MCB 3020, Spring 2005 Concepts of Immunology

1. MCB 3020, Spring 2005 Concepts of Immunology

2. Concepts of Immunology I: I. The immune system II. Nonspecific immunity III. Specific immunity IV. Antibodies

3. I. The immune system Cells, proteins, and supporting systems that kill or inactivate invaders and monitor every cell in the body for cancer. TB

4. A. Main activities of the immune system bacteria viruses toxins Kills or affects host cells cells infected with bacteria or viruses cancer cells transplanted tissues (rejection) sometimes attacks self (autoimmunity) contributes to allergies Kills or inactivates invaders TB

5. B. Recognition of nonself The immune system detects antigens expressed by pathogens and cancer cells. Antigens are "nonself"(foreign)molecules that interact with specific components of the immune system usually > 10,000 molecular weight proteins many polysaccharides certain teichoic acids TB

6. C. Key components 1. Blood cells 2. Lymphatic system TB

7. 1. Blood cells a. erythrocytes: red blood cells non-nucleated b. platelets: clotting aids non-nucleated c. leukocytes: white blood cells nucleated (contain nucleus) TB

8. c. Leukocytes (white blood cells) i. Phagocytes Neutrophils Monocytes Macrophages ii. Lymphocytes B-cells (antibody production) T-cells (cell-mediated immunity) Natural killer cells TB

9. Blood cells red blood cell monocyte neutrophil (polymorphonuclear leukocyte, PMN) TB

10. Bone marrow stem cell common precursor to blood and lymph cells Bone marrow stem cell Bone marrow stem cell Lymphoid precursor Lymphoid precursor Myeloid precursor Myeloid precursor Platelets Platelets T-cell B-cell T-cell B-cell Monocyte Monocyte PMN PMN Mast cell Mast cell Memory cell Memory cell Macrophage Plasma cell Macrophage Plasma cell

11. Blood fluids Remove cells and platelets Plasma (contains clotting proteins, antibodies, etc.) Remove clotted materials Serum (rich in antibodies) Blood

12. Lymph nodes Thymus Spleen MALT, (mucosal- associated lymphoid tissue) Picture 26 Bone marrow 2. Lymphatic system

13. Lymphatic system Lymph A pale watery fluid similar to blood, but lacking red blood cells. It contains immune proteins such as complement and antibodies and well as leukocytes (white blood cells) which are key cells of the immune system. TB

14. Lymphatic system Basic components a. Vessels for lymph circulation similar to veins b. Primary lymphoid organs Thymus Site of T-cell maturation Bone marrow Site of B-cell maturation c. Secondary lymphoid organs TB

15. c. Secondary lymphoid organs Organs rich in immune cells that filter the blood and lymph by trapping antigens and also provide sites for immune cell maturation • lymph nodes • spleen • MALT (Mucosal Associated Lymphoid Tissue) TB

16. • Lymph nodes Filter tissue fluids. Their size is somewhere between a grain of sand and a bean. Fluids from tissue spaces Lymph node Lymph vessels sites for antigen trapping and immune cell maturation, rich in T-cell, B-cells and macrophages TB

17. • Spleen Filters antigens from the blood. It is about the size of a fist and is located on the left side of the abdominal cavity. splenic vein spleen splenic artery TB the interior of the spleen is rich in immune cells

18. • MALT (Mucosal Associated Lymphoid Tissue) Collects antigens from the mucus membranes such as the respiratory and gastrointestinal tracts. It can be diffuse or as aggregated follicles. It is rich in immune cells. TB

19. Lymphatic pumping • Breathing and skeletal muscle contraction • pumps lymph. • Valves prevent back flow • Exercise increase lymph flow 10-15x TB

20. D. Circulation of immune system components Watery fluids containing various proteins and small molecules slowly leak out of the veins and into tissues. Pressure build in the tissues and these protein-containing fluids are taken up by lymph capillaries forming lymph. Lymph moves through the lymphatic system and returns to the bloodstream through either the thoracic duct or the right lymphatic duct. Each day about 50% of total blood proteins leak out of the capillaries and return to blood vial lymphatic vessels. 1. proteins TB

21. Lymphatic capillaries tissue cells curved arrows indicate fluid flow blood vessels lymphatic capillary TB spaces between cells are called interstitial spaces

22. 2. Circulation of leukocytes (white blood cells) Blood cells are made in the bone marrow and released into the blood stream. Leukocytes move from the blood to the spaces between tissue cells by "extravasation". Leukocytes then re-enter the lymphatic system and return to the blood stream thought the thoracic or right lymphatic ducts. TB

23. Extravasation Movement of cells through blood vessel walls tissue white blood cell vein interior endothelial cells tissue TB

24. II. Nonspecific immunity Immunity effective against many different invaders. anatomical defenses inflammation and fever professional phagocytes TB

25. A. Defenses of the skin dead skin cells epidermis dermis salt-skin associated lymphoid tissue, SALT. subcutaneous tissue TB

