

32. The actions of alpha and beta interferons Figure 15.7

33. The Second Line of Defense: Nonspecific Defenses • Fever Response • Pyrogens released (from macrophages) increase basal temperature • May aid in preventing some bacterial growth • Stimulates phagocytosis & repair

34. Table 9.1

35. The Third Line of Defense: Specific Defenses-The Immune Response • Specific defenses respond to antigens. • Lymphocytes recognize an antigen due to antigen receptors whose shape allows them to combine with a specific antigen. • Immunity is primarily the result of the action of B lymphocytes and T lymphocytes.

36. The Third Line of Defense: Specific Defenses-The Immune Response (Cont.) • B-lymphocytes and antibody-mediated immunity. • Main end products: Antibodies and memory B-lymphocytes. • Antibodies bind to pathogens; they help complement to work; help neutrophilsand macrophages find and engulf them.

38. Primary response (initial encounter with antigen) Antigen Antigen binding to a receptor on a specific B cell (B cells with non-complementary receptors remain inactive) Proliferation to form a clone Activated B cells Figure 12.12 Clonal selection of a B cell. Plasma cells Memory B cell Secreted antibody molecules Subsequent challenge by same antigen results in more rapid response Secondary response (can be years later) Clone of cells identical to ancestral cells Plasma cells Secreted antibody molecules Memory B cells

39. Structure of most common antibody: IgG

40. Six functions of antibodies (f) Complement Activation Figure 16.6

42. The Third Line of Defense: Specific Defenses-The Immune Response (Cont.) • B-lymphocyte Review • Provide antibody-mediated immunity against bacteria • Produced and mature in bone marrow. • Reside in spleen and lymph nodes • Directly recognize antigen and then undergo clonal selection • Clonal expansion produces antibody-secreting plasma cells and memory B cells • Antibodies circulate in blood and lymph

43. The Third Line of Defense: Specific Defenses-The Immune Response (Cont.) • T-lymphocytes and cell-mediated immunity. • Two Types of T-cells: • CD4 T-cells • become Helper T-cells & Memory T-cells • CD8 T-cells • become Cytotoxic T-cells

44. T Cells: Cell-Mediated Immunity Helper T-cells Secrete cytokines, which stimulate other immune system cells Play a key role in directing the immune response Are target of HIV infection Cytotoxic T-cells Directly attack and destroy abnormal (tumor or viral-infected) cells and foreign cells Memory T-cells Reactivate during later exposures

45. T Cells: Cell-Mediated Immunity T-cells must be presented with antigen in conjunction with Major Histocompatibility Complex (MHC) protein by antigen-presenting cells (APCs) APCs include Macrophages B cells

46. Major histocompatibility complex protein (MHC) Antigen Antigen-Presenting Cell (APC): Macrophage Pathogen 1 The macrophage engulfs a pathogen. Lysosome 2 Vesicle with MHC molecules Lysosomes partially digest the pathogen. 3 A vesicle containing MHC molecules binds to the digestive vesicle. 4 The MHC molecules and a fragment of the antigen form an antigen-MHC complex. 5 The antigen-MHC complex is displayed on the surface of the cell when the vesicle fuses with the cell membrane and releases its digestive products. Antigen-MHC complex Figure 9.12

47. Antigen “Presented” antigen Cell-mediated immunity (attack on infected cells) Cytotoxic (killer) T cell Figure 12.17 T cell activation and interactions with other cells of the immune response. T cell antigen receptor Helper T cell Dendritic cell Cytokines Humoral immunity (secretion of antibodies by plasma cells) Self- protein Antigen processing B cell Cytokines

48. MHC molecule CD4 T-cell: Activation to Helper T-cell Antigen-presenting cell (APC) CD4 receptor Antigen fragment Inactive helper-T cell Activation Memory T cells Clonal expansion These Helper T-cells help both B-cell & T-cell responses Cytokine production Figure 9.13

49. MHC molecule Virus infected Antigen-presenting cell (APC) CD8 T-cell: Activation to Cytotoxic T-cell CD8 receptor Antigen fragment Inactive cytotoxic T cell Activation Memory T cells Clonal expansion Attack on target cell Figure 9.14

50. Cytotoxic T cell Cytotoxic T-cell killing a target cell Target cell a) Cytotoxic T cells (blue) attaching to a target cell (pink). Cytotoxic T cell Vesicle Perforin Granzyme Cytotoxic T cell membrane Intercellular space 3 Completed pore; granzyme passing through 2 1 Perforin pore partially assembled Intact target cell membrane Target cell b) How cytotoxic T cells kill a target cell. Figure 9.15