Chapter 8

1. Chapter 8 Biology 25: Human Biology Prof. Gonsalves Los Angeles City College Loosely Based on Mader’s Human Biology,7th edition

3. Introduction Resistance: Ability to ward off disease. • Nonspecific Resistance: Defenses that protect against all pathogens. • Specific Resistance: Protection against specific pathogens. Susceptibility: Vulnerability or lack of resistance.

4. Protection Against Invading Pathogens 1. First Line of Defense: Non-specific natural barriers which restrictentry of pathogen. Examples: Skin and mucous membranes. 2. Second Line of Defense: Non-specific defenses that provide rapid local response to pathogen after it has entered body. Examples: Fever, phagocytes (macrophages and neutrophils), inflammation, and interferon. 3. Third lineof defense: Antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense. Examples: Antibodies and lymphocytes.

5. Defenses Against Infection

6. First Line of Defense: Skin is an Effective Barrier Against Infection by Most Pathogens

7. Second Line of Defense: Interferon is Nonspecific Inhibitor of Viral Infection

8. Inflammation is a Nonspecific Defense 1. Damaged cells release chemical signals: Histamine and other molecules. 2. Local response to chemical signals: • Increase in local blood flow and vascular permeability • Redness • Heat • Swelling • Pain 3. Phagocytic white blood cells come into area: Engulf bacteria, dead cell parts, and other microbes. 4. Tissue heals

9. Nonspecific Immunity • Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by bacteria. • Bacterial carbohydrates flag the cell for phagocytic attack. • 3 major groups of phagocytic cells: • Neutrophils: 1st to arrive at infection. • Mononuclear phagocyte system: • Macrophages and monocytes. • Organ-specific phagocytes.

10. Inflammatory Response: Nonspecific Defenses

12. Phagocytosis • Neutrophils and monocytes are able to squeeze through tiny gaps between adjacent endothelial cells.

13. Phagocytosis • Phagocytes engulf particles similar to amoeba. • Particle becomes surrounded by pseudopods. • Forms vacuole. • Vacuole fuses with lysosomes which digest the particle. • Lysosomes can be released into the infected area.

14. Phagocytes Intracellular killing of microbes Chemical secretion Regulate inflammation Extracellular killing Activation of clotting or anti-clotting Hormonal regulation

15. Fever • Cell wall of gram – bacteria contains endotoxin. • Endotoxin stimulate release of cytokines: • Interleukin-1, interleukin-6 and tumor necrosis factor: • Produce fever, increase sleepiness, and decrease plasma iron. • May be a component of nonspecific defense system.

16. Nonspecific Immunity • Endogenous pyrogens: • Cell wall of gram – bacteria contains endotoxin. • Endotoxin stimulates monocytes and macrophages to release cytokines: • Interleukin-1, interleukin-2, TNF. • Increased activity of neutrophils. • Increased production of interferon. • Produce fever, increase sleepiness, and decrease plasma iron.

17. Nonspecific Immunity • Interferons (cytokines) • Nonspecific, short-acting resistance to viruses. • Act as messengers that protect other cells in the vicinity from viral infection. • a inhibit viral replication, increases NK cells, induces MHC-I antigens. • b inhibit viral replication, increases NK cells, induces MHC-I antigens. • g activates macrophages, induces MHC-II antigens.

18. Third Line of Defense: The Immune Response Immunity: “Free from burden”. Ability of an organism to recognize and defend itself against specific pathogens or antigens. Immune Response: Involves production of antibodies and generation of specialized lymphocytes against specific antigens. Antigen: Molecules from a pathogen or foreign organism that provoke a specific immune response.

19. Antigens • Molecules that stimulate the production of antibodies. • Combine specifically with antibodies produced. • Foreign to blood and other body fluids. • Immune system can distinguish “self” molecules from nonself antigens. • Large, complex molecules can have different antigenic determinant sites.

20. Lymphatic and Immune System Components: Lymph, lymphatic vessels, bone marrow, thymus, spleen, and lymph nodes. Functions: • Defends against infection: bacteria, fungi, viruses, etc. • Destruction of cancer and foreign cells. • Synthesis of antibodies and other immune molecules. • Synthesis of white blood cells. Homeostatic Role: • Returns fluid and proteins that have leaked from blood capillaries into tissues. • Up to 4 liters of fluid every day. • Fluid returned near heart/venae cavae.

21. Lymphatic System

25. The Immune Response Destroys Specific Invaders Antigen: Molecule that elicits an immune response. “Antibody generating”. • Microbial antigens: Viral capsid, bacterial call wall, etc. • Nonmicrobial antigens: Pollen, latex, food, etc. Antibody: Protein found in blood plasma that attaches to antigen and helps counteract its effects. Vaccination or Immunization: Process in which harmless forms of antigen or pathogen are introduced into body to provoke an immune response.

26. Lymphocytes • Derived from stem cells in the bone marrow. • Stem cells produce the specialized blood cells. • Replace themselves by cell division so the stem cell population is not depleted. • Lymphocytes seed the thymus, spleen, and lymph nodes.