26. • Viruses cannot replicate on the dead cells of the outer skin. • Dead skin cells slough off taking adherent microbes with them. • Langerhans cells associated with the SALT phagocytose and destroy incoming microbes • The SALT initiates a specific immune response. • Cuts, insect bits and burns can breach the defenses of the skin. TB

27. B. Defenses of the mucus membranes microbes trapped in mucus mucus sloughed cell with adherent microbe epithelial cells MALT deeper tissues TB

28. • Mucus which is made of a mixture of proteins and polysaccharides sloughs off taking trapped microbes with it. • Mucus also contains lysozyme. • The MALT contains macrophages which engulf and destroy bacteria. • The MALT also initiates a specific immune response. TB

29. C. Professional phagocytes • Cells that can engulf and kill microbes • Most effective against extracellular • microbes. 1. neutrophils 2. monocytes 3. macrophages TB

30. engulf and destroy invading bacteria first line of defense against bacteria; motile (circulating) cells 2. Monocytes Circulating cells that migrate to tissues and become macrophages. 1. Neutrophils (PMNs) (polymorphonuclear leukocytes) TB

31. noncirculating cells engulf and kill bacteria and protozoa clean up dead cells and cell debris present antigens produce cytokines 3. Macrophages TB

32. a. Macrophage killing phagosome 1. engulfment macrophage bacterium lysosomes

33. phagolysosome fusion

34. 2. Digestion with lysosomal enzymes lysozyme proteases lipases nucleases TB

35. 3. Generation of oxidizing agents 1O2 (singlet oxygen) O2- (superoxide) H2O2 (hydrogen peroxide) HOCl (hypoclorous acid) These reactive oxygen species are generated within the phagolysosome TB

36. D. Microbial defense mechanisms against phagocytes carotenoids (quench singlet O2) phenolic glycolipids (scavenge reactive oxygen) leukocidins (kill phagocytes) capsules (polysacch. outside cell wall) (prevent phagocyte adherence) TB

37. III. Specific immunity Immunity effective against specific pathogens Involves antigen-specific leukocytes (white blood cells) B-lymphocytes (B-cells) T-lymphocytes (T-cells) TB

38. A. Properties of Specific Immunity specificity: recognizes specific target memory: rapid immune response in subsequent exposure to antigen (basis for vaccination) tolerance: usually doesn’t hurt self TB

39. B. B-cells •produce antibodies • involved in humoral immunity • each B-cell makes only one type of antibody C. T-cells •we'll talk about T-cells next time • some kill abnormal host cells • some regulate other immune cells TB

40. B-cells memory cells plasma cells (long-lived) (short lived) antigen restimulation several hours memory plasma antibodies cells cells activation several days TB

41. IV. Antibodies A. Importance B. Major Classes C. Structure D. Digestion E. Antigen binding TB

42. antigen antibodies Antibodies (immunoglobulins) Soluble immune system proteins that bind specific antigens. TB

43. A. Importance of antibody binding 2. marks invaders for attack by other immune system components 1. inactivates toxins 3. aids phagocytosis TB

44. B. Major classes IgG Major circulating antibody IgM First to appear after infection IgA Major secretory antibody IgE Involved in allergic reactions IgD Function not well understood TB

45. C. Structure IgG antigen binding sites heavy chain light chain disulfide bonds variable region = yellow (striped) constant region = light blue (solid) TB

46. D. Antibody structure: Fc and Fab fragments Fc fragment Fab fragments TB IgG papain (a protease)

47. Notes on IgG structure • Y-shaped molecule • four polypeptide chains • many disulfide bridges • 2 light chains (short chains) • 2 heavy chains • *Bivalent: two antigen binding sites TB

48. Notes on IgG structure • note the composition of Fab and Fc Fc fragment Fab fragments • variable regions form the antigen- binding site and  define specificity • constant regions are nearly identical in most IgG molecules TB

49. E. Antigen binding antigen antibodies epitope = antigenic determinant the part of the antigen bound by the antibody (can be as few as 4 to 5 amino acids) TB

50. Study objectives 1. What are the main functions of the immune system? 2. Know the cell types of the immune system and their functions. Leukocytes (white blood cells) are a key components of the immune system. Leukocytes include lymphocytes (B-cells and T-cells,) monocytes, neutrophils and natural killer cells. B-cells make antibodies. T-cells kill virus-infected cells and regulate other immune cells. Monocytes become tissue macrophages which phagocytose invading microorganisms, foreign bodies, and damaged an old cells. Neutrophils phagocytose and destroy invading bacteria. Natural killer cells kill virus infected cells and some tumor cells. 3. Know what antigens and antibodies are. 4. Know the basic components of the lymph system and their functions. The primary lymphoid organs are the bone marrow and the thymus. All blood cells are made in the bone marrow. B-cells mature in the bone marrow and T-cells mature in the thymus. The secondary lymphoid organs are the lymph nodes, spleen and mucosal associated lymphoid tissue (MALT). The lymph nodes filter tissue fluids. The spleen filters the blood and the MALT collects antigens from the respiratory and gastrointestinal tracts.