The Lymphatic System and Immunity

1. The Lymphatic System and Immunity Lymph, lymph capillaries, ducts, nodes and other lymphoid organs

2. Functions • Filter and absorb excess tissue fluid and return it back into circulation • Transport of dietary lipids via lacteals • Carry out immune responses

3. Lymph and Lymph Capillaries • Lymph - clear, watery fluid resembling interstitial fluid • Lymph capillaries - begin as blind-ended capillaries consisting of simple squamous epithelium allowing one-way movement of fluid

4. Lymph Vessels • Formed from merging capillaries • Have thin walls and posses valves • Thoracic duct originates as cisterna chyli draining abdomen, extremities, and left side of body • Right lymphatic duct - drains lymph from the right arm and upper right side of body

6. Elephantiasis • Blockage of the lymphatic system by parasitic worms • Transmitted by mosquitos • Causes severe swelling

8. Lymph nodes • Oval structures clustered along lymphatic vessels that serve to filter lymph • Consists of capsule, cortex, and medulla • Cortex contains mostly lymphocytes • Medulla filled with macrophages

10. Accessory Structures • Spleen • Thymus • Tonsils • pharyngeal • palatine • lingual

12. Spleen • Size of a fist • Located in left superior abdominal cavity • Functions: • Lymphocyte storage & surveillance • Blood cleansing • Recycles blood products • Fetal erythrocyte production • Stores blood platelets

13. Thymus • Located in lower neck, upper thoracic region • Secretes hormones, thymosin & thymopoietin • Function: T-cell maturation • Decreases in size with age

14. Tonsils • Form ring around entrance to throat • Epithelial surface invaginates to form crypts that trap bacteria & particulate matter • Types: • Palatine tonsils - visible tonsils • Pharyngeal tonsil (adenoids) • Lingual tonsil - at base of tongue • Tubal tonsils - surround the openings to the auditory tubes

15. Other aggregates of lymphoid tissue • Peyer’s patches - nodules located in the ileum portion of the small intestine • Appendix • Destroy bacteria in the digestive system • Belong to MALT (Mucosa-Associated Lymphatic Tissue

16. Disorders of the Lymphatic System • Hodgkin’s disease - malignant cancer of the lymph nodes • Lymphoma - any tumor of the lymphoid tissue (benign or malignant) • Non-Hodgkin’s lymphoma - all cancers of lymphoid tissues except Hodgkin’s disease

17. Tonsilitis - inflammation of the tonsils • Mononucleosis - caused by Epstein-barr virus attacking the B-lymphocytes which are in turn attacked by oversized T-lymphocytes. These were misidentified orginally as monocytes.

18. Nonspecific Resistance

19. Mechanical Barriers • Skin - epidermis • Mucous membranes • Cilia - hair, mucus • Flushing mechanisms

20. Chemical Protection • Lysozymes - in tears & saliva • Sebum - • Gastric juice • Body secretions - • Acid = pH 3-5 • Mucus

21. Antimicrobial substances • Interferons • defend against viruses, suppress tumors and enhance phagocytosis; • stimulates production of PKR which interferes with viral replication • Complement • >20 proteins that attach and “lyse” the cell • opsonization (enhances phagocytosis) • enhances the inflammatory response

22. Non-specific Immunity • Phagocytosis • Macrophages, Neutrophils • chemotaxis, adherence, ingestion, destroy • Natural Killer Cells (NK) • Large granular lymphocytes • Attach and release “perforins”

23. Inflammation • swelling, redness, pain, heat • histamines = promote dilation & permeability • Phagocyte mobilization • Leukocytosis - leukocyte production • Margination - neutrophils collect inside nearby capillaries • Diapedesis - neutrophils squeeze out of capillaries into tissues • Chemotaxis - neutrophils are attracted to injury • Monocytes follow; become Macrophages

24. Fever • Pyrogens released by leukocytes & macrophages raise body temperature • Inhibits growth of microorganisms • Increases metabolic rate of cells • Can denature enzymes

25. Specific Immunity Characteristics: specificity memory self recognition

26. Types of Cells • Lymphocytes arise from hemocytoblasts in the bone marrow • B cells develop immunocompetence in the bone marrow • T cells - mature in thymus

27. Types of Immunity • Antibody-mediated immunity • humoral immunity • involves B cells and the production of antibodies • Cell - mediated immunity • cellular immunity • involves the destruction of intracellular pathogens by T cells

28. Antigens • Any substance that can elicit an immune response • Immunogenicity - “antibody-generating” • Haptens - incomplete antigens (allergens) • Major histocompatibility complex antigens (MHC-I, MHC-II) ; “Self”-proteins • Class I - found on all cells • Class II - found only on certain cells

29. Antibodies = immunoglobulins • Highly specific soluble proteins secreted by plasma cells in response to an antigen • Structure of an antibody • Heavy and light chains • Variable and constant regions • Up to a Billion different variables • Antigen-binding sites

32. Antibodies • Five classes of antibodies • IgM - first released; can fix complement • IgA - usually found in secretions • IgD - B-cell receptor • IgG - most abundant; crosses placenta; can fix complement • IgE - causes allergic reactions

33. Antibody - Mediated Immunity • B cells are activated by the presence of a foreign antigen which is taken into the B cell, processed and then displayed in combination with an MHC-II molecule the on the cell’s surface • Activated B cells develop into clones of antibody producing plasma cells • Plasma cells produce antibodies (2,000/sec) • Costimulation by Helper T cells useful

34. Functions of Antibodies • Agglutination • Precipitation • Neutralization • Enhanced phagocytosis • Complement activation

35. Immunological Memory • Primary response - first exposure • Secondary response - 2nd, 3rd, 4th, etc. • Faster • Higher Levels • More efficient

37. Active & Passive Immunity • Active = caused by encounter with antigens • Natural - acquired by infection & disease • Artificial - acquired by vaccination • Passive = caused by encounter with antibodies • Natural - acquired from Mom; antibodies cross placenta • Artificial - acquired from immune sera such as: gamma globulin, antivenom, antitoxins

38. Cell - Mediated Immunity • T cells recognize and respond only to processed antigen presented by an APC (antigen presenting cell) • Binding of T cell to macrophage causes secretion of interleukin-I which helps activate T helper cells (also called CD4 or T4 cells) • TH cells secrete IL-2 which enhances B cell activity and costimulates cytotoxic T cells (CD8 or T8 cells)

39. Types of Lymphocytes • Helper T cells - TH • Stimulates other B & T cells (co-stimulation) • Cytotoxic (killer)T cells - T8 • Kills invaded cells, cancer cells, rejects tissue • Delayed Hypersensitivity T cells - TDH • Stimulates macrophages • Suppressor T cells - TS • Slows or stops B & T cells • Memory T cells • remain in body for years for secondary response

40. Cytokines • Interferons • Interleukins • Lymphotoxins • Macrophage migration inhibitory factor • Perforins • Supressor factors • Complement

41. Immunodeficiencies • SCID - Severe Combined Immunodeficiency Syndrome • Acquired Immunodeficiencies • Disease induced; Hodgkins, Leukemia • Chemically induced; immune suppressing drugs • AIDS • Diagnosed 1981; Began ?

42. AutoImmune Disorders • Multiple Sclerosis - affects white matter of CNS • Myasthenia Gravis - destroys Ach receptors between nerves & muscles • Graves’ Disease - causes hyperthyroidism • Type I Juvenile Diabetes - destroys insulin-producing cells • Systemic Lupus Erythematosus - • Rheumatoid Arthritis - attacks joint tissues