27. Lymphocytes • Lymphocytes that seed the thymus become T lymphocytes (T cells). • Have surface characteristics and immunological function that differ from other lymphocytes. • Do not secrete antibodies. • Must come in close or direct contact to destroy them. • T cells are 65 – 85% of the lymphocytes in blood and most in the germinal centers of lymph nodes and spleen.

28. Lymphocytes • Most of the lymphocytes that are not T cells are B lymphocytes (B cells). • Processed in the bone marrow. • Function in specific immunity. • B cells combat bacterial infections as well as some viral infections by secreting antibodies into the blood and lymph. • Provide humoral immunity (blood and lymph are body fluids (humors).

29. Lymphocytes Mount a Dual Immune Defense 1. Cell Mediated Immunity • Immunity that requires cell to cell contact. • Carried out by T cells: • Develop in the thymus. • Only recognize antigen associated with self-protein. • T cytotoxic cells: Important in defense against: • Cancer cells • Self cells infected with fungi, viruses, protozoans, and bacteria. • T helper cells: Play a central role in immunity. Act indirectly by controlling the immune functions of other cells: • Increased antibody production by B cells. • Increased phagocytosis by macrophages. • Increased killing of foreign and cancer cells.

31. Development of T and B Lymphocytes

32. T helper cells play a central role in immunity

33. Lymphokines • Interleukin-1: • Secreted by macrophages and other cells. • Activates T cells. • Interleukin-2: • Released by helper T cells. • Activates killer T cells. • Interleukin-3: • Serves as a growth factor. • Activates killer T cells. • Interleukin-4: • Secreted by T cells. • Required for proliferation and clone development of B cells.

34. Lymphocytes Mount a Dual Immune Defense 2. Humoral (Antibody Mediated) Immunity • Antibodies are found in our body fluids: • Blood • Lymph • Interstitial fluid • Antibodies are produced by B cells. • B cells develop in bone marrow. • Antibodies are specific molecules that circulate through out our body and attach to foreign antigens, marking them for destruction. • Foreign antigen does not have to be associated with a self antigen to be recognized. • Antibodies can be passed from one individual to another: • Mother-child: Mother’s antibodies cross placenta. Also found in breast milk. • Serum: Snake bite antivenom.

35. Antibodies • Antibody proteins are also known as immunoglobulins. • Found in the gamma globulin class of plasma proteins. • Different antibodies have different structure, as the antibodies have specific actions.

36. Antibodies Immunoglobulin Functions lgG Main form of antibodies in circulation: production increased after immunization; secreted during secondary response lgA Main antibody type in external secretions, such as saliva and mother’s milk lgE Responsible for allergic symptoms in immediate hypersensitivity reactions lgM Function as antigen receptors on lymphocyte surface prior to immunization; secreted during primary response lgD Function as antigen receptors on lymphocyte surface prior to immunization; other functions unknown

37. Active Immunity • Primary response: • First exposure to pathogen, immune response insufficient to combat disease. • Latent period of 5-10 days before measurable amounts of specific antibodies appear in blood.

38. Active Immunity • Secondary response: • Subsequent exposure to same antigen. • Antibody production is much more rapid. • Maximum antibody concentration reached in < 2 hrs. • Maintained longer period of time.

39. Clonal Selection Theory • B lymphocytes inherit the ability to produce a particular antibody. • T lymphocytes inherit the ability to respond to particular antigens. • Inherited specificity reflected in antigen receptor proteins on surface of lymphocytes.

40. Clonal Selection Theory • Exposure stimulates specific lymphocytes to divide many times until a large population of genetically identical cells (clone) is produced. • Antigens select lymphocytes that are already able to make antibodies.

43. Antibody Structure • 100 million trillion antibody molecules that contain 4 polypeptide chains. • Fab regions are variable, provide a specific bonding site for antigen. • B lymphocytes have antibodies that serve as receptors for antigens • Provides active immunity.

44. Antibodies are Protein Molecules that Recognize Specific Foreign Antigens

46. Antibodies Help Eliminate Foreign Antigens

47. Complement Proteins • Nonspecific defense system. • The combination of antibodies with antigens does not cause destruction of the antigens or pathogen. • Antibodies serve to identify the targets for immunological attack. • Identified antibodies activate the complement against specific invaders.

48. Activated Complement Proteins Direct destruction by MAC Vasodilation Increased capillary permeability Chemotaxis Opsinization

49. Complement Types • There are 11 complement proteins, designated C-1 to C-9. • Complement proteins can be subdivided into 3 components: • C1: recognization. • C4, C2, C3: activation. • C5-C9: attack (complement fixation).

50. Complement Fixation • Complement proteins attach to the cell membrane and destroy it. • Antibodies of IgG and IgM attach to antigens on invading cell membranes, bind to C1 activating the process. • Activated C1 hydrolyzes C4 into C4a and C4b. • C4b binds to the cell membrane. • C4b splits C2 into C2a and C2b.